Evaluation and Treatment of Tinnitus Com
Evaluation and Treatment of Tinnitus Com
Number 122
Evaluation and
Treatment of Tinnitus:
Comparative
Effectiveness
Comparative Effectiveness Review
Number 122
Prepared for:
Agency for Healthcare Research and Quality
U.S. Department of Health and Human Services
540 Gaither Road
Rockville, MD 20850
www.ahrq.gov
Prepared by:
McMaster University Evidence-based Practice Center
Hamilton, Ontario, Canada
Investigators:
M. Kathleen Pichora-Fuller, Ph.D.
Pasqualina Santaguida, Ph.D.
Amanda Hammill, M.A.
Mark Oremus, Ph.D.
Brian Westerberg, M.D.
Usman Ali, M.D., M.Sc.
Christopher Patterson, M.D.
Parminder Raina, Ph.D.
The information in this report is intended to help health care decisionmakers—patients and
clinicians, health system leaders, and policymakers, among others—make well-informed
decisions and thereby improve the quality of health care services. This report is not intended to
be a substitute for the application of clinical judgment. Anyone who makes decisions concerning
the provision of clinical care should consider this report in the same way as any medical
reference and in conjunction with all other pertinent information, i.e., in the context of available
resources and circumstances presented by individual patients.
This report may be used, in whole or in part, as the basis for development of clinical practice
guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage
policies. AHRQ or U.S. Department of Health and Human Services endorsement of such
derivative products may not be stated or implied.
This document is in the public domain and may be used and reprinted without special
permission. Citation of the source is appreciated.
Persons using assistive technology may not be able to fully access information in this report. For
assistance contact [email protected].
None of the investigators have any affiliations or financial involvement that conflicts with the
material presented in this report.
ii
Preface
The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-based
Practice Centers (EPCs), sponsors the development of systematic reviews to assist public- and
private-sector organizations in their efforts to improve the quality of health care in the United
States. These reviews provide comprehensive, science-based information on common, costly
medical conditions, and new health care technologies and strategies.
Systematic reviews are the building blocks underlying evidence-based practice; they focus
attention on the strength and limits of evidence from research studies about the effectiveness and
safety of a clinical intervention. In the context of developing recommendations for practice,
systematic reviews can help clarify whether assertions about the value of the intervention are
based on strong evidence from clinical studies. For more information about AHRQ EPC
systematic reviews, see www.effectivehealthcare.ahrq.gov/reference/purpose.cfm.
AHRQ expects that these systematic reviews will be helpful to health plans, providers,
purchasers, government programs, and the health care system as a whole. Transparency and
stakeholder input are essential to the Effective Health Care Program. Please visit the Web site
(www.effectivehealthcare.ahrq.gov) to see draft research questions and reports or to join an
email list to learn about new program products and opportunities for input.
We welcome comments on this systematic review. They may be sent by mail to the Task
Order Officer named below at: Agency for Healthcare Research and Quality, 540 Gaither Road,
Rockville, MD 20850, or by email to [email protected].
iii
Acknowledgments
The researchers at the Evidence-based Practice Center (EPC) would like to acknowledge the
following people for their contributions.
We are grateful to our Task Order Officers at the Agency for Healthcare Research and
Quality, Supriya Janakiraman and Chuck Shih, for their support and guidance throughout the
development of this report. Members of the Technical Expert Panel were instrumental in the
formation of the parameters and goals of this review. They are listed below.
We would also like to thank those who worked so conscientiously retrieving and screening
citations, abstracting data, preparing figures, and editing the report: Julianna Beckett, Judy
Brown, Amy Bustamam, Patricia Carson, Bryan Cheeseman, Roxanne Cheeseman, Louise Don-
Wauchope, Angela Eady, Mary Gauld, Suzanne Johansen, Sara Kaffashian, Meghan Kenny,
Leah Macdonald, Maureen Rice, Carrie Sniderman, Rob Stevens, Marroon Thabane, and Ian
White. Our thanks to Harry Shannon and Nancy Santesso for providing statistical assistance
along the way.
Thank you to our Peer Reviewers for the thoughtful comments.
Key Informants
In designing the study questions, the EPC consulted several Key Informants who represent
the end-users of research. The EPC sought the Key Informant input on the priority areas for
research and synthesis. Key Informants are not involved in the analysis of the evidence or the
writing of the report. Therefore, in the end, study questions, design, methodological approaches,
and/or conclusions do not necessarily represent the views of individual Key Informants.
Key Informants must disclose any financial conflicts of interest greater than $10,000 and any
other relevant business or professional conflicts of interest. Because of their role as end-users,
individuals with potential conflicts may be retained. The Task Order Officer and the EPC work
to balance, manage, or mitigate any conflicts of interest.
The list of Key Informants who participated in developing this report follows:
iv
Keith Folkert, M.D., M.H.A.
Medical Director
Blue Cross Blue Shield of Minnesota
St. Paul, MN
v
James A. Henry, Ph.D.
Research Career Scientist
National Center for Rehabilitative Auditory Research
VA Medical Center
Research Professor in Otolaryngology/Head and Neck Surgery
Oregon Health & Science University
Portland, OR
Peer Reviewers
Prior to publication of the final evidence report, EPCs sought input from independent Peer
Reviewers without financial conflicts of interest. However, the conclusions and synthesis of the
scientific literature presented in this report does not necessarily represent the views of individual
reviewers.
Peer Reviewers must disclose any financial conflicts of interest greater than $10,000 and any
other relevant business or professional conflicts of interest. Because of their unique clinical or
content expertise, individuals with potential nonfinancial conflicts may be retained. The TOO
and the EPC work to balance, manage, or mitigate any potential nonfinancial conflicts of interest
identified.
The list of Peer Reviewers follows:
vi
Michael Borenstein, Ph.D.
Director, Biostat Inc.
Englewood, NJ
vii
Evaluation and Treatment of Tinnitus: Comparative
Effectiveness
Structured Abstract
Objectives. A review was undertaken to evaluate the peer-reviewed literature on three areas of
tinnitus management for the following Key Questions (KQs): (1) measures used to assess
patients for management needs (KQ1); (2) effectiveness of treatments (KQ2); and (3)
identification of prognostic factors (KQ3).
Results. From 9,725 citations, 52 eligible publications were extracted for data. None were
eligible for KQ1 or KQ3. From the 52 publications eligible for KQ2, 17 evaluated
pharmacological interventions; 11 evaluated medical interventions (low-level laser, acupuncture,
transcranial magnetic stimulation); 5 evaluated sound technologies; and 19 evaluated
psycholocal/behavioral interventions. Data on adverse effects were generally poorly collected
and reported.
Conclusions. There is low strength of evidence (SOE) indicating that cognitive behavioral
therapy interventions improve tinnitus-specific quality of life relative to inactive controls. For
pharmacological interventions, SOE is low for improvements to subjective loudness from
neurotransmitter drugs versus placebo; insufficient for antidepressants, other drugs, and food
supplements with respect to subjective loudness; and insufficient for all other outcomes. There is
insufficient SOE to suggest that medical interventions improve outcomes relative to inactive
controls; sleep and global quality of life were not evaluated for medical interventions. The SOE
for the adverse effect of sedation in pharmacological studies was judged insufficient. Future
research should address the substantial gaps identified for KQ1 and KQ3. For KQ2, future
research should concentrate on improving collection of adverse effects, calculating sample size,
and specifying doses for interventions.
viii
Contents
Executive Summary .................................................................................................................ES-1
Introduction ....................................................................................................................................1
Background ................................................................................................................................1
Classification........................................................................................................................2
Measurement ........................................................................................................................2
Treatment .............................................................................................................................3
Scope and Key Questions ..........................................................................................................7
Key Questions and Eligibility Data .....................................................................................8
Analytic Framework ................................................................................................................12
Methods .........................................................................................................................................13
Topic Refinement.....................................................................................................................13
Search Strategy ........................................................................................................................13
Grey Literature ...................................................................................................................14
Criteria for Inclusion/Exclusion of Studies in the Review ......................................................14
Data Extraction ........................................................................................................................17
Assessment of Methodological Risk of Bias of Individual Studies .........................................18
Assessing Applicability .....................................................................................................18
Data Synthesis ..........................................................................................................................19
Qualitative Synthesis .........................................................................................................19
Quantitative Synthesis .......................................................................................................19
Rating the Body of Evidence ...................................................................................................20
Peer Review and Public Comment ..........................................................................................21
Results ...........................................................................................................................................22
KQ1. In patients with symptoms of tinnitus (e.g. ringing in the ears, wooshing sounds, etc.)
what is the comparative effectiveness of methods used to identify patients for further
evaluation or treatment? ...........................................................................................................22
KQ2. In adults with subjective idiopathic (nonpulsatile) tinnitus, what is the comparative
effectiveness (and/or potential harms) of medical/surgical, sound treatment/technological, or
psychological/behavioral interventions, including combinations of interventions? ................23
Pharmacological or Food Supplement Interventions .........................................................23
Medical Interventions ........................................................................................................48
Characteristics of Included Studies ..............................................................................48
Risk of Bias for Medical Interventions ........................................................................56
Results for Medical Interventions by Outcome ...........................................................57
Sound Technology Interventions .......................................................................................66
Characteristics of Included Studies ..............................................................................67
Risk of Bias for Sound Technologies ..........................................................................69
Results for Sound Technologies by Outcome ..............................................................70
Psychological and Behavioral Interventions ......................................................................72
Characteristics of Included Studies ..............................................................................73
Risk of Bias for Psychological/Behavioral Interventions ............................................81
Results for Psychological/Behavioral Interventions by Outcome ...............................82
KQ3. For adults with subjective idiopathic tinnitus, what prognostic factors, patient
characteristics, and/or symptom characteristics affect final treatment outcomes? ................102
ix
Discussion....................................................................................................................................103
Overview ................................................................................................................................103
Studies Involving Pharmacological and Food Supplement Interventions .......................106
Studies Involving Medical Interventions .........................................................................108
Studies Involving Sound Technologies ...........................................................................109
Studies Involving Psychological/Behavioral Interventions .............................................110
Applicability ..........................................................................................................................111
Comparative Effectiveness Review Limitations ....................................................................113
Summary/Conclusions ...........................................................................................................114
Future Research Recommendations .......................................................................................115
Population ........................................................................................................................115
Intervention ......................................................................................................................116
Comparator and Study Design .........................................................................................116
Outcomes .........................................................................................................................116
Other ................................................................................................................................117
References ...................................................................................................................................118
Tables
Table A. Inclusion and exclusion criteria ..................................................................................ES-4
Table B. Summary of findings for Key Question 2: Pharmacological or food supplement
interventions ...............................................................................................................................ES-7
Table C. Summary of findings for Key Question 2: Medical interventions ..............................ES-8
Table D. Summary of findings for Key Question 2: Sound technology interventions ............ES-10
Table E. Summary of findings for Key Question 2: Psychological and behavioral
interventions .............................................................................................................................ES-11
Table 1. Some pharmacological treatments for tinnitus ..................................................................4
Table 2. Inclusion and exclusion criteria .......................................................................................15
Table 3. Interventions and comparators used in studies that evaluate pharmacological and food
supplement interventions and outcomes ........................................................................................26
Table 4. Outcome measurements used in pharmacological and food supplement intervention
studies ............................................................................................................................................28
Table 5. Strength of evidence: Studies that evaluate pharmacological and food supplement
interventions compared to inactive control and report tinnitus-specific quality of life outcomes.32
Table 6. Strength of evidence: Studies that evaluate pharmacological and food supplement
interventions compared to inactive control and report subjective loudness outcomes ..................33
Table 7. Strength of evidence: Studies that evaluate pharmacological and food supplement
interventions compared to inactive control and report sleep disturbance outcomes .....................34
Table 8. Strength of evidence: Studies that evaluate pharmacological and food supplement
interventions compared to inactive control and report anxiety symptoms outcomes ....................35
Table 9. Strength of evidence: Studies that evaluate pharmacological and food supplement
interventions compared to inactive control and report depression symptoms outcomes...............36
Table 10. Strength of evidence: Studies that evaluate pharmacological and food supplement
interventions compared to inactive control and report global quality of life outcomes ................37
Table 11. Treatment emergent adverse effects reported in studies evaluating pharmacological and
food supplement interventions .......................................................................................................38
Table 12. Strength of evidence: Studies that evaluate pharmacological and food supplement
interventions compared to inactive control and report on the adverse effect of sedation..............41
x
Table 13. Details of the devices, dose and placement of rTMS and electromagnetic stimulation
interventions ...................................................................................................................................50
Table 14. Interventions and comparators used in studies that evaluate medical interventions and
outcomes ........................................................................................................................................54
Table 15. Outcome measurements used in medical intervention studies ......................................56
Table 16. Strength of evidence by medical interventions in the treatment of tinnitus for the
outcome of tinnitus-specific quality of life in studies with inactive comparators .........................59
Table 17. Strength of evidence by medical interventions in the treatment of tinnitus for the
outcome of loudness for studies with inactive comparators ..........................................................61
Table 18. Strength of evidence by medical interventions in the treatment of tinnitus for the
outcome of anxiety symptoms for studies with inactive comparators ...........................................61
Table 19. Strength of evidence by medical interventions in the treatment of tinnitus for the
outcome of depression symptoms for studies with inactive comparators......................................62
Table 20. Description of reported adverse effects in the medical intervention studies .................63
Table 21. Interventions and comparators used in studies that evaluate sound
treatment/technology interventions and outcomes.........................................................................68
Table 22. Outcome measurements used in sound technology intervention studies .......................69
Table 23. Interventions and comparators used in studies that evaluate psychological and
behavioral interventions and outcomes ..........................................................................................76
Table 24. Outcome measurements used in psychological and behavioral intervention studies ....80
Table 25. Strength of evidence by psychological and behavioral interventions in the treatment of
tinnitus for the outcome of tinnitus-specific quality of life ...........................................................85
Table 26. Strength of evidence by psychological and behavioral interventions in the treatment of
tinnitus for the outcome of subjective loudness .............................................................................87
Table 27. Strength of evidence by psychological and behavioral interventions in the treatment of
tinnitus for the outcome of sleep disturbance ................................................................................89
Table 28. Strength of evidence by psychological and behavioral interventions in the treatment of
tinnitus for the outcome of anxiety symptoms ...............................................................................90
Table 29. Strength of evidence by psychological and behavioral interventions in the treatment of
tinnitus for the outcome of depression symptoms .........................................................................93
Table 30. Strength of evidence by psychological and behavioral interventions in the treatment of
tinnitus for the outcome of global quality of life ...........................................................................95
Figures
Figure A. Analytic framework ...................................................................................................ES-2
Figure 1. Analytic framework ........................................................................................................12
Figure 2. Flow diagram of citations in the Comparative Effectiveness Review of tinnitus ..........22
Figure 3. Distribution of methodological risk of bias criteria of randomized controlled trials for
the pharmacological and food supplement interventions...............................................................30
Figure 4. Studies with inactive comparators that evaluate pharmacological and food supplement
interventions and report tinnitus-specific quality of life outcomes ...............................................42
Figure 5. Studies with inactive comparators that evaluate pharmacological and food supplement
interventions and report subjective loudness outcomes .................................................................43
Figure 6. Studies with inactive comparators that evaluate pharmacological and food supplement
interventions and report sleep disturbances outcomes ...................................................................44
Figure 7. Studies with inactive comparators that evaluate pharmacological and food supplement
interventions and report anxiety symptom outcomes ....................................................................45
xi
Figure 8. Studies with inactive comparators that evaluate the pharmacological and food
supplement interventions and report depression symptoms outcomes ..........................................46
Figure 9. Studies with inactive comparators that evaluate pharmacological and food supplement
interventions and report global quality of life outcomes ...............................................................47
Figure 10. Proportion of medical intervention studies achieving criteria for risk of bias .............57
Figure 11. Studies with inactive comparators that evaluate medical interventions and report
tinnitus-specific quality of life outcomes .......................................................................................64
Figure 12. Studies with inactive comparators that evaluate medical interventions and report
subjective loudness outcomes ........................................................................................................65
Figure 13. Distribution of methodological risk of bias criteria of randomized controlled trials for
the sound technology interventions ...............................................................................................70
Figure 14. Distribution of risk of bias scores of randomized controlled trials for the
psychological and behavioral category (n=19) ..............................................................................82
Figure 15. Studies with inactive comparators that evaluate psychological and behavioral
interventions and report tinnitus-specific quality of life outcomes ...............................................96
Figure 16. Studies with inactive comparators that evaluate psychological and behavioral
interventions and report subjective loudness outcomes .................................................................97
Figure 17. Studies with inactive comparators that evaluate psychological and behavioral
interventions and report sleep disturbance outcomes ....................................................................98
Figure 18. Studies with inactive comparators that evaluate psychological and behavioral
interventions and report anxiety symptoms outcomes ...................................................................99
Figure 19. Studies with inactive comparators that evaluate psychological and behavioral
interventions and report depression symptoms outcomes ...........................................................100
Figure 20. Studies with inactive comparators that evaluate psychological and behavioral
interventions and report global quality of life outcomes .............................................................101
Appendixes
Appendix A. Search Strategy
Appendix B. Data Extraction Forms
Appendix C. Excluded Studies
Appendix D. Publications Not Eligible for Extraction
Appendix E. Characteristics of Included Studies Evidence Tables
Appendix F. List of Ongoing Clinical Trials Evaluating Interventions To Treat Idiopathic
Tinnitus Registered in Clinicaltrials.gov
xii
Executive Summary
Background
Tinnitus is the perception of sound in the absence of an external auditory stimulus; as such,
tinnitus is a symptom, not a disease. An estimated 16 percent of the American population (50
million people) experience tinnitus, with up to 16 million seeking medical help and 2 million
being unable to lead a normal life.1 The prevalence of tinnitus increases with age and noise
exposure.2,3 Additionally, tinnitus is an increasing problem in more recent birth cohorts.4
A variety of conditions and experiences can lead to tinnitus, but the exact physiology is still
unknown. Patients are often described as presenting with symptoms of either objective or
subjective tinnitus. Objective tinnitus is perceptible by patients and examiners. Subjective
tinnitus is perceptible only by patients, yet is not due to a hallucination. Both forms of tinnitus
may or may not be idiopathic. Some investigators have argued that tinnitus should be classified
by origin, either as somatic or neurophysiologic.5 In this review, we will use the term subjective
idiopathic tinnitus, rather than neurophysiologic tinnitus, because it is the term most commonly
used in the current literature. Subjective idiopathic tinnitus is also the most commonly diagnosed
type of tinnitus.6
Treatments for subjective idiopathic tinnitus are wide ranging in scope and may include
medical/surgical treatments, sound treatments/technologies, and psychological/behavioral
treatments. For the present review, treatment groups revolve around four main categories of
intervention: pharmacological or food supplement, medical/surgical, sound technology, and
psychological/behavioral.
Analytic Framework
Following consultation with Key Informants, the Agency for Healthcare Research and
Quality (AHRQ) Task Order Officer, and the investigative team, key research questions were
ES-1
developed. Figure A shows a flow diagram indicating the relationship between research
questions in this comparative effectiveness review (CER). This framework depicts the KQ as
outlined in the PICOTS (population(s), interventions, comparators, outcomes, timing or
followup, and setting) format. The PICOTS components for each KQ are provided in full detail
in Table A.
Methods
Search Strategy
The search was conducted in six databases—MEDLINE®, Embase®, Cochrane CENTRAL,
PsycINFO®, AMED©, and CINAHL®—as well as the grey literature, from January 1970 to June
2012. The search strategy used medical subject headings (MeSH®), keywords, and text words,
including “tinnitus” and “humans not animals,” with a limit to English-language citations. The
search also included the following Web sites: American Tinnitus Association, Association for
Research in Otolaryngology, American Academy of Audiology, Emory University Tinnitus and
Hyperacusis Center, Tinnitus Research Initiative, and Deafness Research UK. Reference lists of
eligible studies were also reviewed at full-text screening.
ES-2
pathologies (mechanics, otitis media, otosclerosis, etc.), when interventions were stapedectomy
or tympanoplasty, or when interventions were focused on determining whether patients had
psychosomatic tinnitus. See Table A for inclusion and exclusion criteria.
ES-3
Table A. Inclusion and exclusion criteria (continued)
Category Inclusion Criteria Exclusion Criteria
Interventions KQ1: Direct observation or observation of sound KQ1: Nondirect observations
with stethoscope; referral to a health professional KQ2: No exclusions for interventions
with expertise on managing tinnitus (i.e., KQ3: No exclusions for interventions
otolaryngologist, audiologist, neurologist, mental
health professional); administration of
scales/questionnaires to assess severity (THI, TRQ,
TSI, VAS, etc.)
KQ2: Any treatment/therapy used to reduce/help
cope with tinnitus, including but not limited to the
following:
Medical/Surgical
• Pharmacological treatments:
• Tricyclic antidepressants (e.g.,
amitriptyline, nortriptyline, and
trimipramine)
• Selective serotonin-reuptake inhibitors:
fluoxetine and paroxetine
• Other: trazodone; anxiolytics (e.g.,
alprazolam); vasodilators and vasoactive
substances (e.g., prostaglandin E1);
intravenous lidocaine; gabapentin; Botox
(botulinum toxin type A); and pramipexole)
• Laser treatments
• TMJ treatment: dental orthotics and self-care,
surgery
• Transcranial magnetic stimulation
• Hyperbaric oxygen therapy
• Complementary and alternative medicine
therapies: Gingko biloba extracts; acupuncture;
diet, lifestyle, and sleep modifications (caffeine
avoidance, exercise)
Sound Treatments/Technologies
• Hearing aids, cochlear implants, sound
generators, maskers
• Neuromonics
Psychological/Behavioral
• Cognitive behavioral therapy, biofeedback,
education, relaxation therapies, Progressive
Tinnitus Management, tinnitus retraining therapy
Combination Therapies
• Any combination of tinnitus interventions (e.g.,
pharmacological treatment with cognitive
behavioral therapy)
KQ3: Any treatment/therapy used to
reduce/help/cope with tinnitus, including but not
limited to those described in KQ2
ES-4
Table A. Inclusion and exclusion criteria (continued)
Category Inclusion Criteria Exclusion Criteria
Comparators KQ1: Different clinical evaluation methods used to KQ1: No exclusions
characterize a diagnosis and measure severity of KQ2: No comparator/control
subjective idiopathic tinnitus KQ3: No exclusions
KQ2: Placebo, no treatment, wait list, treatment as
usual, other intervention/treatment with control
KQ3:
• Prognostic factors: length of time to treatment
after onset, audiological factors (degree and type
of hearing loss, hyperacusis, loudness tolerance,
masking criteria, etc.), head injury, anxiety
symptoms, mental health disorders, and duration
of tinnitus
• Patient characteristics: age, sex, race, medical or
mental health comorbidities, socioeconomic
factors, noise exposure (environmental,
recreational, and work related [including active
and past military duty, and occupational
hazards]), involvement in litigation, third-party
coverage
• Symptom characteristics: origin/presumed
etiology of tinnitus, tinnitus duration since onset,
subcategory of tinnitus, severity of tinnitus
Outcomes KQ1: Final outcome: no treatment, need for No exclusions
specialized treatment (e.g., audiology,
otolaryngology, neurology, mental health care),
extent of intervention
KQ2: Sleep disturbance, discomfort, anxiety
symptoms, depression symptoms, subjective
loudness, quality of life, tinnitus severity, adverse
effects (worsening of tinnitus, sedation, surgical
complications)
KQ3: Time until improvement, sleep disturbance,
discomfort, anxiety symptoms, depression
symptoms, subjective loudness, quality of life,
return to “normal” work, adverse effects (worsening
of tinnitus, sedation, surgical complications)
Publication English Non-English
language
Study design All KQs: RCTs or observational studies with true • Systematic reviews and narrative
control groups (e.g., cohort studies, case-control reviews (excluded but pulled for full
studies) reference list review), case
All KQs: Original research studies providing reports/studies, and case series
sufficient detail about methods and results to enable • Editorials, comments, letters, opinion
use and aggregation of the data and results pieces, abstracts, and Webcasts
All KQs: Possibility of extracting relevant outcomes
from data in the papers
Controlled experimental studies (manipulation of
treatment)
Setting All KQs: Primary care, specialty care (audiology, No exclusions
otolaryngology, neurology, mental health),
university research, Internet
ES-5
Table A. Inclusion and exclusion criteria (continued)
Category Inclusion Criteria Exclusion Criteria
Other criteria Studies must address 1 or more of the following for No other exclusions
tinnitus:
KQ1: Instruments used to identify patients for
further evaluation or treatment
KQ2: Treatment modality
KQ3: Predictors of treatment outcomes (prognostic
factors, patient characteristics, and symptom
characteristics)
Abbreviations: Dx = diagnosis; KQ = Key Question; RCT = randomized controlled trial; THI = Tinnitus Handicap Inventory;
TMJ = temporomandibular joint; TRQ = Tinnitus Reaction Questionnaire; TSI = Tinnitus Severity Index; VAS = visual analog
scale
Results
The initial literature search yielded 9,725 citations; 834 citations (8.6 percent) passed title
and abstract screening. From the studies screened at full text, 52 eligible publications were
extracted for data. None were eligible for KQ1 or KQ3.
KQ1. In patients with symptoms of tinnitus (ringing in the ears, whooshing
sounds, etc.), what is the comparative effectiveness of methods used to
identify patients for further evaluation or treatment?
No studies were found to address this KQ.
KQ2. In adults with subjective idiopathic (nonpulsatile) tinnitus, what is the
comparative effectiveness (and/or potential harms) of medical/surgical,
sound treatment/technological, or psychological/behavioral interventions,
including combinations of interventions?
ES-6
Deanxit versus placebo (with each participant given 1 mg clonazepam in addition to Deanxit or
placebo).24 Four papers evaluated food supplements, with two25,26 focused on Gingko biloba,
one27 on zinc, and one28 on honeybee larvae. All food supplements were compared with placebo
(which was hydrogenated dextrin in the larvae study). All of the studies were RCTs.
Adverse effects spanned a range of clinical severity, from dry or sour mouth14,15 to
confusion,18 but generally subsided after discontinuation of treatment. Four studies14,15,18,19
reported symptoms of sedation (sleepiness, drowsiness) during the use of antidepressants
(trazodone and paroxetine) and neurotransmitter drugs (baclofen, alprazolam). The findings for
sedation were inconsistent and imprecise, as estimates of affected patients were poorly
characterized; the SOE for sedation was insufficient in patients with tinnitus.
ES-7
Table B. Summary of findings for Key Question 2: pharmacological or food supplement
interventions (continued)
Outcome # of Articles Overall Strength of Evidence Comment
12-14,16,24,28
Depression 6 Insufficient for antidepressants, The strength of evidence is insufficient to conclude
symptoms food supplements, and other whether sertraline, paroxetine, nortriptyline, honeybee
drugs larvae, and Deanxit showed improvements in
depression symptoms compared with placebo.
Medical Interventions
Eleven studies were included for medical interventions in KQ2 (Table C). Six29-34 of these
evaluated repetitive transcranial magnetic stimulation (rTMS) or electromagnetic stimulation;
three evaluated low-level laser therapy (LLLT);35-37 and one each evaluated acupuncture38 and
acoustic coordinated reset neuromodulation (ACRN) therapy.39 All the studies in the medical
intervention group have small sample sizes (n<60).
Adverse effects were not consistently reported or specified in the methods of the studies.
None of the studies in the medical interventions group reported dropouts related to adverse
effects. In general, adverse effects were transient and mild.
ES-8
Table C. Summary of findings for Key Question 2: medical interventions
Outcome # of Articles Overall Strength of Evidence Comment
29,30,32,33,35-
Tinnitus- 9 Insufficient for all interventions Although most interventions showed no differences
39
specific relative to placebo, the overall strength of evidence was
quality of life insufficient because of high risk of bias and inconsistent
and imprecise effect estimates.
ES-9
Table D. Summary of findings for Key Question 2: sound technology interventions
Outcome # of Articles Overall Strength of Evidence Comment
40-43
Tinnitus- 4 Insufficient There were no statistically significant differences
specific between treatments in any of the studies, although
quality of life benefits were reported for hearing aids, sound
generators, and Neuromonics. However, the overall
strength of evidence is insufficient to conclude whether
these findings represent true effects because of high
risk of bias and imprecise estimates.
41-43
Subjective 3 Insufficient There were no statistically significant differences
loudness between treatments in any of the studies, although
benefits were reported for both hearing aids and sound
generators. However, the overall strength of evidence
is insufficient to conclude whether these findings
represent true effects because of high risk of bias and
imprecise estimates.
Sleep 0 Not applicable Not applicable.
disturbance
41
Anxiety 1 Insufficient All groups in the study demonstrated improvement, but
symptoms adding a noise generator to tinnitus education or
cognitive behavioral therapy did not increase treatment
benefits. However, the overall strength of evidence is
insufficient to conclude whether these findings
represent true effects because of high risk of bias and
imprecise estimates of unknown consistency.
41
Depression 1 Insufficient A single study with high risk of bias showed no benefit
symptoms from cognitive behavioral therapy with or without noise
generation.
41-43
Global 3 Insufficient Benefit was reported for all interventions involving
quality of life hearing aids or sound generators, but there were no
43
differences depending on the technology used. No
benefits were reported for any other interventions.
However, the overall strength of evidence is insufficient
to conclude whether these findings represent true
effects because of high risk of bias and imprecise
estimates.
ES-10
Table E. Summary of findings for Key Question 2: psychological and behavioral interventions
Outcome # of Articles Overall Strength of Evidence Comment
45-63
Tinnitus- 19 Low evidence of effect for CBT Benefit for TSQoL is suggested by 6 CBT interventions.
specific However, because of high risk of bias and imprecise
quality of life effect estimates (i.e., only studies with group sample
sizes greater than 20 showed results significantly in
favor of treatment compared with inactive controls),
confidence is low that these findings lie close to the
true effects for this outcome.
Insufficient for TRT and yoga Only single studies with high risk of bias evaluated
TRT and yoga.
51,53,56,60,63
Anxiety 5 Low evidence of no effect for Although treatment benefits were shown for 1
symptoms CBT intervention (self-help book + telephone therapy),
overall, consistent evidence suggests that there was no
effect for CBT on anxiety symptoms. However,
because of high risk of bias and imprecise effect
estimates, confidence is low that these findings lie
close to the true effects for this outcome.
Insufficient for TRT and Only single studies with high risk of bias evaluated
relaxation TRT and relaxation.
ES-11
Table E. Summary of findings for Key Question 2: psychological and behavioral interventions
(continued)
Outcome # of Articles Overall Strength of Evidence Comment
49,51,53,55-
Depression 11 Low evidence of no effect for Although there are some treatment benefits with
60,62,63
symptoms CBT various forms of CBT, as well as an intervention
involving relaxation and distraction, overall, consistent
evidence suggests that there was no effect for CBT on
depression symptoms. However, because of high risk
of bias and imprecise effect estimates, confidence is
low that these findings lie close to the true effects for
this outcome.
KQ3. For adults with subjective idiopathic tinnitus, what prognostic factors,
patient characteristics, and/or symptom characteristics affect final treatment
outcomes?
No studies were found to address this KQ.
ES-12
years.4 The finding of generational differences suggests that reports of tinnitus tend to increase
with more recent birth cohorts compared with earlier birth cohorts. Researchers should explore
age and cohort differences as programs to treat, and possibly even programs to prevent, tinnitus
continue to be developed and evaluated.
Tinnitus is a chronic condition. The longest followups in the included studies did not exceed
16 weeks in pharmacological and food supplement studies and 26 weeks in medical
interventions. However, followup was extended to 12 months in all of the studies evaluating
sound-based treatments40,42,43 and even to 18 months for one study.41 For the psychological and
behavioral interventions, many studies evaluated the effectiveness of treatment immediately after
treatment, as well as at one or more later followups (up to 18 months60). Thus, for the
pharmacological and medical intervention categories, the included studies did not provide data
on the medium- to long-term effects of the active treatments.
Many of the studies in this review were conducted in Europe, where the professional model
of hearing care/audiology is different from that typically seen in the United States. In the United
States, the coping/CBT-oriented interventions fall more within the scope of practice of
psychologists than audiologists. If future interventions were to require more of this type of
psychological intervention, there would need to be a shift in the training of audiologists or a shift
to more team-oriented practice involving both audiologists and psychologists.
In general, drawing overall conclusions about treatment benefits proved challenging due to
the diversity of interventions and outcomes in the included studies. Studies were heterogeneous
in terms of populations, treatments, treatment modalities, study duration and followup periods,
and outcome measures. Some interventions showed positive benefits, but it was difficult to judge
the degree of clinical significance of the changes observed. Standardized mean differences were
estimated for each study because different outcomes were used; the use of diverse outcomes
makes it more difficult to assess clinical significance across studies. Even if differences in
treatment-placebo scale scores were statistically significant, these differences may not be
clinically meaningful. Future research must consider pilot work to establish the validity of many
of the outcomes used in the included studies; moreover, specific adaptations of measures
validated in nontinnitus populations (e.g., study-specific visual analog scale) should be
established in the tinnitus population, particularly for the attributes of change over time. For
some of the tinnitus-specific outcomes, it is critical that clinically important differences be
established.
ES-13
The only intervention that consistently showed statistically significant effects on multiple
outcomes was sertraline, which was evaluated against placebo in a 16-week study of 63 persons
who had a mean age of 42 years. These persons were recruited from a specialized audiology
clinic and given 50 mg/day of the active therapy or placebo. Sertraline was shown to be more
efficacious than placebo in reducing loudness, improving global quality of life, and alleviating
severity. Sertraline also had a greater impact on reducing depression symptoms, although the
reduction failed to reach statistical significance at the 5-percent level on one of the three scales
used to measure depression.
Overall, little evidence was found to suggest that the therapies led to improvements over
placebo on any of these outcomes. These results are in agreement with the conclusions of
previous systematic reviews, which found insufficient, inconsistent, or no evidence of treatment
effects.65-70
In terms of SOE, there is insufficient ability to assess whether the published evidence reflects
true effects. Effect-size estimates were inconsistent or imprecise, and risk of bias was moderate.
Furthermore, most treatments were evaluated in single studies, which may or may not represent
the true effect of any particular therapy. Sample sizes tended to be small (<100 persons), and
power calculations were largely absent from the published reports, leading to the possibility that
many studies were underpowered to detect true effects. Lengths of followup were too short to
assess the durability of treatment over time, and the validity and discriminative ability of many
outcome measurement instruments was questionable.
Medical Interventions
Eleven studies evaluated four different types of medical interventions that included
rTMS,29,30,32-34 electromagnetic stimulation,31 LLLT,35-37 ACRN,39 and acupuncture.38 Almost all
studies in this group evaluated TSQoL. In general, SOE for TSQoL is rated as insufficient based
on the high risk of bias, and the small sample sizes, lack of power calculations, and lack of
specification of the primary outcomes are factors related to the imprecise rating. Many of the
studies did not show statistical differences between groups, but limited statistical power is likely
an important factor. A clear trend for harms was difficult to specify across the differing
interventions. The relative potential for long-term harms could not be evaluated in the short-term
treatment trials included in this group.
When considering the individual types of interventions and efficacy with respect to TSQoL,
the studies consistently showed no significant difference between treatment and inactive
comparators. For rTMS and electromagnetic stimulation, the evidence was rated as insufficient.
There was some evidence that longer term effects (improvement in TSQoL scores) occurred with
low-frequency rTMS (1 Hz) at up to 6 months followup,29 but this single study had high risk of
bias. Our review also showed that adverse effects were generally poorly evaluated and reported.
A previous systematic review71 reached similar conclusions, suggesting that the evidence of
benefit for rTMS is limited, and also noted the lack of long-term monitoring within the studies
with respect to safety.
With respect to the interventions of ACRN, LLLT, and acupuncture, SOE was rated as
insufficient for TSQoL.
Only five trials evaluated the outcome of perceived loudness,32,35,36,38,39 and most trials
showed no statistical differences between treatment and inactive control groups; however, the
studies had small sample sizes and high risk of bias. SOE was rated as insufficient. One
intervention (ACRN) showed small differences for one stimulation parameter compared with
ES-14
sham stimulation.39 However, due to the added problem of the diversity of the medical
interventions that evaluated this outcome, we rate the SOE as insufficient for all of these
interventions.
A single study examining LLLT relative to sham LLLT evaluated an outcome capturing
anxiety symptoms and depression symptoms,36 and was judged to have insufficient SOE. No
studies evaluated the effect of these interventions on sleep disturbance and global quality of life.
Future research should provide a more coherent rationale for the particular treatment
approaches based on current neurological science principles, including justification for the dose
of the intervention.
ES-15
Future Research Recommendations
Key Question 1
• Develop studies to evaluate the comparative effectiveness of instruments used to assess
the severity and status of subjective idiopathic tinnitus.
Key Question 2
Population
• Include a broader spectrum of adult patients with respect to age, sex (equal proportion of
men), and ethnicity (broader representation of ethnic groups).
• Include patients recruited from primary care settings.
• Capture detailed information about prior treatments and ensure that future studies do not
sample only from subjects for whom previous treatments were not effective.
• Specify patient medical histories more clearly.
• Collect information on the use of concomitant interventions.
Intervention
• Explain the dosing rationale for off-label medications.
• Collect information on concomitant medications.
• Specify the training and experience of the person(s) delivering the interventions.
Outcomes
• Identify outcomes as primary or secondary.
• Use scales with established psychometric properties in populations with subjective
idiopathic tinnitus to measure patient-reported outcomes.
• Assess the responsiveness to change of outcome measurement instruments (e.g., visual
analog scale) in persons with tinnitus.
• Back-translate scales prior to use in languages other than the language in which they were
developed.
• Measure global quality of life to capture how persons value the risk-benefit tradeoff
between efficacy and adverse effects.
• Use the Consolidated Standards of Reporting Trials (CONSORT)74 guidelines for
reporting adverse effects (harms).
Other
• Report RCT results in conformity with CONSORT.74
ES-16
• Register study protocols in clinical trial registries and update trial information in these
registries regularly.
Key Question 3
• Develop studies to evaluate the natural history and prognostic factors in persons with
subjective idiopathic tinnitus.
References
1. American Tinnitus Association. ATA’s Top 10. Owens DK, Lohr KN, Atkins D, et al.
10 Most Frequently Asked Questions. AHRQ series paper 5: grading the strength
www.ata.org/for-patients/faqs. Accessed of a body of evidence when comparing
April 11, 2013. medical interventions--Agency for
Healthcare Research and Quality and the
2. Davis A, El Rafaie A. Epidemiology of
Effective Health-care program. J Clin
tinnitus. In: Tyler RS, ed. Tinnitus
Epidemiol. 2010;63(5):513-23. PMID:
Handbook. San Diego, CA: Singular
19595577.
Publishing Group; 2000:chapter 1:1-24.
11. Hayden JA, Cote P, Bombardier C.
3. Davis A, Smith P, Ferguson M, et al.
Evaluation of the quality of prognosis
Acceptability, benefit and costs of early
studies in systematic reviews. Ann Intern
screening for hearing disability: a study of
Med. 2006;144(6):427-37. PMID:
potential screening tests and models. Health
16549855.
Technol Assess. 2007;11(42):iii-xii, 1-154.
PMID: 17927921. 12. Zoger S, Svedlund J, Holgers KM. The
effects of sertraline on severe tinnitus
4. Nondahl DM, Cruickshanks KJ, Huang GH,
suffering--a randomized, double-blind,
et al. Generational differences in the
placebo-controlled study. J Clin
reporting of tinnitus. Ear Hear.
Psychopharmacol. 2006;26(1):32-9. PMID:
2012;33(5):640-4. PMID: 22588269.
16415703.
5. Henry JA., Research Professor in
13. Holgers K-M, Zoger S, Svedlund J. The
Otolaryngology, Oregon Hearing Research
impact of sertraline on health-related quality
Center. Key Informant interview; July 26,
of life in severe refractory tinnitus: a double-
2011.
blind, randomized, placebo-controlled study.
6. Henry JA, Zaugg TL, Myers PJ, et al. A Audiol Med. 2011;9(2):67-72.
triage guide for tinnitus. J Fam Pract.
14. Robinson SK, Viirre ES, Bailey KA, et al.
2010;59(7):389-93. PMID: 20625568.
Randomized placebo-controlled trial of a
7. Wells GA, Shea B, O’Connell D, et al. The selective serotonin reuptake inhibitor in the
Newcastle-Ottawa Scale (NOS) for treatment of nondepressed tinnitus subjects.
Assessing the Quality of Nonrandomised Psychosom Med. 2005;67(6):981-8. PMID:
Studies in Meta-Analyses. 16314604.
www.ohri.ca/programs/clinical_epidemiolog
15. Dib GC, Kasse CA, Alves de Andrade T, et
y/oxford.asp. Accessed April 11, 2013.
al. Tinnitus treatment with Trazodone. Braz
8. Jadad AR, Moore RA, Carroll D, et al. J Otorrinolaringol. 2007;73(3):390-7. PMID:
Assessing the quality of reports of 17684661.
randomized clinical trials: is blinding
16. Sullivan M, Katon W, Russo J, et al. A
necessary? Control Clin Trials.
randomized trial of nortriptyline for severe
1996;17(1):1-12. PMID: 8721797.
chronic tinnitus. Effects on depression,
9. Atkins D, Chang S, Gartlehner G, et al. disability, and tinnitus symptoms. Arch
Assessing applicability when comparing Intern Med. 1993;153(19):2251-9. PMID:
medical interventions: AHRQ and the 8215728.
Effective Health Care Program. J Clin
Epidemiol. 2011;64(11):1198-207.
ES-17
17. Piccirillo JF, Finnell J, Vlahiotis A, et al. 28. Aoki M, Wakaoka Y, Hayashi H, et al.
Relief of idiopathic subjective tinnitus: is Effect of lyophilized powder made from
gabapentin effective? Arch Otolaryngol enzymolyzed honeybee larvae on tinnitus-
Head Neck Surg. 2007;133(4):390-7. PMID: related symptoms, hearing levels, and
17438255. hypothalamus-pituitary-adrenal axis-related
hormones. Ear Hear. 2012;33(3):430-6.
18. Westerberg BD, Roberson JB Jr, Stach BA.
PMID: 21971082.
A double-blind placebo-controlled trial of
baclofen in the treatment of tinnitus. Am J 29. Anders M, Dvorakova J, Rathova L, et al.
Otol. 1996;17(6):896-903. PMID: 8915419. Efficacy of repetitive transcranial magnetic
stimulation for the treatment of refractory
19. Johnson RM, Brummett R, Schleuning A.
chronic tinnitus: a randomized, placebo
Use of alprazolam for relief of tinnitus. A
controlled study. Neuroendocrinol Lett.
double-blind study. Arch Otolaryngol Head
2010;31(2):238-49. PMID: 20424590.
Neck Surg. 1993;119(8):842-5. PMID:
8343245. 30. Marcondes RA, Sanchez TG, Kii MA, et al.
Repetitive transcranial magnetic stimulation
20. Sharma DK, Kaur S, Singh J, et al. Role of
improve tinnitus in normal hearing patients:
acamprosate in sensorineural tinnitus. Indian
a double-blind controlled, clinical and
J Pharmacol. 2012;44(1):93-6.
neuroimaging outcome study. Eur J Neurol.
21. Azevedo AA, Figueiredo RR. Tinnitus 2010;17(1):38-44. PMID: 19614962.
treatment with acamprosate: double-blind
31. Ghossaini SN, Spitzer JB, Mackins CC, et
study. Braz J Otorrinolaringol.
al. High-frequency pulsed electromagnetic
2005;71(5):618-23. PMID: 16612523.
energy in tinnitus treatment. Laryngoscope.
22. Topak M, Sahin-Yilmaz A, Ozdoganoglu T, 2004;114(3):495-500. PMID: 15091224.
et al. Intratympanic methylprednisolone
32. Chung HK, Tsai CH, Lin YC, et al.
injections for subjective tinnitus. J Laryngol
Effectiveness of theta-burst repetitive
Otol. 2009;123(11):1221-5. PMID:
transcranial magnetic stimulation for
19640315.
treating chronic tinnitus. Audiol Neuro Otol.
23. Mazurek B, Haupt H, Szczepek AJ, et al. 2012;17(2):112-20. PMID: 21865723.
Evaluation of vardenafil for the treatment of
33. Plewnia C, Vonthein R, Wasserka B, et al.
subjective tinnitus: a controlled pilot study. J
Treatment of chronic tinnitus with theta
Negative Results Biomed. 2009;8:3. PMID:
burst stimulation: a randomized controlled
19222841.
trial. Neurology. 2012;78(21):1628-34.
24. Meeus O, De RD, Van de Heyning P. PMID: 22539568.
Administration of the combination
34. Langguth B, Kleinjung T, Frank E, et al.
clonazepam-Deanxit as treatment for
High-frequency priming stimulation does
tinnitus. Otol Neurotol. 2011;32(4):701-9.
not enhance the effect of low-frequency
PMID: 21358561.
rTMS in the treatment of tinnitus. Exp Brain
25. Rejali D, Sivakumar A, Balaji N. Ginkgo Res. 2008;184(4):587-91. PMID: 18066684.
biloba does not benefit patients with
35. Teggi R, Bellini C, Piccioni LO, et al.
tinnitus: a randomized placebo-controlled
Transmeatal low-level laser therapy for
double-blind trial and meta-analysis of
chronic tinnitus with cochlear dysfunction.
randomized trials. Clin Otolaryngol Allied
Audiol Neuro Otol. 2009;14(2):115-20.
Sci. 2004;29(3):226-31. PMID: 15142066.
PMID: 18843180.
26. Drew S, Davies E. Effectiveness of Ginkgo
36. Mirz F, Zachariae R, Andersen SE, et al.
biloba in treating tinnitus: double blind,
The low-power laser in the treatment of
placebo controlled trial. BMJ.
tinnitus. Clin Otolaryngol Allied Sci.
2001;322(7278):73 PMID: 11154618.
1999;24(4):346-54. PMID: 10472473.
27. Arda HN, Tuncel U, Akdogan O, et al. The
role of zinc in the treatment of tinnitus. Otol
Neurotol. 2003;24(1):86-9. PMID:
12544035.
ES-19
37. Cuda D, De CA. Effectiveness of combined 47. Malouff JM, Noble W, Schutte NS, et al.
counseling and low-level laser stimulation in The effectiveness of bibliotherapy in
the treatment of disturbing chronic tinnitus. alleviating tinnitus-related distress. J
Int Tinnitus J. 2008;14(2):175-80. PMID: Psychosom Res. 2010;68(3):245-51. PMID:
19205171. 20159209.
38. Vilholm OJ, Moller K, Jorgensen K. Effect 48. Henry JA, Loovis C, Montero M, et al.
of traditional Chinese acupuncture on severe Randomized clinical trial: group counseling
tinnitus: a double-blind, placebo-controlled, based on tinnitus retraining therapy. J
clinical investigation with open therapeutic Rehabil Res Dev. 2007;44(1):21-32. PMID:
control. Br J Audiol. 1998;32(3):197-204. 17551855.
PMID: 9710337.
49. Weise C, Heinecke K, Rief W. Biofeedback-
39. Tass PA, Adamchic I, Freund H-J, et al. based behavioral treatment for chronic
Counteracting tinnitus by acoustic tinnitus: results of a randomized controlled
coordinated reset neuromodulation. Restor trial. J Consult Clin Psychol.
Neurol Neurosci. 2012;30(2):137-59. 2008;76(6):1046-57. PMID: 19045972.
40. Davis PB, Paki B, Hanley PJ. Neuromonics 50. Kaldo V, Levin S, Widarsson J, et al.
tinnitus treatment: third clinical trial. Ear Internet versus group cognitive-behavioral
Hear. 2007;28(2):242-59. PMID: 17496674. treatment of distress associated with tinnitus:
a randomized controlled trial. Behav Ther.
41. Hiller W, Haerkotter C. Does sound
2008;39(4):348-59. PMID: 19027431.
stimulation have additive effects on
cognitive-behavioral treatment of chronic 51. Kaldo V, Cars S, Rahnert M, et al. Use of a
tinnitus? Behav Res Ther. 2005;43(5):595- self-help book with weekly therapist contact
612. PMID: 15865915. to reduce tinnitus distress: a randomized
controlled trial. J Psychosom Res.
42. Dineen R, Doyle J, Bench J, et al. The
2007;63(2):195-202. PMID: 17662757.
influence of training on tinnitus perception:
an evaluation 12 months after tinnitus 52. Rief W, Weise C, Kley N, et al.
management training. Br J Audiol. Psychophysiologic treatment of chronic
1999;33(1):29-51. PMID: 10219721. tinnitus: a randomized clinical trial.
Psychosom Med. 2005;67(5):833-8. PMID:
43. Parazzini M, Del Bo L, Jastreboff M, et al.
16204446.
Open ear hearing aids in tinnitus therapy: an
efficacy comparison with sound generators. 53. Andersson G, Porsaeus D, Wiklund M, et al.
Int J Audiol. 2011;50(8):548-53. Treatment of tinnitus in the elderly: a
controlled trial of cognitive behavior
44. Dineen R, Doyle J, Bench J. Managing
therapy. Int J Audiol. 2005;44(11):671-5.
tinnitus: a comparison of different
PMID: 16379495.
approaches to tinnitus management training.
Br J Audiol. 1997;31(5):331-44. PMID: 54. Zachriat C, Kroner-Herwig B. Treating
9373742. chronic tinnitus: comparison of cognitive-
behavioural and habituation-based
45. Biesinger E, Kipman U, Schatz S, et al.
treatments. Cognit Behav Ther.
Qigong for the treatment of tinnitus: a
2004;33(4):187-98. PMID: 15625793.
prospective randomized controlled study. J
Psychosom Res. 2010;69(3):299-304. 55. Kroner-Herwig B, Frenzel A, Fritsche G, et
PMID: 20708452. al. The management of chronic tinnitus:
comparison of an outpatient cognitive-
46. Abbott JA, Kaldo V, Klein B, et al. A cluster
behavioral group training to minimal-contact
randomised trial of an internet-based
interventions. J Psychosom Res.
intervention program for tinnitus distress in
2003;54(4):381-9. PMID: 12670617.
an industrial setting. Cognit Behav Ther.
2009;38(3):162-73. PMID: 19675959. 56. Andersson G, Stromgren T, Strom L, et al.
Randomized controlled trial of internet-
based cognitive behavior therapy for distress
associated with tinnitus. Psychosom Med.
2002;64(5):810-6. PMID :12271112.
ES-20
57. Henry JL, Wilson PH. An evaluation of two 66. Hoare DJ, Kowalkowski VL, Kang S, et al.
types of cognitive intervention in the Systematic review and meta-analyses of
management of chronic tinnitus. Scand J randomized controlled trials examining
Behav Ther. 1998;27(4):156-66. tinnitus management. Laryngoscope.
2011;121(7):1555-64. PMID: 21671234.
58. Henry JL, Wilson PH. The psychological
management of tinnitus: comparison of a 67. Hoekstra CE, Rynja SP, van Zanten GA, et
combined cognitive educational program, al. Anticonvulsants for tinnitus. Cochrane
education alone and a waiting list control. Database Syst Rev. 2011;(7):CD007960.
Int Tinnitus J. 1996;2:9-20. PMID: 21735419.
59. Kroner-Herwig B, Hebing G, van Rijn- 68. Karkos PD, Leong SC, Arya AK, et al.
Kalkmann U, et al. The management of ‘Complementary ENT’: a systematic review
chronic tinnitus--comparison of a cognitive- of commonly used supplements. J Laryngol
behavioural group training with yoga. J Otol. 2007;121(8):779-82. PMID:
Psychosom Res. 1995;39(2):153-65. PMID: 17125579.
7595873.
69. Hilton M, Malcolm P, Stuart EL, et al.
60. Westin VZ, Schulin M, Hesser H, et al. Ginkgo biloba for tinnitus. Cochrane
Acceptance and commitment therapy versus Database Syst Rev. 2010;(3):CD003852.
tinnitus retraining therapy in the treatment of
70. Baldo P, Doree C, Molin P, et al.
tinnitus: a randomised controlled trial.
Antidepressants for patients with tinnitus.
Behav Res Ther. 2011;49(11):737-47.
Cochrane Database Syst Rev.
PMID: 21864830.
2009;(1):CD003853.
61. Cima RF, Maes IH, Joore MA, et al.
71. Meng Z, Liu S, Zheng Y, et al. Repetitive
Specialised treatment based on cognitive
transcranial magnetic stimulation for
behaviour therapy versus usual care for
tinnitus. Cochrane Database Syst Rev.
tinnitus: a randomised controlled trial.
2011;(10):CD007946 PMID: 21975776.
Lancet. 2012;379(9830):1951-9. PMID:
22633033. 72. Henry JA, Zaugg TL, Myers PJ, et al. The
role of audiologic evaluation in progressive
62. Scott B, Lindberg P, Lyttkens L, et al.
audiologic tinnitus management. Trends
Psychological treatment of tinnitus. Scand
Amplification. 2008;12(3):170-87. PMID:
Audiol. 1985;14(4):223-30.
18628281.
63. Ireland CE, Wilson PH, Tonkin JP, et al. An
73. Henry JA, Zaugg TL, Myers PJ, et al.
evaluation of relaxation training in the
Progressive audiologic tinnitus management.
treatment of tinnitus. Behav Res Ther.
ASHA Leader. 2008;13(8):14-7.
1985;23(4):423-30. PMID: 3896227.
www.asha.org/Publications/leader/2008/080
64. Kochkin S, Tyler R, Born J. MarkeTrak 617/f080617b.htm.. Accessed April 4, 2013.
VIII: the prevalence of tinnitus in the United
74. Ioannidis JPA, Evans SJW, Gotzsche PC, et
States and the self-reported efficacy of
al. Better reporting of harms in randomized
various treatments. Hear Rev.
trials: an extension of the CONSORT
2011;18(12):10-27.
statement. Ann Intern Med.
65. Savage J, Waddell A. Tinnitus. Clin Evid 2004;141(10):781-8. PMID: 15545678.
(Online). 2012 Feb 3:2012. pii:0506. PMID:
22331367.
ES-21
Introduction
Background
Tinnitus is a not a disease but rather a symptom or condition that can result from a number of
underlying causes. In general, tinnitus is the perception of sound in the absence of an external
auditory stimulus. The World Health Organization (WHO) describes tinnitus as a “symptom of
hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, roaring
or other noises in the ear.”1 Note that in the WHO International Classification of Diseases (ICD),
tinnitus is coded as H93.1, which is not a specific ICD-10-CM diagnosis code and cannot be
used to indicate a medical diagnosis.1
Tinnitus can disturb one’s day-to-day life in a number of ways including: causing distress
and annoyance, disruption of sleep, anxiety symptoms, and depression symptoms. An estimated
16 percent of the American population (approximately 50 million people) experience tinnitus to
some extent, with up to 16 million seeking medical help and 2 million being unable to lead a
normal life.2 The prevalence of tinnitus increases with age and noise exposure.3,4 Similarly,
hearing loss also increases with age and noise exposure. Although tinnitus is often associated
with hearing loss, tinnitus can affect those who do not have clinically significant hearing loss and
not all people who have hearing loss have tinnitus.
A variety of conditions and experiences can lead to tinnitus, but its exact physiology is still
unknown. As a symptom, it may be associated with a number of conditions, including various
auditory system pathologies, ranging from impacted wax to acoustic tumors, that warrant
medical attention. According to the American Tinnitus Association (ATA), noise exposure is the
largest attributed cause of tinnitus.5 People may acquire tinnitus and hearing loss when they are
exposed to hazardous levels of industrial, recreational, or military noise. Tinnitus is the most
common service-connected disability among U.S. veterans.2 Tinnitus is common in active-duty
service members and veterans who have had traumatic brain injury (concussion) whether or not
they have clinically significant hearing loss. There is growing concern that exposure to
recreational noise may result in tinnitus in teenagers and young adults.6 Tinnitus can also be a
side effect of potentially ototoxic drugs, ranging from aspirin taken to alleviate arthritic pain to
aminoglycoside antibiotics and life-saving drugs used to treat cancer.7 These effects may be
temporary but, especially with respect to aminoglycoside antibiotics and cancer
chemotherapeutics, in particular cisplatin, can be permanent.
The severity of tinnitus experienced by patients may vary with, or depend upon,
comorbidities. Tinnitus often co-occurs with hearing loss, and the bothersome effects of tinnitus
may be alleviated by the use of hearing aids. Individuals who are dual sensory impaired (deaf
and blind) may be confused by tinnitus because they do not have visual information to help them
understand that their tinnitus is not an external sound. It is common for frequent tinnitus to be
associated by mental health conditions, particularly generalized anxiety disorder.8-10 Although
relatively little is known about tinnitus in younger people compared to what is known about
middle-aged and older adults, the connection between tinnitus and mental health issues has been
observed in teenagers with hearing loss.11 It is often regarded as a “chronic stressor, creating a
vicious circle of stress and exacerbation of tinnitus.”12
1
Classification
In both clinical and academic contexts, there is no consensus on the classification of tinnitus
subcategories. A patient is often described as presenting with symptoms of either objective or
subjective tinnitus. Objective tinnitus is perceptible by both patient and examiner. Other terms
sometimes used for objective tinnitus are “somatosounds” or “somatic tinnitus” or “somatically
modulated” tinnitus. Subjective tinnitus is perceptible only by the patient yet is not due to a
hallucination. Both forms of tinnitus may or may not be idiopathic. Some investigators have
argued that tinnitus should be classified by origin, either as somatic or neurophysiologic.13
In this classification by origin, somatic tinnitus is categorized as tinnitus with an underlying
medical condition that creates internal acoustic mechanical sounds; e.g., the tinnitus has a
vascular, muscular, respiratory, or temporomandibular joint (TMJ) origin.14 The sounds
associated with somatic tinnitus (somatosounds) are most commonly pulsatile and may be heard
by an observer either directly or through the use of a stethoscope or microphone. Somatic
tinnitus requires an examination by a physician ear-specialist (e.g., otolaryngologist) who may be
able to identify and treat the underlying condition.14 Although serious pathology is rarely a cause
of tinnitus, pulsatile somatic tinnitus, tinnitus in only one ear (unilateral tinnitus), and tinnitus
associated with vertigo require referral to a specialist.15
In this review, the term subjective idiopathic tinnitus will be used rather than
neurophysiologic tinnitus because it is the term most commonly used in the current literature. As
well, subjective idiopathic tinnitus is the most commonly diagnosed type of tinnitus.14 It is
nonpulsatile, most often bilateral (perceived in both ears), and can only be heard by the patient
and not directly observed by a physician, making it difficult to evaluate. Audiological protocols
can be used to match the loudness and pitch of the tinnitus perceived by a patient to external
sounds with known acoustical parameters.16 The “phantom sounds” heard by the patient with this
type of tinnitus are attributed to a disruption in the neurological auditory pathway. With
advances in neuroscience over the last decade, theories have shifted from an emphasis on
peripheral to central auditory system involvement. There has also been a shift from
conceptualizing tinnitus as a primarily auditory problem to be silenced, to considering it to be a
psychological problem with which people can cope.17-19
Measurement
It is essential to distinguish chronic tinnitus from temporary ear noises that would not be
considered pathological (sudden, unilateral, tonal sounds that typically last for up to a minute
before decaying). If the patient reports a constant or near-constant perception of tinnitus, the
condition is identified as chronic. Typically, chronic tinnitus has a duration of at least 6
months.14
Various measures can be used to evaluate the presence and severity of the tinnitus.20 There
are at least a dozen validated questionnaires for assessing the impact of tinnitus. Psychological
grading scales can aid in the discrimination between clinically significant and nonsignificant
degrees of tinnitus.21
Visual analog scales (VAS) are well known psychometric measures of subjective attitudes
and characteristics. With a VAS, patients specify their level of agreement to a statement by
indicating a position along a continuous line between two endpoints. The VAS can be used to
assess loudness, pitch, and disturbance of the tinnitus.22 Tinnitus questionnaires contain a series
of questions and patients select a response to each question from the given choices (usually a
2
graded scale). Questionnaires, such as the Tinnitus Handicap Inventory (THI) and the Tinnitus
Reaction Questionnaire (TRQ), are useful for grading tinnitus severity. However, these and most
other tinnitus questionnaires are limited in that they were not designed nor validated to measure
the effectiveness of tinnitus interventions.23 Such effectiveness is referred to as “responsiveness,”
which emphasizes effect sizes, content validity, and response scaling that enables detection of
change.24,25 The Tinnitus Functional Index (TFI) is a self-report questionnaire that has
documented validity both for scaling the severity and negative impact of tinnitus and for
measuring treatment-related changes in tinnitus. At this time it has not yet been used to evaluate
comparative effectiveness of treatments.26
Treatment
Following a medical examination, some patients with subjective idiopathic tinnitus may not
receive a recommendation for further treatment, although the practitioner may provide
information and assurance of the benign nature of the phenomenon. The complex relationships
between tinnitus and a range of physical and mental health conditions have complicated the
development and evaluation of intervention strategies. Comorbidities such as hearing loss,
mental health problems, or sleep disorders may modulate the experience of tinnitus and direct
treatment of those conditions may help to alleviate reactions to tinnitus. For cases of subjective
idiopathic tinnitus in which a tinnitus-specific intervention is indicated, there is a wide range of
interventions which can include (but are not limited to) pharmacological/food supplements,
medical interventions, sound technologies, and psychological/behavioral interventions, as
outlined below. These interventions may differ markedly in many dimensions, including the type
of expertise required to deliver the treatment, the size and nature of the caseload being treated,
and the costs associated with the method of delivery. Some interventions may be offered as
programs designed to be cost-effective for large caseloads (e.g., internet CBT), while some may
be extremely costly, individualized treatments suitable for only a small number of candidates and
requiring a sophisticated technology and a high level of expertise on the part of the practitioner
(e.g., cochlear implantation). It is also possible that multiple treatments be provided in
combination or in a progressive approach, depending on the needs of the patient.
Pharmacological Treatments
No drug has been approved by the U.S. Food and Drug Administration (FDA) for treating
tinnitus. However, various pharmacological treatments, including antidepressants, anxiolytics,
vasodilators, and vasoactive substances, and intravenous lidocaine, have been prescribed for
tinnitus.27-31 See Table 1 for examples. For the most part, these treatments have been indirect
solutions because they focus on tinnitus-associated symptoms, such as depression symptoms,
stress, or sleep disturbance.32 However, newer medications that attempt to modulate the central
auditory pathways, such as pramipexole, are being investigated and may have promise for
reducing the perception of tinnitus.33
3
Table 1. Some pharmacological treatments for tinnitus
Drug Class Agents (Examples)
Antidepressants Tricyclics: amitriptyline, nortriptyline, trimipramine
Selective serotonin-reuptake inhibitors (SSRI): fluoxetine, paroxetine
Other: trazodone
Anxiolytics Alprazolam
Vasodilators/Vasoactive Prostaglandin E1
Substances
®
Other Lidocaine, gabapentin, Botox , pramipexole
Abbreviations: Botox = botulinum toxin type A; SSRI = selective serotonin-reuptake inhibitors
Food Supplements
Food supplements, such as Gingko biloba extracts, are also being used by patients with
tinnitus. Extracts from Gingko biloba leaves are a traditional Chinese medicinal treatment used
to increase blood flow, inhibit the platelet-activating factor, alter neuron metabolism, and prevent
free radicals from damaging cell membranes. These improvements, as well as relief from
tinnitus, are claimed by some to be attributed to the chemical compounds flavonoid and
terpenoid, which are found within the Gingko biloba plant.34
Medical Interventions
Low Level Laser Treatments
Low level laser therapy (LLLT) has been used to treat tinnitus. Various rationales for using
laser therapy have been proposed but not yet validated. It is suggested that laser irradiation can
improve cell proliferation, increase blood flow in the inner ear canal, and activate cellular
activities that repair hair cells.35 A variety of LLLT types have been used in patients and no
specific dose recommendations exist regarding total energy density and method of application.
4
pressured chamber containing an atmosphere of 100 percent oxygen, which increases the oxygen
supply to body tissues.
Dietary Modifications
Limiting the intake of high-sodium foods, caffeine, chocolate, and other stimulants and
avoiding refined sugars, artificial sweeteners, saturated and unsaturated fats, and monosodium
glutamate are examples of diet modifications.42-44 This is not a comprehensive list.
Sound Technologies
5
The acoustic component of the treatment is designed to provide “stimulation to auditory
pathways deprived by hearing loss, engage positively with the limbic system, and allow
intermittent, momentary tinnitus perception within a pleasant and relaxing stimulus, thereby
facilitating desensitization to the tinnitus signal.”53 The device with headphones (likened to an
MP3 player in appearance) delivers musical sound customized to the hearing loss of the
individual. The typical treatment program lasts 6 months.
Psychological/Behavioral Treatments
In addition to its association with many physical health problems, tinnitus is also associated
with many clinical and subclinical psychological health problems, both as a cause and
consequence of tinnitus. For example, individuals with tinnitus may experience difficulties with
attention and anxiety symptoms and those who are most distressed by tinnitus may be
psychologically vulnerable.54 Treatments in this category enlist the use of psychological and/or
behavioral interventions to reduce the negative consequences of tinnitus.
6
technology; for example individuals with hearing loss would be expected to try hearing aids to
address communication needs whether or not there is an intention for hearing aids to provide
relief from tinnitus.
7
protocol has yet to be adopted by any government or agency because the evidentiary base has not
yet been evaluated.66 The usability of the TRI flowchart is limited as it reflects a biomedical
approach: an approach that would be used by medical physicians, but not by providers such as
audiologists or psychologists who implement behavioral methods. Organizations such as the
ATA provide information on a variety of treatment options, but do not endorse or recommend
any specific treatment. In 2009, the Department of Health in the United Kingdom issued the
“Provision of Services for Adults with Tinnitus: A Good Practice Guide”56 for the
commissioning of tinnitus services and for managing tinnitus from primary care onwards.67 The
TRI flowchart and the United Kingdom Good Practice Guide reflect current best practices
recommendations. Guidelines are currently not standardized in the United States, although the
efforts and strategies of individual researchers appear in the research literature.14,68
As there is no “cure” for tinnitus, the absence of firm guidelines and management strategies
demonstrates the need for further evaluation of current treatment options. This review aims to
explore prognostic factors and strategies for the optimal management of tinnitus and to clarify
the effectiveness of the various tinnitus treatments currently in use and their measurable
outcomes. It also identifies gaps in the existing literature that will inform directions for future
research.
Population(s)
Adult patients (18 and over) presenting with symptoms of tinnitus.
Interventions
Direct observation or observation of sound with stethoscope; referral to a health professional
with expertise on managing tinnitus (e.g., otolaryngologist, audiologist, neurologist, mental
health professional); administration of scales/or questionnaires to assess severity (e.g., THI,
TRQ, TFI, VAS).
Comparators
Different clinical evaluation methods used to characterize a diagnosis and measure severity
of subjective idiopathic tinnitus.
Outcomes
Final outcome: (1) No treatment; (2) need for specialized treatment (e.g., audiology,
otolaryngology, neurology, mental health care); (3) extent of intervention.
Timing or Followup
No restrictions.
8
Setting
Primary care; specialty care (audiology, otolaryngology, neurology, mental health care).
Note: For KQ2 and KQ3, adults diagnosed with unilateral and/or pulsatile tinnitus need to be
evaluated for other medical conditions, such as acoustic neuromas. This review will include only
those cases in which a medically serious underlying pathology as the source of the tinnitus has
already been ruled out.
KQ2. In adults with subjective idiopathic (nonpulsatile) tinnitus, what is the
comparative effectiveness (and/or potential harms) of medical/surgical,
sound treatment/technological, or psychological/behavioral interventions,
including combinations of interventions?
Population(s)
Adult patients (18 and over) with a diagnosis of subjective idiopathic (nonpulsatile) tinnitus
who are sufficiently bothered by tinnitus that they seek a treatment intervention.
Interventions
Any treatment/therapy used to reduce/help cope with tinnitus including but not limited to the
following:
Medical Interventions
• Low level laser treatments (LLLT)
• TMJ treatment: dental orthotics and self-care; surgery
• Transcranial magnetic stimulation (TMS)
• Hyperbaric oxygen therapy
• Dietary modifications
• Complementary and alternative medicine (CAM) therapies that are not food supplements;
acupuncture; diet, lifestyle, and sleep modifications (e.g., caffeine avoidance, exercise)
• Other related interventions that require administration by a clinician
9
Psychological/Behavioral Interventions
• Cognitive behavioral therapy (CBT), coping training, psychotherapy
• Tinnitus retraining therapy (TRT)
• Biofeedback
• Education
• Relaxation therapies
• Progressive tinnitus management (PTM)
Combination Therapies
• Any combination of tinnitus interventions (e.g., pharmacological treatment with CBT)
Comparators
Inactive controls (including placebo; no treatment; wait list; sham interventions).
Active controls (including treatment as usual; other intervention/treatments).
Outcomes
Included Outcomes of Benefit
1. Tinnitus-specific Quality of Life
2. Sleep disturbance
3. Anxiety symptoms
4. Depression symptoms
5. Subjective loudness
6. Global Quality of Life
Excluded
Studies that reported outcomes on a non-numeric scale, such as loudness in decibels (dBs).
No other outcomes were used to exclude studies.
Timing or Followup
No restrictions.
Setting
Primary care; specialty care (audiology, otolaryngology, neurology, and mental health care.
Setting was not used as an exclusion criterion.
10
KQ3. For adults with subjective idiopathic tinnitus, what prognostic factors,
patient characteristics, and/or symptom characteristics affect final treatment
outcomes?
Population(s)
Adults (18 and over) with a diagnosis of subjective idiopathic tinnitus sufficiently bothered
by tinnitus that they are seeking a treatment intervention.
Interventions
Any treatment/therapy used to reduce/help/cope with tinnitus including, but not limited to,
those described in KQ2.
Comparators
• Prognostic factors: length of time to treatment after onset, audiological factors (degree
and type of hearing loss, hyperacusis, loudness tolerance, masking criteria, etc.), head
injury, anxiety symptoms, mental health disorders, and duration of tinnitus
• Patient characteristics: age, sex, race, medical or mental health comorbidities,
socioeconomic factors, noise exposure (environmental, recreational and work-related
(including active and past military duty, and occupational hazards)), involvement in
litigation, third-party coverage
• Symptom characteristics: origin/presumed etiology of tinnitus, tinnitus duration since
onset, subcategory of tinnitus, severity of tinnitus
Outcomes
Final Outcomes
1. Time until improvement
2. Sleep disturbance
3. Tinnitus-specific Quality of Life
4. Anxiety symptoms
5. Depression symptoms
6. Subjective loudness
7. Global Quality of Life
8. Return to “normal” work
Adverse Effects
1. Worsening of tinnitus
2. Sedation
3. Surgical complications
4. Any other treatment-emergent adverse effects.
Timing or Followup
No restrictions.
Setting
Primary care; specialty care (audiology, otolaryngology, neurology, mental health).
11
Analytic Framework
Following consultation with key informants, the Agency for Healthcare Research and Quality
(AHRQ) Task Order Officer (TOO), and the investigative team, key research questions were
developed. Figure 1 shows a flow diagram indicating the relationship between research questions
in this Comparative Effectiveness Review (CER). This framework depicts the KQ as outlined in
the PICOTS format (Population(s), Interventions, Comparators, Outcomes, Timing or followup,
and Setting). The PICOTS components for each KQ are provided in full detail in Table 2.
*Any studies that used the terms “annoyance” or “distress” to describe their outcomes were included under the category of
“discomfort.”
**The outcome “severity” was added during data extraction. As severity was an outcome reported in 18 of 34 papers, it was
decided that it should not be collapsed into any other outcome category.
12
Methods
Topic Refinement
The topic of this report and preliminary Key Questions (KQs) were developed through a
process involving the public, the Scientific Resource Center for the Effective Health Care
program of the Agency for Healthcare Research and Quality (AHRQ), and various stakeholder
groups. The KQs developed as a result of this process were posted on AHRQ’s website for
public comment in October 2012 for 4 weeks and revised as needed. Study, patient, intervention,
eligibility criteria, and outcomes, were refined and agreed upon through discussions between the
McMaster University Evidence-based Practice Center (EPC), the Technical Expert Panel (TEP)
members, the AHRQ Task Order Officer (TOO), and comments received from the public posting
of the Key Questions. (www.effectivehealthcare.ahrq.gov/ehc/products/371/811/
Tinnitus_Protocol_20120222.pdf).
The EPC convened a group of experts in the fields of Tinnitus and systematic review
methods to form the TEP. Members of the TEP provided input to help interpret the KQs guiding
this review, identify important issues, and define parameters for the review of evidence.
Search Strategy
The search was conducted in six databases: MEDLINE®, EMBASE®, Cochrane Central,
PsycINFO®, AMED©, and CINAHL®. These databases were chosen because they represent the
best sources for a broad range of high-quality literature relevant to this topic. In particular,
Embase® seems to index a wider range of audiology journals than MEDLINE®, including
Audiological Medicine. AMED® and CINAHL® have been included because of the inclusion of
complementary and alternative medicine therapies in the interventions considered in this review.
Tinnitus is well indexed in the medical bibliographic databases, and there were few
alternative terms that needed to be included in the search strategy. The search strategy used
combinations of controlled vocabulary (medical subject headings (MeSH®), keywords) and text
words. The search was restricted to human-focused studies (specifically removing those results
that only include animal data), and certain citation types not included in this review were
removed as part of the search (see Appendix A for detailed search strategy by database). The
databases were searched from January 1970 to June 2012. The basic search strategy is listed
below.
1. Tinnitus/or tinnitus.ti.
2. animals/not humans/
3. 1 not 2
4. limit 3 to English language
5. limit 4 to (case reports or comment or editorial or in vitro or interview or letter or
newspaper article or webcasts)
6. 4 not 5
Citations meeting this search criteria were downloaded into Reference Manager® 12
(Thomson Reuters, New York, NY) and then imported into a systematic review software
program, DistillerSR (Evidence Partners Inc., Ottawa, Canada), for screening. Once in
DistillerSR, citations were screened in duplicate by trained members of the synthesis team using
the specified eligibility criteria for the review. Articles marked for inclusion by either team
13
member proceeded to full text rating, which was also completed independently by two reviewers.
All disagreements were resolved through discussions with the synthesis team, and inclusion
results were reviewed by a third person.
In addition to the electronic database search, review of reference lists of eligible studies at
full text screening was undertaken. Systematic reviews and meta-analyses were separately coded
for retrieval during screening, and the reference lists were reviewed. Any potentially relevant
citations were cross-checked within the citation database. Any references not found within the
database were retrieved, added, and screened at full text.
Grey Literature
Three types of grey literature sources were searched: regulatory agency Web sites, clinical
trial databases, and conference sources. The regulatory information included the U.S Food and
Drug Administration (FDA), Health Canada, and the European Medicines Agency. The clinical
trial databases searched include: clinicaltrials.gov, clinicaltrialsregister.eu, metaRegister of
Current Controlled Trials, Clinical Trial Registries, Clinical Study Results, and World Health
Organization Clinical Trials. Conference papers were searched in the Conference Papers Index
for the last 2 years only. This was to allow for the inclusion of studies that have been presented at
conferences but have not yet had the chance to be published.
In addition, the Web sites of the following tinnitus-related organizations were searched for
additional citations:
• The American Tinnitus Association
• The Association for Research in Otolaryngology
• American Academy of Audiology
• Emory University Tinnitus and Hyperacusis Center
• Tinnitus Research Initiative
• Deafness Research (United Kingdom)
The Scientific Resource Center also requested the Scientific Information Packages for drugs
and devices and any missing relevant studies were added to the screening process.
14
pulsatile in nature), or the intervention was a stapedectomy or tympanoplasty; and/or certain
study designs/methods of presenting data (e.g., only determined various effects, a
nonrandomized head-to-head design, or did not give sufficient detail of data for analyses).
Refer to Appendix B for Screening and Data Extraction Forms and the accompanying help
sheets.
15
Table 2. Inclusion and exclusion criteria (continued)
Category Inclusion Criteria Exclusion Criteria
Comparators KQ1: Different clinical evaluation methods used to characterize a KQ1: No exclusions
diagnosis and measure severity of subjective idiopathic tinnitus KQ2: No exclusions
KQ2: KQ3: No exclusions
• Inactive controls (including placebo; no treatment; wait list; sham
interventions)
• Active controls (including treatment as usual; other
intervention/treatments)
KQ3:
• Prognostic factors: length of time to treatment after onset,
audiological factors (e.g., degree and type of hearing loss,
hyperacusis, loudness tolerance, masking criteria), head injury,
anxiety symptoms, mental health disorders, and duration of tinnitus.
• Patient characteristics: age, sex, race, medical or mental health
comorbidities, socioeconomic factors, noise exposure
(environmental, recreational, work-related (including active and past
military duty, and occupational hazards)), involvement in litigation,
third-party coverage
Symptom characteristics: origin/presumed etiology of tinnitus,
tinnitus duration since onset, subcategory of tinnitus, severity of
tinnitus
Comparators KQ1: Different clinical evaluation methods used to characterize a KQ1: No exclusions
diagnosis and measure severity of subjective idiopathic tinnitus KQ2: No exclusions
KQ2: KQ3: No exclusions
• Inactive controls (including placebo; no treatment; wait list; sham
interventions)
• Active controls (including treatment as usual; other
intervention/treatments)
KQ3:
• Prognostic factors: length of time to treatment after onset,
audiological factors (e.g., degree and type of hearing loss,
hyperacusis, loudness tolerance, masking criteria), head injury,
anxiety symptoms, mental health disorders, and duration of tinnitus.
• Patient characteristics: age, sex, race, medical or mental health
comorbidities, socioeconomic factors, noise exposure
(environmental, recreational, work-related (including active and past
military duty, and occupational hazards)), involvement in litigation,
third-party coverage
• Symptom characteristics: origin/presumed etiology of tinnitus,
tinnitus duration since onset, subcategory of tinnitus, severity of
tinnitus
Outcomes KQ1: Final outcome: No treatment; need for specialized treatment Studies where outcomes were
(e.g., audiology, otolaryngology, neurology, mental health care); reported on non-numeric
extent of intervention scales (such as loudness in
KQ2: Tinnitus-specific Quality of Life, Sleep disturbance, depression dB).
symptoms, subjective loudness, Global quality of life, tinnitus severity,
adverse effects (worsening of tinnitus, sedation, surgical
complications, other treatment emergent events)
KQ3: Time until improvement, sleep disturbance, discomfort, anxiety
symptom, depression symptoms, subjective loudness, quality of life,
return to “normal” work, adverse effects (worsening of tinnitus,
sedation, surgical complications)
Publication English Non-English
languages
16
Table 2. Inclusion and exclusion criteria (continued)
Category Inclusion Criteria Exclusion Criteria
Study design All KQs: All KQs:
• RCTs or non-randomized (quasi-randomized, controlled clinical Studies where:
studies) with at least one comparator group • Only scatter plots and bar
• Original research studies must provide sufficient detail about graphs (no numerical data)
methods and results to enable use and aggregation of the data and presented
results • Effect size could not be
• Relevant outcomes must be able to be extracted from data in the estimated (i.e., only p values
papers reported with no outcome
• Controlled experimental studies (manipulation of treatment) measure data)
• Outcome results reported
results in the form of
improvement (percent) or
responder versus non-
responder
• If the studies did not state a
priori that the results would
be reported in this way
KQ2:
• Cross-over studies that did
not report first period data
• Observational studies without
comparators (case reports,
case series, before-after
studies)
• Observational studies without
interventions (case-control
studies, population cohort
studies)
• Systematic reviews and
narrative reviews (evaluated
for reference list review)
• Editorials, comments, letters,
opinion pieces, and abstracts
Setting Primary care; specialty care (audiology, otolaryngology, neurology, No exclusions
mental health)
Other criteria Studies must address one or more of the following for tinnitus:
KQ1: Instruments used to identify patients for further evaluation or
treatment
KQ2: Treatment modality
KQ3: Predictors of treatment outcomes (prognostic factors, patient
characteristics, and symptom characteristics)
Abbreviations: DBT = cognitive behavioral therapy; dB = decibals; Dx = diagnosis; KQ = Key Question; LLLT = low level
laser LL treatment; PTM = progressive tinnitus management; RCT = randomized controlled trial; THI = Tinnitus Handicap
Inventory; TMJ = temporomandibular joint; TRQ = Tinnitus Reaction Questionnaire; TRT = tinnitus retraining therapy; TSI =
Tinnitus Severity Index; VAS = visual analogue scale; yrs = years
Data Extraction
The Evidence-based Practice Center staff members and clinical experts conducting this
review jointly developed the evidence table that was used to abstract data from the studies
(Appendix B). The table was designed to provide enough information to enable readers to
understand the studies, including types of study design, descriptions of the study populations (for
applicability), description of the intervention, appropriateness of comparison groups, validated
questionnaire measures used, baseline and outcome data on constructs of interest, and followup
conducted. Details of the patient population extracted included age, sex, duration of tinnitus,
17
severity of tinnitus, audiological factors, and comorbidities. Data were also collected about the
site where study participants were recruited and the professional setting (primary care,
audiology, otolaryngology, neurology, or mental health). In addition to outcomes related to
treatment effectiveness, all available data on harms or adverse effects of treatments were
extracted.
To ensure quality control, the team extracted several articles into the evidence table and then
reconvened as a group to discuss the utility of the table design. This process was repeated until it
was decided that the table included the appropriate categories to gather the information contained
in the articles. All team members shared the task of initially entering information into the
evidence table. Another team member then reviewed the articles and edited all initial table
entries for accuracy, completeness, and consistency. The full research team met regularly during
the article abstraction period to discuss any conflicts or issues related to the data abstraction
process.
Assessing Applicability
Applicability may be affected by differences between what occurs in research and what
happens in everyday clinical practice. Applicability was assessed in accordance with AHRQ
standards.74 The basis for applicability assessment of findings was limited to the populations,
interventions, outcomes, and settings described in the protocol and the PICOTS. Comorbidities,
age of subjects, location where study subjects were recruited, specific treatment provider, and
length of time to treatment are examples of a priori factors that may limit applicability. Subgroup
factors that may cause or explain heterogeneity of treatment effect may include patients provided
with proper audiological care before tinnitus treatment, psychological and hearing loss
comorbidities, and subtyping by prognostic, patient, and symptom characteristics that may
interact with treatment outcome.
18
Data Synthesis
Qualitative Synthesis
Study results are presented in three sections based on the three KQs. All included studies
have been summarized in narrative form, and summary tables have been created showing key
study characteristics, methodological limitations, and any other important aspect related to each
Key Question.
Quantitative Synthesis
The outcomes of interest in each study were reported using different outcome measures on a
continuous scale. With the intention to perform meta-analysis using continuous data, immediate
post-treatment data (mean, standard deviation, and sample size) for each treatment group were
utilized. The DerSimonian and Laird random effects models with inverse variance method were
selected to generate the summary measures of effect in the form of standardized mean difference
(SMD) for each outcome. The SMD was selected as a summary statistic because the studies in
this systematic review often assessed the same outcome domains using a variety of measures and
scales. In this situation, it was necessary to standardize the results of the studies before they
could be compared across studies or combined in a quantitative synthesis. SMD was calculated
using change from baseline data, (i.e., mean difference between pre-treatment (baseline) and
post-treatment (final/endpoint) scores, along with its standard deviation for both intervention and
control groups). In studies where change from baseline data was not reported for treatment
groups, the mean difference was calculated from pre- and post-treatment scores provided and
standard deviation was computed using the following equation:
2 2
𝑆𝐷𝐶ℎ𝑎𝑛𝑔𝑒 = �𝑆𝐷𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒 + 𝑆𝐷𝐹𝑖𝑛𝑎𝑙 − (2 × 𝐶𝑜𝑟𝑟 × 𝑆𝐷𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒 × 𝑆𝐷𝐹𝑖𝑛𝑎𝑙 )
Where, SDchange = Standard deviation of mean difference (pre and post treament),
SDBaseline = Standard deviation if pre-treatment score,
SDFinal = Standard deviation of post-treatment score,
Corr = Correlation between pre-treatment and post-treatment scores.
19
Rating the Body of Evidence
The strength of evidence (SOE) was assessed for each KQ using the EPC method for
intervention studies, which is based on methods developed by the GRADE Working Group.76
The judgments for the strength of evidence were determined by two of the study authors. The
combination of authors varied with the section. The raters were experienced in undertaking
systematic reviews or in audiology. Several domains of quality across studies may influence the
overall SOE for these KQs, including:
1. Risk of bias (how the study design and conduct may have contributed to systematic
error). This is judged as high, moderate, or low risk of bias.
2. Consistency of results (concerns homogeneity in direction and magnitude of results
across different studies). In the context of intervention studies, this is the degree of
heterogeneity of the summary effect size and can be evaluated with statistical tests of
heterogeneity; these tests evaluate the null hypothesis that all studies in the meta-analysis
have the same underlying magnitude of effect. When no summary effect size estimate is
possible, then how widely the point estimate varies across studies and the degree of
overlap between confidence intervals across studies was considered.75 The importance of
the direction relative to the magnitude of the effect will be judged for each group of
interventions and outcomes.77
3. Directness of the evidence (concerns whether the evidence being assessed reflects a
single, direct link between the interventions of interest (tinnitus treatment) and the
ultimate health outcome under consideration). Directness also applies to comparisons
between interventions. For intervention studies, consideration should be given to how
similar the test or the treatment is being used in practice reflecting the external validity or
generalizability of the intervention.
4. Precision refers to the degree of certainty surrounding an effect estimate for each
outcome (i.e., width of confidence intervals (CI)) for diagnostic accuracy outcomes, and
treatment outcomes monitoring; this domain is related to study sample size and number
of events).77
5. Other key domains (publication bias, dose-response association, and strength of
association [i.e., magnitude of effect]) were all considered when relevant). From these
dose-response and strength of association were not considered with respect to
downgrading the evidence.
We assessed the SOE for the six outcomes of benefit: TSQoL, perceived loudness, sleep
disturbance, anxiety symptoms, depression symptoms, and global quality of life, as well as
outcomes of harm. The SOE was classified into four grades based on the AHRQ EPC Program
approach: high, moderate, low, or insufficient76,78 as follows:
High quality SOE: Further research is very unlikely to change the confidence in the estimate of
effect.
High SOE indicates that there are consistent findings (direction of effect and magnitude
of effect) among 80% of the included comparative studies (RCT, CCT) with low risk of
bias that are generalizable to the population in question. There are sufficient data
(greater than 30 patients per intervention group for 80% of the included studies), with
narrow confidence intervals. There are no known or suspected reporting or publication
20
biases. Criteria for determining that there are no serious threats to validity are met in all
domains (studies are at low risk of bias, consistent, direct, precise, and free of reporting
and publication bias).
Moderate quality SOE: Further research is likely to have an important impact on the
confidence in the estimate of effect and may change the estimate.
The majority of studies (80 % of included studies for each outcome) are at high or
medium risk of bias or criteria for one of the other domains (consistency, precision,
directness, or publication bias) is not met.
Low quality SOE: Further research is very likely to have an important impact on the confidence
in the estimate of effect and is likely to change the estimate.
Criteria for two of the domains are not met or there are serious concerns in a single
domain that affect the validity of the results.
Insufficient quality evidence: An estimate of effect is very uncertain. Criteria for at least three
domains are not met.
No evidence: No comparative studies were identified that evaluated any the outcome of interest
(since the quality is evaluated for each outcome).
Judgment of study limitations was anchored by the presence of a minimum of one RCT with
a rating of ‘good’, or a rating of greater than 7 points from 12, indicating low risk of bias. For a
number of interventions, there is only a single study result to be reported. For those, the
consistency is unknown; similarly, for single studies the precision was rated as unknown.
Consistency for the remaining groupings was judged within the SOE tables, on the stability
of the direction of the effect (favoring treatment or favoring control) based on the point estimate
and the degree of overlap between confidence intervals.
For small sample sizes (30 or less per treatment group) and wide confidence intervals, all the
intervention groupings were ranked as being imprecise.
For most interventions, fewer than 10 studies were eligible and as such publication bias could
not be formally assessed using statistical approaches. The risk of publication bias is greater for
reviews that are based on small randomized trials.79 Based on this potential risk, it was assumed
that all intervention groupings were at risk in this systematic review and rated all groupings as
“suspected” for publication bias.
21
Results
Figure 2 provides details of the flow of studies and the final papers for review for the Key
Questions (KQ).80 The search yielded 9,725 unique citations. This includes five citations added
as a result of the grey literature search (one from the Scientific Information Packages (SIPs) that
were received, (two from clinical trial registries and two from conference abstracts). During two
levels of title and abstract screening, 8,891 articles were excluded. A total of 834 citations
proceeded to full text screening. After the final eligibility screening, 73 publications passed
through full text screening. From these, 52 publications (51 studies) were eligible for data
extraction for KQ2. Appendix C contains the list of studies excluded at full text screening.
Not included in the results, 22 reports (21 studies) did not present measures of variance123-139
or they presented results as proportions.140-144 Details of these studies may be found in Appendix
D.
22
KQ2. In adults with subjective idiopathic (nonpulsatile) tinnitus, what is the
comparative effectiveness (and/or potential harms) of medical/surgical,
sound treatment/technological, or psychological/behavioral interventions,
including combinations of interventions?
A total of 51 studies (52 included publications)10,17,18,28,35,53,57,61,62,64,81-122 address KQ2. We
organized the eligible studies based on intervention groupings suggested by the Technical Expert
Panel. Results for this comparative effectiveness review (CER) are organized by type of
intervention (i.e., pharmacological/food supplement; medical; sound technologies; and,
psychological/behavioral). Within each intervention section, the discussion of the data is then
organized by the primary outcomes: tinnitus-specific quality of life (TSQoL), perceived
loudness, sleep disturbance, anxiety symptoms, depression symptoms, and global quality of life.
From the 51 eligible studies (52 publications), 21 studies (and one companion publication123)
were not included in the results because they did not present measures of variance123-139 or they
presented results as proportions.140-144 Where possible, forest plots were created for each
outcome within the four groups of interventions showing the different treatments relative to
inactive control. Forest plots for head-to-head trials were not generated as none of the active
comparators were similar.
Subjective Loudness
• Neurotransmitter drugs showed improvement in subjective loudness versus placebo;
however SOE was low because risk of bias was medium and effect estimates were
imprecise.
• SOE was insufficient for the anti-depressant, other drug, and food supplement groups
(single studies in each of these groups evaluated the outcome).
Sleep Disturbance
• Paroxetine and vardenafil showed improvement in sleep disturbance versus placebo; no
improvement was observed with Deanxit.
• However, SOE was insufficient because only one study for each intervention considered
this outcome.
23
Depression Symptoms
• Sertraline, paroxetine, and nortriptyline showed improvements in depression symptoms
versus placebo; however, SOE was insufficient because the risk of bias was moderate and
effects were inconsistent and imprecise.
• Improvements were also seen in honeybee larvae versus hydrogenated dextrin; however,
SOE was insufficient because only one honeybee larvae study evaluated this outcome.
Intervention
Four studies (five publications)90,99,113,115,122 investigated anti-depressant drugs versus
placebo. These drugs included sertraline,99,122 paroxetine,113 trazodone,90 and nortriptyline.115
Dosage levels in the sertraline, paroxetine, and nortriptyline articles were at the recommended
levels for treating depression. However, the dosage level in the trazodone study was below the
recommended dose for depression; the dosage level was instead suitable for use as a sleep aid.
Five publications28,82,109,114,119 involving placebo comparators examined neurotransmitter drugs
that enhance or stimulate γ-aminobutyric acid (GABA). The neurotransmitter drugs were
gabapentin,109 baclofen,119 alprazolam,28 and acamprosate.82,114 Three studies investigated other
drugs, including methylprednisolone versus placebo,117 vardenafil versus placebo,106 and Deanxit
versus placebo (all participants received 1 mg clonazepam in addition to Deanxit or placebo).107
24
Four papers evaluated food supplements, with two93,111 focused on gingko biloba, one86 on zinc,
and one85 on honeybee larvae. All food supplements were compared to placebo (which was
hydrogenated dextrin in the larvae study).
Mean length of followup was 11 weeks. The shortest followup period was 3 weeks119 and the
longest was 16 weeks.122
Comparators
Table 3 shows the interventions and comparators for studies in this grouping.
25
Table 3. Interventions and comparators used in studies that evaluate pharmacological and food supplement interventions and
outcomes
Pharma/Food Anxiety Depression Global Tinnitus- Adverse
Specific Intervention Sleep Loudness
Intervention # Symptoms Symptoms QoL Specific QoL Effects
Anti-depressant INACTIVE COMPARATOR
drugs 1 Sertraline (SSRI antidepressant) vs. HAS ,
* *
HDS , *
TSQ
placebo CPRS-S-A, CPRS-S-A, VAS PGWB Yes
122 99 VAS
Zoger, 2006 and Holgers, 2011 PGWB-sub PGWB-sub
2 Paroxetine (SSRI antidepressant) vs. *
HADS-A, * THQ ,
placebo PSQI * HADS-D, BDI QWB Yes
113 BAI Likert-scale
Robinson, 2005
3 Trazodone (SARI antidepressant) vs. *
VAS-s
placebo VAS Yes
90 VAS-d
Dib, 2007
nd
4 Nortriptyline (2 gen tricyclic *
Sheehan’s IOWA ,
antidepressant) vs. placebo HDS Yes
115 Disability Likert-scale
Sullivan, 1993
Neuro-transmitter INACTIVE COMPARATOR
drugs 1 Gabapentin (GABA analogue – GABAergic)
vs. placebo THI Yes
109
Piccirillo, 2007
2 Baclofen (selective GABAB1 receptor
119 Subjective THI Yes
agonist) vs. placebo Westerberg, 1996
3 Alprazolam (benzodiazepine – anxiolytic)
vs. placebo VAS Yes
28
Johnson, 1993
4 Acamprosate (glutamate antagonist &
GABA agonist) vs. placebo VAS Subjective None
114
Sharma, 2012
5 Acamprosate vs. placebo
82 Subjective Yes
Azevedo 2005, 2005
Other drugs INACTIVE COMPARATOR
1 Methylprednisolone (intratympanic injection)
vs. placebo Self-rated TSI Yes
117
Topak, 2009
2 Vardenafil (PDE5 inhibitor) vs. placebo TQ- Yes
106 SF-36 TQ
Mazurek, 2009 sub
3 Deanxit vs. placebo TQ- TQ
107 BDI VAS None
Meeus, 2011 sub VAS-Ann
26
Table 3. Interventions and comparators used in studies that evaluate pharmacological and food supplement interventions and
outcomes (cont’d)
Pharma/Food Anxiety Depression Global Tinnitus-Specific Adverse
Specific Intervention Sleep Loudness
Intervention # Symptoms Symptoms QoL QoL Effects
Food supplements INACTIVE COMPARATOR
1 Gingko Biloba vs. placebo
111 GHSI THI Yes
Rejali, 2004
2 Gingko vs. Placebo: only effect
size reported VAS TSQ (21-item) Yes
93
Drew, 2001
3 Enzymolyzed honey bee larvae
vs. placebo, THI-subscale THI, VAS Yes
85
Aoiki, 2012
4 Zinc vs. placebo
86 Subjective Yes
Arda, 2003
Abbreviations: Ann = annoyance; BAI = Beck Anxiety Inventory; BDI = Beck Depression Inventory; CPRS-S-A = Comprehensive Psychopathological Rating Scale – Anxiety
subscale; GABAB1 = gamma-aminobutyric acid B1; gen = generation; GHSI = Glasgow Health Status Inventory; HADS = Hospital Anxiety and Depression Scale; HADS-A =
Hospital Anxiety and Depression Scale – Anxiety subscale; HADS-D = Hospital Anxiety and Depression Scale – Depression subscale; HAS = Hamilton Anxiety Rating Scale;
HDS = Hamilton Depression Rating Scale; IOWA = IOWA disability scale for Tinnitus; HDS = Hospital Depression Scale; PDE5 = phosphodiesterase type 5; Pharma =
Pharmacological; PGWB = Psychological General Well-Being index; PSQI = Pittsburg Sleep Quality Index; QoL = Quality of Life; QWB = Quality of Well-being Scale; SARI =
serotonin antagonist reuptake inhibitor; SF-36 = Medical Outcomes Study 36-Item Short-Form Health Survey; SSRI = selective serotonin reuptake inhibitor; THI = Tinnitus
Handicap Inventory; THQ = Tinnitus Handicapped Questionnaire; TQ = Tinnitus Questionnaire; TSI = Tinnitus Severity Index; TSQ = Tinnitus Severity Questionnaire; VAS =
visual analogue scale; vs. = versus
*
Indicates the test used to measure outcomes which were selected to represent the domain in the forest plots (and subsequent SOE decisions)
27
Outcomes
Of the six outcomes of interest, tinnitus-specific QoL was evaluated in 13
studies,82,85,90,93,106,107,109,111,113,115,117,119,122 subjective loudness in eight
studies,28,86,93,107,114,117,119,122 sleep disturbance in three studies,106,107,113 anxiety symptoms in
three studies,113,115,122 depression symptoms in five studies,85,107,113,115,122 and global QoL in six
studies (Table 4).90,106,111,113,114,122 Adverse effects were reported in all except two studies.107,114
See Table 3 and Appendix E, Table E1.
Setting
Twelve studies28,86,106,107,109,111,113-115,117,119,122 were set in specialty clinics (i.e., ear-nose-
throat). Three studies82,85,109 recruited participants through a university hospital, and another93
through advertisements in the national press or a tinnitus publication. One study90 did not report
its setting.
Country
The studies were carried out in several different countries: Sweden;122 the United
States;28,109,113,115,119 Brazil;82,90 India;114 Germany;106 Belgium;107 United Kingdom;93,111
Japan;85 and Turkey.86,117
28
Sources of Funding
Sources of funding were not reported in seven publications.28,82,86,90,111,114,117 In one of these
studies, the author holds a patent for the use of the drug in Tinnitus.82 Ten publications received
funding from research councils, foundations, and government departments and non-profit
associations.85,93,106,107,109,113,115,119,122
29
Figure 3. Distribution of methodological risk of bias criteria of randomized controlled trials for the
pharmacological and food supplement interventions
30
The nortriptyline study115 used a battery of instruments to measure discomfort. These
instruments included the Multidimensional Pain Inventory (MPI) self and spouse evaluations,
two VAS which measure life disruptions due to tinnitus (one examining ‘internally referred’
disruptions, another ‘externally referred’ disruptions), and a 5-point overall tinnitus disruption
scale. The active treatment group had lower (better) mean scores on all instruments except the
MPI spouse evaluation, with mean differences in score being significant on the MPI self-
evaluation (mean difference=0.6; p<0.01) and VAS internal disruption (mean difference=0.9;
p<0.05) (Figure 4).
Turning to the 12 studies85,90,93,106,107,109,111,113,115,117,119,122 that measured tinnitus-specific QoL
as severity, a multitude of different instruments were used to assess the outcome. In 10 studies,
between group differences were not statistically significant at the 5 percent level on the
following instruments: Tinnitus Handicap Questionnaire (and a supplemental 8-point Likert
scale, as well as the Disability Inventory),113 10-point VAS,85,90 Iowa Disability Scale,115
Tinnitus Handicap Inventory,109,111,119 Tinnitus Severity Index,117 Tinnitus Questionnaire,106 and
a 21-item severity questionnaire based on existing instruments.93
In the sertraline study,122 the treated group experienced greater reductions in severity over 16
weeks of followup relative to the placebo group, as evidenced by larger mean changes in score
on the Tinnitus Severity Questionnaire (i.e., 4.69 vs. 2.12; p=0.024).
In the Deanxit crossover trial,107 the authors subtracted mean scores on the Tinnitus
Questionnaire after 7 weeks of followup from baseline scores. They reported that mean changes
in score were higher in the group that received placebo followed by Deanxit (mean score
change=11.0; p<0.001), compared to the group that received Deanxit followed by placebo (mean
score change=7.9; p=0.001). However, conclusions about efficacy from this study are limited
because the authors were investigating the sequence of treatment rather than a direct comparison
of the effects of Deanxit versus placebo.
31
Table 5. Strength of evidence: Studies that evaluate pharmacological and food supplement
interventions compared to inactive control and report tinnitus-specific quality of life outcomes
Intervention Specifics # of Studies Risk of Consistency Directness Precision Magnitude SOE
Group (n) Bias of the Effect
SMD Range
(CI)
*90,99,113,115,122
Anti- Nortriptyline 4 Medium Inconsistent Direct Imprecise -0.61 Insufficient
depressants Paroxetine (-1.03 to -
Sertraline 0.19)
Trazodone to 0.12
(-0.31 to
0.54)
82,109,119
Neuro- Acamprosate 3 Medium Inconsistent Direct Imprecise -1.57 Insufficient
transmitter Baclofen (-2.28 to -
drugs Gabapentin 0.86) to -0.01
(-0.38 to
0.35)
106,107,117
Other drugs Deanxit, 3 Medium Inconsistent Direct Imprecise -0.68 Insufficient
MEP, (-1.21 to -
vardenafil 0.16) to 0.35
(-0.26 to
0.86)
85,93,111
Food Gingko 3 Medium Inconsistent Direct Imprecise -0.21 Insufficient
supplement biloba (-0.72 to
Honeybee 0.30) to
larvae -0.21
(-0.72 to
0.30)
Abbreviations: CI = confidence interval; n = number; SOE = strength of evidence; SMD = standard mean difference
Note: all drugs were compared to placebo except honeybee larvae (versus hydrogeneated dextrin); Deanxit comparison was a
crossover trial of Deanxit versus placebo, with each participant given 1 mg clonazapam in addition to Deanxit or placebo.
*
four studies, five publications
Subjective Loudness
Eight publications28,86,93,107,114,117,119,122 examined loudness, primarily using subjective VAS-
type scales (Tables 3 and 4). In two studies,86,122 active treatments had more impact on loudness
than comparators. A group receiving sertraline had a greater mean reduction in score over the
course of followup, measured on a 100 mm VAS, than placebo (15.21 vs. 5.15; p=0.014).122 A
study comparing zinc (50 mg/day for 8 weeks) to placebo in 41 persons seen at ear-nose-throat
clinics found the mean score to be 1.41 points lower in the zinc group (p<0.05) after 8 weeks of
followup, as measured using a 7-item subjective loudness questionnaire (higher scores indicated
more loudness).86
Four studies failed to find any differences (p>0.05) in loudness between treatment arms.
These studies included baclofen (10 to 30 mg/day twice daily for 3 weeks) vs. placebo in 58
persons recruited from a tinnitus referral center (subjective 10-point scale),119
methylprednisolone solution (0.3 to 0.4 ml intratympanic injection of 62.5 mg/ml
methylprednisolone) vs. saline in 59 persons recruited from an unreported setting (subjective 10-
point scale),117 Deanxit vs. placebo (0 to 100 VAS),107 and ginkgo biloba (50 mg given 3 times
daily) vs. placebo in persons who were recruited through advertisements placed in the national
press and a tinnitus publication (6-point loudness scale) (Figure 5).93
In a study28 of alprazolam (25 to 50 mg/day) versus placebo in 36 persons recruited from a
tinnitus registry and followed for 12 weeks, loudness was measured using a 10-point VAS and
Norwest SG-1 tinnitus synthesizer. The authors did not provide between-group comparisons on
32
each outcome; however, they stated that four of 17 persons in the alprazolam group, and 18 of 19
persons in the placebo group, experienced stable or increased loudness on either the VAS or
synthesizer. Using these data, one may compute a relative risk of 0.25 (95% CI, 0.10 to 0.59),
which means that the risk of stable or increased loudness was 75 percent less in the alprazolam
group compared to the placebo group.
A crossover trial114 of acamprosate (333 mg twice daily for 45 days) versus placebo in 40
persons who were outpatients at an ear-nose-throat hospital measured loudness on a 10 cm VAS.
The authors only present within-group comparisons in the text, but do mention that 92.5 percent
of the treated group, and 12.5 percent of the placebo group, displayed improvement over the
course of followup. However, the authors do not define improvement, which appears to be an
amalgam of the loudness and global QoL outcomes. Nor do the authors conduct a statistical test
to compare improvement between the two groups.
Table 6. Strength of evidence: Studies that evaluate pharmacological and food supplement
interventions compared to inactive control and report subjective loudness outcomes
Intervention Specifics # of Risk of Bias Consistency Directness Precision Magnitude of SOE
Group Studie the Effect
s (n) SMD Range (CI)
*99,122
Anti- Sertraline 1 Low Unknown Direct Imprecise -0.45 Insufficient
depressants (single study) (-0.95 to 0.05)
28,114,1
Neuro- Baclofen, 3 Medium Consistent Direct Imprecise -2.08 Low
19
transmitter alprazolam (-2.87 to -1.30)
drugs acamprosate to -0.29
(-0.79 to 0.22)
107,117
Other drugs MEP, 2 Medium Unknown Direct Imprecise -0.07 Insufficient
Deanxit (single study) (-0.58 to 0.44)
(Cannot
calculate
SMD in
Deanxit
107
study )
86,93
Food Gingko biloba 2 Medium Unknown Direct Imprecise -0.91 Insufficient
supplement Zinc (single study) (-1.60 to -0.22)
(Cannot
calculate
SMD in zinc
86
study )
Abbreviations: CI = confidence interval; MEP = methylprednisolone injections; n = number; SOE = strength of evidence; SMD
= standard mean difference
Note: all drugs were compared to placebo; Deanxit comparison was a crossover trial of Deanxit versus placebo, with each
participant given 1 mg clonazapam in addition to Deanxit or placebo.
*
one study, two publications
33
Sleep Disturbance
Three studies looked at the outcome of sleep disturbance (Tables 3 and 4). One study113
investigating sleep compared paroxetine (50 mg/day) and placebo in 115 persons over 14 weeks
of followup. Between-group differences in sleep quality, measured using the Pittsburg Sleep
Quality Index (PSQI), were not statistically significantly different at the end of followup. Two
studies106,107 examined sleep using the sleep disturbance subscale of the Tinnitus Questionnaire
(TQ). The first106 of these two studies compared vardenafil (10 mg taken twice daily) against
placebo and found no between-group differences (p=0.88) on the sleep disturbance subscale. The
second of these two studies, a crossover trial107 of Deanxit (flupentixol 0.5 mg and melitracen 10
mg) and clonazepam (1 mg), compared to placebo and clonazepam, reported decreases in score
following the first treatment phase, and increases in score following the second treatment phase,
regardless of whether Deanxit or placebo was received first. However, the authors do not report a
statistical comparison of these subscale results (Figure 6).
Table 7. Strength of evidence: Studies that evaluate pharmacological and food supplement
interventions compared to inactive control and report sleep disturbance outcomes
Intervention Specifics # of Risk of Bias Consistency Directness Precision Magnitude of SOE
Group Studies the Effect
(n) SMD Range
(CI)
113
Anti- Paroxetine 1 Low Unknown Direct Imprecise 0.31 Insufficient
depressant (single study) (-0.06 to 0.67)
106,107
Other drugs Vardenafil, 2 Medium Unknown Direct Imprecise -0.09 Insufficient
Deanxit (single study) (-0.69 to 0.52)
(Cannot
calculate
SMD in
Deanxit
107
study )
Abbreviations: CI = confidence interval; n = number; SOE = strength of evidence; SMD = standard mean difference
Note: all drugs were compared to placebo; Deanxit comparison was a crossover trial of Deanxit versus placebo, with each
participant given 1 mg clonazapam in addition to Deanxit or placebo.
Anxiety Symptoms
Three placebo-controlled studies113,115,122 included anxiety as an outcome (Tables 3 and 4).
Two studies (sertraline,122 paroxetine113) measured anxiety with the Hamilton Anxiety Rating
Scale (HAS); one study113 also utilized the Beck Anxiety Inventory (BAI). The third study,115 of
nortriptyline (50 to 150 mg/mL for 6 weeks) versus placebo, used Sheehan’s Disability Scales
(SDS). The paroxetine study113 found greater improvements in score for the placebo group on the
HAS and BAI, although the differences were not statistically significant. Conversely, a study122
of sertraline (50 mg/day) versus placebo in 63 persons found the mean score change over
followup on the HADS to be larger in the treated group compared to the placebo group (8.51 vs.
34
4.09; p=0.04). On the SDS,115 the nortriptyline group showed slight improvement relative to the
placebo group, but the difference was not statistically significant.
The sertraline study122 also measured anxiety using the Comprehensive Psychopathological
Rating Scale (CPRS) anxiety subscale and in a companion paper,99 the Psychological General
Well-being Index (PGWB), which contains an anxiety subindex. Over the course of followup,
the sertraline group displayed a larger mean score change on the CPRS relative to the placebo
group (4.38 vs. 0.73; p=0.013), which indicates a greater reduction in anxiety for persons
receiving the active treatment. Likewise, the sertraline group also showed a larger mean score
change versus the placebo group on the PGWB (4.59 vs. 0.61; p=0.002) (Figure 7).
Table 8. Strength of evidence: Studies that evaluate pharmacological and food supplement
interventions compared to inactive control and report anxiety symptoms outcomes
Intervention Specifics # of Risk of Consistency Directness Precision Magnitude of the SOE
Group Studies Bias Effect
(n) SMD Range (CI)
113,115,1
Anti- Sertraline 3 Medium Inconsistent Direct Imprecise -1.13 Insufficient
22
depressants Paroxetine (-1.57 to -0.69) to
Nortriptyline 0.28
(-0.09 to 0.64)
Abbreviations: CI = confidence interval; n = number; SOE = strength of evidence; SMD = standard mean difference; SSRI =
serotonin reuptake inhibitors
Note: all drugs were compared to placebo
Depression Symptoms
Five studies considered depression, with two113,122 utilizing more than one outcome measure
(Tables 3 and 4). Three113,115,122 of the five trials measured depression with the Hamilton
Depression Rating Scale (HAM-D), two107,113 with the Beck Depression Inventory (BDI), one
with the CPRS depression subscale and PGWB depression subindex,99,122 and one85 with the
depression question on the Tinnitus Handicap Inventory (THI). On the HAM-D, treated groups
showed greater improvement than placebo when treated with sertraline (difference not
significant)122 and nortriptyline (difference in mean score change over followup=3.7; p<0.05).115
In the sertraline study,99,122 the mean changes in score over followup on the CPRS depression
subscale and PGWB depression subindex favored the treated group (CPRS: difference in mean
change score=5.88, p=0.002; PGWB: difference in mean change score=2.22, p=0.002). For the
paroxetine-placebo comparison,113 changes in score on the HAM-D and BDI were greater in the
placebo group over the course of followup, although the differences were not statistically
significant relative to the treated group. The authors of the Deanxit crossover107 wrote that they
did not find between-group differences on the BDI; however, they did not report any numerical
results or statistical calculations.
The final study in this outcome domain85 compared lyophilized powder of enzymolyzed
honeybee larvae (720 mg given 4 times daily) to hydrogenated dextrin over 12 weeks of
35
followup. The authors administered the THI to the 58 study participants and found only one
between-group difference after conducting subgroup analyses for each of the THI’s 25 questions.
On the depression question, the mean score difference at week 12 favored the honeybee larvae
group (MSD=0.08; p<0.05) (Figure 8).
Table 9. Strength of evidence: Studies that evaluate pharmacological and food supplement
interventions compared to inactive control and report depression symptoms outcomes
Intervention Specifics # of Risk of Consistency Directness Precision Magnitude of the SOE
Group Studies Bias Effect
(n) SMD Range (CI)
113,115,1
Anti- Sertraline 3 Medium Inconsistent Direct Imprecise -1.13 Insufficient
22
depressants Paroxetine (-1.57 to -0.69) to
Nortriptyline 0.21
(-0.16 to 0.57)
107
Other drugs Deanxit 1 Medium Unknown Direct Imprecise Insufficient
(single study)
(Cannot
calculate SMD
in Deanxit
107
study )
85
Food Honeybee 1 Medium Unknown Direct Imprecise -0.49 Insufficient
supplement larvae (single study) (-1.01 to 0.04)
Abbreviations: CI = confidence interval; n = number; SOE = strength of evidence; SMD = standard mean difference; SSRI =
serotonin reuptake inhibitors
Note: all drugs were compared to placebo except honeybee larvae (versus hydrogeneated dextrin); Deanxit comparison was a
crossover trial of Deanxit versus placebo, with each participant given 1 mg clonazapam in addition to Deanxit or placebo
Global Quality-of-Life
Six studies examined global QoL (Tables 3 and 4)90,106,111,113,114,122 and only one study
(sertraline122) showed improvement versus placebo. The sertraline trial122 reported QoL results,
measured using the PGWB, in a companion paper:99 after 16 weeks of followup, the
improvement in mean score compared to baseline was greater in the treated group relative to the
placebo group (20.83 vs. 2.79; p=0.001). In four other studies, global QoL was assessed using
the Quality of Well-being Scale,113 a 10-point VAS,90 Short Form 36,106 or Glasgow Health
Status Inventory.111 In these four studies, between-group differences in mean score changes over
followup were extremely minimal and not suggestive of any particular direction of effect (Figure
9).
The acamprosate study114 utilized an unspecified QoL instrument that was linked to an
incorrect citation. The authors combined outcomes and reported 92.5 percent improvement in the
treated group and 12.5 percent improvement in the placebo group, although the paper does not
indicate the portion of this improvement attributable to QoL.
36
Strength of Evidence—Global Quality-of-Life
The SOE is insufficient for anti-depressants versus placebo in global QoL, for the same
reasons as outlined in the depression symptoms section above (Table 10). SOE is insufficient for
acamprosate,114 vardenafil,106 and ginkgo biloba111 because only one study evaluated each of
these interventions.
Table 10. Strength of evidence: Studies that evaluate pharmacological and food supplement
interventions compared to inactive control and report global quality of life outcomes
Intervention Specifics # of Risk of Consistency Directness Precision Magnitude of SOE
Group Studies Bias the Effect
(n) SMD Range (CI)
90,113,122
Anti- Sertraline 3 Medium Inconsistent Direct Imprecise -0.24 Insufficient
depressants Paroxetine (-0.60 to 0.13) to
Trazodone 1.06
(0.53 to 1.59)
114
Neuro- Acamprosate 1 Medium Unknown Direct Imprecise 1.53 Insufficient
transmitter (single study) (0.82 to 2.25)
drugs
106
Other drugs Vardenafil 1 Low Unknown Direct Imprecise -0.22 Insufficient
(single study) (-0.83 to 0.38)
111
Food Ginkgo 1 Medium Unknown Direct Imprecise -0.07 Insufficient
supplement biloba (single study) (-0.58 to 0.44)
Abbreviations: CI = confidence interval; n = number; SOE = strength of evidence; SMD = standard mean difference; SSRI =
serotonin reuptake inhibitors
Note: all drugs were compared to placebo
Adverse Effects
Adverse effects spanned a range of clinical severity, from dry or sour mouth90,113 to
confusion,119 but generally subsided after discontinuation of treatment (Table 11). Incidence of
adverse effects varied from 3 percent122 to 67 percent.117 One study114 did not report adverse
effects and one trial85 only reported that 2 persons withdrew due to ‘discomfort’.
Among the anti-depressant trials, adverse effects were minimal in one trial,122 with one
sertraline participant reporting sexual dysfunction and one placebo participant reporting an
unspecified problem. Eighty-eight percent of participants in the trazodone study90 were free of
adverse effects with seven reported effects in the treated group, the most serious being
hypertensive crisis, and three in the placebo group: sour mouth, insomnia, sleepiness. For
paroxetine,113 eight different effects occurred during followup: sexual dysfunction, drowsiness,
dry mouth, sweating, insomnia, gastrointestinal distress, tremor, and headache. The incidence of
sexual dysfunction, drowsiness, and dry mouth were statistically significantly greater in the
paroxetine group relative to the placebo group. One study115 reported anticholinergic effects and
sedation.
Turning to neurotransmitter drugs, nine persons withdrew from the gabapentin study109 due
to nausea (n=3), weight gain (n=2), sleep disturbance (n=2), or dizziness (n=1). These persons
were assigned to the active treatment group. The baclofen trial119 saw higher incidences (p<0.05)
of confusion, dizziness, and drowsiness in the treated group, with no differences (p>0.05)
between treatment and placebo groups in terms of gastrointestinal problems, weakness, or
worsening tinnitus. Twelve of 17 persons who received alprazolam28 reported side effects,
including drowsiness (n=7), insomnia (n=1), difficulty functioning at work (n=1), or more
dreams during sleep (n=4). The authors of the acamprosate trial82 indicated that 12 percent of the
37
acamprosate group and 20 percent of the placebo group reported adverse effects (p=0.35), which
included epigastralgia and choking (no specific numbers reported).
In the methylprednisolone vs. saline study,117 the authors reported percentage incidences of
four types of adverse effects, with higher percentages in the treated vs. placebo group: pain (67
vs. 52 percent; p>0.05); burning sensation (57 vs. 17 percent; p=0.002); vertigo (57 vs. 38
percent; p>0.05); and bitter taste (40 vs. 7 percent; p=0.003). Turning to the vardenafil study,106
six persons in the vardenafil group and two persons in the placebo group experienced adverse
effects, which included headache, diarrhea, nasal congestion, and priapism.
The authors of the two ginkgo biloba trials reported side effects. In the smaller study
(n=60),111 the authors noted that diarrhea occurred in 6 percent of placebo and 3 percent of
treated participants, while headaches occurred in 3 percent of the persons in each group. In the
larger study,93 the authors reported numerous adverse effects, with the highest incidence
observed for gastrointestinal effects (3.1 percent in both study groups) and the lowest for
hyperacusis (0 percent in the treated group, 0.4 percent in the placebo group). Overall, the
between-group differences in incidence were not statistically significant for any adverse effect in
the larger trial. In the zinc trial,86 two patients in the intervention group reported minor gastric
disturbances. Similarly, two patients in the honeybee larvae RCT85 dropped out due to
‘discomfort’ (one patient in each study group).
Table 11. Treatment emergent adverse effects reported in studies evaluating pharmacological and
food supplement interventions
Pharmacological Specific Dropouts Eue to AE AE Info Treatment Emergent AE (did not
Intervention Intervention (% of dropouts) Collected drop out of study)
Category Reason(s) Reason(s)
Antidepressant Sertraline (SSRI NR Yes NR
drugs antidepressant) vs.
99,122
placebo
Paroxetine (SSRI 22/26 (84.6%) Yes NR
antidepressant) vs. Sexual dysfunction
113
placebo Tx n=17(29.8%)
Pl n=4 (6.9%) p=0.001
Drowsiness
Tx n=11(19.3%)
Pl n=2 (3.4%) p=0.007
Dry mouth
Tx n=8(14.0%)
Pl n=1 (1.7%) p=0.015
NS results:
Sweat (11), Insomnia (11), GI
distress (7), Tremor (1),
Headache (5)
Trazodone (SARI 0 NR Sleepiness
antidepressant) vs. Tx n=3 (7%) Pl n=1 (2.4%)
90
placebo
nd
Nortriptyline (2 14/25 (56.0%) NR NR
gen tricyclic Anticholinergic side effects and
antidepressant) vs. sedation (11)
115
placebo
38
Table 11. Treatment emergent adverse effects reported in studies evaluating pharmacological and
food supplement interventions (continued)
Pharmacological Specific Dropouts Eue to AE AE Info Treatment Emergent AE (did not
Intervention Intervention (% of dropouts) Collected drop out of study)
Category Reason(s) Reason(s)
Neurotransmitter Gabapentin(GABA 9/20 (45.0%) Yes NR
drugs analogue – Nausea n=3
GABAergic) vs. Weight gain n=2
109
placebo Sleep disturbance n=2
Dizziness n=1
Baclofen (selective 8/11 (72.7%) Yes Confusion
GABAB1 receptor All withdrew because of side Tx n=8 (26.7%) Pl n=0
agonist) vs. effects (not specified) <0.005
119
placebo Dizziness
Tx n=12 (40.0%) Pl n=1 (3.4%)
<0.001
Drowsiness
Tx n=15 (50.0%) Pl n=3 (10.3%)
<0.001
Alprazolam 2/4 (50%) Yes Excessive drowsiness
(benzodiazepine – Excessive drowsiness 7/17 (41%)
anxiolytic) vs.
28
placebo
Acamprosate vs. NR NR NR
114
placebo
Acamprosate vs. 9/50 (18%) Yes Epigastralgia and choking were
82
placebo 2 in Tx group and 7 in Pl group reported in 12% of Tx group and
(AEs included epigastralgia, 20% of Pl group, including 9
choking, depression (n=1); participants who withdrew
authors did not break down
AEs by group or percentage)
Other Drugs Methylprednisolone 0 NR Pain during injection
(intratympanic Tx: 67% Pl 52% NS
injection) vs. Burning sensation:
117
placebo Tx 57% Pl 17% p=0.002
Vertigo
Tx 57%, Pl 38% NS
Bitter taste
Tx 40%, Pl 7% p=0.003
Deanxit + NR NR NR
clonazepam vs.
placebo +
107
clonazepam
Vardenafil (PDE5 5/7 (71.4%) NR Headache
inhibitor) vs. Tx n=1; Pl n=2
106
placebo Diarrhea
Tx n=2; Pl n=0
Nasal congestion
Tx n=2; Pl n=0
Prolonged penile erection
Tx n=1; Pl n=0
39
Table 11. Treatment emergent adverse effects reported in studies evaluating pharmacological and
food supplement interventions (continued)
Pharmacological Specific Dropouts Eue to AE AE Info Treatment Emergent AE (did not
Intervention Intervention (% of dropouts) Collected drop out of study)
Category Reason(s) Reason(s)
40
Table 12. Strength of evidence: Studies that evaluate pharmacological and food supplement
interventions compared to inactive control and report on the adverse effect of sedation
Intervention Specifics # of Risk of Consistency Directness Precision Magnitude of SOE
Group Studies Bias the Effect
(n) SMD Range
(CI)
90,113
Pharmacological Anti- 2 Low Inconsistent Direct Imprecise N/A Insufficient
depressant
Drowsiness or vs. placebo
excessive Neuro- 2
28,119
Low Inconsistent Direct Imprecise N/A Insufficient
sleepiness transmitter
Drugs
(Baclofen,
Alprazolam)
vs. placebo
Abbreviations: CI = confidence interval; n = number; SOE = strength of evidence; SMD = standard mean difference
41
Figure 4. Studies with inactive comparators that evaluate pharmacological and food supplement interventions and report tinnitus-
specific quality of life outcomes
42
Figure 5. Studies with inactive comparators that evaluate pharmacological and food supplement interventions and report subjective
loudness outcomes
Anti-depressant drugs
Neurotransmitter drugs
Other drugs
Food supplements
-2.87 0 2.87
43
Figure 6. Studies with inactive comparators that evaluate pharmacological and food supplement interventions and report sleep
disturbances outcomes
Anti-depressant drugs
Other drugs
-.694 0 .694
Favors Treatment Favors Control
44
Figure 7. Studies with inactive comparators that evaluate pharmacological and food supplement interventions and report anxiety
symptom outcomes
Anti-depressant drugs
-1.57 0 1.57
45
Figure 8. Studies with inactive comparators that evaluate the pharmacological and food supplement interventions and report
depression symptoms outcomes
Anti-depressant drugs
Food supplements
Aoki 2012, {Lyophilized powder (honeybee larvae) vs. Placebo} THI-sub 29 29 -0.49 (-1.01, 0.04)
-1.57 0 1.57
46
Figure 9. Studies with inactive comparators that evaluate pharmacological and food supplement interventions and report global quality
of life outcomes
Anti-depressant drugs
Neurotransmitter drugs
Other drugs
Food supplements
-2.25 0 2.25
47
Medical Interventions
Key Messages
Eleven studies were included for medical interventions in KQ2:35,83,88,89,94,103,105,108,110,116,118
• Six evaluated Repetitive Transcranial Magnetic Stimulation (rTMS) or electromagnetic
stimulation83,88,94,103,105,110
• Three evaluated low level laser therapy (LLLT)35,89,108
• One evaluated acupuncture118
• One evaluated acoustic coordinated reset neuromodulation (ACRN) therapy116
All the studies in the medical intervention grouping have relatively small sample sizes (less
than 60 subjects total).
The risk of bias in the 11 studies evaluating medical interventions was generally fair (n=9
fair,35,83,89,94,103,105,108,116,118 n=1 poor,88 n=1 good110).
Subjective Loudness
• This outcome was evaluated in four studies. The SOE was insufficient for studies
evaluating LLLT (n=2), ACRN (n=1) and acupuncture (n=1) because of high risk of bias
and imprecise estimates.
Sleep Disturbance
• No studies evaluated this outcome.
Anxiety Symptoms
• A single study evaluating LLLT evaluated this outcome and the SOE was deemed
insufficient.
Depression Symptoms
• A single study evaluating LLLT evaluated this outcome and the SOE was deemed
insufficient.
48
three evaluated low level laser therapy (LLLT)35,89,108 and one each evaluating acupuncture118
and acoustic coordination reset neuromodulation (ACRN) therapy.116 See Appendix E for the
Characteristics of Included Studies Evidence Tables.
49
Table 13. Details of the devices, dose and placement of rTMS and electromagnetic stimulation
interventions
Study Device Dose and Duration Information About the Location and
Method of Treatment Application as
Specified Within the Studies
94
Ghossaini, Device: Diapulse Electromagnetic energy group: High- Treatment was accomplished by placing
2004 (model D103); Frequency Pulsed Electromagnetic the center of the head of the Diapulse unit
Diapulse Energy (Diapulse) set to produce pulsed approximately 1 inch lateral to the auricle.
Corporation of electromagnetic energy at 27.12 MHz in
America 65 µs burst with repetition of 600 pulses Treatment was placed only on one side of
per second at 975 W peak. the skull. Patients with bilateral tinnitus
received treatment to the ear with louder
Patients received 30-minute treatments tinnitus.
with the Diapulse device (model D103)
3 times per wk for 1 month.
Sham group:
Received an identical protocol to the
active-stimulation group, but with the
sham coil tilted away from the skull.
50
Table 13. Details of the devices, dose and placement of rTMS and electromagnetic stimulation
interventions (continued)
Study Device Dose and Duration Information About the Location and
Method of Treatment Application as
Specified Within the Studies
110
Plewnia, Device: Magstim rTMS group. Because the primary auditory cortex cannot
2012 SuperRapid; Continuous theta burst stimulation be reached adequately by rTMS and in
(The Magstim (cTBS) which was standardized to 80% order to compare the effects of cTBS to
Company Ltd., individual active motor threshold. cTBS secondary and higher order processing
Whitland, UK). was applied to each hemisphere in areas, the 10–20 EEG electrode placement
alternating order. Each stimulation train system was used to localize.
Coil: Figure- (40s) consisted of 600 stimuli applied in
eight-shaped coil burst of 3 pulses at 50 Hz given every Temporal cortex (Brodmann area 39 (TAC:
(diameter of each 200 msec (i.e.,5 Hz). halfway between T5/P3 and T6/P4)) and
winding 70 mm, Temporoparietal cortex (Brodmann area
biphasic stimuli Fifteen minutes after the first 2 trains, a 42/22 [SAC: halfway between T3/C3 and
of 250 us) second pair of cTBS trains was given (a T4/C4]).
total of 2,400 stimuli per day). Applying Sham (behind the mastoid)
a second train 15 minutes later has
previously been shown to prolong the The coil was hand-held during stimulation
inhibitory effects. trains to allow for optimal fixation. All
patients were seated in a comfortable chair
Patients received daily cTBS for 4 while they were receiving 4 x 40 s of cTBS.
weeks (20 sessions). There was no other input to or activity of
the patients during stimulation. Disposable
®
Sham group: earplugs (ColorPlux ; noise reduction
for adequate masking of the patients, rating 35 decibels) were used while cTBS
sham stimulation was performed as per was applied.
cTBS but behind the mastoid.
103
Langguth, Medtronic (90 The study aimed to investigate whether A neuronavigational system (Brainvision,
2008 mm outer priming stimulation enhances the Brainlab) based on frameless stereotaxy
diameter, efficacy of low-frequency rTMS and adapted for magnetic stimulation
Medtronic, allowed for navigation of the coil on the
Minneapolis, MN, Intervention: Priming protocol (960 surface of the skull over the auditory cortex
USA) stimuli; 6 Hz) preceded rTMS (1,040 according to the individual MRI data. The
stimuli; 1 Hz and an intensity of 90% handle of the coil was pointing upwards.
Figure 8 coil motor threshold (16 trains lasting 10 s
separated by 20 s). Treatment over the left auditory cortex
(independent of right or left handedness).
Stimulation was provided over 10
consecutive days.
51
That pattern is repeated periodically. The random variation of the tone sequences and the 3:2 “on
and off” pattern optimizes the desynchronizing ACRN effect.
In this study, four different stimulation groups and one placebo group were evaluated.
Groups 1, 3, and 4 (G1, G3, G4) used four tones grouped around the tinnitus frequency for each
patient (ft); G3 differed only in repetition rate being adapted to the individual EEG (i.e., band
peak). For group 2 (G2) each ACRN cycle was formed by a varying composition of four tones
chosen out of twelve tones from the surrounding frequencies. Placebo stimulation or group 5
(G5) was formed similar to G1 using a down-shifted stimulation-frequency (fp) (fp=0.7071·ft/
(2n), fp within (300 Hz, 600 Hz)) outside the synchronized tinnitus focus. Note that a
readjustment of stimulation parameters could be undertaken if the matched tinnitus frequency
had changed relative to baseline.
Treatment in G1, G2, and G3 was applied for 4 to 6 hours per day and applied continuously
or split into several sessions not less than 1 hour. In contrast, G4 and G5 received stimulation for
only 1 hour daily. Patients were stimulated for 12 weeks using portable acoustic device and
comfortable earphones; this 3 month treatment was followed by an additional off stimulation
period of 4 weeks and an optional 24 week off-label extension period. Although not specified, it
is likely that the stimulation was administered by the patient (as the device was portable) but it is
not clear what role if any the neurologist had in administering the treatment (but EEG was used
to optimize the frequencies selected for individual patients and thus specialized professional
expertise was required in the initial assessment of tinnitus frequency for the purposes of selecting
the characteristics of the acoustic stimulation). The primary authors of the study have a
contractual relationship with the manufacturer or hold shares within the company of the device
and the study was funded by the manufacturers.
52
projected onto the tympanic membrane through a 17-degree diverging lens, creating a spot size
of 1 cm. Duration of irradiation was 20 min a day resulting in an energy density of about 6 J at
the tympanic membrane; the treatment lasted 3 months. All subjects had unilateral tinnitus and
although not reported in the study, it is assumed that only one ear was treated. Note that the laser
was administered by the patient at their home. The second study89 using the TinniTool EarLaser,
describes the system as one composed of a laser probe that was placed at the entrance of the
external auditory canal, from where the laser ray was directed toward the eardrum. The laser
probe was to be used with a wearable ear hook. Patients were trained to use the device for 20
minutes per day, for 3 months. In this study, although the largest proportion of subjects had
bilateral tinnitus (63 percent), it is not clear if the study subjects were instructed to treat both
ears.
This second study89 using the TinniTool EarLaser also combined counseling (10 sessions of
40 minutes, distributed over the 3 month treatment period) with both the active LLLT and the
sham LLLT groups. The counseling intervention included a multi-modal approach and combined
tinnitus retraining therapy principles and psychosomatic approaches (both hypnotic and
relaxation techniques) over the 10 sessions.
Acupuncture
One study reviewed the effects of Chinese acupuncture relative to sham acupuncture.118
Treatments were given over 2 months where subjects received three blocks of treatments (10, 5,
and 10, separated by 1 week) for a total of 25 sessions. The treatment was administered daily for
30 minutes. All subjects were treated over five different points (SI -19, G 2, SJ 17, SJ 19, DU
20); however, distal points and the “methods of manipulation” varied with individual patients.
Bilateral treatment was administered irrespective of whether the patient suffered with unilateral
or bilateral tinnitus. A non-penetrating Japanese acupuncture needle was used as the sham
acupuncture. The sham needles were inserted superficially into the skin over random non-
acupuncture sites for 30 minutes.
Comparators
Table 14 shows the types of comparators in the included in the studies. Description of the
sham interventions are described in the interventions section.
53
Table 14. Interventions and comparators used in studies that evaluate medical interventions and outcomes
Medical Anxiety Depression Global Tinnitus- Adverse
Specific Intervention Sleep Loudness
Intervention Symptoms Symptoms QoL Specific QoL Effects
RTMS INACTIVE COMPARATOR
*
1 rTMS vs. sham THI ,
83
Anders, 2012 TQ-modified, Yes
VAS
2 rTMS vs. sham
105 THI None
Marcondes, 2010
*
3 rTMS vs. sham, THI
88 VAS None
Chung, 2012 TQ
4 rTMS (cTBS) secondary auditory cortex vs. sham,
110 TQ Yes
Plewnia, 2012
rTMS (cTBS) temporoparietal cortex vs. sham,
110 TQ Yes
Plewnia, 2012
*
5 High-Frequency Pulsed Electromagnetic Energy vs. sham THI ,
94 Yes
Ghossaini, 2004 TMR
HEAD-TO-HEAD
1 rTMS Standard protocol (2000 stimuli; 1 Hz) vs.
rTMS Priming protocol (960 stimuli; 6 Hz+1040 stimuli;1
TQ None
Hz)
103
Langguth, 2007
2 rTMS (cTBS) secondary auditory cortex vs. rTMS (cTBS)
temporoparietal cortex, TQ Yes
110
Plewnia, 2012
Acupuncture INACTIVE COMPARATOR
*
1 Acupuncture vs. sham VAS-Ann ,
118 VAS NR
Vilholm, 1998 VAS-Awr
Laser INACTIVE COMPARATOR
*
1 Laser Therapy vs. sham THI ,
108
Mirz, 1999 STAI BDI VAS VAS-Ann, None
VAS-Att
2 Laser Therapy vs. sham
35 VAS THI Yes
Teggi, 2009
HEAD-TO-HEAD
1 Experimental (LLS+): low level laser + counseling
Control (LLS-): same counseling as LLS+ plus faked
THI NR
stimulation device
89
Cuda, 2008
54
Table 14. Interventions and comparators used in studies that evaluate medical interventions and outcomes (continued)
Medical Anxiety Depression Global Tinnitus- Adverse
Specific Intervention Sleep Loudness
Intervention Symptoms Symptoms QoL Specific QoL effects
Neuromodul INACTIVE COMPARATOR
ation 1 ACRN G1 vs. placebo TQ
*
116 VAS Yes
Tass, 2012 VAS
116 *
ACRN G2 vs. placebo Tass, 2012 TQ
VAS Yes
VAS
116 *
ACRN G3 vs. placebo Tass, 2012 TQ
VAS Yes
VAS
116 *
ACRN G4 vs. placebo Tass, 2012 TQ
VAS Yes
VAS
Head-to-head
*
1 ACRN G1 vs. G2, TQ
116 VAS Yes
Tass, 2012 VAS
*
ACRN G2 vs. G3, TQ
116 VAS Yes
Tass, 2012 VAS
*
ACRN G3 vs. G4, TQ
116 VAS Yes
Tass, 2012 VAS
*
ACRN G1 vs. G3, TQ
116 VAS Yes
Tass, 2012 VAS
*
ACRN G1 vs. G4, TQ
116 VAS Yes
Tass, 2012 VAS
*
ACRN G2 vs. G4, TQ
116 VAS Yes
Tass, 2012 VAS
Abbreviations: ACRN = acoustic coordinated reset neuromodulation; Ann = annoyance; Att = attention; Awr = awareness; BDI = Beck Depression Inventory; cTBS = continuous
Theta Burst Stimulation; G(1, 2, 3, 4) = group (1, 2, 3, 4); Hz = hertz; LLS = low level laser; NR = not reported; QoL = quality of life; rTMS = repetitive transcranial magnetic
stimulation; STAI = State-Trait Anxiety Inventory; THI = Tinnitus Handicap Inventory; TMR = Tinnitus Magnitude Rating; TQ = Tinnitus Questionnaire; VAS = visual analogue
scale; vs. = versus
*Indicates the test used to measure outcomes which were selected to represent the domain in the forest plots (and subsequent SOE decisions)
55
Outcomes
Most studies reported data on more than one outcome (Table 14, and Appendix E, Table
E2.). The outcome measurement instruments used varied for the same outcomes (Table 15). For
example, nine different instruments were used to measure the outcome of severity of tinnitus.
Setting
The research settings were in departments of Otolaryngology/Otorhinolaryngology,83,89,105,108
Audiology,118 Otorhinolaryngology and Psychiatry,110 Psychiatry,103 and Ear, nose and throat.35
Other settings included tinnitus clinics116 and a university medical hospital.88 One paper did not
report on the research setting.94
Country
The studies were carried out in seven different countries: the United States;94 China;88
Germany;103,110,116 Denmark;108,118 Italy;35,89 Spain;105 and the Czech Republic.83 See Appendix
E, Table E2.
Sources of Funding
Sources of funding were not reported in six studies.35,89,105,108,110,118 One study reported
industry funding,116 and one received a loan of the equipment being tested.94 The remaining
studies received funding from research councils, foundations, and government departments and
non-profit associations.83,88,103
56
inadequate concealment of allocation (n=10, 91%),35,83,88,89,94,103,105,108,116,118 analysis not based
on intention-to-treat principle (n=9, 82%),35,83,88,94,103,105,108,116,118 and inadequate justification of
sample size (n=8, 73%).35,83,88,89,94,105,108,118
Figure 10. Proportion of medical intervention studies achieving criteria for risk of bias
57
showed at 1 week post treatment (p <0.01), but not at 1 month. The second study110 was at low
risk of bias, and administered treatment for 20 consecutive days but showed no significant
differences between treatment and sham groups immediately post treatment using the THI; this
study also showed no differences at 2, 4 and 12 weeks post treatment.
One study94 at high risk of bias examined high-frequency (27.2 MHz) electromagnetic
energy using the THI as the outcome measure. The high frequency study94 failed to detect any
differences between groups. The shape of the electromagnetic stimulator appears to be encased
in a round head; all other studies in this group used a figure eight coil; it is not clear how the
properties of generating an electromagnetic field differ as a result of the different shaped
stimulator.
Laser
Two studies at high risk of bias35,108 evaluated LLLT compared to an inactive control, and
one study89 comparing LLLT plus counseling to sham LLLT and counseling (also at high risk of
bias). All of these three studies measured Tinnitus-specific quality of life using the THI.89,108,118
All studies showed no statistical differences between the treatment and comparator groups using
the THI. It is noteworthy that one study108 used a markedly different form of LLLT relative to
the other two studies35,89 which used a self-administered applied for a minimum of 3 months.
One study108 evaluated 100 mm VAS for annoyance and found no between-group differences
(p=0.81). Similarly, a VAS for attention to symptoms was evaluated and showed no statistical
differences 1 month post treatment (p=0.52).
Acupuncture
A single trial118 compared traditional Chinese acupuncture to sham acupuncture over 2
months of treatment and evaluated up to 4 months of followup. Results on an unspecified VAS
were not statistically significantly different at the 5 percent level for either annoyance or
awareness (no p-values reported in trial publication). This trial was at high risk of bias and had
only 54 subjects in total included in the study. Adverse effects were not systematically evaluated
and none were reported.
58
varied from small to large (0.02 to -1.23). With respect to risk of bias, the studies were
categorized as high risk of bias and only one study110 achieved a score greater than 7 from 12.
No dose response pattern was observed; there was a trend that longer term effects (improvement
in THI scores) occurred with low frequency rTMS (1 Hz) up to 6 months followup. Risk of
publication bias is high given the small sample sizes of the studies. The SOE for rTMS alone for
the outcome of TSQoL is rated as insufficient as the criteria for more than three of the domains
were not met (Table 16).
For LLLT studies, there is insufficient evidence (two studies, 95 participants) that TSQoL
improves when compared with sham treatment for idiopathic tinnitus immediately post treatment
or after short term followup. Both studies were rated as high risk of bias. One study showed no
difference between groups and the other favored control but was not statistically significant; the
effect sizes varied from small to moderate (-0.0 to 0.33) and were deemed inconsistent (Table
16). Although the confidence intervals overlapped substantially, the small sample sizes (less than
30 per group), and lack of power calculations were factors that led to a rating of imprecise.
Additionally, the types of LLLT (frequency and treatment intensity and duration) can be
considered to be very different types of laser energy administration. Risk of publication bias is
high given the small sample sizes of the study and limited to single publications. There is
insufficient evidence for LLLT affecting TSQoL, as the criteria for more than three domains
were not met.
There is insufficient evidence that high frequency electromagnetic stimulation, ACRN, or
acupuncture interventions, improve TSQoL relative to inactive controls. All of these studies were
at high risk of bias, had unknown consistency, and small sample sizes (less than 30 per group).
Risk of publication bias is high for these interventions represented in a single study. The SOE
was judged as insufficient for these interventions, as three or more of the criteria for domains
were not met.
Table 16. Strength of evidence by medical interventions in the treatment of tinnitus for the
outcome of tinnitus-specific quality of life in studies with inactive comparators
Intervention Group Specifics # of Risk Consistency Directness Precision Magnitude of SOE
Studies (n) of the Effect SMD
Bias Range (CI)
83,88,105,110
rTMS vs. sham N/A 4 High Inconsistent Direct Imprecise -1.23 Insufficient
(-2.16,-0.30) to
-0.02
(-0.67, 0.72)
94
Hi-frequency N/A 1 High Unknown Direct Imprecise -0.13 Insufficient
electromagnetic (-0.86, 0.60)
energy vs. sham
116
ACRN vs. sham N/A 1 High Unknown Direct Imprecise -0.50 Insufficient
(-1.56, 0.56) to
-0.03
(-1.07, 1.02)
35,108
Laser therapy vs. N/A 2 High Inconsistent Direct Imprecise -0.00 Insufficient
sham (-0.54, 0.53) to
0.33
(-0.29, 0.94)
118
Acupuncture vs. N/A 1 High Unknown Direct Imprecise -0.10 Insufficient
placebo (-0.63, 0.10)
Abbreviations: ACRN = acoustic coordinated reset neuromodulation; RCT = randomized controlled trial; rTMS = repetitive
transcranial magnetic stimulation; SMD = standard mean difference; SOE = strength of evidence; vs. = versus; WLC = wait list
control
59
Subjective Loudness
Four studies with high risk of bias,35,108,116,118 (summary risk of bias score did not exceed 7
from 12) examined loudness as an outcome in persons given medical interventions including
LLLT, ACRN, and acupuncture (Table 15). Figure 12 shows the standardized mean difference
for the studies that measured this outcome. All studies used VAS for subjective loudness (see
Appendix E, Table E2, for full study details for this outcome).
One study116 evaluated the impact of ACRN on subjective loudness (VAS) measured after 12
weeks of treatment, and all groups except placebo (G5) had statistically significant changes
relative to baseline scores (within group) for the on stimulation condition; for the off stimulation
condition, only G1 and G3 groups showed significant differences relative to baseline. The
estimates of effect size based on the standardized mean difference (see Figure 12) would suggest
that G1 treatment protocol was favored relative to G5 placebo. However, the study reports that
there were no differences for a matched subgroup from G1 (subgroup n=5), relative to placebo
group G5 (n=5).
Two studies involved LLLT versus sham LLLT, with one article35 finding no statistical
difference in self-reported loudness (measured on a 10 cm VAS, with 0 indicating no tinnitus and
100 indicating the highest loudness level) in the treatment group after 3 months of patient-
administered daily treatment (p=0.69). Similarly, the second LLLT study,108 using Ga-Al-As
diode laser administered by a clinician, no differences between groups were found on a 100 mm
VAS after 3 weeks of treatment and at the 1 month of followup (mean difference=4.1 favoring
placebo; p=0.53).
In the acupuncture study,118 the authors found no differences between groups on active
versus sham acupuncture, measured using an undefined VAS, over 5 weeks of followup (mean
difference=5.0 favoring active acupuncture; p>0.05).
60
Table 17. Strength of evidence by medical interventions in the treatment of tinnitus for the
outcome of loudness for studies with inactive comparators
Intervention Specifics # of Risk of Bias Consistency Directnes Precision Magnitude of SOE
Group Studies (n) s the Effect
SMD Range
(CI)
116
ACRN vs. N/A 1 High Unknown Direct Imprecise -1.15 Insufficient
sham (-2.18, -0.12) to
-0.41
(-1.47, 0.64)
35,108
Laser N/A 2 High Consistent Direct Imprecise 0.23 Insufficient
therapy vs. (-0.34, 0.80) to
sham 13
(-0.40, 0.66)
118
Acupuncture N/A 1 High Unknown Direct Imprecise -0.27 Insufficient
vs. placebo (-0.81, 0.27)
Abbreviations: CI = confidence interval; n = number; SOE = strength of evidence; SMD = standard mean difference; vs. =
versus
Sleep Disturbance
None of the studies evaluating medical interventions measured the impact on sleep
disturbance.
Anxiety Symptoms
One study at high risk of bias108 evaluated active versus sham LLLT (Ga-Al-As, diode laser)
administered by a clinician (Table 15). The State Trait Anxiety Inventory (STAI) was evaluated
at baseline and 1 month following treatment. For laser,108 mean score on the STAI was lower in
the LLLT group yet not statistically significant (p=0.74).
Table 18. Strength of evidence by medical interventions in the treatment of tinnitus for the
outcome of anxiety symptoms for studies with inactive comparators
Intervention Specifics # of Risk of Bias Consistency Directness Precision Magnitude of SOE
Group Studies the Effect
(n) SMD Range
(CI)
108
Laser therapy N/A 1 High Unknown Direct Imprecise 0.39 Insufficient
vs. sham (-0.18, 0.95)
Abbreviations: CI = confidence interval; n = number; SOE = strength of evidence; SMD = standard mean difference; vs. =
versus
Depression Symptoms
A single study at high risk of bias108 evaluated depression symptoms following the use of
LLLT (Ga-Al-As, diode laser) administered by a clinician (Table 14). The Beck Depression
Inventory (BDI) was evaluated at baseline and 1 month following treatment. After one month of
61
followup, the difference on the BDI, while favoring the active LLLT group, was small and non-
significant (mean difference=0.2; p=0.58).
Table 19. Strength of evidence by medical interventions in the treatment of tinnitus for the
outcome of depression symptoms for studies with inactive comparators
Intervention Specifics # of Risk of Consistency Directness Precision Magnitude of SOE
Group Studies Bias the Effect
(n) SMD Range
(CI)
108
Laser therapy N/A 1 High Unknown Direct Imprecise 0.33 Insufficient
vs. sham (-0.24, 0.89)
Abbreviations: CI = confidence interval; n = number; SOE = strength of evidence; SMD = standard mean difference; vs. =
versus
62
Table 20. Description of reported adverse effects in the medical intervention studies
Medical Specific Intervention Dropouts AE Info Treatment Emergent AE (did not drop out of
Intervention Due to AE Collected study)
Category Reason(s)
83
rTMS and rTMS vs. sham 0 NR Worsening
electromagnetic of Tinnitus symptoms (n=2)
Stimulation rTMS vs. sham
105
0 NR All patients tolerated rTMS without relevant side
effects
88
rTMS vs. sham 0 NR Transient jaw soreness (n=5)
Temporary orbital twitching (n=3)
Facial myalgia (n=1)
110
rTMS vs. sham 0 Yes* Headache (SAC 2, TAC 2, PLC 3),
worsening tinnitus (SAC 1, TAC 2, PLC 3),
increased sensitivity to noise (TAC 1, PLC 1),
painful local sensation (SAC 1),
sleep disturbance (SAC 1)
103
rTMS vs. rTMS 0 NR Treatment was well tolerated. No serious A/E were
observed.
High-Frequency Pulsed 0 NR Worsening
Electromagnetic Energy of Tinnitus symptoms
94
vs. sham Tx n=4 (26.6%); Pl n=5 (35.7%)
116
ACRN ACRN vs. sham 0 NR 15 AEs occurred in total:
13 AEs during blinded phase, 2 AEs in LTE. Two
SAEs (an abdominal pregnancy and avascular
necrosis of the femoral head, not associated with
treatment) were reported.
All other AEs were of mild to moderate intensity
and none was permanent. 8 AEs were judged to
be treatment related of which 3 AEs were
associated with a transient increase of tinnitus
loudness; all 3 patients continued treatment into
the LTE.
108
LLLT LLLT vs. sham 0 NR Some experienced warmth inside the ear canal
No serious untoward AE noticed
35
LLLT vs. sham 2/4 (50%) NR Increase in tinnitus loudness n=2
Laser + counseling vs. 0 NR NR
89
sham + counseling
118
Acupuncture Acupuncture vs. sham 0 NR NR
Abbreviations: ACRN = acoustic coordinate reset neuromodulationl; AE = adverse effect(s); CBT = cognitive behavioral
training; CI = confidence interval;LLLT = low level laser treatment; LTE = longterm evaluation; med/surg = medical/surgical; n
= sample size; NR = not reported; NS = not significant; Pl = placebo; PLC = placebo; psych/beh = psychological/behavioral;
RCT = randomized controlled trial; rTMS = repetitive transcranial magnetic stimulation; SAC = secondary auditory cortex; SARI
serotonin antagonist reuptake inhibitor; SMD = standard mean difference; SOE = strength of evidence; SSRI = selective
serotonin reuptake inhibitor; TAC = temporoparietal association cortex; Tx = treatment; vs. = versus; WLC = wait list control
* All patients underwent a standard otolaryngologicalphysical examination as a safety assessment. At every treatment visit,
tolerability and safety was assessed by spontaneous adverse effect reports. At baseline and after 2 and 4 weeks of treatment
audiologic testing was performed, including subjective tinnitus matching, puretone audiometry, and speech audiometry in quiet
using the Freiburg speech test and in noise with the Oldenburg sentence test.
63
Figure 11. Studies with inactive comparators that evaluate medical interventions and report tinnitus-specific quality of life outcomes
Study Scale/Study N_INT N_CTRL SMD (95% CI)
RTMS
**Plewnia, 2012 {temporoparietal cortex rTMS vs. Placebo} TQ 16 16 0.02 (-0.67, 0.72)
**Plewnia, 2012 {secondary auditory cortex rTMS vs. Placebo} TQ 16 16 0.05 (-0.65, 0.74)
Chung, 2012 {Magnetic stimulation-rTMS vs. Placebo} THI 12 10 -1.23 (-2.16, -0.30)
Anders, 2010 {Magnetic stimulation-rTMS vs. Placebo} THI 22 20 -0.11 (-0.72, 0.50)
Marcondes, 2010 {Magnetic stimulation-rTMS vs. Placebo} THI 10 9 -0.55 (-1.47, 0.37)
Ghossaini, 2004 {Hi-Freq E-magnetic energy vs. Placebo} THI 14 15 -0.13 (-0.86, 0.60)
Neuromodulation
**Tass 2012 {ACR neuromodulation (G1) vs. Placebo (G5)} TQ 22 5 -0.45 (-1.43, 0.53)
**Tass 2012 {ACR neuromodulation (G2) vs. Placebo (G5)} TQ 12 5 0.39 (-0.66, 1.44)
**Tass 2012 {ACR neuromodulation (G3) vs. Placebo (G5)} TQ 12 5 -0.50 (-1.56, 0.56)
**Tass 2012 {ACR neuromodulation (G4) vs. Placebo (G5)} TQ 12 5 -0.03 (-1.07, 1.02)
Laser
Teggi, 2009 {Laser therapy vs. Placebo} THI 27 27 -0.00 (-0.54, 0.53)
Mirz, 1999 {Laser therapy vs. Placebo} THI 21 20 0.33 (-0.29, 0.94)
Acupuncture
-2.16 0 2.16
64
Figure 12. Studies with inactive comparators that evaluate medical interventions and report subjective loudness outcomes
Study Scale N_INT N_CTRL SMD (95% CI)
Neuromodulation
**Tass 2012 {ACR neuromodulation (G1) vs. Placebo (G5)} VAS 22 5 -1.15 (-2.18, -0.12)
**Tass 2012 {ACR neuromodulation (G2) vs. Placebo (G5)} VAS 12 5 -0.49 (-1.55, 0.57)
**Tass 2012 {ACR neuromodulation (G3) vs. Placebo (G5)} VAS 12 5 -0.71 (-1.79, 0.37)
**Tass 2012 {ACR neuromodulation (G4) vs. Placebo (G5)} VAS 12 5 -0.41 (-1.47, 0.64)
Laser
Teggi, 2009 {Laser therapy vs. Placebo} VAS 27 27 0.13 (-0.40, 0.66)
Mirz, 1999 {Laser therapy vs. Placebo} VAS 24 24 0.23 (-0.34, 0.80)
Acupuncture
-2.18 0 2.18
65
Sound Technology Interventions
Key Messages
Four head-to-head studies (with sample sizes per group less than 50) evaluated five different
interventions alone and/or in combination with other forms of treatment.53,61,92,98
The interventions compared were:
• TRT with either hearing aids or sound generators,
• information only, with relaxation training, with long-term low-level white noise masking
(LTWN), with both relaxation and LTWN
• CBT only, tinnitus education (TE) only, NG with CBT, NG with TE
• Neuromonics with one stage or two stages of stimulus conditions.
All studies had insufficient SOE. No study demonstrated a significant difference between the
technologies used in the treatments evaluated on any measure.
Subjective Loudness
All but one study53 evaluated this outcome.
There were no significant differences between treatments in the three studies in which this
outcome was measured, although benefits were reported for both TRT treatments. However, the
SOE was insufficient for studies evaluating the effects on sound technology interventions on
subjective loudness.
Sleep Disturbance
No study in this category evaluated this outcome.
Anxiety
One study98 evaluated this outcome.
All groups in the study demonstrated improvement, but adding NG to TE or CBT did not
increase benefit and may even have decreased it. However, the SOE was insufficient for studies
evaluating the effects on sound technology interventions on anxiety.
Depression
One study98 evaluated this outcome, but only for the groups receiving CBT and not for the
groups receiving TE because few participants had clinically significant results pre-treatment.
There was no benefit from CBT with or without NG. However, the SOE was insufficient for
studies evaluating the effects on sound technology interventions on depression.
66
Global Quality of Life
Three studies61,92,98 evaluated this outcome using a variety of different measures.
Benefit was reported for all interventions involving TRT, but there were no differences
depending on the technology used.61 No benefits were reported in the other two studies.
However, the SOE was insufficient for studies evaluating the effects on sound technology
interventions on global QoL.
Head-to-Head Interventions
All four studies53,61,92,98 categorized under the sound treatments/technology category (Table
21, and Appendix E, Table E3.) focused on head-to-head comparison including: hearing aids
versus sound generators;61 one stage intermittent perception plus two stage complete covering of
perception initially, then intermittent;53 information only, information plus relaxation training,
information plus long-term low level white noise (LTWN), information plus relaxation training
plus LTWN;92 and cognitive behavioral therapy (CBT) with noise generator (NG), CBT alone,
tinnitus education (TE) plus NG, and TE with no NG.98
67
Table 21. Interventions and comparators used in studies that evaluate sound treatment/technology interventions and outcomes
Sound Treat Anxiety Depression Tinnitus- Adverse
Specific Intervention Sleep Loudness Global QoL
Intervention Symptoms Symptoms Specific QoL Effects
HEAD-TO-HEAD
1 Hearing aids vs. SG
61 subjective VAS THI NR
Parazzini, 2011
nd
2 Neuromonics Tinnitus Treatment – 2 study
One-stage: Intermittent perception
TRQ
Two-stage: complete covering of perception initially, then VAS NR
VAS
intermittent
53
Davis, 2007
3 Group I: Information Only TRQ, VAS
Group IR: information plus relaxation training
DSP (total
Group ID: information plus LTWN VAS VAS (coping), NR
stress)
Group IDR: information plus relaxation plus LTWN change in
91,92
Dineen, 1997,1999 awareness
4 CBT with NG
TQ,
CBT alone WI VAS NR
98 T-cog
Hiller, 2004 STUDY A
TE plus NG TQ,
TE no NG T-cog,
98 SCL-90R,
Hiller, 2004 STUDY B WI VAS VAS, NR
PSDI
Diary of
symptoms
Abbreviations: DSP=Derogatis Stress Profile; LTWN = long-term low level white noise; med/surg = medical/surgical; NG = noise generator; NR = not reported; PDPSDI =
Positive Symptom Distress Index; QoL = Quality of Life; SG = sound generator; T-cog = Tinnitus Cognition Scale; TE = tinnitus education; THI = Tinnitus Handicap Inventory;
TQ = Tinnitus Questionnaire; VAS = visual analogue scale; WI = Whiteley Index
68
Outcomes
Most studies reported data on more than one outcome (Table 21, also Appendix E, Table
E3.). The outcome measurement instruments used varied for the same outcomes (Table 22). For
example, four different instruments were used to measure the outcome of TSQoL. Upon
discussion with clinical experts, the following decisions regarding outcomes were made. All
results that addressed the outcomes of interest were extracted. However, when a clinical outcome
was measured using multiple scales within the same study, the outcome was reported once for
that study. Data was extracted for the most widely used scale for that outcome, even if both
scales were validated. This approach was implemented to facilitate better comparability between
studies. The results of any studies that used the terms ‘annoyance’ or ‘distress’ were included to
describe outcomes in the category of ‘discomfort.’
Setting
The research settings were a tinnitus clinic,61 a university hearing clinic,92 and an outpatient
department.98 One paper did not report the setting (Appendix E, Table E3).53
Country
The studies were carried out in Australia53,92 the United States and Italy,61 and Germany.98
Sources of Funding
Sources of funding included the Australian Commonwealth Government via a Biotechnology
Innovation Fund,53 grants from a Tinnitus Research Initiative,61 and financial support from the
German Tinnitus Association.98 One paper did not reveal the source of funding.92
69
Figure 13. Distribution of methodological risk of bias criteria of randomized controlled trials for
the sound technology interventions
70
Subjective Loudness
All but one of the studies61,92,98 evaluated the effects of intervention on the subjective
loudness of the tinnitus.61,92,98 Significant reductions in subjective loudness were reported in one
study61 in which TRT was delivered with either sound generators or open ear hearing aids;
however, there was no difference between treatments on this outcome measure. In a study
comparing four treatments with information, white noise, relaxation or combinations of these
components, no change in subjective loudness was found for any of the treatments.92 No
significant differences between treatments in reduction of subjective loudness were reported in a
study comparing the benefit of combining the use of NG with either CBT or TE.98
Overall, it seems that the effects of intervention on subjective loudness did not differentiate
the interventions that were compared.
Sleep Disturbance
No studies evaluated the effects of the interventions on sleep.
Anxiety
Only one study98 evaluated the effects of intervention on anxiety. In one study98 that sought
to determine if the addition of sound stimulation provided by the use of low level white-noise
generators would enhance the effects of CBT or TE, the Whiteley Index (WI) was used to
measure health-related anxieties. All groups demonstrated improvement on the WI, but no
statistically significant additional benefit due to NG was observed when it was combined with
either TE or CBT and in fact, adding NG seemed to have a deleterious effect on the WI outcome
measure.98
Depression
Only one study reported the effects of the interventions on depression symptoms. No
significant effect of CBT treatment either with or without NG was found when the SCL-90R was
used to measure depression,98 but changes due to the TE with or without NG were not reported
because not all participants had clinically significant conditions pre-treatment.
71
Strength of Evidence—Sound Technologies
The types of sound technologies and comparator groups within each study were markedly
diverse. For this reason we did not prepare formal SOE tables as all would have a similar rating
of insufficient irrespective of the outcome being measured. All the studies evaluating sound
technologies relative to different active comparators were considered to be at high risk of bias
and unknown consistency. The very small sample sizes within the studies is a factor contributing
to the rating of ‘imprecise’. Overall, there is insufficient information to judge the SOE for the
head-to-head studies evaluating sound technologies.
The research settings were varied; some studies recruited patients from ENT, audiology or
psychology clinics at hospitals or universities and others recruited volunteers using newspapers
or the internet.
Most studies recruited participants from the general population of middle-aged or older
adults experiencing subjective idiopathic tinnitus. Three studies focused on specific
subpopulations: veterans,97 industrial workers,81 and older adults.84
Eligibility criteria in terms of duration and severity of tinnitus varied.
Some studies restricted participation to those without significant depression or anxiety.
Nine studies in the psychological/behavioral grouping have sample sizes greater than 20
subjects per group and most had less than 50 subjects per group.
Subjective Loudness
Eight RCT studies with WLCs investigated the effects of 16 interventions on subjective
loudness. Although benefits in subjective loudness were suggested by two CBT interventions,
CBT combined with biofeedback18 and a self-help book with telephone therapy,100 overall, there
was low SOE for no effect in subjective loudness from CBT.
SOE was insufficient for other interventions.
Sleep Disturbance
Five RCT studies with WLCs investigated the effects of nine interventions on sleep.
Although benefits in sleep were suggested by two studies in the CBT sub-category, biofeedback-
based CBT,18 and self-help book with telephone therapy,100 overall, there was low SOE for no
effect in sleep from CBT.
SOE was insufficient for other interventions.
72
Anxiety Symptoms
Five RCT studies with WLCs investigated anxiety symptoms in nine interventions as one of
the main outcomes57,62,84 or as a secondary outcome100,120 that was compared to a WLC group.
Although benefits in anxiety were noted in one study in the CBT sub-category: self-help book
with telephone therapy,100 overall, there was low SOE for no effect in anxiety from CBT.
SOE was insufficient for other interventions.
Depression Symptoms
Eleven RCT studies with WLCs investigated the effects of 22 interventions on depression
symptoms, but depression was a primary outcome in only two studies57,62 and a secondary
outcome in the others. Although benefits in depression were suggested for four interventions in
the CBT sub-category: self-help with telephone therapy,100 CR with or without ACI,96 and
biofeedback-based CBT18 and benefit was also suggested for two interventions using relaxation
and distraction,10,62 overall, there was low SOE for no effect in depression symptoms from CBT.
SOE was insufficient for other interventions.
73
‘disabling chronic uni- or bi-lateral.’108 Some studies required specific scores on tinnitus severity
scales to meet study inclusion criteria. These include: a score of 10 or greater on the Tinnitus
Reaction Questionnaire (TRQ);100,101 a distress score greater than 17 points on the TRQ;95,96 a
score greater than 46 (high annoyance) on the Tinnitus Questionnaire (TQ) Modified version;18 a
score of greater than 40 on nine scales assessing the disruptive effects of tinnitus;17 a Visual
Analogue Scale (VAS) score (range=0 to 10) of greater than 3;112 ≥30 on the Tinnitus Handicap
Inventory (THI) scale;120and a tinnitus of grade 2 or 3.10,147
Interventions
There is considerable heterogeneity among the treatments categorized as Psychological and
Behavioral Interventions and also within each of the four sub-categories of CBT, TRT,
relaxation and other. For the purposes of the present review, general characteristics of the
therapies rather than the specific details of the therapeutic protocols guided the placement of
studies in the sub-categories (Table 23).
CBT does not exist as a distinct therapeutic technique and has no strict definition. It is a form
of psychotherapy that emphasizes the important role of thinking in how we feel and what we do.
Insofar as it involves psychotherapy, it features an interaction between a clinician and patient,
but the format could be individual or group, and it could be delivered in person or at a distance
with telephone or internet contact. Studies were considered to be in the CBT subcategory if the
author described the intervention as CBT or as being CBT-based or involving tinnitus coping
training (TCT) or a cognitive approach such as attention control and imagery (ACI), cognitive
restructuring (CR), or acceptance and commitment therapy (ACT). CBT for the elderly84 was
compared to no treatment, and internet CBT57 and TCT17 were compared to an inactive control.
CBT combined with biofeedback18 and a psychophysiological-oriented intervention combining
CBT and relaxation components112 were compared to WLCs. In one study,102 comparisons were
made between four conditions: a WLC, the same CBT intervention administered by two different
clinicians (TCT1 and TCT2), and yoga. In another study,96 comparisons were made between
three conditions: a WLC and two types of cognitive intervention, ACI and CR provided alone or
in combination. In another study,95 comparisons were made between three conditions: a WLC,
CBT with education and education alone. An additional two studies compared CBT to other
treatments: an information only intervention81 or to internet-based self-help.101 A final study121
compared TCT to two other interventions, habituation-based treatment (HT) and education.
TRT is a well-known intervention that features both the use of sound and a particular type of
structured directive counseling. Studies were placed in the TRT category if the intervention was
described as TRT or included a component based on TRT principles, and it was compared to
either an inactive control or in a head-to-head comparison to another psychological/behavioral
intervention. Three articles64,97,120 evaluated forms of TRT with an emphasis on the behavioral
aspect of TRT (note that one other article61focused on comparing the sound technology aspect of
TRT and it was included in the section on Sound Technology Interventions). In one study,
interventions in which TRT principles were applied to either a traditional support group or to
group education and counseling were compared to a WLC or each other.97 In the other study,120
TRT was compared to a WLC and to ACT. A final additional study compared a combination of
CBT and TRT to usual care.64
Relaxation may be incorporated into the protocols of many interventions, but studies
evaluating interventions in which relaxation was the main approach were allocated to the
relaxation sub-category. Three articles10,17,62 compared interventions focused on relaxation to
74
WLCs. In one of the studies,62 the relaxation therapy was administered in the same way to four
groups, with instructions that were either neutral or counter-demand (participants were told not
to expect improvements until after five weeks) and with two groups recruited for each instruction
condition; thus, comparisons between the four groups and the WLC could be made as well as
comparisons between groups receiving the same or different instructions.
The “other” sub-category was used to group studies evaluating psychological/behavioral
interventions not assigned to the CBT, TRT or relaxation sub-categories. Some of the studies
involving CBT, TRT and relaxation interventions listed above also included comparisons
between other treatments and a WLC, including: education,17 bibliotherapy,104 Qigong therapy,87
and yoga.102 Finally, one study121 included a head-to-head comparison between HT and
education.
Comparators
Ten articles17,18,57,84,95,96,100,102,112,120 had an inactive control, with either no treatment84 or a
WLC (WLC)17,18,57,95,96,100,102,112,120 compared to various forms CBT administered either alone or
in combination with other treatments. These, along with the head-to-head comparisons are
detailed in Table 23.
Comparators for the articles assessing TRT included no treatment97 and WLC.120 The
comparators for relaxation therapy10,17,62 and for other interventions were also all WLC.17,87,102,104
75
Table 23. Interventions and comparators used in studies that evaluate psychological and behavioral interventions and outcomes
Psych/Beh Specific Intervention Anxiety Depression Global Tinnitus-Specific Adverse
Sleep Loudness
Intervention Symptoms Symptoms QoL QoL Effects
CBT/CBT INACTIVE COMPARISONS
Combination 1 CBT vs. no treatment
*
HADS-A , HADS-D TRQ NR
84
Andersson, 2005 ASI
* *
2 CBT via the internet vs. WLC VAS HADS-A , HADS-D VAS TRQ , VAS-Ann, NR
57
Andersson, 2002 ASI VAS-Ctrl
*
3 CR vs. WLC BDI TRQ , TEQ, NR
96
Henry JL and Wilson PH, 1998 THQ (handicap),
TCSQ (coping)
TCQ
*
CR combined with ACI vs. WLC BDI TRQ , TEQ, NR
96
Henry JL and Wilson PH, 1998 THQ (handicap),
TCSQ (coping)
TCQ
*
ACI vs. WLC, BDI TRQ , TEQ, NR
96
Henry JL and Wilson PH, 1998 THQ (handicap),
TCSQ (coping)
TCQ
*
4 CBT & Education vs. WLC BDI Self-report TRQ , TEQ, NR
95
Henry JL and Wilson PH, 1996 THQ (handicap),
TCSQ (coping),
TCQ (Awareness)
* *
5 CBT- biofeedback-based vs. WLC VAS , TQ-sub BDI VAS GSI TQ , VAS NR
18
Weise, 2008 SCL-90R TRSS
(catastrophizing),
TRCS
(helplessness)
6 TCT1 vs. WLC Diary, TQ Dep-Skala Diary Bef-Skala TQ NR
102 * *
Kroner-Herwig, 1995 subs Bes-Liste Diary
TCT2 vs. WLC Diary, TQ Dep-Skala Diary Bef-Skala TQ NR
102 * *
Kroner-Herwig, 1995 subs Bes-Liste Diary
7 TCT vs. WLC ADS Diary SCL-90R TDI NR
17 *
Kroner-Herwig, 2003 GSI TQ
TC (COPE
subscales)
* *
8 Psychophysiological therapy vs. WLC, Diary HRLS TQ , emotional None
112
Rief, 2005 GSI cognitive distress
SCL-90R
76
Table 23. Interventions and comparators used in studies that evaluate psychological and behavioral interventions and outcomes (continued)
Psych/Beh Anxiety Depression Global Tinnitus-Specific Adverse
Specific Intervention Sleep Loudness
Intervention Symptoms Symptoms QoL QoL Effects
CBT/CBT INACTIVE COMPARISONS (contued)
Combination 9 Self-help book and brief phone therapy vs. WLC THI (handicap)
100 *
(continued) Kaldo, 2007 ISI HADS-A HADS-D VAS TRQ , NR
VAS
10 ACT vs. WLC, THI (Tinnitus
120 ISI HADS-A HADS-D QoLI None
Westin, 2011 Impact)
HEAD-TO-HEAD COMPARISONS
1 CBT vs. Information only X TRQ, VAS,
81
Abbott, 2009 VAS DASS-A DASS-D VAS WHO-QoL OSI-R None
(occupational)
2 Intervention: Internet based self help
THI
Control (usual care) vs. Standard group CBT ISI HADS-A HADS-D VAS NR
101 TRQ, VAS
Kaldo, 2008
*
3 CBT vs. ACI TRQ , TEQ,
96
Henry JL and Wilson PH, 1998 THQ (handicap),
BDI NR
TCSQ (coping)
TCQ
*
CBT vs. CBT combined with ACI TRQ , TEQ,
96
Henry JL and Wilson PH, 1998 THQ (handicap),
BDI NR
TCSQ (coping)
TCQ
*
ACI vs. CBT combined with ACI TRQ , TEQ,
96
Henry JL and Wilson PH, 1998 THQ (handicap),
BDI NR
TCSQ (coping)
TCQ
4 CBT & Education vs. Education WLC TRQ, TEQ,
95
Henry JL and Wilson PH, 1996 BDI Self-report TCSQ(coping), NR
TCQ
5 TCT1 vs. TCT2 Diary Bef-Skala TQ
102 Dep-Skala Diary * NR
Kroner-Herwig, 1995 TQ Bes-Liste Diary
TCT2 vs. yoga Diary Bef-Skala TQ
102 Dep-Skala Diary * NR
Kroner-Herwig, 1995 TQ Bes-Liste Diary
7 TCT vs. EDU Zachriat,121 2004 TQ, TCQ,
Diary VEV JQ, Diary NR
(awareness)
121
TCT vs. HT Zachriat, 2004 TQ, TCQ,
Diary VEV JQ, Diary NR
(awareness)
77
Table 23. Interventions and comparators used in studies that evaluate psychological and behavioral interventions and outcomes (continued)
Psych/Beh Anxiety Depression Global Tinnitus-Specific Adverse
Specific Intervention Sleep Loudness
Intervention Symptoms Symptoms QoL QoL Effects
TRT INACTIVE CONTROL
1 Group education counseling (TRT principles) vs. no
treatment TSI None
97
Henry, 2007
2 TRT vs. WLC, THI (Tinnitus
120 ISI HADS-A HADS-D QoLI None
Westin, 2011 Impact)
HEAD-TO-HEAD
1 CBT with TRT vs. usual care or no treatment TQ
64 HADS HUI None
Cima, 2012 THI (impairment)
2 TRT vs. ACT, THI (Tinnitus
120 ISI HADS-A HADS-D QoLI None
Westin, 2011 Impact)
3 Group education counseling (TRT principles) vs.
Traditional support group TSI None
97
Henry, 2007
Relaxation INACTIVE COMPARATOR
1 Relaxation therapy vs. WLC Self-report-
10 Self-report-R Self-report-D Yes
Scott, 1985 D
2 Relaxation therapy Counter-demand vs. WLC Tinnitus
62
Ireland, 1985 STAI BDI Self-report interference (self- NR
report)
Relaxation therapy Neutral-demand. vs. WLC Tinnitus
62
Ireland, 1985 STAI BDI Self-report interference (self- NR
report)
Relaxation therapy Counter-demand -2vs. WLC Tinnitus
62
Ireland, 1985 STAI BDI Self-report interference (self- NR
report)
Relaxation therapy Neutral-demand -2vs. WLC Tinnitus
62
Ireland, 1985 STAI BDI Self-report interference (self- NR
report)
3 Relaxation vs. WLC TDI (disability),
17 *
Kroner-Herwig, 2003 GSI TQ
ADS Diary NR
SCL-90R TC (COPE-
subscales)
78
Table 23. Interventions and comparators used in studies that evaluate psychological and behavioral interventions and outcomes (continued)
Psych/Beh Anxiety Depression Global Tinnitus-Specific Adverse
Specific Intervention Sleep Loudness
Intervention Symptoms Symptoms QoL QoL Effects
Relaxation HEAD-TO-HEAD
(cont’d) 1 Relaxation therapy Counter-demand vs. Neutral Demand Tinnitus
62
Ireland, 1985 STAI BDI Self-report interference (self- NR
report)
2 Relaxation therapy-2 vs. Neutral-demand-2 Tinnitus
62
Ireland, 1985 STAI BDI Self-report interference (self- NR
report)
Other INACTIVE COMPARATOR
1 Education vs. WLC TDI (disability),
17 *
Kroner-Herwig, 2003 GSI TQ
ADS Diary NR
SCL-90R TC (COPE-
subscales)
2 Education alone vs. WLC TRQ, TEQ
95
Henry JL and Wilson PH, 1996 THQ (handicap),
BDI Self-report NR
TCSQ (coping),
TCQ (Awareness)
3 Traditional support group vs. no treatment
97 TSI None
Henry, 2007
4 Bibliotherapy vs. WLC
104 GHQ-12 TRQ None
Malouff, 2010
5 Qigong therapy vs. WLC *
87 TBF-12 , VAS None
Biesinger, 2010
6 Yoga vs. WLC Diary Bef-Skala
102 Dep-Skala Diary TQ NR
Kroner-Herwig, 1995 TQ Bes-Liste
HEAD-TO-HEAD
121
1 EDU vs. HT Zachriat, 2004 TQ, TCQ, JQ,
Diary VEV NR
Diary(awareness)
Abbreviations: ACI = attention control and imagery traiing; ACT = acceptance and commitment therapy; ADS = A Depression Scale, The German version of CES-D “Center for
Epidemiologic Studies Depression scale”; Ann = annoyance; ASI = Anxiety Sensitivity Index; BDI = Beck Depression Inventory; CBT = cognitive behavioral training; CR = cognitive
restructuring; DASS-A = Depression and Anxiety Stress Scale; DASS-D = Depression and Anxiety Stress Scale; EDU = educational control-group; EDU = education; GHQ = general health
questionnaire; HADS = Hospital Anxiety and Depression Scale; HADS-A = Hospital Anxiety and Depression Scale – Anxiety subscale; HADS-D = Hospital Anxiety and Depression Scale
– Depression subscale; HRLS = health-related life satisfaction; HT = habituation-based treatment; ISI = Insomnia Severity Index; JQ = Jastreboff Questionnaire; NR = not reported; OSI-R =
Occupational Stress Inventory–Revised; psych/beh = psychological/behavioral; QoL = Quality of Life; QoLI = Quality of Life Questionnaire Instrument; SCL-90R = Symptom Checklist,
general psychopathology; STAI = State-Trait Anxiety Inventory; TBF-12 = Tinnitus Questionnaire; TCT = tinnitus coping therapy; TCQ = Tinnitus Cognitions Questionnaire; TCSQ =
Tinnitus Coping Strategies Questionnaire; TDI = Tinnitus Disability Questionnaire; THI = Tinnitus Handicap Inventory; THQ = Tinnitus Handicapped Questionnaire; TQ = Tinnitus
Questionnaire; TRCS = The Tinnitus-Related Control Scale; TRQ = The Tinnitus Reaction Questionnaire; TRSS = Tinnitus-Related Self-Statements Scale; TRT = tinnitus retraining
therapy; TSI = Tinnitus Severity Index; VAS = visual analogue scale; VEV = changes in wellbeing and adaptive behavior; vs. = versus; WLC = wait list control. *Indicates the test used to
measure outcomes which were selected to represent the domain in the forest plots (and subsequent SOE decisions)
79
Outcomes
Most studies reported data on more than one outcome (Table 23). The outcome measurement
instruments used varied for the same outcomes (Table 24). For example, 19 different instruments
were used to measure the outcome of TSQoL. Upon discussion with clinical experts, the
following decisions regarding outcomes were made. All results that addressed the outcomes of
interest were extracted. However, when a clinical outcome was measured using multiple scales
within the same study; the outcome was reported once for that study. Data was extracted for the
most widely used scale for that outcome, even if both scales were validated. This approach was
implemented to facilitate better comparability between studies. The results of any studies that
used the terms “annoyance” or “distress” were included to describe outcomes in the category of
“discomfort.”
Table 24. Outcome measurements used in psychological and behavioral intervention studies
Outcome Outcome Measurement Used
57,81,84,95,96,100,101,104
Tinnitus- TRQ (The Tinnitus Reaction Questionnaire)
95,96
Specific TEO (Tinnitus Effects Questionnaire)
95,96
Quality of Life THQ (Tinnitus Handicapped Questionnaire)
95,96
TCSQ (Tinnitus Coping Strategies Questionnaire)
95,96,121
TCQ (Tinnitus Cognitions Questionnaire)
17,18,64,112,121
TQ (Tinnitus Questionnaire)
18,57,81,87,100,101
VAS (Visual Analogue Scale)
18
TRSS (Tinnitus-Related Self-Statements Scale)
18
TRCS (The Tinnitus-Related Control Scale)
17
TCT (Tinnitus Coping Training)
81
OSI-R (Occupational Stress Inventory–Revised)
64,100,101,120
THI (Tinnitus Handicap Inventory)
97
TSI (Tinnitus Severity Index)
10,62
Self-report Direct and Retrospect
17
TDI (Tinnitus Disability Questionnaire)
121
JQ (Jastreboff Questionnaire)
121
Diary (awareness)
87
TBF-12 (Tinnitus Questionnaire)
102,121
Diary-D,I,C,TQPQ, TQSC
18,57,81,100,101
Subjective VAS (Visual Analogue Scale)
10,62,95
loudness Self-rated/reported scale/score
17,102,112,121
Diary
18,57,81
Sleep VAS (Visual Analog Scale)
100,101,120
Disturbance ISI (Insomnia Severity Index)
18,102
TQ (Tinnitus Questionnaire subscale – sleep disturbance)
102
Diary
57,84,100,101,120
Anxiety HADS-A (Hospital Anxiety and Depression Scale – Anxiety subscale)
81
Symptoms DASS-A (Depression and Anxiety Stress Scale)
62
STAI (State-Trait Anxiety Inventory)
57,84
ASI (Arabic Scale of Insomnia)
57,84,100,101,120
Depression HADS-D (Hospital Anxiety and Depression Scale – Depression subscale)
18,62,95,96
Symptoms BDI (Beck Depression Inventory)
81
DASS-D (Depression and Anxiety Stress Scale )
ADS (A Depression Scale, The German version of CES-D “Center for Epidemiologic Studies
17
Depression scale”)
10
Self-report Retrospect
64
HADS (Hospital Anxiety and Depression Scale - Depression and Anxiety composite)
102
Depressivitats-Skala
80
Table 24. Outcome measurements used – Psychological/behavioral interventions (continued)
Outcome Outcome Measurement Used
64
Global Quality HUI-3 (Health Utilities Index-3)
18
of Life GSI (Global Severity Index – Symptom Checklist self-rating questionnaire)
81
WHO-Social (Quality of Life Questionnaire)
120
QoLI (Quality of Life Questionnaire Instrument)
17
SLR-90R (Symptom Checklist self-rating questionnaire)
112
HRLS (psychological symptoms short form of SCL-90R)
112
GSI (General Symptomatic Index)
104
GPD
VEV (Changes in wellbeing and adaptive behavior induced by treatment which go beyond
121
modification of tinnitus related illness)
102
Befindlichkeits-Skala, Beschwerden liste
102
TQ
Setting
The research settings were in departments of audiology,10,102,120 psychology,121 psychology
outpatient,18 psychotherapy outpatient,112 university clinic,62 hospital (department not reported),97
clinic,62,64,101 phone/mail,100 newspaper and radio advertisements,96 and the internet.57,81,84,101,104
Three papers did not report the research setting.17,87,95
Country
The studies were carried out in several different countries: Sweden;10,57,84,100,101,120 the United
States;97 Australia;62,81,95,96,104 Germany;17,18,87,102,112,121 and the Netherlands.64
Sources of Funding
Sources of funding were not reported in seven studies.62,87,95,96,101,102,112 Twelve publications
received funding from research councils, foundations, and government departments and non-
profit associations.10,17,18,57,64,81,84,97,100,104,120,121
81
Figure 14. Distribution of risk of bias scores of randomized controlled trials for the psychological
and behavioral category (n=19)
82
to those who received TCT (TCT1 and TCT2 were delivered by different clinicians) reported
that TCT significantly reduced psychological impairment due to tinnitus as measured with a
German version of the TQ (F(1,32)=4.43, p ≤0.04)). In another study comparing TQ outcomes
for a WLC group to a group receiving cognitive behavioral TCT intervention,17 significant
effects in favor of treatment were reported (F(1,34)=9.22, p <0.01). A psychophysiological CBT
intervention112 yielded a significant reduction in tinnitus distress on the TQ in comparison to the
WLC group (group x time interaction: F(1,41)=6.74, p <0.05, g=0.64), as did a biofeedback-
based CBT intervention18 (F(1,109)=55.40, p <0.001, g=1.15). A significant reduction in tinnitus
handicap as measured using the THI was reported in a study in which ACT was compared to a
WLC group120 (group x time interaction: F(1,42)=12.16, p=0.001).
Two RCT studies with inactive controls evaluated the effect of three interventions involving
TRT on tinnitus-specific handicap using the THI or severity using the TSI. Compared to a WLC
group, TRT did not yield a significant improvement on the THI immediately post-treatment in
one study.120 In the other study,97 a group counseling intervention based on TRT principles was
compared to a WLC and to traditional group support using the TSI;97 significant group effects
were not found at the 1-month followup, but the study reported a significant pre- vs. post-
treatment improvement on the TSI for the counseling intervention based on TRT and at the 6-
month and 1-year followup the counseling intervention yielded significantly greater
improvements compared to either the WLC or the support group.
Three RCT studies evaluated the effect on TSQoL for six interventions involving
relaxation.10,17,62 A significant effect of treatment on the TDI was reported for a minimal contact
relaxation intervention compared to the WLC group (F(1,34)=6.79, p <0.01), but not on the
TQ.17 For the other interventions involving relaxation, tinnitus-specific outcomes were measured
by a single self-report item. In one study,10 a VAS ‘direct’ form (10-cm line with end-points
labeled ‘none’ and ‘maximum’) was completed four times each day with a tinnitus discomfort/
annoyance rating item pertaining to the last half-hour and a second retrospective form completed
in the evening with a discomfort/annoyance rating item pertaining to the participant’s experience
over the course of the day (with end points labeled ‘absent/very weak’ and ‘very loud/maximal’).
A significant effect on both direct (group x time interaction: F(1,21)=6.01, p <0.05) and
retrospective measures (group x time interaction: F(1,21)=7.92, p <0.01) was reported for a 10-
week treatment consisting of training in relaxation, self-control by distraction, and how to apply
these methods in everyday situations.10 In another study,62 no effect of a relaxation intervention,
delivered with either neutral or counter-demand instructions to two different groups, was found
when the extent to which tinnitus interfered with daily activities was measured using one item
with a 4-point scale on a monitoring form that was completed daily for a 2-week period.62
Six RCT studies evaluated the effect of other psychological behavioral interventions
compared to an inactive control on TSQoL.17,87,95,97,102,104 One study87 reported that Qigong
(mindful exercise) significantly reduced tinnitus handicap as measured using the TBF-12 (a
German version of the THI) (group x time interaction: F(3,66)=3.7, p=0.015). In another
study,102 psychological impairment due to tinnitus measured with a German version of the TQ
was not reduced by a yoga intervention. In a study comparing the TQ scores for a WLC group to
a group receiving a minimal educational intervention,17 no significant effect in favor of treatment
were reported. As mentioned above, one study95 evaluated the effect of CBT combined with
education and an education alone intervention compared to a WLC on TRQ score and did not
find a significant effect of the education alone treatment. One study evaluated the effect of
treatment on tinnitus distress using the TRQ comparing a WLC to bibliotherapy104 and a
83
significant reduction in tinnitus distress was found (F(1,122)=6.23, p =.01, d=0.28), but there
was no significant effect when an intention-to-treat analysis was conducted for the bibliotherapy
intervention.104 Finally, a traditional support group did not differ from the inactive control.97
As seen in the forest plots (Figure 15), almost all of the interventions tended to result in mean
effects in favor of treatment. However, only the studies that had group sample sizes greater than
2017,18,57,97,100,104,112,120 showed results that could be considered to be significantly in favor of
treatment in comparison to an inactive control group. Such positive effects were observed for a
number of interventions in the CBT sub-category, including biofeedback-based CBT,18 psycho-
physiologic CBT,112 internet CBT,57 cognitive TCT,17 self-help book with telephone therapy,100
and ACT,120 as well as one intervention in each of the other sub-categories, including group
education with TRT principles,97 minimal contact relaxation17 and bibliotherapy.104
84
for relaxation therapy for the outcome of TSQoL is rated as insufficient, as the criteria for three
domains were not met.
When considering the interventions grouped in the ‘other’ category (six studies, 398
participants, six different interventions), the evidence was deemed insufficient given the
heterogeneity of the interventions, the high risk of bias, and small sample sizes. Risk of
publication bias is high for these interventions given the small sample sizes within the single
studies for each intervention type.
Overall, it seems that there is low quality evidence that CBT interventions have a beneficial
effect on TSQoL relative to inactive controls as the criteria for two domains were not met. The
other interventions are rated as insufficient SOE as the criteria for at least three domains were not
met (Table 26).
Table 25. Strength of evidence by psychological and behavioral interventions in the treatment of
tinnitus for the outcome of tinnitus-specific quality of life
Intervention Specifics # of Risk of Consistency Directness Precision Magnitude of SOE
Group Studies Bias the Effect
(n) SMD Range
(CI)
17,18,57,84,
CBT/CBT N/A 10 High Consistent Direct Imprecise -1.56 Low
95,96,100,102,1
combination (-1.98,-1.13) to
12,120
vs. WLC or no -0.13
treatment (-0.93, 0.67)
97,120
TRT vs. WLC N/A 2 High Inconsistent Direct Imprecise -0.60 Insufficient
or no (0-0.93,-0.26) to
treatment -0.12
(-0.46, 0.23)
10,17,62
Relaxation vs. N/A 3 High Inconsistent Direct Imprecise -1.02 Insufficient
WLC (-2.20, 0.17) to
0.17
(-1.02, 1.36)
17
Other psych/ MC-E vs. 1 High Unknown Direct Imprecise -0.38 Insufficient
behavioral WLC (-1.05, 0.28)
104
BLT vs. 1 High Unknown Direct Imprecise -0.33 Insufficient
WLC (-0.68, 0.02)
87
Qigong 1 High Unknown Direct Imprecise -0.14 Insufficient
training (-0.82, 0.54)
vs. WLC
102
Yoga vs. 1 High Unknown Direct Imprecise -0.17 Insufficient
WLC (-0.96, 0.63)
Abbreviations: ACT = acceptance and commitment therapy; BLT = bibliotherapy; BPT = brief phone therapy; CBT = cognitive
behavioral training; CI = confidence interval; MC-E = minimal contact education; n = sample size; psych = psychological;
SMD = standard mean difference; SOE = strength of evidence; vs. = versus; TRT = Tinnitus Retraining Therapy; WLC = wait
list control
Subjective Loudness
Eight RCT studies with WLCs investigated the effects of 16 interventions on the subjective
loudness of tinnitus.10,17,18,62,95,100,102,112 See Table 23.
In all studies, subjective loudness was measured on a single item presented using a variety of
self-report measures that were administered over a number of days during pre- and post-
treatment monitoring periods. These measures included a daily diary entry for 1 week using a 10-
point VAS to rate loudness,18,100,112 a loudness rating item with a 4-point scale on a monitoring
form that was completed daily for a 1-week period95 or a 2-week period,62 a daily diary entry
85
(scale unspecified) completed over a two-week period,17 a VAS ‘direct’ form (10-cm line with
end-points labeled ‘none’ and ‘maximum’) that was completed four times each day with an
loudness rating item pertaining to the immediate moment and a second retrospective form
completed in the evening with a loudness rating item pertaining to the participant’s experience
over the course of the day (with end points labeled ‘absent/very weak’ and ‘very
loud/maximal’),10 and a VAS 10-point scale with a loudness rating item that was completed three
times per day over a 2-week monitoring period.102
The effect on loudness was evaluated for seven interventions in the CBT category. A
significant beneficial effect of biofeedback-based CBT18 was reported (group x time interaction:
F(1,109) = 10.83, p <0.001) and a significant effect of treatment on subjective loudness was
reported for an intervention using a self-help book with telephone therapy (group x time
interaction: F(1,69) = 6.7, p=0.012). No significant effects of treatment on subjective loudness
were reported for the other interventions in this category, including internet CBT,57
psychophysiological therapy,112 a CBT plus education intervention,95 a CBT plus TCT
intervention,17 and a TCT intervention delivered by two different clinicians.102
The effect on loudness was evaluated for six interventions involving relaxation that were
investigated in three studies with sample sizes of less than 20 per group.10,17,62 A significant
effect on subjective loudness on both direct (group x time interaction: F(1,21) = 7.03, p <0.01)
and retrospective measures (group x time interaction: F(1,21) = 5.35, p <0.05) was reported for a
10-week treatment consisting training in relaxation, self-control by distraction, and how to apply
these methods in everyday situations.10 No significant effect of treatment on subjective loudness
was reported for the other treatments in this category, including a minimal contact relaxation
intervention,17 and relaxation delivered with either neutral or counter-demand instructions to two
different groups.62
The effect of loudness on three other psychological behavioral interventions was
examined.17,95,112 No significant effects of treatment were reported for education
interventions17,95 or for yoga.102
The forest plot (Figure 16) for subjective loudness as an outcome of treatment indicates that
biofeedback-based CBT18and intervention using a self-help book with telephone therapy100 show
beneficial effects of treatment. However, the other interventions, all of which were evaluated in
treatment groups with a sample size below 30, did not significantly reduce subjective loudness.
86
There is insufficient evidence (three studies, 104 participants) that relaxation therapy
interventions improve subjective loudness when compared with inactive controls for patients
with idiopathic tinnitus in the immediate or short term followup. All of the studies were at high
risk of bias. The sample sizes were less than 30 per group, and the effect size estimates showed
wider confidence intervals suggesting imprecision. All but one study favored relaxation therapy
relative to inactive control and one study favored control; none of the studies showed statistically
significant differences between groups. The effect size magnitude varied from small to large, as
such, this evidence was rated as inconsistent. No dose response pattern was observed. Risk of
publication bias is high given the small sample sizes of the studies. The SOE for relaxation
therapy for the outcome of loudness is rated as insufficient as the criteria for three domains were
not met.
When considering the interventions grouped in the “other category”, the evidence was
deemed insufficient given the diversity of interventions, the high risk of bias, and the small
sample sizes. Risk of publication bias is high for these interventions given the small sample sizes
of the study and the single studies for each intervention type.
Overall, it seems that there is low quality evidence that CBT interventions have no effect on
subjective loudness relative to inactive controls as the criteria for two domains were not met. The
other interventions are rated as insufficient SOE as the criteria for at least three domains were not
met (Table 26).
Table 26. Strength of evidence by psychological and behavioral interventions in the treatment of
tinnitus for the outcome of subjective loudness
Intervention Specifics # of Risk of Consistency Directness Precision Magnitude of SOE
Group Studies Bias the Effect SMD
(n) Range (CI)
17,18,57,95,
CBT/CBT N/A 7 High Consistent Direct Imprecise -0.72 Low
100,102,112
combination vs. (-1.10,-0.33) to
WLC or no 0.01
treatment (-0.61, 0.63)
10,17,62
Relaxation vs. N/A 3 High Inconsistent Direct Imprecise -1.16 Insufficient
WLC (-2.65, 0.34) to
0.21
(-0.45, 0.87)
17
Other MC-E vs. 1 High Unknown Direct Imprecise 0.21 Insufficient
psychological WLC (-0.45, 0.87)
95
Education 1 High Unknown Direct Imprecise -0.27 Insufficient
vs. WLC (-0.89, 0.35)
102
Yoga vs. 1 High Unknown Direct Imprecise -0.06 Insufficient
WLC (-0.86, 0.73)
Abbreviations: ACT = acceptance and commitment therapy; BLT = bibliotherapy; BPT = brief phone therapy; CBT = cognitive
behavioral training; CI = confidence interval; MC-E = minimal contact education; n = sample size; psych/behav =
psychological/behavioral; SMD = standard mean difference; SOE = strength of evidence; vs. = versus; TRT = Tinnitus
Retraining Therapy; WLC = wait list control
Sleep Disturbance
Five RCT studies with WLCs investigated the effects of interventions on sleep as a
secondary outcome measure.18,57,100,102,120 See Table 23 and Appendix E, Table E4.
In one study,18 the effect of a biofeedback-based CBT on sleep was measured using a diary
VAS measure as well as the sleep subscale of the TQ; there were 52 participants in the
intervention group and 52 participants in the WLC group who later underwent treatment and
87
completed post-treatment evaluation. Significant improvements due to biofeedback-based CBT
were reported (time x group interaction F(1,109) = 9.93, p=0.01 on the VAS diary measure and
F(1,109) = 13.78, p=0.001 on the TQ subscale). Another study of CBT delivered by internet57
reported no significant effect of intervention on sleep.
A third study in the CBT sub-category102 which had a very small sample size (less than 10
per group), the sleep subscale of the TQ was used to evaluate the effectiveness of two treatments
compared to a WLC: cognitive behavioral tinnitus coping training (TCT) administered by two
clinicians and yoga. There was no significant effect of these treatments on sleep.
In two other studies with small sample sizes (30 or less per group), one investigating TRT
and ACT120 and the other100 investigating a self-help book and telephone therapy, the effects of
the interventions on sleep were evaluated using the ISI. The studies reported a significant
beneficial effect of the self-help book and telephone therapy100 on sleep (time x group interaction
F(1,69) = 11.2, p <0.001), as well as a significant beneficial effect of ACT120 on sleep (time x
group interaction F(1,41) = 5.67, p=0.022), but no significant effect of TRT.
The findings reported in these studies are in general agreement with moderate heterogeneity
among outcomes shown in the forest plot (Figure 17). A significant beneficial effect on the VAS
measure in favor of treatment for the biofeedback-based CBT18 and a significant beneficial effect
on the ISI of the self-help book with telephone therapy100 can be seen in the forest plot, as well as
a mean effect in favor of treatment for ACT.120 No benefit from internet CBT,57 TCT,102 TRT,120
or yoga102 is evident in the forest plots; however, the sample sizes are smaller and the confidence
intervals are larger for these treatments than for the biofeedback-based CBT treatment where
benefit from treatment is most apparent.
88
Table 27. Strength of evidence by psychological and behavioral interventions in the treatment of
tinnitus for the outcome of sleep disturbance
Intervention Specifics # of Risk of Consistency Directness Precision Magnitude of SOE
Group Studies Bias the Effect SMD
(n) Range (CI)
18,57,100,102,
CBT/ CBT N/A 5 High Consistent Direct Imprecise -0.70 Low
120
combination (-1.08, -0.31) to
vs. WLC or no 0.61
treatment (-0.23, 1.46)
120
TRT vs. WLC N/A 1 High Unknown Direct Imprecise 0.12 Insufficient
or no treatment (-0.49, 0.72)
102
Other psych / Yoga vs. 1 High unknown Direct Imprecise 0.10 Insufficient
behavioral WLC (-0.70, 0.89)
Abbreviations: CBT = cognitive behavioral training; CI = confidence interval; n = sample size; psych = psychological; SMD =
standard mean difference; SOE = strength of evidence; vs. = versus; TRT = Tinnitus Retraining Therapy; WLC = wait list control
Anxiety
Five RCT studies57,62,84,100,120 evaluated anxiety symptoms as one of the main outcomes57,62,84
or as a secondary outcome100,120 that was compared to a WLC group (Table 23). The group mean
pre-treatment scores on the STAI suggest that the participants had mild levels of anxiety62 and
results on the HADS-A57,84,100,120 suggest that anxiety symptoms were minimal. Indeed, the
HADS-A score was used in one study100 as an eligibility criterion to rule out anxiety as a major
problem. Two studies57,84 used the ASI as a second measure of anxiety.
No significant improvement due to group CBT was found using either the HADS-A or ASI
in a study with a very small sample size.84 However, in another study,57 significant effects of
CBT delivered by internet to a larger sample size were reported when the change scores for the
treatment and wait list groups were compared on both the HADS-A and ASI measures (t(70) =
3.05, p = 0.004 on HADS-A and t(70) = 2.48, p = 0.015 on ASI). In another study,100 a
significant reduction in anxiety on the HADS-A was reported when the treatment was a self-help
book with telephone therapy (time x group interaction: F(1,70) = 10.1, p = 0.002). Significant
improvement on the HADS-A immediately post-treatment was reported in one study for ACT
(time x group interaction: F(1,41) = 4.40, p = 0.042; Cohen’s d effect size = 0.80, 95% CI (0.14-
1.42)), but there was no significant effect of TRT on anxiety.120 When relaxation therapy was
provided with either neutral or counter-demand instructions, no significant effect of treatment on
anxiety was found using the STAI.62
As shown in the forest plot (Figure 18), a clear beneficial effect on anxiety was found for the
self-help book and telephone therapy,100 although this study is considered to have a high risk of
bias. There also seems to be a moderate beneficial effect of ACT on anxiety,120 but this study
also has a high risk of bias. CBT delivered over the internet57 and CBT delivered to a small
group84 have mean beneficial effects on anxiety, but these effects are not significant and the
studies have moderate risk of bias. Relaxation62 and TRT120 seem to have little or no beneficial
effect on anxiety.
89
showed that the point estimates favored treatment, but only one study100 was statistically
significant; this was the only study with a sample size of greater than 30 subjects per group. The
magnitude of the effect size is moderate in all studies and the confidence intervals overlapped
substantively; as such, these studies were rated as having a consistent effect. No dose response
pattern was observed. Risk of publication bias is high given the small sample sizes of the studies.
The SOE for CBT interventions for the outcome of anxiety symptoms is rated as low because the
criteria for two domains were not met (Table 28).
There is insufficient evidence that TRT interventions (one study, 42 participants) or
relaxation therapy (one study, 44 participants) improve anxiety symptoms when compared with
inactive controls for patients with idiopathic tinnitus in the immediate or short term followup.
For these single studies the consistency for each intervention is unknown. The studies have wide
confidence intervals and very small sample sizes (less than 30 per group) and are the effect
estimate is judged as imprecise. Dose response cannot be assessed and risk of publication bias is
high for these interventions given the small sample sizes. The SOE for TRT and Relaxation
therapy interventions for affecting anxiety symptoms is rated as insufficient because the criteria
for three domains were not met (Table 28).
Table 28. Strength of evidence by psychological and behavioral interventions in the treatment of
tinnitus for the outcome of anxiety symptoms
Intervention Specifics # of Studies Risk of Consistency Directness Precision Magnitude of SOE
Group (n) Bias the Effect SMD
Range (CI)
57,84,100,120
CBT/CBT N/A 4 High Consistent Direct Imprecise -0.61 Low
combination (-1.08, -0.14) to
vs. WLC or no -0.27
treatment (-0.76, 0.22)
120
TRT vs. WLC N/A 1 High Unknown Direct Imprecise -0.19 Insufficient
or no (-0.80, 0.41)
treatment
62
Relaxation vs. N/A 1 High Unknown Direct Imprecise -0.08 Insufficient
WLC (-1.26, 1.11) to
0.46
(-0.65, 1.57)
Abbreviations: CBT = cognitive behavioral training; CI = confidence interval; n = sample size; psych = psychological; SMD =
standard mean difference; SOE = strength of evidence; vs. = versus; TRT = Tinnitus Retraining Therapy; WLC = wait list control
Depression Symptoms
Eleven RCT studies10,17,18,57,62,84,95,96,100,102,120 investigated the effects of treatments on
depression symptoms by comparing treatments to WLCs (Table 23). The BDI was used to
measure depression symptoms in four studies,18,62,95,96 the HADS-D was used in four
studies,57,84,100,120 the ADS was used in one study,17 a retrospective measure was used in one
study10 and the Depressivitäts Skala was used in one study.102 As well, the ATQ was used as a
second measure of depression symptoms in one study.96 Note that depression was used as a
primary outcome measure in some studies,57,62 but in most studies10,17,18,84,95,96,100,102,120 it was
considered to be only a secondary or general outcome measure not specifically related to
tinnitus. Also note that the eligibility criteria for some studies selected for participants who did
not have major problems with depression100 and the mean pre-treatment scores on standardized
measures of depression indicated no more than mild depression.
Nine studies tested treatments in the CBT sub-category,17,18,57,84,95,96,100,102,120 four using the
HADS-D,57,84,100,120 three using the BDI,18,95,96 one using the ADS17 and one using the
90
Depressivitäts Skala to evaluate the same treatment administered by two different clinicians.102
Some beneficial effects of treatment were reported in five studies18,57,96,100,102 and no significant
effects were reported in the other four.17,84,95,120
The four CBT interventions that evaluated depression using the HADS-D included one CBT
intervention with six weekly group sessions for adults 65 years of age and older that was
compared to a WLC group who later received a shorter version of the treatment,84 and an
internet-based CBT intervention with six self-help modules that was compared to a WLC.57 For
the treatment provided to older adults,84 there was no effect on depression measured, whereas for
the internet intervention,57 there was significantly greater improvement for the treatment group
compared to the control group for pre-post (t(70)=3.14, p =0.002) and for pre-followup at 1 year
(F(1,94)=5.4, p=0.02). One study100 used the HADS-D to investigate the effect on depression
symptoms of a treatment involving a self-help book and telephone therapy and a significant
beneficial effect was found (time x group interaction; F(1,70)=5.3, p=0.024). Finally, one study
used the HADS-D to evaluate the effect of ACT and found no significant benefit of treatment.120
The effects on depression as measured with the BDI were studied in three studies in the CBT
sub-category:18,95,96 one CBT intervention consisted of eight weekly sessions involving attention
control and imagery and cognitive restructuring (ACI + CR) compared to an ACI-only treatment,
a CR-only treatment and a WLC,96another CBT intervention was a 12-session biofeedback-based
CBT delivered over 3 months compared to a WLC,18 and a third CBT intervention was an 6-
week intervention involving cognitive coping skills training (attention diversion, imagery
training and thought management) that was compared to an education only treatment and a
WLC.95 In the study comparing ACI and CR treatments alone and in combination, it was
reported that those who received treatment improved more than the WLC group (F(1,46)=7.28, p
<0.01);96 as seen in the forest plot, the benefits of treatment reached significance for the CR plus
ACI treatment and the CR alone treatment, but not for the ACI treatment alone. Biofeedback-
based CBT resulted in medium pre-post, but only small pre-followup effect sizes and the small
improvements in BDI compared to the WLC did not reach significance in the intention-to-treat
analysis.18 There was no significant effect on depression of the cognitive coping skills or
education treatments on depression symptoms.95
The ADS, a German version of the CES-D designed to evaluate the effect on depression
symptoms of an 11-session CBT Tinnitus Coping Training (TCT) group intervention was
compared to a WLC as well as two minimal contact (MC) interventions, one entailing two group
sessions focused on education about tinnitus (MC-E) and the other group sessions focused on
education and music-supported relaxation.17 There was no effect of treatment on depression and
the absence of an effect was attributed to the low levels of depression found at baseline.
The Depressivitäts Skala was used to evaluate the effect on depression when TCT was
delivered by two different clinicians compared to a WLC and to yoga.102 Although one of the
TCT groups showed a significant reduction in depression, there was no significant effect on
depression reported for the second TCT group or for the yoga group.
The effect of TRT on depression symptoms was evaluated in one study,120 and no significant
effects were found.
Three interventions focused on relaxation were evaluated: one treatment was the music-
supported relaxation intervention that was compared to CBT,17 one involved relaxation with
neutral or counter-demand instructions with each version of the treatment delivered to two
groups or stages,62 and the third was a treatment emphasizing coping through the use of
relaxation and distraction techniques.10 There was no significant effect of the music-supported
91
relaxation as measured with the ADS.17 For the relaxation intervention with different
instructions, the only significant effect reported was pre- to post-treatment improvement on BDI
(overall pre-treatment mean 12.2 to overall post-treatment mean 8.3), but each group has less
than ten participants and this small difference was observed for both the treatment and WLC
groups. For the study using relaxation and distraction to enable coping,10 depression symptoms
were measured using a VAS whereby participants marked a 10cm line (from ‘none’ to
‘maximal’) at the end of the day for periods of 4 weeks pre- and post-treatment. A statistically
significant difference between pre- and post-treatment was reported (t(20)=2.90, p <0.01) as well
as a small difference between the treatment and control groups that favored the treatment group
(F(1,21)=4.76, p <0.05).
Three studies17,95,102 investigated the effects of other treatments on depression symptoms. The
study already mentioned that investigated the effects of TCT using the ADS also evaluated the
effects of education (ME-E) on depression symptoms, with no significant benefit reported.17 The
study already mentioned that used the BDI to investigate the effects on depression symptoms of
CBT with education also evaluated the effects of education alone and found no significant
benefit.95 As mentioned above, no significant effect of yoga on depression symptoms was
reported.102 The forest plots (see Figure 19) are consistent with the findings reported in the
studies regarding the effect of the treatments on depression symptoms. Overall, less than half of
the treatments yielded a significant effect in favor of the treatment in comparison to a WLC.
92
in these studies, earning a rating of imprecise. All the studies were at high risk of bias. No dose
response pattern was observed. Risk of publication bias is high given the small sample sizes of
the studies. The SOE for relaxation interventions for the outcome of depression symptoms is
rated as insufficient as the criteria for three domains were not met.
There is insufficient evidence that MC education (one study, 36 participants), education (one
study, 40 participants), or yoga (one study, 28 participants) improves depression symptoms when
compared with inactive controls for patients with idiopathic tinnitus in the immediate or short
term followup. When considering the three interventions grouped in the “other category”, the
evidence was deemed insufficient given the high risk of bias for the studies, unknown
consistency, and small sample sizes of less than 30 per group (imprecision). Risk of publication
bias is high for these interventions given the small sample sizes and the single studies within this
group. The SOE for MC education, education and yoga interventions for the outcome of
depression symptoms is rated as insufficient as the criteria for three domains were not met.
Table 29. Strength of evidence by psychological and behavioral interventions in the treatment of
tinnitus for the outcome of depression symptoms
Intervention Specifics # of Risk of Consistency Directness Precision Magnitude of SOE
Group Studies (n) Bias the Effect
SMD Range
(CI)
17,18,57,84,95,
CBT/ CBT N/A 9 High Consistent Direct Imprecise -1.05 Low
96,100,102,120
combination (-1.92, -0.19) to
vs. WLC or -0.04
no treatment (-0.57, 0.49)
120
TRT vs. WLC N/A 1 High Unknown Direct Imprecise 0.05 Insufficient
or no (-0.55, 0.66)
treatment
10,17,62
Relaxation N/A 3 High Inconsistent Direct Imprecise -1.85 Insufficient
vs. WLC (-3.59, -0.11) to
-0.06
(-1.24, 1.13)
17
MC-E vs. 1 High Unknown Direct Imprecise -0.31 Insufficient
WLC (-0.97, 0.35)
95
Education 1 High Unknown Direct Imprecise 0.08 Insufficient
vs. WLC (-0.54, 0.70)
102
Yoga vs. 1 High Unknown Direct Imprecise -0.32 Insufficient
WLC (-1.12, 0.48)
Abbreviations: CBT = cognitive behavioral training; CI = confidence interval; MC-E = minimal contact education; n = sample
size; psych = psychological; SMD = standard mean difference; SOE = strength of evidence; vs. = versus; TRT = Tinnitus
Retraining Therapy; WLC = wait list control
93
life based on responses in six domains; the HRLS was used in one study112as a secondary
measure to assess the importance of and satisfaction with eight health-related issues, with a
composite index for health-related life satisfaction.
The effect on global QoL was evaluated for six interventions in the CBT category (Figure
20). A significant effect favoring CBT was found for an intervention using biofeedback-based
CBT18 which was evaluated with the SCL-90-R (group x time interaction: F(1,109)=7.61, p
<0.01). No significant effect of treatment was reported for CBT using a psychophysiological
approach evaluated with the HRLS.112 CBT with TCT and TCT were evaluated in two studies,
one using the SCL-90-R17 and the other using the Beschwerden-Liste;102 no significant
immediate post-treatment effects between the WLC and the treatment groups were reported in
either study. ACT120 was evaluated with the QoLI and no benefit was found,
The effect on global quality of life by TRT was evaluated in one study120 using the QoLI, but
no significant effect of treatment was reported.
The effect on global QoL by a relaxation intervention with minimal contact was evaluated in
one study17 using the SCL-90-R, but no significant effect of treatment was reported.
The effect on global QoL was evaluated for three other psychological behavioral treatments:
bibliotherapy with the GHQ-12,104 education with minimal contact with the SCL-90-R,17 and
yoga with the Beshwerden-Liste.102 No significant effects of treatment on global QoL were
reported for education,17 or yoga.102 However, a significant reduction in general stress measured
with the GHQ-12 with a small effect size was reported for bibliotherapy.104
As seen in the forest plot (Figure 20), the two most promising interventions are biofeedback-
based CBT and bibliotherapy; however, these were the only two studies with sample sizes
greater than 50.18,104
94
Table 30. Strength of evidence by psychological and behavioral interventions in the treatment of
tinnitus for the outcome of global quality of life
Intervention Specifics # of Risk of Consistency Directness Precision Magnitude of SOE
Group Studies Bias the Effect
(n) SMD Range
(CI)
17,18,102,
CBT/ CBT N/A 5 High Consistent Direct Imprecise 0.64 Low
112,120
combination (0.02, 1.26) to
vs. WLC or no -0.06
treatment (-0.59, 0.47)
120
TRT vs. WLC N/A 1 High Unknown Direct Imprecise 0.06 Insufficient
or no (-0.55, 0.66)
treatment
104
Other BLT vs. 1 High Unknown Direct Precise 0.45 Low
WLC (0.1, 0.81)
17
MC-E vs. 1 High Unknown Direct Imprecise 0.32 Insufficient
WLC (-0.35, 0.98)
102
Yoga vs. 1 High Unknown Direct Imprecise 0.26 Insufficient
WLC (-0.54, 1.05)
Abbreviations: ACT = acceptance and commitment therapy; BLT = bibliotherapy; BPT = brief phone therapy; CBT = cognitive
behavioral training; CI = confidence interval; MC-E = minimal contact education; n = sample size; psych/behav =
psychological/behavioral; SMD = standard mean difference; SOE = strength of evidence; vs. = versus; TRT = Tinnitus
Retraining Therapy; WLC = wait list control
95
Figure 15. Studies with inactive comparators that evaluate psychological and behavioral interventions and report tinnitus-specific
quality of life outcomes
CBT / CBT combination
**Westin, 2011 {Acceptance & Commitment Therapy vs. WL} THI 22 22 -1.12 (-1.76, -0.48)
Kaldo, 2007 {self-help book + telephone vs. W L} TRQ 34 38 -0.64 (-1.11, -0.16)
**Henry, 1998 {Cognitive restructuring(CR) vs. WL} TRQ 12 12 -0.70 (-1.53, 0.13)
**Henry, 1998 {Attention control+Imagery(ACI) vs. WL} TRQ 12 12 -0.13 (-0.93, 0.67)
**Henry, 1996 {Cognitive coping + Education vs. WL} TRQ 20 20 -0.47 (-1.10, 0.16)
**Kroner-Herwig, 1995 {TCT 1-Tinnitus coping vs. WL} TQ-PI 7 19 -0.63 (-1.51, 0.26)
**Kroner-Herwig, 1995 {TCT 2-Tinnitus coping vs. WL} TQ-PI 8 19 -0.44 (-1.28, 0.39)
**Westin, 2011 {Tinnitus Retraining Therapy vs. WL} THI 20 22 -0.18 (-0.78, 0.43)
**Henry, 2007 {Grp Education Counseling vs. No Trt} TSI 67 73 -0.60 (-0.93, -0.26)
Relaxation therapy
**Ireland, 1985 {Stage 1_Relaxation Counterdemand vs. WL} self-report 7 6 -1.02 (-2.20, 0.17)
**Ireland, 1985 {Stage 2_Relaxation Counterdemand vs. WL} self-report 4 5 -0.23 (-1.55, 1.10)
**Ireland, 1985 {Stage 1_Relaxation Neutraldemand vs. WL} self-report 5 6 -0.17 (-1.36, 1.02)
**Ireland, 1985 {Stage 2_Relaxation Neutraldemand vs. WL} self-report 6 5 0.17 (-1.02, 1.36)
Scott, 1985 {Relaxation therapy vs. WL} self-report-D 12 12 -0.74 (-1.58, 0.09)
Biesinger, 2010 {Qigong training vs. WL} TBF-12 15 19 -0.14 (-0.82, 0.54)
**Henry, 2007 {Traditional support Group vs. No Trt} TSI 60 73 -0.12 (-0.46, 0.23)
**Henry, 1996 {Education alone vs. WL} TRQ 20 20 0.08 (-0.54, 0.70)
-2.2 0 2.2
96
Figure 16. Studies with inactive comparators that evaluate psychological and behavioral interventions and report subjective loudness
outcomes
Study Scale N_INT N_CTRL SMD (95% CI)
Kaldo, 2007 {self-help book + telephone vs. W L} VAS 34 38 -0.55 (-1.02, -0.07)
Rief, 2005 {Psychophysiologic therapy vs. WL} Diary 22 20 -0.03 (-0.64, 0.58)
**Kroner-Herwig, 2003 {CBT-Tinnitus coping vs. WL} Diary 43 20 -0.13 (-0.67, 0.40)
**Henry, 1996 {Cognitive coping + Education vs. WL} Self-report 20 20 0.01 (-0.61, 0.63)
**Kroner-Herwig, 1995 {TCT 1-Tinnitus coping vs. WL} Diary 7 19 -0.15 (-1.01, 0.72)
**Kroner-Herwig, 1995 {TCT 2-Tinnitus coping vs. WL} Diary 8 19 -0.06 (-0.89, 0.77)
Relaxation therapy
Scott, 1985 {Relaxation therapy vs. WL} Self-report-D 12 12 -0.72 (-1.55, 0.11)
**Ireland, 1985 {Stage 1_Relaxation Counterdemand vs. WL} Self-report 7 6 -0.61 (-1.73, 0.52)
**Ireland, 1985 {Stage 2_Relaxation Counterdemand vs. WL} Self-report 4 5 -1.16 (-2.65, 0.34)
**Ireland, 1985 {Stage 1_Relaxation Neutraldemand vs. WL} Self-report 5 6 -0.52 (-1.73, 0.70)
**Ireland, 1985 {Stage 2_Relaxation Neutraldemand vs. WL} Self-report 6 5 -0.61 (-1.83, 0.62)
**Henry, 1996 {Education alone vs. WL} Self-report 20 20 -0.27 (-0.89, 0.35)
-2.65 0 2.65
97
Figure 17. Studies with inactive comparators that evaluate psychological and behavioral interventions and report sleep disturbance
outcomes
98
Figure 18. Studies with inactive comparators that evaluate psychological and behavioral interventions and report anxiety symptoms
outcomes
99
Figure 19. Studies with inactive comparators that evaluate psychological and behavioral interventions and report depression symptoms
outcomes
Study Scale N_INT N_CTRL SMD (95% CI)
**Westin, 2011 {Acceptance & Commitment Therapy vs. WL} HADS-D 22 22 -0.19 (-0.78, 0.40)
Kaldo, 2007 {self-help book + telephone vs. WL} HADS-D 34 38 -0.54 (-1.01, -0.07)
**Kroner-Herwig, 2003 {CBT-Tinnitus coping vs. WL} ADS 43 20 -0.04 (-0.57, 0.49)
**Henry, 1998 {Cognitive restructuring(CR) vs. WL} BDI 12 12 -1.05 (-1.92, -0.19)
**Henry, 1998 {Attention control+Imagery(ACI) vs. WL} BDI 12 12 -0.34 (-1.14, 0.47)
**Henry, 1996 {Cognitive coping + Education vs. WL} BDI 20 20 -0.35 (-0.98, 0.27)
**Kroner-Herwig, 1995 {TCT 1-Tinnitus coping vs. WL} Dep-Skala 7 19 -0.73 (-1.63, 0.16)
**Kroner-Herwig, 1995 {TCT 2-Tinnitus coping vs. WL} Dep-Skala 8 19 -0.11 (-0.94, 0.72)
**Westin, 2011 {Tinnitus Retraining Therapy vs. WL} HADS-D 20 22 0.05 (-0.55, 0.66)
Relaxation therapy
Scott, 1985 {Relaxation therapy vs. WL} self-report-R 12 12 -0.89 (-1.73, -0.04)
**Ireland, 1985 {Stage 1_Relaxation Counterdemand vs. W L} BDI 7 6 -0.06 (-1.15, 1.03)
**Ireland, 1985 {Stage 2_Relaxation Counterdemand vs. W L} BDI 4 5 -1.85 (-3.59, -0.11)
**Ireland, 1985 {Stage 1_Relaxation Neutraldemand vs. W L} BDI 5 6 -0.06 (-1.24, 1.13)
**Ireland, 1985 {Stage 2_Relaxation Neutraldemand vs. W L} BDI 6 5 -0.93 (-2.21, 0.35)
**Henry, 1996 {Education alone vs. WL} BDI 20 20 0.08 (-0.54, 0.70)
-3.59 0 3.59
100
Figure 20. Studies with inactive comparators that evaluate psychological and behavioral interventions and report global quality of life
outcomes
Study Scale N_INT N_CTRL SMD (95% CI)
**Westin, 2011 {Acceptance & Commitment Therapy vs. WL} QOLI 22 22 0.15 (-0.44, 0.75)
Rief, 2005 {Psychophysiologic therapy vs. WL} HRLS 22 20 0.64 (0.02, 1.26)
**Kroner-Herwig, 2003 {CBT-Tinnitus coping vs. WL} SCL–90–R 43 20 -0.06 (-0.59, 0.47)
**Kroner-Herwig, 1995 {TCT 1-Tinnitus coping vs. WL} Bes-Liste 7 19 0.53 (-0.35, 1.41)
**Kroner-Herwig, 1995 {TCT 2-Tinnitus coping vs. WL} Bes-Liste 8 19 0.25 (-0.58, 1.08)
**Westin, 2011 {Tinnitus Retraining Therapy vs. WL} QOLI 20 22 0.06 (-0.55, 0.66)
Relaxation therapy
-1.41 0 1.41
101
KQ3. For adults with subjective idiopathic tinnitus, what prognostic factors,
patient characteristics, and/or symptom characteristics affect final treatment
outcomes?
No data addressing this question were identified in the literature search.
102
Discussion
Overview
In a rehabilitative context, those with tinnitus are more likely than those without tinnitus to
seek professional help and accept hearing aids, presumably because the combination of tinnitus
and hearing loss increases disability.4,65 However, for the large number of people with hearing
loss and tinnitus, typical audiological interventions focus on the remediation of hearing loss
rather than on treatments for tinnitus per se.4 Tinnitus is a complex condition for which a variety
of interventions have been applied. This Comparative Effectiveness Review (CER) attempted to
evaluate Key Questions (KQ) 1 and 3 regarding methods to assess different treatment strategies,
and possible prognostic factors, related to tinnitus outcomes. Although the search was
comprehensive, there was no literature eligible for KQ1 and KQ3, thereby identifying some
significant gaps in the literature. For KQ2, which examined treatments for tinnitus, this CER has
identified and shown that the strength of evidence (SOE) is generally of low quality, suggesting
that the results of these studies do not necessarily reflect the true effect of these interventions and
that future research is very likely to change both the direction and magnitude of the effects for
these interventions. This evidence review demonstrates the research gaps with respect to KQ1
(methods to identify further evaluation and treatment) and KQ3 (prognostic factors).
A critical discussion for each of the KQ is presented below.
KQ1. In patients with symptoms of tinnitus (e.g., ringing in the ears,
whoosing sounds) what is the comparative effectiveness of methods used
to identify patients for further evaluation or treatment?
The intention of this question was to determine if some methods were more effective than
other methods when used by primary care providers or specialists in tinnitus care to determine if
a patient with tinnitus should be referred for rehabilitation. Note that the type of tinnitus was not
restricted for KQ1. The criteria for including studies allowed methods that involved direct
observation or observation of sound with a stethoscope, the administration of
scales/questionnaires to assess severity. Importantly, these studies were restricted to primary and
specialty care with the specific outcomes of the method establishing any of the following: 1) no
treatment necessary; 2) need for specialized treatment; and, 3) extent of intervention. This last
criterion was the one that most affected eligibility for this systematic review.
There are several validated questionnaires23 currently being used for assessing the symptoms
and the impact of tinnitus and very recently a new comprehensive instrument, the Tinnitus
Functional Index (TFI),26was developed by consensus among a large number of researchers who
had introduced earlier measures. Nevertheless, no research has contrasted one measure with
another existing instrument in order to evaluate which was better for addressing candidacy for
further treatment or the type and amount of treatment required. Similarly, psychological grading
scales, which can help discriminate between clinically significant and non-significant degrees of
tinnitus, were not compared directly. Furthermore, the relative suitability of different methods
for evaluating candidacy for and likely outcomes of specific treatments has not been studied.
Some attributes regarding the potential usefulness of different measures and the criteria for
treatment candidacy are suggested in the studies examined in regard to KQ2. Future research in
this area is critical in order for the field to move forward.
103
It is noteworthy that, in parallel with the evolution of behavioral interventions, tinnitus-
specific measurement tools have evolved to incorporate more of the psychological aspects of
stress/distress with reduced focus on auditory perception. This reflects the historical development
and understanding that tinnitus as a symptom is to be managed rather than a disease to be cured.
It also highlights the potential problem of comparing studies using different instruments to
establish either the candidacy for or the efficacy of treatments when the instruments are based on
vastly different assumptions about the nature of the problems associated with tinnitus. Future
evidence syntheses will have to judiciously consider the various domains within complex
instruments encompassing multiple areas of quality of life or symptoms. Specifically, many of
the tinnitus-specific measures (Table 5) include questions concerning multiple outcomes of
interest in the present review. It is noteworthy that this dilemma is not unique to the area of
tinnitus; efforts to bank individual items rather than summary scores when making outcome
comparisons is endemic in rehabilitation areas where disorders are complex. Comparison of
findings across studies when outcomes contain different domains and weightings of items within
these domains has necessitated consensus work to establish core measures (a minimal set of
functions or items) to capture important domains based on the International Classification of
Function (ICF) (see example for stroke148). Note that an ICF core set for hearing has almost been
completed (http://www.icf-research-branch.org/icf-core-sets-projects/other-health-conditions/icf-
core-set-for-hearing-loss.html). Ultimately, it would be useful to develop such a core set for
tinnitus and the TFI promises to be an important step in this regard.
KQ2. In adults with subjective idiopathic (nonpulsatile) tinnitus, what is the
comparative effectiveness (and/or potential harms) of pharmacological,
medical, sound treatment/technological, or psychological/behavioral
interventions (including combinations of interventions)?
In general, it is difficult to draw overall conclusions about treatment benefits given the
diversity of interventions and outcomes in the studies that satisfied the inclusion criteria for this
research question. Studies were heterogeneous in terms of populations, treatments, treatment
modalities (e.g., many different types of CBT), study duration and followup periods, and
outcome measures. Although we estimated effect sizes using standardized mean differences, they
are difficult to interpret. Some interventions did show positive benefits, but it was difficult to
judge the degree of clinical significance of the changes across studies. Even if differences in
treatment-placebo scale scores were statistically significant, these differences may not be
clinically meaningful. Future research must consider pilot work to establish the validity of many
of the outcomes used in the studies eligible for this question; moreover, specific adaptations of
measures validated in non-tinnitus populations (i.e., study-specific visual analogue scales (VAS)
should be established in the tinnitus population, particularly for the attributes of change over
time (responsiveness). For some of the tinnitus-specific outcomes, it is critical that clinically
important differences be established.
For some interventions (e.g., pharmacological agents, acupuncture, Qigong, etc.), only single
studies were evaluated and many of these were very small with respect to sample sizes. One
clear trend was that, given their sample sizes, many studies were likely underpowered to detect
differences. Thus, there is little or no confidence in the findings of studies that showed no
differences relative to placebo or inactive control comparators, and it is prudent to assume that
these do not reflect the true effect of the interventions being evaluated.
104
Perhaps the heterogeneity among studies reflects differing paradigms based on evolving
knowledge about the nature of tinnitus. It would be important that future studies designed to
evaluate interventions be well grounded in neuroscience and reflect a conceptual framework
providing rationales that take into account the auditory, cognitive, emotional, and stress circuits
thought to underpin the characteristics of the disorder. It may also turn out that different subtypes
of tinnitus will be identified according to whether the main feature of the tinnitus relates to
auditory, cognitive, emotional, or other disorders. Recent research findings from cognitive and
auditory neuroscience studies have advanced knowledge of the biological mechanisms for some
forms of tinnitus, while findings from clinical psychology studies have underscored the
interactions among the auditory, cognitive, affective, and mental health issues that must be
considered when designing and evaluating interventions to meet the needs of clinical
subpopulations of patients.
The perspective brought to this evidence synthesis is that tinnitus is a symptom or condition
and not a disease, suggesting that it is multi-factorial and complex. As such, it is not surprising
that the focus of interventions is shifting from “curing” tinnitus by trying to mask or eliminate
the perception of tinnitus to providing strategies for coping/control/relief. The auditory aspect of
tinnitus was an early focus of many of the treatment approaches to manage it, with many of those
suffering from tinnitus seeking medical rather than psychological treatments; in contrast, the
present understanding of the problem would suggest that the “sound” per se is not the only
issue.18 Rather, the reaction to the sound suggests that it is more than just an auditory problem;
tinnitus often entails psychological distress.12 Nevertheless, new sound generating technologies
continue to be developed and tested.116 The implications of this for future research are to
continue to broaden baseline assessments and types of outcomes to capture these additional
dimensions. A systems approach that addresses the interaction of the auditory, emotional, and
cognitive aspects of tinnitus could be considered.
The diversity of interventions and treatments eligible in this review did not provide guidance
with respect to the dose of the treatment interventions (for how long and how much) to achieve
an acceptable effect. The studies evaluating CBT provide some information about the amount of
clinician-patient contact required to achieve statistically significant outcomes; the primary
motivation being to design programs that can be self-administered or delivered over the phone or
internet in order to improve cost/benefit, accessibility, varying needs of patients, and efficiencies
in the allocation of limited clinician resources. Future studies may need to consider earlier phase
trial designs to establish adequate doses for the various interventions. Contextual parameters also
need to be considered with respect to the setting and the personnel providing the service and
what type of specialization is required for the specific intervention.
This review considered adverse effects related to tinnitus symptoms (worsening of tinnitus,
sedation symptoms, and surgical complications). From these, the SOE for sedation (drowsiness,
excessive sleepiness) could be evaluated and this effect was reported in studies evaluating
primarily pharmacological interventions. The evidence was rated as insufficient for the outcome
of sedation, due to the diversity of drugs and the few studies that reported this adverse effect.
Some of the studies evaluating other pharmacological and medical interventions also attempted
to capture and report other types of treatment emergent adverse effects. However, almost none of
the psychological behavioral interventions evaluated or reported adverse effects and those that
did indicated that there were no adverse effects. In some studies, worsening of tinnitus-related
symptoms was noted.92 Although, it may be difficult to identify potential unintended effects with
these types of psychological and behavioral therapies, it would still be important to consider
105
what some of these might entail. Whereas patients who see no effect with a medical/surgical
intervention, such as a drug, may tend to feel that the medication failed them and not that they
failed the medication. In contrast, participants in psychological/behavioral interventions may
tend to feel that they failed the psychotherapies. For example, the patient who commits to
psychological therapy and then experiences no improvement might tend to be emotionally
troubled by this result (if they had tried harder, been more open, done the homework,
participated in group more, etc.). In general, it was observed that the majority of studies
evaluating these interventions did not adequately identify or collect potential adverse effects. The
inability to distinguish whether the studies measured these harms as opposed to simply not
reporting them, either because no events occurred or they occurred at the lowest frequencies,
makes rating SOE for outcomes of harm problematic.
Future research should adequately capture harms, particularly if head-to-head trials
comparing two different treatments are of interest. That is, if there is no meaningful difference in
the potential outcomes of benefit, the margins between benefits and harms become narrower.
Given that many of the treatments evaluated were likely to have no difference or are potentially
equivalent, evaluation of harms takes on a greater importance for judging the relative efficacy of
the two interventions.
Trial registries were reviewed to ascertain what future trials are ongoing (Appendix F) and 26
registered trials were found. The largest number of trials are evaluating sound technologies
interventions using varied sensory stimulation devices (n=6); additionally, four trials will be
evaluating repetitive transcranial magnetic stimulation (rTMS), and two assessing vagal nerve
stimulation. Five trials are registered to evaluate pharmacological agents (i.e., cilostazol, NST-
001, AM-101, and neramexane mesylate) or food supplements (i.e., magnesium). One trial will
compare the efficacy of a behavioral intervention to a pharmacological agent. There are seven
trials registered that will evaluate psychological/behavioral interventions. Overall, this reflects
significant research activity in interventions aimed at remediating problems associated with
subjective idiopathic tinnitus using a wide range of interventions.
106
The only intervention that consistently showed statistically significant effects on multiple
outcomes was sertraline, which was evaluated against placebo in a 16-week study of 63 persons
who had a mean age of 42 years. These persons were recruited from a specialized audiology
clinic and given 50 mg/day of the active therapy or placebo. Sertraline was shown to be more
efficacious than placebo in reducing loudness, improving global QoL, and alleviating severity.
Sertraline also had a greater impact on reducing depression symptoms, although the reduction
failed to reach statistical significance at the 5 percent level on one of the three scales used to
measure depression.
Several issues must be considered when interpreting the results described above. Although
sertraline does appear to have beneficial effects on certain tinnitus outcomes, this medication has
only been evaluated in one 2006 study.122 More evidence is required prior to drawing firmer
conclusions about the drug’s usefulness against tinnitus. The same caution is relevant for the
other therapies that did not show any benefits against tinnitus. Further research is required for us
to assess whether or not these treatments are beneficial for persons with tinnitus.
Thirteen of the 16 studies had sample sizes of less than 100 persons. Most of these papers
were bereft of sample size calculations or author commentaries on the adequacy of their sample
sizes. This issue raises the question of whether the studies had adequate power to detect
statistically significant differences, let alone minimum clinically meaningful differences.
Although the three largest studies93,109,113 did not find differences between the treatment and
placebo groups, these results cannot be used to conclude that the smaller studies would also not
have found differences had they employed larger samples. Each of the three large studies
evaluated a different active therapy and, in only a single case did a smaller study examine one of
the same therapies as in a larger study.93,111 Thus, the results of the larger studies are therapy-
specific and in no way generalizable to the findings for the other treatments.
The issue of minimum clinically meaningful differences is important when one considers the
characteristics of the outcome measurement instruments used in the included studies. Few of the
authors commented on the validity of their instruments, both in terms of measuring the outcomes
of interest or for assessing these outcomes specifically in persons with tinnitus. Even though
some instruments might be suitable measures of tinnitus-specific outcomes (e.g., Tinnitus
Handicap Inventory for symptom severity), and other instruments might be valid measures of
constructs such as depression (e.g., HAM-D), the authors did not provide details on the minimum
changes in instrument scores that would be considered clinically meaningful. For example, the
sertraline study122 used a 100 mm VAS to measure loudness and the authors reported that the
mean change in score between baseline and the end of 16 weeks of followup was 15.21 (standard
deviation=20.38) in the treated group and 3.21 (standard deviation=20.91) in the placebo group.
For clinicians or persons with tinnitus, does a mean score change of 15.21 indicate that a
majority of patients on the active treatment were clinically improved? Also, is the treatment-
placebo difference in mean score change at the end of followup (i.e., 12.00) indicative of an
important clinical difference between the study groups? The same questions apply to all of the
instruments used in the included studies (AS and validated instruments alike. It is recommended
that authors justify their choice of outcome measures from the standpoint of validity.
Additionally, authors should specify (and justify) the minimum differences in instrument scores
that are claimed to be clinically important.
Another important issue to consider is the ability of an instrument to discriminate between
treatment effects across study groups (in other words, the ability to detect minimum clinically
meaningful differences). Even valid instruments might contain a certain degree of imprecision
107
that blurs between-group differences. In some cases, the imprecision might be large enough to
prevent researchers from detecting true effects. In other cases, the presentation of summary scale
scores might obfuscate the imprecision and make the differences between treatments appear
larger than in reality. To see an illustration of the latter point, the standard deviations associated
with the mean VAS scores in the previous paragraph exceed the mean scores themselves.
Assuming the data are normally distributed, a standard deviation of 20.38 for the sertraline group
means that 34.1 percent of the 29 persons who received this drug (n~10) actually had a change in
score of somewhere between -5.17 (worsening loudness) and 15.21 on the VAS (mean –
standard deviation). Also, 15.8 percent (n~4 - 5) had a change in score that was worse than -5.17.
For the placebo group, 34.1 percent of the 34 persons who received placebo (n~11 - 12) had
changes in score between 3.21 and 24.12 (mean + standard deviation). A further 15.8 percent of
the placebo group (n~5) had changes in score that exceeded 24.12. When considered in this
fashion, the differences between the active and placebo groups do not appear as great as the
means suggest. Authors must carefully consider an discriminative ability of an instrument prior
to use in a study. Such consideration will mitigate the potential of a type II error (failing to reject
the null hypothesis when it should be rejected) or prevent treatment differences from appearing
larger than in reality.
108
error cannot be ruled out. Issues related to statistical power, poor characterization of study
participants, and poor study conduct (high risk of bias) all likely contributed to the nonsignificant
results observed across the different interventions. Future research should provide a more
coherent rationale for the particular treatment approaches based on current neurological science
principles, including justification for the dose of the intervention.
109
studies derived a similar conclusion suggesting insufficient evidence7 or remarked upon the
diversity of interventions and the lack of evidence overall.150
110
Behavioral interventions (i.e., relaxation, education, TRT) employed an isolated approach
that did not confer the same degree of benefit and were rated insufficient, being plagued with the
same problems as the studies evaluating pharmacological and medical interventions. It was
observed that CBT combined with other behavioral interventions (e.g., EMG biofeedback18 in
this review) were common treatment options. There has also been a movement attempt to tease
apart the active ingredient of some complex interventions or to compare treatments with
demonstrated benefit to each other. Two recently published RCTs151,152 that were not indexed at
the time the databases were searched for this CER illustrate this point. The first report151showed
that both internet CBT and internet ACT yielded equivalent benefit with the conclusion that
either are viable treatment alternatives that may be chosen by or for patients. It is interesting that
there is active development of progressive46,63 or staged treatments,64 which could be a promising
avenue to further explore in future studies. The second report152 is an example of a staged
treatment study in which benefits on a new measure of tinnitus-specific quality of life were
found. The group receiving a psychoeducational intervention, followed by 6 weekly sessions of
mindfulness training that emphasized acceptance, showed benefit but the same
psychoeducational intervention followed by a relaxation therapy did not. However, trials
evaluating complex interventions are problematic if a simple parallel design is employed.
Factorial designs will assist in disentangling the relative benefits of the different components of
multi-modal interventions.151,152
KQ3. For adults with subjective idiopathic symptoms of tinnitus, what
prognostic factors, patient characteristics, and/or symptom characteristics
affect final treatment outcomes?
The intent had been to identify from the literature important patient characteristics, symptom
characteristics and/or prognostic factors that might affect final treatment outcomes. This
systematic review did not identify any literature relevant to addressing this Key Question that
met inclusion criteria. Although most studies identified baseline population characteristics,
between group analyses of treatment effect were only presented for the main treatment and
control groups and not for subgroups differing in the characteristics targeted by KQ3.
Furthermore, relationships between patient characteristics and outcomes were not tested (e.g.,
multivariate regression models evaluating independent contributions of different factors to
predict the outcomes of interest). For the included studies, when subgroup results were
presented, the focus was not on predicting the effect on prognosis, rather the analysis was more
descriptive rather than predictive. This identifies another important gap in the literature. In part
this can be related to the evolving issues of diagnosing or establishing the severity of tinnitus, as
well as the changing paradigm from the neuroscience perspective.
Applicability
When considering the applicability of study findings in general, the study populations were
relatively homogeneous and were limited to mostly middle aged (≥50 years of age) persons
suffering from predominantly subjective idiopathic tinnitus of mild to moderate severity. Of
course, age-related hearing loss also increases markedly with age starting in the fourth decade
and hearing loss and tinnitus often co-occur.4 Nevertheless, tinnitus is not only a problem for
older adults or for people with clinically significant hearing loss. A recent survey estimated
tinnitus was prevalent in 12.2 percent of the U.S. population under 44 years of age.113,153
However, there is little evidence upon which to draw conclusions about the efficacy of the
111
therapies in persons younger than 42 years of age. Some studies did focus on industrial workers81
or veterans,97 but these specialized populations may differ from the general population of
working-aged people because of the relevance of the link between tinnitus and their occupational
exposure to noise and trauma. Importantly, it seems that there may be generational differences in
the experience of tinnitus based on recent epidemiological research on adults over the age of 45
years.154 The finding of generational differences suggests that reports of tinnitus tend to increase
with more recent birth cohorts compared with earlier birth cohorts,154 with participants in a given
generation being significantly more likely to report tinnitus than participants from a generation
20 years earlier (OR=1.78; 95% CI, 1.44 to 2.21). Such cohort differences could extend to
younger adults, especially given recent concerns about a rise in tinnitus related to exposure to
recreational noise.6 The generational differences in the reporting of tinnitus may reflect actual
changes in prevalence related to lifestyle and environmental differences across cohorts. They
may also reflect changes in health attitudes or knowledge that awareness of, and willingness to
report, the symptoms. In any case, it is possible that the effectiveness of treatments may differ
with age or cohort and it will be important to explore these differences as programs to treat, and
possibly even programs to prevent, tinnitus continue to be developed and evaluated.
Tinnitus is a chronic condition and the longest followups in the included studies did not
exceed 16 weeks in pharmacological and food supplement studies and 26 weeks in medical
interventions. However, followup was extended to 12 months in all of the studies evaluating
sound-based treatments53,61,92 and even to 18 months for one study.98 For the psychological and
behavioral interventions, many studies evaluated the effectiveness of treatment immediately
post-treatment as well as at one or more later followups. The time intervals ranged from a
minimum of 6 weeks10 to 2 months,62 or 3 months84,87,102 to 6 months,96 but most continued to 1
year17,57,95,97,100,104 or even 18 months.120 Thus, for the pharmacological and medical intervention
categories of intervention, the included studies did not provide data on the medium- to long-term
effects of the active treatments. Longer term followup was provided in the studies involving
sound-based therapy and psychological/behavioral therapies. These therapies are usually
provided by rehabilitative professionals, such as audiologists and psychologists whose practice
may put greater emphasis on establishing and maintaining change due to intervention.
Most studies were recruited from clinical or specialty settings. Fewer studies recruited
subjects from newspapers and the Internet (open to the public, including associations for
tinnitus/hearing loss), which is reflective of the population most likely to benefit from the
interventions. However, this method of recruitment might account for the high attrition rates in
these studies. Also, for some studies, the subjects represented those who had failed to respond to
previous treatments; although the subjects were seen in otolaryngology clinics, they were treated
by psychologists, often in conjunction with audiologists. It is not clear what proportion of all
tinnitus patients fall into this “failed treatment group”. Two of the studies with failed populations
focused on high risk groups. While one of these studies suggests that group educational
counseling can be of significant benefit to many tinnitus patients,97 the focus on subjects who are
veterans may limit the applicability to the general population. This is also an issue for the study
that focused only on those 65 years of age and older.84
As noted previously, it is difficult to judge the applicability of the doses for the varied
interventions in the included studies. The pharmacological and food supplements, sound
technologies, and medical interventions would be readily available in primary care,
rehabilitation, and audiology settings. Some of the psychological interventions might be more
problematic to implement across different healthcare systems.
112
Many of the studies in this review were conducted in Europe, where the professional model
of ‘hearing care/audiology’ is different from that typically seen within the United States. In the
United States, the coping/CBT-oriented interventions fall more within the scope of the practice
of psychologists, rather than audiologists. If future interventions were to require more of this
type of psychological intervention, there would need to be a shift in the training of audiologists
or a shift to more team-oriented practice involving both audiologists and psychologists. Added to
this, interventions delivered via the Internet are now in use.57 Translating all of this into practice
has some implications for the education of various health professionals and for the cost/benefit of
these newer treatment delivery methods.
113
Summary/Conclusions
Key Question 1
No studies were found addressing the comparative effectiveness of tools used to determine
candidacy for treatment. A gap in the literature has been identified.
Key Question 2
Medical Interventions
Four different medical interventions were evaluated in 11 randomized trials. There was low
SOE for rTMS and insufficient evidence for LLLT, ACRN, and acupuncture for improving
TSQoL. The studies were generally at high risk of bias, with small sample sizes and were poorly
reported. Few studies evaluated subjective loudness, anxiety symptoms, and depression
symptoms. There were insufficient studies to evaluate the evidence. No studies evaluating
medical interventions assessed the impact on sleep disturbance or global QoL. A clear trend for
harms was difficult to specify across the differing interventions. The relative potential for long-
term harms was not evaluable in the short term treatment trials included in this grouping.
114
Psychological and Behavioral Interventions
Four subcategories of psychological/behavioral interventions were examined: CBT (n=10)
and related treatments, TRT-related treatments (n=2), treatments involving primarily relaxation
(n=3), and other interventions (n=5), including one involving reading tinnitus books, two
emphasizing education, one with yoga, and one with Qigong. Outcomes for TSQoL (19
treatments), subjective loudness (13 treatments), sleep (6 treatments), anxiety (9 treatments),
depression symptoms (17 treatments), and global QoL (8 treatments) were measured using a
large variety of measures. The SOE for psychological/behavioral interventions was rated as low
for the outcome of anxiety symptoms. Low SOE indicates that future research will likely change
the magnitude and possibly the direction of the observed effects. Interventions involving CBT
were deemed to have low SOE for the outcomes of TSQoL, perceived loudness, anxiety,
depression global QoL suggesting that the impact of future research will likely change the
magnitude of the effect size to a lesser degree than the other interventions rated as low. Adverse
effects were largely not reported in this intervention group. Some studies reported an absence of
adverse effects, with the exception of one study where some patients reported that the self-
monitoring of the loudness and discomfort caused by their tinnitus resulted in the worsening of
those symptoms.
Key Question 3
No studies were found identifying potential prognostic factors. A significant gap in the
literature has been identified.
Population
1. Include a broader representation of adult patients with respect to age (range of middle age
to old/elderly), gender (equal proportion of men), and ethnicity (increased proportion of
non-white or non-Caucasian, or provide broader representation of ethnic groups)
2. Include patients recruited from primary care settings to incorporate a complete spectrum
of participants who have tinnitus
3. Capture detailed information about the prior treatments and ensure that future studies do
not sample only from subjects who “failed to respond” to previous treatments when
receiving new treatments
4. More adequately specify patient medical and mental health histories (i.e., medical
comorbidities and previous mental health issues)
5. Collect information on the use of other co-interventions, including psychiatric and
complementary and alternative medicine therapies that have the potential to confound
and contaminate study interventions
115
Intervention
1. Establish a clear rationale for the dose used for off-label medications
2. Measure the concomitant use of co-interventions that have the potential to confound
interventions (e.g., other pharmacological agents)
3. Specify the training and experience of the person(s) providing the interventions
4. Standards for reporting beam parameters when evaluating LLLT; this will assist in the
accurate estimation of the total energy and dose used to administer this treatment.161
Outcomes
1. Aim to encompass three principle components of tinnitus, that include: a) auditory
feature of tinnitus perception (intensity, location, masking and pitch), b) emotional
features ( distress), and c) attentional features (awareness of tinnitus in daily life).159
2. Identify primary and secondary outcomes within the studies
3. Consider the inclusion of patient-reported outcomes using scales with established
psychometric properties, including responsiveness, in the population with subjective
idiopathic tinnitus
4. Assess the validity and responsiveness (change over time) of outcome measurement
instruments (VAS) in persons with tinnitus prior to using these instruments to evaluate
the efficacy of tinnitus interventions
5. Ensure back translation of outcome measurement instruments prior to use in languages
other than the language of development.
6. Measure global quality-of-life to capture how persons value the risk-benefit trade-off
between the efficacy and adverse effects profiles of treatments under evaluation
7. Conform to the Consolidated Standards of Reporting Trials (CONSORT)163 reporting
standards for harms. As such, severe and serious events should be defined a priori and
the use of standardized instruments or terminology for reporting harms should be
adopted. Long-term followup may be required to capture harms adequately
116
Other
1. Develop or improve theoretical models about tinnitus severity and how distress is
maintained or exacerbated in these patients.
2. Promote clarity in research and facilitate critical appraisal of the literature, whether for
the benefit of a clinician who is seeking practice guidance or a systematic reviewer who
is synthesizing evidence, authors of RCT should follow the (CONSORT) Statement. This
set of guidelines encourages explicit reporting of RCT features so that readers may
understand a study’s design, conduct, and analysis
3. Continue to register study protocols in clinical trial registries to allow researchers to
evaluate the potential for publication bias and selective outcome reporting. Authors
should endeavor to regularly update the information reported within these registries.
4. Studies should be developed to evaluate the natural history and prognostic factors in
persons with subjective idiopathic tinnitus
117
References
1. 2013 ICD-10-CM Diagnosis Code H93.1. 12. Weber C, Arck P, Mazurek B, et al. Impact
2013; www.icd10data.com/ of a relaxation training on psychometric and
ICD10CM/Codes/H60-H95/H90-H94/H93- immunologic parameters in tinnitus
/H93.1. Accessed: April 11, 20013. sufferers. J Psychosom Res. 2002;52(1):29-
33. PMID:11801262
2. American Tinnitus Association. Top 10
most frequently asked questions. 13. Henry,J.A. 2011 Jul 26; Key informant
www.ata.org/for-patients/faqs. interview.
Accessed:April 11, 2013.
14. Henry JA, Zaugg TL, Myers PJ, et al. A
3. Davis A, El Rafaie A. Epidemiology of triage guide for tinnitus. J Fam Pract.
tinnitus. In: Tyler RS, editors. Epidemiology 2010;59(7):389-93. PMID:20625568
of Tinnitus, San Diego,CA: Singular
15. British Tinnitus Association. Tinnitus:
Publishing Group; 2000. 1 p. 1-24.
Guidelines for primary care.
4. Davis A, Smith P, Ferguson M, et al. www.tinnitus.org.uk/ten-top-tinnitus-tips-
Acceptability, benefit and costs of early for-gps. Accessed:April 11, 2013.
screening for hearing disability: A study of
16. Holgers K-M. Mechanisms and
potential screening tests and models. Health
classification of tinnitus: A discussion paper.
Technol Assess. 2007;11(42):iii-xii, 1-154.
Audiol Med. 2003;1(4):238-41.
PMID:17927921
17. Kroner-Herwig B, Frenzel A, Fritsche G, et
5. Press release: Two ATA Scientific Advisory
al. The management of chronic tinnitus:
Committee members receive Department of
Comparison of an outpatient cognitive-
Defense grant. www.ata.org/about-ata/news-
behavioral group training to minimal-contact
pubs/press-releases#DoDGrant.
interventions. J Psychosom Res.
Accessed:April 11, 2013.
2003;54(4):381-9. PMID:12670617
6. Holgers KM, Juul J. The suffering of
18. Weise C, Heinecke K, Rief W. Biofeedback-
tinnitus in childhood and adolescence. Int J
based behavioral treatment for chronic
Audiol. 2006;45(5):267-72.
tinnitus: Results of a randomized controlled
PMID:16717016
trial. J Consult Clin Psychol.
7. Savage J, Waddell A. Tinnitus. Clin Evid. 2008;76(6):1046-57. PMID:19045972
2012;Feb 3: PMID:22331367
19. Dobie RA. A review of randomized clinical
8. Shargorodsky J, Curhan GC, Farwell WR. trials in tinnitus. Laryngoscope.
Prevalence and characteristics of tinnitus 1999;109(8):1202-11. PMID:10443820
among US adults. Am J Med.
20. McCombe A, Baguley D, Coles R, et al.
2010;123(8):711-8. PMID:20670725
Guidelines for the grading of tinnitus
9. Zoger S, Erlandsson S, Svedlund J, et al. severity: The results of a working group
Benefits from group psychotherapy in the commissioned by the British Association of
treatment of severe refractory tinnitus. Otolaryngologists, Head and Neck
Audiol Med. 2008;6(1):62-72. Surgeons, 1999. Clin Otolaryngol Allied
Sci. 2001;26(5):388-93. PMID:11678946
10. Scott B, Lindberg P, Lyttkens L, et al.
Psychological treatment of tinnitus. Scand 21. Erlandsson S. Psychological profiles of
Audiol. 1985;14(4):223-30. tinnitus in patients. In: Tinnitus Handbook,
Tyler RS, ed. San Diego, CA: Singular
11. Brunnberg E, Linden-Bostrom M, Berglund
Publishing Group; 2000. 2 p. 25-58.
M. Tinnitus and hearing loss in 15-16-year-
old students:Mmental health symptoms, 22. Figueiredo RR, Azevedo AA, Oliveira PM.
substance use, and exposure in school. Int J Correlation analysis of the visual-analogue
Audiol. 2008;47(11):688-94. scale and the Tinnitus Handicap Inventory in
PMID:19031227 tinnitus patients. Revista Brasil
Otorrinolaringol. 2009;75(1):76-9.
PMID:19488564
118
23. Kamalski DM, Hoekstra CE, van Zanten 34. Hilton M, Stuart E. Ginkgo biloba for
BG, et al. Measuring disease-specific health- tinnitus. Cochrane Database Syst Rev.
related quality of life to evaluate treatment 2004;(2):CD003852. PMID:15106224
outcomes in tinnitus patients: A systematic
35. Teggi R, Bellini C, Piccioni LO, et al.
review. Otolaryngol Head Neck Surg.
Transmeatal low-level laser therapy for
2010;143(2):181-5.
chronic tinnitus with cochlear dysfunction.
24. Lipsey MW. Design sensitivity: Statistical Audiol Neuro Otol. 2009;14(2):115-20.
power for experimental research. Newburry PMID:18843180
Park, CA: Sage Publications, Inc.; 1990.
36. Tuz HH, Onder EM, Kisnisci RS.
25. Kazdin AE. Research design in clinical Prevalence of otologic complaints in patients
psychology. 4th. Needham Heights, MA: with temporomandibular disorder. Am J
Allyn & Bacon; 2003. Orthod Dentofacial Orthop.
2003;123(6):620-3. PMID:12806339
26. Meikle M, Henry JA, Griest S, et al. The
Tinnitus Functional Index: Development of 37. Wright EF, Syms CA, III, Bifano SL.
a new clinical measure for chronic, intrusive Tinnitus, dizziness, and nonotologic otalgia
tinnitus. Ear Hear. 2012;33(2):153-76. improvement through temporomandibular
PMID: 22156949 disorder therapy. Milit Med.
2000;165(10):733-6. PMID:11050868
27. Baldo P, Doree C, Lazzarini R, et al.
Antidepressants for patients with tinnitus. 38. Ash CM, Pinto OF. The TMJ and the middle
Cochrane Database Syst Rev. ear: Structural and functional correlates for
2006;(4):CD003853. PMID:17054188 aural symptoms associated with
temporomandibular joint dysfunction. Int J
28. Johnson RM, Brummett R, Schleuning A.
Prosthodont. 1991;4(1):51-7.
Use of alprazolam for relief of tinnitus. A
PMID:2012671
double-blind study. Arch Otolaryngol Head
Neck Surg. 1993;119(8):842-5. 39. Langguth B, Hajak G, Kleinjung T, et al.
PMID:8343245 Repetitive transcranial magnetic stimulation
and chronic tinnitus. Acta Otolaryngol
29. Jalali MM, Kousha A, Naghavi SE, et al.
Suppl. 2006;(556):102-5. PMID:17114153
The effects of alprazolam on tinnitus: A
cross-over randomized clinical trial. Med 40. Henry JA, Dennis KC, Schechter MA.
Sci Mon. 2009;15(11):I55-I60 General review of tinnitus: Prevalence,
PMID:19865063 mechanisms, effects, and management. J
Speech Lang Hear Res. 2005;48(5):1204-35.
30. Kalcioglu MT, Bayindir T, Erdem T, et al.
PMID:16411806
Objective evaluation of the effects of
intravenous lidocaine on tinnitus. Hear Res. 41. Bennett M, Kertesz T, Yeung P. Hyperbaric
2005;199(1-2):81-8. PMID:15574302 oxygen therapy for idiopathic sudden
sensorineural hearing loss and tinnitus: A
31. Agarwal L, Pothier DD. Vasodilators and
systematic review of randomized controlled
vasoactive substances for idiopathic sudden
trials. J Laryngol Otol. 2005;119(10):791-8.
sensorineural hearing loss. Cochrane
PMID:16259656
Database Syst Rev. 2009;(4):CD003422.
PMID:19821308 42. Keate, B. Diet and tinnitus: What to eat …
and what not to eat. Tinnitus Library.
32. Noble W. Treatments for tinnitus. Trends
www.tinnitusformula.com/infocenter/article
Amplification. 2008;12(3):236-41.
s/treatments/diet.aspx. Accessed: April 11,
PMID:18635586
2013.
33. Sziklai I, Szilvassy J, Szilvassy Z. Tinnitus
43. New Tinnitus Treatments Blog. Tinnitus and
control by dopamine agonist pramipexole in
your diet. www.tinnitustreatments.org/
presbycusis patients: A randomized,
tinnitus-and-your-diet.html. Accessed:April
placebo-controlled, double-blind study.
11, 2013.
Laryngoscope. 2011;121(4):888-93.
PMID:21433025
119
44. Tinnitus Remedies Web Site. Tinnitus relief 54. Langguth B, Kleinjung T, Landgrebe M.
through diet - Foods to avoid to relieve Tinnitus: The complexity of standardization.
tinnitus. www.thetinnitussite.info/tinnitus- Eval Health Prof. 2011;34(4):429-33.
relief-2/tinnitus-relief-through-diet-foods-to- PMID:21224265
avoid-to-relieve-tinnitus. Accessed:April 11,
55. Martinez-Devesa P, Perera R, Theodoulou
2013.
M, et al. Cognitive behavioural therapy for
45. National Center for Complementary and tinnitus. Cochrane Database Syst Rev.
Alternative Medicine (NCCAM). What is 2010;(9):CD005233. PMID:20824844
Complementary and Alternative Medicine?
56. Department of Health. Provision of services
www.nccam.nih.gov/health/whatiscam.
for adults with tinnitus: A good practice
Accessed:April 11, 2013.
guide. London: Central Office of
46. Henry JA, Zaugg TL, Myers PJ, et al. Information; 2009.
Progressive audiologic tinnitus management.
57. Andersson G, Stromgren T, Strom L, et al.
ASHA Leader. 2008;13(8):14-7.
Randomized controlled trial of internet-
www.asha.org/Publications/leader/2008/080
based cognitive behavior therapy for distress
617/f080617b.htm
associated with tinnitus. Psychosom Med.
47. Punte AK, Vermeire K, Hofkens A, et al. 2002;64(5):810-6. PMID:12271112
Cochlear implantation as a durable tinnitus
58. Hesser H, Weise C, Westin VZ, et al. A
treatment in single-sided deafness. Cochlear
systematic review and meta-analysis of
Implants International. 2011;12(Suppl
randomized controlled trials of cognitive-
1):S26-S29 PMID:21756468
behavioral therapy for tinnitus distress.
48. Amoodi HA, Mick PT, Shipp DB, et al. The Clinical Psychology Review.
effects of unilateral cochlear implantation on 2011;31(4):545-53. PMID:21237544
the tinnitus handicap inventory and the
59. Phillips JS, McFerran D. Tinnitus Retraining
influence on quality of life. Laryngoscope.
Therapy (TRT) for tinnitus. Cochrane
2011;121(7):1536-40. PMID:21647911
Database Syst Rev. 2010;(3):CD007330.
49. Arts RA, George EL, Stokroos RJ, et al. PMID:20238353
Review: Cochlear implants as a treatment of
60. Jastreboff PJ, Hazell JW. A
tinnitus in single-sided deafness. Curr Opin
neurophysiological approach to tinnitus:
Otolaryngol Head Neck Surg.
Clinical implications. Br J Audiol.
2012;20(5):398-403. PMID:22931903
1993;27(1):7-17. PMID:8339063
50. Hobson J, Chisholm E, El RA. Sound
61. Parazzini M, Del Bo L, Jastreboff M, et al.
therapy (masking) in the management of
Open ear hearing aids in tinnitus therapy: An
tinnitus in adults. Cochrane Database Syst
efficacy comparison with sound generators.
Rev. 2010;12:CD006371. PMID:21154366
Int J Audiol. 2011;50(8):548-53.
51. CIGNA medical coverage policy No. 0220.
62. Ireland CE, Wilson PH, Tonkin JP, et al. An
Tinnitus treatment services and devices.
evaluation of relaxation training in the
www.cigna.com/assets/docs/health-care-
treatment of tinnitus. Behav Res Ther.
professionals/coverage_positions/mm_0220
1985;23(4):423-30. PMID:3896227
_coveragepositioncriteria_tinnitus_instr_dev
ices_retraining_ther.pdf. Accessed:April 11, 63. Henry JA, Zaugg TL, Myers PJ, et al. The
2013. role of audiologic evaluation in progressive
audiologic tinnitus management. Trends
52. Davis PB, Wilde RA, Steed LG, et al.
Amplification. 2008;12(3):170-87.
Treatment of tinnitus with a customized
PMID:18628281
acoustic neural stimulus: A controlled
clinical study. Ear Nose Throat J. 64. Cima RF, Maes IH, Joore MA, et al.
2008;87(6):330-9. PMID:18561116 Specialised treatment based on cognitive
behaviour therapy versus usual care for
53. Davis PB, Paki B, Hanley PJ. Neuromonics
tinnitus: A randomised controlled trial.
tinnitus treatment: Third clinical trial. Ear
Lancet. 2012;379(9830):1951-9.
Hear. 2007;28(2):242-59. PMID:17496674
PMID:22633033
120
65. Humphrey C, Herbst KG, Faurqi S. Some 75. Guyatt GH, Oxman AD, Kunz R, et al.
characteristics of the hearing-impaired GRADE guidelines: 7. Rating the quality of
elderly who do not present themselves for evidence--inconsistency. J Clin Epidemiol.
rehabilitation. Br J Audiol. 1981;15(1):25- 2011;64(12):1294-302. PMID:21803546
30. PMID:7214067
76. Owens DK, Lohr KN, Atkins D, et al.
66. Searchfield G. A commentary on the AHRQ series paper 5: Grading the strength
complexity of tinnitus management: Clinical of a body of evidence when comparing
guidelines provide a path through the fog. medical interventions--Agency for
Eval Health Prof. 2011;34(4):421-8. Healthcare Research and Quality and the
PMID:21224266 Effective Health-care program. J Clin
Epidemiol. 2010;63(5):513-23.
67. Hoare DJ, Gander PE, Collins L, et al.
PMID:19595577
Management of tinnitus in English NHS
audiology departments: An evaluation of 77. Grading the strength of a body of evidence
current practice. J Eval Clin Pract. when assessing health care interventions: An
2010;18(2):326-34. PMID:21087449 update [Draft]. Rockville, MD: Agency for
Healthcare Research and Quality; 2012.
68. Henry JA, Schechter MA, Loovis CL, et al.
Clinical management of tinnitus using a 78. Hayden JA, Cote P, Bombardier C.
“progressive intervention” approach. J Evaluation of the quality of prognosis
Rehabil Res Dev. 2005;42(4:Suppl 2):95- studies in systematic reviews. Ann Intern
116. PMID:16470467 Med. 2006;144(6):427-37. PMID:16549855
69. Juni P, Holenstein F, Sterne J, et al. 79. Guyatt GH, Oxman AD, Montori V, et al.
Direction and impact of language bias in GRADE guidelines: 5. Rating the quality of
meta-analyses of controlled trials: Empirical evidence--publication bias. J Clin
study. Int J Epidemiol. 2002;31(1):115-23. Epidemiol. 2011;64(12):1277-82.
PMID:21802904
70. Moher D, Pham B, Klassen T, et al. What
contributions do languages other than 80. Moher D, Liberati A, Tetzlaff J, et al.
English make on the results of meta- Preferred reporting items for systematic
analysis? J Clin Epidemiol. 2000;53(9):964- reviews and meta-analyses: The PRISMA
72. statement. Ann Intern Med.
2009;151(4):264-9, W64. PMID:19622511
71. Agency for Healthcare Research and
Quality. Methods guide for effectiveness 81. Abbott JA, Kaldo V, Klein B, et al. A cluster
and comparative effectiveness reviews. randomised trial of an internet-based
Rockville, MD: Agency for Healthcare intervention program for tinnitus distress in
Research and Quality; 2011. an industrial setting. Cognit Behav Ther.
2009;38(3):162-73. PMID:19675959
72. Wells, G. A., Shea, B., O’Connell, D. et al.
The Newcastle-Ottawa Scale (NOS) for 82. Azevedo AA, Figueiredo RR. Tinnitus
assessing the quality of nonrandomised treatment with acamprosate: Double-blind
studies in meta-analyses. study. Revista Brasil Otorrinolaringol.
www.ohri.ca/programs/clinical_epidemiolog 2005;71(5):618-23. PMID:16612523
y/oxford.asp. Accessed:April 11, 2013.
83. Anders M, Dvorakova J, Rathova L, et al.
73. Jadad AR, Moore RA, Carroll D, et al. Efficacy of repetitive transcranial magnetic
Assessing the quality of reports of stimulation for the treatment of refractory
randomized clinical trials: Is blinding chronic tinnitus: A randomized, placebo
necessary? Control Clin Trials. controlled study. Neuroendocrinol Lett.
1996;17(1):1-12. PMID:8721797 2010;31(2):238-49. PMID:20424590
74. Atkins D, Chang S, Gartlehner G, et al. 84. Andersson G, Porsaeus D, Wiklund M, et al.
Assessing applicability when comparing Treatment of tinnitus in the elderly: A
medical interventions: AHRQ and the controlled trial of cognitive behavior
Effective Health Care Program. J Clin therapy. Int J Audiol. 2005;44(11):671-5.
Epidemiol. 2011;64(11):1198-207. PMID:16379495
121
85. Aoki M, Wakaoka Y, Hayashi H, et al. 95. Henry JL, Wilson PH. The psychological
Effect of lyophilized powder made from management of tinnitus: Comparison of a
enzymolyzed honeybee larvae on tinnitus- combined cognitive educational program,
related symptoms, hearing levels, and education alone and a waiting list control.
hypothalamus-pituitary-adrenal axis-related Int Tinnitus J. 1996;2:9-20.
hormones. Ear Hear. 2012;33(3):430-6.
96. Henry JL, Wilson PH. An evaluation of two
PMID:21971082
types of cognitive intervention in the
86. Arda HN, Tuncel U, Akdogan O, et al. The management of chronic tinnitus. Scand J
role of zinc in the treatment of tinnitus. Otol Behav Ther. 1998;27(4):156-66.
Neurotol. 2003;24(1):86-9. PMID:12544035
97. Henry JA, Loovis C, Montero M, et al.
87. Biesinger E, Kipman U, Schatz S, et al. Randomized clinical trial: Group counseling
Qigong for the treatment of tinnitus: A based on tinnitus retraining therapy. J
prospective randomized controlled study. J Rehabil Res Dev. 2007;44(1):21-32.
Psychosom Res. 2010;69(3):299-304. PMID:17551855
PMID:20708452
98. Hiller W, Haerkotter C. Does sound
88. Chung HK, Tsai CH, Lin YC, et al. stimulation have additive effects on
Effectiveness of theta-burst repetitive cognitive-behavioral treatment of chronic
transcranial magnetic stimulation for tinnitus? Behav Res Ther. 2005;43(5):595-
treating chronic tinnitus. Audiol Neuro Otol. 612. PMID:15865915
2012;17(2):112-20. PMID:21865723
99. Holgers K-M, Zoger S, Svedlund J. The
89. Cuda D, De CA. Effectiveness of combined impact of sertraline on health-related quality
counseling and low-level laser stimulation in of life in severe refractory tinnitus: A
the treatment of disturbing chronic tinnitus. double-blind, randomized, placebo-
Int Tinnitus J. 2008;14(2):175-80. controlled study. Audiol Med. 2011;9(2):67-
PMID:19205171 72.
90. Dib GC, Kasse CA, Alves de AT, et al. 100. Kaldo V, Cars S, Rahnert M, et al. Use of a
Tinnitus treatment with Trazodone. Revista self-help book with weekly therapist contact
Brasil Otorrinolaringol. 2007;73(3):390-7. to reduce tinnitus distress: A randomized
PMID:17684661 controlled trial. J Psychosom Res.
2007;63(2):195-202. PMID:17662757
91. Dineen R, Doyle J, Bench J. Managing
tinnitus: A comparison of different 101. Kaldo V, Levin S, Widarsson J, et al.
approaches to tinnitus management training. Internet versus group cognitive-behavioral
Br J Audiol. 1997;31(5):331-44. treatment of distress associated with tinnitus:
PMID:9373742 A randomized controlled trial. Behav Ther.
2008;39(4):348-59. PMID:19027431
92. Dineen R, Doyle J, Bench J, et al. The
influence of training on tinnitus perception: 102. Kroner-Herwig B, Hebing G, van Rijn-
An evaluation 12 months after tinnitus Kalkmann U, et al. The management of
management training. Br J Audiol. chronic tinnitus--Comparison of a cognitive-
1999;33(1):29-51. PMID:10219721 behavioural group training with yoga. J
Psychosom Res. 1995;39(2):153-65.
93. Drew S, Davies E. Effectiveness of Ginkgo
PMID:7595873
biloba in treating tinnitus: Double blind,
placebo controlled trial. BMJ. 103. Langguth B, Kleinjung T, Frank E, et al.
2001;322(7278):73 PMID:11154618 High-frequency priming stimulation does
not enhance the effect of low-frequency
94. Ghossaini SN, Spitzer JB, Mackins CC, et
rTMS in the treatment of tinnitus. Exp Brain
al. High-frequency pulsed electromagnetic
Res. 2008;184(4):587-91. PMID:18066684
energy in tinnitus treatment. Laryngoscope.
2004;114(3):495-500. PMID:15091224 104. Malouff JM, Noble W, Schutte NS, et al.
The effectiveness of bibliotherapy in
alleviating tinnitus-related distress. J
Psychosom Res. 2010;68(3):245-51.
PMID:20159209
122
105. Marcondes RA, Sanchez TG, Kii MA, et al. 115. Sullivan M, Katon W, Russo J, et al. A
Repetitive transcranial magnetic stimulation randomized trial of nortriptyline for severe
improve tinnitus in normal hearing patients: chronic tinnitus. Effects on depression,
A double-blind controlled, clinical and disability, and tinnitus symptoms. Arch
neuroimaging outcome study. Eur J Neurol. Intern Med. 1993;153(19):2251-9.
2010;17(1):38-44. PMID:19614962 PMID:8215728
106. Mazurek B, Haupt H, Szczepek AJ, et al. 116. Tass PA, Adamchic I, Freund H-J, et al.
Evaluation of vardenafil for the treatment of Counteracting tinnitus by acoustic
subjective tinnitus: A controlled pilot study. coordinated reset neuromodulation. Restor
J Negative Results Biomed. 2009;8:3. Neurol Neurosci. 2012;30(2):137-59.
PMID:19222841
117. Topak M, Sahin-Yilmaz A, Ozdoganoglu T,
107. Meeus O, De RD, Van de Heyning P. et al. Intratympanic methylprednisolone
Administration of the combination injections for subjective tinnitus. J Laryngol
clonazepam-Deanxit as treatment for Otol. 2009;123(11):1221-5.
tinnitus. Otol Neurotol. 2011;32(4):701-9. PMID:19640315
PMID:21358561
118. Vilholm OJ, Moller K, Jorgensen K. Effect
108. Mirz F, Zachariae R, Andersen SE, et al. of traditional Chinese acupuncture on severe
The low-power laser in the treatment of tinnitus: A double-blind, placebo-controlled,
tinnitus. Clin Otolaryngol Allied Sci. clinical investigation with open therapeutic
1999;24(4):346-54. PMID:10472473 control. Br J Audiol. 1998;32(3):197-204.
PMID:9710337
109. Piccirillo JF, Finnell J, Vlahiotis A, et al.
Relief of idiopathic subjective tinnitus: Is 119. Westerberg BD, Roberson JB, Jr., Stach BA.
gabapentin effective? Arch Otolaryngol A double-blind placebo-controlled trial of
Head Neck Surg. 2007;133(4):390-7. baclofen in the treatment of tinnitus. Am J
PMID:17438255 Otol. 1996;17(6):896-903. PMID:8915419
110. Plewnia C, Vonthein R, Wasserka B, et al. 120. Westin VZ, Schulin M, Hesser H, et al.
Treatment of chronic tinnitus with theta Acceptance and commitment therapy versus
burst stimulation: A randomized controlled tinnitus retraining therapy in the treatment of
trial. Neurology. 2012;78(21):1628-34. tinnitus: A randomised controlled trial.
PMID:22539568 Behav Res Ther. 2011;49(11):737-47.
PMID:21864830
111. Rejali D, Sivakumar A, Balaji N. Ginkgo
biloba does not benefit patients with 121. Zachriat C, Kroner-Herwig B. Treating
tinnitus: A randomized placebo-controlled chronic tinnitus: Comparison of cognitive-
double-blind trial and meta-analysis of behavioural and habituation-based
randomized trials. Clin Otolaryngol Allied treatments. Cognit Behav Ther.
Sci. 2004;29(3):226-31. PMID:15142066 2004;33(4):187-98. PMID:15625793
112. Rief W, Weise C, Kley N, et al. 122. Zoger S, Svedlund J, Holgers KM. The
Psychophysiologic treatment of chronic effects of sertraline on severe tinnitus
tinnitus: A randomized clinical trial. suffering—A randomized, double-blind,
Psychosom Med. 2005;67(5):833-8. placebo-controlled study. J Clin
PMID:16204446 Psychopharmacol. 2006;26(1):32-9.
PMID:16415703
113. Robinson SK, Viirre ES, Bailey KA, et al.
Randomized placebo-controlled trial of a 123. Neri G, De SA, Baffa C, et al. Treatment of
selective serotonin reuptake inhibitor in the central and sensorineural tinnitus with orally
treatment of nondepressed tinnitus subjects. administered Melatonin and Sulodexide:
Psychosom Med. 2005;67(6):981-8. Personal experience from a randomized
PMID:16314604 controlled study. Acta Otorhinolaryngol Ital.
2009;29(2):86-91. PMID:20111618
114. Sharma DK, Kaur S, Singh J, et al. Role of
acamprosate in sensorineural tinnitus. Indian
J Pharmacol. 2012;44(1):93-6.
123
124. Figueiredo RR, Langguth B, Mello de OP, et 134. Mason JD, Rogerson DR, Butler JD. Client
al. Tinnitus treatment with memantine. centred hypnotherapy in the management of
Otolaryngol Head Neck Surg. tinnitus—Is it better than counselling? J
2008;138(4):492-6. PMID:18359360 Laryngol Otol. 1996;110(2):117-20.
PMID:8729491
125. Akkuzu B, Yilmaz I, Cakmak O, et al.
Efficacy of misoprostol in the treatment of 135. Pandey S, Mahato NK, Navale R. Role of
tinnitus in patients with diabetes and/or self-induced sound therapy: Bhramari
hypertension. Auris Nasus Larynx. Pranayama in Tinnitus. Audiol Med.
2004;31(3):226-32. PMID:15364356 2010;8(3):137-41.
126. Bayar N, Boke B, Turan E, et al. Efficacy of 136. Erlandsson SI, Rubinstein B, Carlsson SG.
amitriptyline in the treatment of subjective Tinnitus: Evaluation of biofeedback and
tinnitus. J Otolaryngol. 2001;30(5):300-3. stomatognathic treatment. Br J Audiol.
PMID:11771024 1991;25(3):151-61. PMID:1873582
127. Dobie RA, Sakai CS, Sullivan MD, et al. 137. Bonaconsa A, Mazzoli MM, Antonia M, et
Antidepressant treatment of tinnitus patients: al. Posturography measures and efficacy of
Report of a randomized clinical trial and different physical treatments in somatic
clinical prediction of benefit. Am J Otol. tinnitus. Int Tinnitus J. 2010;16(1):44-50.
1993;14(1):18-23. PMID:8424470 PMID:21609913
128. Suckfüll M, Althaus M, Ellers-Lenz B, et al. 138. Neri G, Baffa C, De SA, et al. Management
A randomized, double-blind, placebo- of tinnitus: Oral treatment with melatonin
controlled clinical trial to evaluate the and sulodexide. Journal of Biological
efficacy and safety of neramexane in Regulators & Homeostatic Agents.
patients with moderate to severe subjective 2009;23(2):103-10. PMID:19589291
tinnitus. BMC Ear Nose Throat Disord.
139. Lindberg P, Scott B, Melin L, et al. The
2011;11(1):1.
psychological treatment of tinnitus: An
129. Dehkordi MA, Abolbashari S, Taheri R, et experimental evaluation. Behav Res Ther.
al. Efficacy of gabapentin on subjective 1989;27(6):593-603. PMID:2692553
idiopathic tinnitus: A randomized, double-
140. Gungor A, Dogru S, Cincik H, et al.
blind, placebo-controlled trial. Ear Nose
Effectiveness of transmeatal low power laser
Throat J. 2011;90(4):150-8.
irradiation for chronic tinnitus. J Laryngol
130. Jakes SC, Hallam RS, McKenna L, et al. Otol. 2008;122(5):447-51. PMID:17625032
Group cognitive therapy for medical
141. Roland NJ, Hughes JB, Daley MB, et al.
patients: An application to tinnitus. Cognit
Electromagnetic stimulation as a treatment
Ther Res. 1992;16(1):67-82.
of tinnitus: A pilot study. Clin Otolaryngol
131. Herraiz C, Diges I, Cobo P, et al. Auditory Allied Sci. 1993;18(4):278-81.
discrimination training for tinnitus PMID:8877185
treatment: The effect of different paradigms.
142. Khedr EM, Rothwell JC, Ahmed MA, et al.
Eur Arch Otorhinolaryngol.
Effect of daily repetitive transcranial
2010;267(7):1067-74. PMID:20044759
magnetic stimulation for treatment of
132. Olzowy B, Canis M, Hempel JM, et al. tinnitus: Comparison of different stimulus
Effect of atorvastatin on progression of frequencies. J Neurol Neurosurg Psychiatry.
sensorineural hearing loss and tinnitus in the 2008;79(2):212-5. PMID:18202212
elderly: Results of a prospective,
143. Podoshin L, Ben-David Y, Fradis M, et al.
randomized, double-blind clinical trial. Otol
Idiopathic subjective tinnitus treated by
Neurotol. 2007;28(4):455-8.
biofeedback, acupuncture and drug therapy.
PMID:17529847
Ear Nose Throat J. 1991;70(5):284-9.
133. Searchfield GD, Kaur M, Martin WH. PMID:1914952
Hearing aids as an adjunct to counseling:
Tinnitus patients who choose amplification
do better than those that don’t. Int J Audiol.
2010;49(8):574-9. PMID:20500032
124
144. Muehlmeier G, Biesinger E, Maier H. Safety 155. Hoekstra CE, Rynja SP, van Zanten GA, et
of intratympanic injection of AM-101 in al. Anticonvulsants for tinnitus. Cochrane
patients with acute inner ear tinnitus. Audiol Database Syst Rev. 2011;(7):CD007960.
Neuro Otol. 2011;16(6):388-97. PMID:21735419
PMID:21252501
156. Karkos PD, Leong SC, Arya AK, et al.
145. Loke YK, Price D, Herxheimer A. ‘Complementary ENT’: A systematic review
Systematic reviews of adverse effects: of commonly used supplements. J Laryngol
Framework for a structured approach. BMC Otol. 2007;121(8):779-82. PMID:17125579
Med Res Methodol. 2007;7:32.
157. Hilton M, Malcolm P, Stuart, et al. Ginkgo
PMID:17615054
biloba for tinnitus. Cochrane Database Syst
146. Montori VM, Guyatt GH. Intention-to-treat Rev. 2010;(3):CD003852.
principle. CMAJ. 2001;165(10):1339-41.
158. Baldo P, Doree C, Molin P, et al.
PMID:11760981
Antidepressants for patients with tinnitus.
147. Klockhoff I, Lindblom U. Meniere’s disease Cochrane Database Syst Rev.
and hydrochlorothiazide (Dichlotride)--A 2009;(1):CD003853.
critical analysis of symptoms and
159. Landgrebe M, Azevedo A, Baguley D, et al.
therapeutic effects. Acta Otolaryngol.
Methodological aspects of clinical trials in
1967;63(4):347-65. PMID:6033658
tinnitus: A proposal for an international
148. Geyh S, Cieza A, Schouten J, et al. ICF Core standard. J Psychosom Res. 2012;73(2):112-
Sets for stroke. J Rehabil Med. 2004;(44 21. PMID:22789414
Suppl):135-41. PMID:15370761
160. Hesser H. Methodological considerations in
149. Meng Z, Liu S, Zheng Y, et al. Repetitive treatment evaluations of tinnitus distress: a
transcranial magnetic stimulation for call for guidelines. J Psychosom Res.
tinnitus. Cochrane Database Syst Rev. 2010;69(3):305-7. PMID:20708453
2011;(10):CD007946 PMID:21975776
161. Jenkins PA, Carroll JD. How to report low-
150. Hoare DJ, Kowalkowski VL, Kang S, et al. level laser therapy (LLLT)/photomedicine
Systematic review and meta-analyses of dose and beam parameters in clinical and
randomized controlled trials examining laboratory studies. Photomed Laser Surg.
tinnitus management. Laryngoscope. 2011;29(12):785-7. PMID:22107486
2011;121(7):1555-64. PMID:21671234
162. Hesser H, Weise C, Rief W, et al. The effect
151. Hesser H, Gustafsson T, Lunden C, et al. A of waiting: A meta-analysis of wait-list
randomized controlled trial of Internet- control groups in trials for tinnitus distress. J
delivered cognitive behavior therapy and Psychosom Res. 2011;70(4):378-84.
acceptance and commitment therapy in the PMID:21414459
treatment of tinnitus. J Consult Clin Psychol.
163. Ioannidis JPA, Evans SJW, Gotzsche PC, et
2012;80(4):649-61. PMID:22250855
al. Better reporting of harms in randomized
152. Philippot P, Nef F, Clauw L, et al. A trials: An extension of the CONSORT
randomized controlled trial of mindfulness- statement. Ann Intern Med.
based cognitive therapy for treating tinnitus. 2004;141(10):781-8. PMID:15545678
Clin Psychol Psychother. 2012;19(5):411-9.
PMID:21567655
153. Kochkin S, Tyler R, Born J. MarkeTrak
VIII: The prevalence of tinnitus in the
United States and the self-reported efficacy
of various treatments. Hear Rev.
2011;18(12):10-27.
154. Nondahl DM, Cruickshanks KJ, Huang GH,
et al. Generational differences in the
reporting of tinnitus. Ear Hear.
2012;33(5):640-4. PMID:22588269
125
Appendix A. Search Strategy
Search Strategy: Tinnitus
Medline-OVID
1946-June 13 2012
1. Tinnitus/ or tinnitus.ti.
2. animals/ not humans/
3. 1 not 2
4. limit 3 to english language
5. limit 4 to (case reports or comment or editorial or in vitro or interview or letter or newspaper
article or webcasts)
7. 4 not 5
Embase-OVID
1980-June 13 2012
1. Tinnitus/ or tinnitus.ti.
2. limit 1 to english language
3. limit 2 to (book or book series or conference abstract or conference paper or editorial or letter
or note)
4. 2 not 3
5. limit 4 to human
PsycINFO-OVID
1967-June 13 2012
1. Tinnitus/ or tinnitus.ti.
2. animals/ not humans/
3. 1 not 2
4. limit 3 to english language
5. limit 4 to (abstract collection or chapter or “column/opinion” or “comment/reply” or
dissertation or editorial or encyclopedia entry or letter or obituary or poetry or review-book or
review-media or review-software & other)
6. 4 not 5
AMED-OVID
1985-June 13 2012
1. Tinnitus/ or tinnitus.ti.
2. animals/ not humans/
3. 1 not 2
4. limit 3 to english language
A-1
Appendix B. Data Extraction Forms
Title & Abstract Screening Form—Level 1
1. This article was published prior to 1970.
o Yes (submit for now)
o No/unsure
2. Is this an animal research study? (hint)
o Yes (stop)
o No/Unclear
3. What is the age group of the research participants? (hint)
o Under 18 years (stop)
o 18 years of age or older/Unclear
4. Is the research limited to a focus on pulsatile tinnitus only? (hint)
o Yes (stop)
o No/Unclear
5. Does the research address any of the following:
a) Tinnitus symptoms [please see (hint) below]
b) Tinnitus diagnosis; or diagnostic instruments/tests
c) Tinnitus treatments/interventions (hint)
o Yes/Unclear
o No (stop)
6. What is the research study design? (hint)
o Randomized control trial, clinical control trial, other randomized trial
o Observational study (cohort, case-control, prospective, retrospective, longitudinal,
cross sectional, case series)
o Systematic review or meta-analysis
o Narrative or descriptive review or book chapter (stop)
o Case study (stop)
o Unclear
7. Is the publication in English?
o Yes/Unclear
o No
B-1
Title & Abstract Level 1 Screening Form Help Sheet
Yes [stop] -- i.e., the research participants are not human, implication of findings are not sufficient to retain citation
in our search. If yes, submit this form now.
No/Unclear
Yes [stop] -- please note: Pulsatile Tinnitus may be referred to as “PT” or “objective tinnitus”. Pulsatile tinnitus can
be heard by a doctor using a stethoscope (like a pulse), an audible sound emanates from the patient’s ears. The
sound may have an identified cause.
No/Unclear
a) Tinnitus symptoms
c) Tinnitus treatments/interventions
a) Symptoms – ringing, buzzing in the ears, qualification of the sound perceived (e.g., pitch, volume)
b) Diagnosis, diagnostic instruments/tests – i.e., evaluation of the perception of sound, source of sound,
and/or impact on patient’s daily life (e.g., physical exam, questionnaires, hearing test, CT scan, MRI)
c) Treatments/interventions – i.e., medical/surgical (e.g., Pharmacological, Laser, TMJ and
Complementary/Alternative Medicine therapies or treatments), technological (e.g., sound maskers, hearing
aids, etc.), psychological (e.g., Tinnitus Retraining therapy, Cognitive Behavioral Therapy, etc.); alternative
medicine; or combinations thereof
No [stop] -- None of the above are addressed or Tinnitus is a result of another pathology (e.g., a symptom or
outcome of another illness/disease/drug, i.e., brain tumor, hypertension, drug side effect/interaction). If so, submit this
form now
RCT or CCT (Randomized control trial, clinical control trial, other research that has been randomized)
B-2
Randomized Controlled Trial RCT: A controlled clinical trial that randomly (by chance) assigns participants to one of
two or more groups. There are various methods to randomize study participants to their groups. Identifying words: –
randomization; Open trials; Single blind trials; Double blind trials; Triple and quadruple-blind trials; explanatory trial.
Example: An example is a randomized controlled trial (RCT) to understand whether calcium tablets work to prevent
broken bones in women with low bone density. Women with low bone density are randomly assigned to one of two
groups. One group receives calcium and the control group receives a placebo (inactive substance). The number of
women who suffer fractures in each group are compared to find out whether calcium works. Controlled Clinical Trial
CCT: A type of clinical trial comparing the effectiveness of one medication or treatment with the effectiveness of
another medication or treatment. In many controlled trials, the other treatment is a placebo (inactive substance) and
is considered the “control”. Example: An example of a controlled clinical trial is one in which people who took a
particular anti-depressive drug were compared with people who did not take the drug to determine its effectiveness in
lowering blood pressure.
Observational study (cohort, case-control, case-series)
Cohort Study: A clinical research study in which people who presently have a certain condition or receive a particular
treatment are followed over time and compared with another group of people who are not affected by the condition.
Example: For example, a study that measures effects of tinnitus on quality of life in the same group of men and
women with different blood pressure levels over a long period of time.
Case-control study (also called a retrospective study): A study that compares two groups of people: those with the
disease or condition under study (tinnitus) and a very similar group of people who do not have the disease or
condition. Researchers study the medical and lifestyle histories of the people in each group to learn what factors may
be associated with the disease or condition. For example, in the case of tinnitus, they may look at environmental
noise influences, current drugs being taken, etc.
Case Series (also known as a clinical series): a medical research observational study that tracks patients with a
known exposure given similar treatment or examines their medical records for exposure and outcome. (Example: 100
patients with tinnitus using a masking device – impact of tinnitus is measured prior to use of device and after; or 100
active-duty soldiers exposed to noise with outcome of tinnitus treated with….). It can be retrospective or prospective
and usually involves a smaller number of patients than more powerful case-control studies or randomized controlled
trials. Case series may be consecutive or non-consecutive, depending on whether all cases presenting to the
reporting authors over a period of time were included, or only a selection. Case series studies do not make
comparisons between groups.
Systematic Review: A summary of the clinical literature. A systematic review is a critical assessment and evaluation
of all research studies that address a particular clinical issue. The researchers use an organized method of locating,
assembling, and evaluating a body of literature on a particular topic using a set of specific criteria. A systematic
review typically includes a description of the findings of the collection of research studies. The systematic review may
also include a quantitative pooling of data, called a meta-analysis. Example: Scientists collect all the published
studies that compare types of treatment for hypertension. They compile the results of these studies, using in-depth
statistical methods (a comparative effectiveness review which is a type of systematic review.)
Case Study Like a case series, but focused only a single case. WE ARE NOT INTERESTED IN SINGLE CASE
STUDIES
Unclear – another type of design is mentioned or the citation does not discuss research design
B-3
Title & Abstract Screening Form—Level 2
1. Do any of the following apply to this abstract? If you check any, you are finished
and can submit.
o This is not a tinnitus study (stop)
o Publication date is prior to 1970 (stop)
o Language other than English (specify and stop)
o Editorial, comment, conference abstract, letter, opinion piece (stop)
o Animal study (stop)
o Population under 18-years (stop)
o Case study (n=1) (stop)
o Case series (stop)
o Narrative or literature review, dissertations, abstract, or study protocol
o Systematic review
o Meta-analysis (stop)
2. Please consider the following carefully. If you check any, you are finished and can
submit this form now.
o Tinnitus symptoms are the side-effect of a drug (ototoxicity)
o The research is focused on another problem/pathology. There are no results
related to tinnitus
o The Research focuses on the pathophysiology of tinnitus (see help sheet for
examples)
o Tinnitus is the symptom of a vestibular schwannoma or acoustic neuroma; and/or
is of a pulsatile nature only
3. The study design includes a comparison/control group (i.e., compares treatment to
placebo; treatment to no treatment; a group being treated to a group on a wait list
for treatment; one treatment to another treatment, with controls)
o Yes/Unclear (continue)
o No (stop)
Note: The following questions will determine the Key Question(s) this study will be assigned
consult review sheet and consider carefully. Check ‘yes’ to all that apply.
B-4
6. This study addresses one or more potential predictors of treatment outcomes. This
could be characteristics, symptom characteristics, or prognostic factors. Consult
review sheet for examples.
o Yes
7. This study is about adults at risk for tinnitus.
o Yes [identify at risk group] __________________
8. It is unclear from the abstract if #4, #5, #6, or #7 apply.
o Yes
o No abstract available
B-5
Question 6: Predictors of treatment outcomes
Prognostic Length of time to treatment after onset, audiological factors (degree and type of hearing loss,
Factors: hyperacusis, loudness tolerance, masking criteria, etc.), head injury, anxiety, mental health
disorders, duration of tinnitus
Patient Age, gender, race, medical or mental health comorbidities, socioeconomic factors, noise
Characteristics exposure (environmental, recreational and work-related, including active military duty
personnel or veterans, and occupational hazards), involvement in litigation, third party
coverage (health insurance)
Symptom Origin/presumed etiology of tinnitus, tinnitus duration since onset, subcategory of tinnitus,
Characteristics severity of tinnitus
B-6
o No, it is a systematic review or meta-analysis (stop)
o No, it is not primary research (e.g., editorial, comment, conference abstract, letter,
opinion piece, protocol, narrative/DESCRIPTIVE study)[Stop]
7. Does the study COMPARE:
o More than one tool/method that RESULT in candidacy for further evaluation or
treatment?
o Group treatment outcomes (e.g. treatment to placebo; treatment to no treatment;
one treatment to another treatment, with controls)
o Both a and b
o None of the above (comparators do not meet inclusion criteria)
o Insufficient detail for aggregation of data/results
B-7
do further evaluation/treatment research with that population, you would not exclude the
study at this point.
3. Is this study only to determine various effects of tinnitus on an individual (e.g., effect on
sleep or brain wave patterns; effect on memory)? Yes [STOP] NOTE: We are not interested
in research on how people with tinnitus have memory problems or what the brain wave
patterns of people with tinnitus are, or the fact that people with tinnitus can’t sleep. If the
study only looks at a way that tinnitus affects an individual but does not look at ways of
determining their candidacy for treatment or is not an evaluation of a treatment outcome, it
should be excluded.
4. Is this study only focused on ways of determining whether a patient has ‘malingering’
tinnitus? Fabricating or exaggerating the symptoms of tinnitus for a variety of “secondary
gain” motives; for example to claim insurance benefits, avoid work, etc.
5. Does this report describe a primary study (i.e., the original publication of new data and
results)
6. Does the study design compare:
a. More than one method of evaluation to determine candidacy for treatment i.e., the study
compares two different scales/questionnaires (tinnitus handicap inventory vs. functional
tinnitus index) used to assess severity of tinnitus in order to determine need for further
treatment.
b. Group treatment outcomes (i.e., one group gets a treatment drug compared to one getting
a placebo; one group gets treatment compared to another group getting no treatment; a
group being treated compared to a group on a waiting list for treatment; one treatment
compared to another treatment; a before/after treatment comparison; within-group
comparison; between-group comparison).
c. Both a and b
d. There is no comparison of methods for evaluating tinnitus or tinnitus treatment outcomes
in this study
Data Extraction
1. Study design:
o Randomized clinical trial
o Nonrandomized trial (quasi-experimental, interrupted time series design, etc.)
o Controlled clinical trial (not randomized)
o Cohort, prospective
o Cohort, retrospective
o Case-control
o Cross-sectional
o Before-after
o Other (identify) ____________________
2. Is there any reason this study should be excluded?
o Yes (identify) ______________________
o No (continue)
B-8
3. Is this a pilot study?
o Yes
o No
4. Country
________________________
5. Setting (e.g., primary care, ENT, audiology, neurology, mental health service,
community, internet, other-identify, etc.)
_______________________________________________
6. Is this the primary diagnosis of subjects in this study subjective (idiopathic,
nonpulsatile) tinnitus?
o Yes
o No, tinnitus is secondary to (a symptom of) another diagnosis [identify primary
diagnosis-for example Meniere’s disease]______________________________
7. If tinnitus is secondary to another diagnosis, are there results provided specific to
the effect of an intervention on the tinnitus symptoms?
o Not applicable
o Yes (continue)
o No (submit form now)
8. Please describe the population included in the study (selection criteria and the
number excluded if provided):
B-9
11. Please report the AGE CHARACTERISTICS (if applicable):
Characteristics All Intervention Control Identify Identify Identify Identify
Patient Group 1 Group Group Group Group Group
n=? (I1) n=?
1 (C1) n=? (I# or C#) (I# or C#) (I# or C#) and (I# or C#) and
________ ________ and n=? and n=? n=? n=?
_______
_________ _________ _________ _________
Mean
Standard Dev.
Standard Error
Median
Min
Max
B-10
13. Please report GENDER (if applicable):
Gender n/% n/% n/% n/% n/%
FEMALE
MALE
B-11
15. Please report RACE/ETHNICITY (if applicable):
Characteristics n/% n/% n/% n/% n/% n/% n/%
White/Caucasian
African-
American/Black
Hispanic
Aboriginal
Asian
Other 1
Other 2
Other 3
B-12
17. Identify the treatment intervention in this study. (Note: if the study is comparing the effectiveness of two or more
interventions, identify all. Use text box to add brief detail- i.e., drug name(s), device name(s), etc.)
o Pharmacological [identify drug(s) being studied] _____________________
o Laser _____________________
o Temporal Mandibular Joint-TMJ (dental orthotics, self-care, surgery) _____________________
o TMS (transcranial magnetic stimulation) _____________________
o Ginko Biloba extracts _____________________
o Acupuncture _____________________
o Hyperbaric oxygen therapy _____________________
o Electrical Stimulation _____________________
o Diet modification(s) [identify] _____________________
o Sleep therapy/modification _____________________
o Lifestyle changes (not diet or sleep) [identify] _____________________
o Hearing aids _____________________
o Cochlear implants _____________________
o Sound generators/maskers (wearable) [identify make if provided] _____________________
o Sound generators/maskers (stationary) [identify make if provided] _____________________
o Neuromonics _____________________
o Tinnitus Retraining Therapy (TRT) _____________________
o Cognitive Behavioral Therapy (CBT) _____________________
o Patient Education _____________________
o Relaxation therapies _____________________
o Progressive Tinnitus Management (PTM) _____________________
o This study is evaluating a combination of tinnitus interventions [identify the combination] _____________________
o Other [identify] _____________________
o Other [identify] _____________________
o Other[identify] _____________________
o Other[identify] _____________________
o Other[identify] _____________________
o This study ONLY focuses on tools/measures that RESULT in candidacy for treatment.
B-13
18. Interventions: *Please describe intervention(s) with sufficient detail for replication.
Include duration of treatment, intensity of treatment, if feasible. (Length of study; number of follow-ups). Include page
number sources of information.
19. If the study only discusses one treatment intervention, what is the Intervention compared to?
o Usual care
o No treatment
o Placebo
o Wait list
o Not-applicable
o Other (identify) _________________
20. Number of participants allocated to Intervention Group 1 at baseline _____________________
21. Number of participants in Intervention Group 1 at final follow-up ________________________
22. Number of participants allocated to Intervention Group 2 at baseline ______________________
23. Number of participants in Intervention Group 2 at final follow-up ________________________
24. Number of participants allocated to the control group (if not a within-subject study). ______________________
25. Number of participants in control group at final follow-up ___________________
26. Reasons for withdrawal? (Identify group, # of withdrawals, and any reasons provided-with # per reason if included)
Additional Notes
B-14
Modified Jadad
1. Is this a RCT study?
o Yes (continue)
o No it is a cross section (stop and use cross-sectional form) _______________
o No it is a cohort (stop and use NOS cohort form)
o Not it is a case control (stop and use case control form)
o Other (identify and stop) _______________
2. Reported as randomized
o Yes (1 Point)
o No
3. Randomization is appropriate
o Yes (1 Point)
o No (-1 Point)
o Not Described
4. Double blinding is reported
o Yes (1 Point)
o No
5. Double blinding is appropriate
o Yes (1 Point)
o No (-1 Point)
o Not Described
6. Withdrawals are reported by number and reason per arm
o Yes (1 Point)
o No
7. Jadad Score (/5)
o 0
o 1
o 2
o 3
o 4
o 5
B-15
8. Method(s) used to assess adverse events is described
o Yes(1 Point)
o No
9. Method(s) of statistical analysis is described
o Yes (1 Point)
o No
10. Inclusion and/or exclusion of the requirements is reported
o Yes (1 point if at least one of the requirements is reported)
o No
11. Modified Jadad score (/8)
o 1
o 2
o 3
o 4
o 5
o 6
o 7
o 8
12. Was the allocation adequately concealed? (e.g., pharmacy controlled randomized scheme, sequentially numbered
opaque, sealed envelope, sequentially numbered/coded identical containers, central randomization by phone)
o Yes
o No
o Unclear
13. Was the analysis based on intention to treat principle?
o Yes
o No
o Unclear
14. Was the sample size justified?
o Yes
o No
o Unclear
B-16
TNT Outcomes Continuous
1. Identify the outcomes of interest in this study (check all that apply):
o Sleep
o Discomfort/distress
o Depression
o Self-reported loudness
o Quality of life
o Time to improvement
o Severity
o Worsening of tinnitus
o Sedation
o Surgical complications
o Other (identify) __________________
o Other (identify) __________________
o Other (identify) __________________
o Other (identify) __________________
o Other (identify) __________________
o Other (identify) __________________
o Other (identify) __________________
B-17
2. Specify the outcome measure(s)for each outcome you identified above (use acronyms where provided)
o Sleep _____________
o Discomfort/distress _____________
o Anxiety _____________
o Depression _____________
o Self-reported loudness _____________
o Quality of life _____________
o Tinnitus severity _____________
o Time to improvement _____________
o Worsening of tinnitus _____________
o Sedation _____________
o Surgical Complication _____________
o Other _____________
o Other _____________
o Other _____________
o Other _____________
o Other _____________
o Other _____________
o Other _____________
3. Further definition of outcomes identified above (e.g., units of measurement, full name of tools/measures –Beck
Depression Inventory, validated instruments –ref#?). Provide page/paragraph numbers. (i.e., p.12,para3)
4. Please identify data type (if continuous AND dichotomous, check both). Use table for continuous and text box below
table for dichotomous):
o Continuous
o Dichotomous
B-18
5. Outline from where you took the data (i.e., variables Sleep and Distress from Table 2, or page and paragraph number).
USE THIS BOX TO REPORT DICHOTOMOUS DATA if applicable.
6. If there is relevant PRE-POST data for the above outcomes that does not fit within the table above, please add here.
B-19
9. Are there any sub-group analyses provided in the paper? (See example sheet for breakdowns/examples. Only identify
groups for which PRE/POST intervention data is provided).
o Analysis of the effect of patient characteristics on treatment outcomes _____________________________
o Analysis of the effect of symptoms characteristics on treatment outcomes __________________________
o Analysis of the effect of prognostic factors on treatment outcomes ________________________________
o None of the above
10. Study design to determine Quality Analysis form:
o RCT, CCT
o Non randomized trial
o Cohort (prospective; retrospective; before-after; time-series)
o Case control
o Cross section
o Other observational
B-20
Appendix C. Excluded Studies
Aazh H, Moore BCJ, Glasberg BR. Simplified form of tinnitus retraining therapy in adults: A
retrospective study. BMC Ear Nose Throat Disord. 2008;8(1):7.
Exclude: Non-randomized head-to-head
Abelson TI. Long-term bilateral tinnitus. JAMA. 1985;253(19):2830. PMID:3989951.
Exclude: Not a primary study
Acrani IO, Pereira LD. Temporal resolution and selective attention of individuals with tinnitus.
Profono. 2010;22(3):233-8. PMID:21103711.
Exclude: Only determined various effects
Adlington P, Warrick J. Stellate ganglion block in the management of tinnitus. -J Laryngol Otol.
1971;85(2):159-68. PMID:4396190.
Exclude: Case study or series
Ahmad R, Raichura N, Kilbane V, et al. Vancomycin: A reappraisal. BMJ Clin Res Ed.
1982;284(6333):1953-4. PMID:6805786.
Exclude: Not a primary study
Ahmad S. Venlafaxine and severe tinnitus. Am Fam Physician. 1995;51(8):1830.
PMID:7762476.
Exclude: Not a primary study
Albrecht III CR, Gambert SR. Botanical and diet-based biological therapies and their use by
older persons: Part I. Clin Geriatr. 2005;13(1):26-34.
Exclude: Not a primary study
Aleksic M, Schutz G, Gerth S, et al. Surgical approach to kinking and coiling of the internal
carotid artery. J Cardiovasc Surg. 2004;45(1):43-8. PMID:15041936.
Exclude: Tinnitus is somatic
Al-Jassim AH. The use of Walkman Mini-stereo system as a tinnitus masker. J Laryngol Otol.
1988;102(1):27-8. PMID:3343558.
Exclude: Non-randomized head-to-head
Almeida TA, Samelli AG, Mecca FN, et al. Tinnitus sensation pre and post nutritional
intervention in metabolic disorders. Profono. 2009;21(4):291-7. PMID:20098946.
Exclude: Insufficient detail of outcome data/not extractable
Andersson G, Airikka M-L, Buhrman M, et al. Dimensions of perfectionism and tinnitus distress.
Psychol Health Med. 2005;10(1):78-87.
Exclude: Only determined various effects
Andersson G, Edsjo L, Kaldo V, et al. Tinnitus and short-term serial recall in stable versus
intermittent masking conditions. Scand J Psychol. 2009;50(5):517-22. PMID:19778399.
Exclude: Only determined various effects
Andersson G, Ingerholt C, Jansson M. Autobiographical memory in patients with tinnitus.
Psychol Health. 2003;18(5):667-75.
Exclude: Only determined various effects
C-1
Andersson G, Juris L, Classon E, et al. Consequences of suppressing thoughts about tinnitus and
the effects of cognitive distraction on brain activity in tinnitus patients. Audiol Neuro Otol.
2006;11(5):301-9. PMID:16837798.
Exclude: Only determined various effects
Andersson G, Kaldo V, Stromgren T, et al. Are coping strategies really useful for the tinnitus
patient? An investigation conducted via the internet. Audiol Med. 2004;2(1):54-9.
Exclude: Only about prevalence
Andersson G, Keshishi A, Baguley DM. Benefit from hearing aids in users with and without
tinnitus. Audiol Med. 2011;9(2):73-8.
Exclude: Non-randomized head-to-head
Andersson G, Kyrre SO, Kaldo V, et al. Future thinking in tinnitus patients. J Psychosom Res.
2007;63(2):191-4. PMID:17662756.
Exclude: Only determined various effects
Andersson G. Prior treatments in a group of tinnitus sufferers seeking treatment. Psychother
Psychosom. 1997;66(2):107-10. PMID:9097339.
Exclude: Insufficient detail of outcome data/not extractable
Andersson G. The role of optimism in patients with tinnitus and in patients with hearing
impairment. Psychol Health. 1996;11(5):697-707.
Exclude: Non-randomized head-to-head
Ansari H, Patankar T, Jackson A. Whispering enigma. Br J Radiol. 2005;78(927):283-4.
PMID:15730998.
Exclude: Case study or series
Anttonen H, Hassi J, Riihikangas P, et al. Impulse noise exposure during military service. Scand
Audiol Suppl. 1980;(Suppl 12):17-24. PMID:6939085.
Exclude: Only about prevalence
Aran JM, Cazals Y. Electrical suppression of tinnitus. Ciba Foundation Symposium.
1981;85:217-31. PMID:6976888.
Exclude: Case study or series
Aran JM. Electrical stimulation of the auditory system and tinnitus control. J Laryngol Otol
Suppl. 1981;(4):153-61. PMID:6975341.
Exclude: Case study or series
Araujo MF, Oliveira CA, Bahmad FM, Jr. Intratympanic dexamethasone injections as a
treatment for severe, disabling tinnitus: Does it work? Arch Otolaryngol Head Neck Surg.
2005;131(2):113-7. PMID:15723941.
Exclude: Insufficient detail of outcome data/not extractable
Ariizumi Y, Hatanaka A, Kitamura K. Clinical prognostic factors for tinnitus retraining therapy
with a sound generator in tinnitus patients. J Med Dent Sci. 2010;57(1):45-53. PMID:20437765.
Exclude: Insufficient detail of outcome data/not extractable
C-2
Arndt S, Aschendorff A, Laszig R, et al. Comparison of pseudobinaural hearing to real binaural
hearing rehabilitation after cochlear implantation in patients with unilateral deafness and tinnitus.
Otol Neurotol. 2011;32(1):39-47. PMID:21068690.
Exclude: Insufficient detail of outcome data/not extractable
Atlas J, Parnes LS. Intratympanic gentamicin for intractable Meniere’s disease: 5-year follow-up.
J Otolaryngol. 2003;32(5):288-93.
Exclude: Insufficient detail of outcome data/not extractable
Atlas JT, Parnes LS. Intratympanic gentamicin titration therapy for intractable Meniere’s disease.
Am J Otol. 1999;20(3):357-63.
Exclude: Tinnitus is somatic
Attias J, Shemesh Z, Shoham C, et al. Efficacy of self-hypnosis for tinnitus relief. Scand Audiol.
1990;19(4):245-9. PMID:2075417.
Exclude: Insufficient detail of outcome data/not extractable
Attias J, Shemesh Z, Sohmer H, et al. Comparison between self-hypnosis, masking and
attentiveness for alleviation of chronic tinnitus. Audiology. 1993;32(3):205-12. PMID:8489481.
Exclude: Insufficient detail of outcome data/not extractable
Axelsson A, Andersson S, Gu LD. Acupuncture in the management of tinnitus: A placebo-
controlled study. Audiology. 1994;33(6):351-60. PMID:7741667.
Exclude: Insufficient detail of outcome data/not extractable
Ayache D, Earally F, Elbaz P. Characteristics and postoperative course of tinnitus in
otosclerosis. Otol Neurotol. 2003;24(1):48-51. PMID:12544028.
Exclude: Non-randomized head-to-head
Aydemir G, Tezer MS, Borman P, et al. Treatment of tinnitus with transcutaneous electrical
nerve stimulation improves patients’ quality of life. J Laryngol Otol. 2006;120(6):442-5.
PMID:16556347.
Exclude: Non-randomized head-to-head
Baguley D. Neurophysiological approach to tinnitus patients. Am J Otol. 1997;18(2):265-6.
PMID:9093687.
Exclude: Not a primary study
Baguley DM, Humphriss RL, Hodgson CA. Convergent validity of the tinnitus handicap
inventory and the tinnitus questionnaire. J Laryngol Otol. 2000;114(11):840-3. PMID:11144832.
Exclude: Non-randomized head-to-head
Baguley DM, McFerran DJ. Current perspectives on tinnitus. Arch Dis Child. 2002;86(3):141-3.
PMID:11861225.
Exclude: Not a primary study
Bahmad FM, Jr., Venosa AR, Oliveira CA. Benzodiazepines and GABAergics in treating severe
disabling tinnitus of predominantly cochlear origin. Int Tinnitus J. 2006;12(2):140-4.
PMID:17260879.
Exclude: Insufficient detail of outcome data/not extractable
C-3
Bakhshaee M, Ghasemi M, Azarpazhooh M, et al. Gabapentin effectiveness on the sensation of
subjective idiopathic tinnitus: A pilot study. Eur Arch Otorhinolaryngol. 2008;265(5):525-30.
PMID:17960408.
Exclude: Insufficient detail of outcome data/not extractable
Baracca GN, Forti S, Crocetti A, et al. Results of TRT after eighteen months: Our experience. Int
J Audiol. 2007;46(5):217-22. PMID:17487669.
Exclude: Insufficient detail of outcome data/not extractable
Barber HO. The diagnosis and treatment of auditory and vestibular disorders after head injury.
Clin Neurosurg. 1972;19:355-70. PMID:4637559.
Exclude: Not a primary study
Baribeau J. Reaching out to the youth suffering from idiopathic tinnitus via the Internet. Ann
Rev Cyberther Telemed. 2006;4:145-52.
Exclude: Non-randomized head-to-head
Barrs DM, Brackmann DE. Section 3: Surgical treatment. Translabyrinthine nerve section: Effect
on tinnitus. J Laryngol Otol. 1983;97(Suppl. 9):287-93.
Exclude: Insufficient detail of outcome data/not extractable
Bartels H, Middel B, Pedersen SS, et al. The distressed (Type D) personality is independently
associated with tinnitus: A case-control study. Psychosomatics. 2010;51(1):29-38.
PMID:20118438.
Exclude: Non-randomized head-to-head
Bartels H, Pedersen SS, van der Laan BF, et al. The impact of Type D personality on health-
related quality of life in tinnitus patients is mainly mediated by anxiety and depression. Otol
Neurotol. 2010;31(1):11-8. PMID:19816233.
Exclude: Only determined various effects
Bartels H, Staal MJ, Holm AF, et al. Long-term evaluation of treatment of chronic,
therapeutically refractory tinnitus by neurostimulation. Stereotact Funct Neurosurg.
2007;85(4):150-7. PMID:17259751.
Exclude: Case study or series
Bartnik G, Fabijanska A, Rogowski M. Effects of tinnitus retraining therapy (TRT) for patients
with tinnitus and subjective hearing loss versus tinnitus only. Scand Audiol Suppl. 2001;52:206-
8. PMID:11318470.
Exclude: Non-randomized head-to-head
Bartnik G, Fabijanska A, Rogowski M. Experiences in the treatment of patients with tinnitus
and/or hyperacusis using the habituation method. Scand Audiol Suppl. 2001;52:187-90.
PMID:11318464.
Exclude: Insufficient detail of outcome data/not extractable
Bauer CA, Brozoski TJ. Effect of gabapentin on the sensation and impact of tinnitus.
Laryngoscope. 2006;116(5):675-81. PMID:16652071.
Exclude: Insufficient detail of outcome data/not extractable
Bauer CA, Brozoski TJ. Effect of tinnitus retraining therapy on the loudness and annoyance of
tinnitus: A controlled trial. Ear Hear. 2011;32(2):145-55. PMID:20890204.
Exclude: Insufficient detail of outcome data/not extractable
C-4
Bauer W. Transcutaneous electrical stimulation. Arch Otolaryngol Head Neck Surg.
1986;112(12):1301-2. PMID:3490266.
Exclude: Not a primary study
Bayazit Y. Neurovascular decompression for tinnitus. J Neurosurg. 1998;89(6):1072-3.
PMID:9833843.
Exclude: Not a primary study
Bayazit YA, Goksu N. Tinnitus and neurovascular compression. ORL. 2008;70(3):209.
PMID:18401197.
Exclude: Not a primary study
Belli S, Belli H, Bahcebasi T, et al. Assessment of psychopathological aspects and psychiatric
comorbidities in patients affected by tinnitus. Eur Arch Otorhinolaryngol. 2008;265(3):279-85.
PMID:17999075.
Exclude: Only determined various effects
Bentler RA, Tyler RS. Tinnitus management. ASHA. 1987;29(5):27-32. PMID:3593456.
Exclude: Article not available
Bentzen O. Treatment of tinnitus with alternative therapy. Acta Otorhinolaryngol Belgica.
1986;40(3):487-91. PMID:3788551.
Exclude: Not a primary study
Berninger E, Nordmark J, Alvan G, et al. The effect of intravenously administered mexiletine on
tinnitus - A pilot study. Int J Audiol. 2006;45(12):689-96. PMID:17132557.
Exclude: Case study or series
Berrios GE, Ryley JP, Garvey TPN, et al. Psychiatric morbidity in subjects with inner ear
disease. Clin Otolaryngol Allied Sci. 1988;13(4):259-66.
Exclude: Only determined various effects
Berry JA, Gold SL, Frederick EA, et al. Patient-based outcomes in patients with primary tinnitus
undergoing tinnitus retraining therapy. Arch Otolaryngol Head Neck Surg. 2002;128(10):1153-7.
PMID:12365886.
Exclude: Case study or series
Bessman P, Heider T, Watten VP, et al. The tinnitus intensive therapy habituation program: A 2-
year follow-up pilot study on subjective tinnitus. Rehabil Psychol. 2009;54(2):133-7.
PMID:19469602.
Exclude: Insufficient detail of outcome data/not extractable
Bezerra Rocha CA, Sanchez TG, Tesseroli de Siqueira JT. Myofascial trigger point: A possible
way of modulating tinnitus. Audiol Neuro Otol. 2008;13(3):153-60. PMID:18075244.
Exclude: Insufficient detail of outcome data/not extractable
Bjorne A. Assessment of temporomandibular and cervical spine disorders in tinnitus patients.
Progr Brain Res. 2007;166:215-9. PMID:17956785.
Exclude: Not a primary study
Blair PA, Reed HT. Amino-oxyacetic acid: A new drug for the treatment of tinnitus. J La State
Med Soc. 1986;138(6):17-9. PMID:3734755.
Exclude: Not a primary study
C-5
Blayney AW, Phillips MS, Guy AM, et al. A sequential double blind cross-over trial of tocainide
hydrochloride in tinnitus. Clin Otolaryngol Allied Sci. 1985;10(2):97-101. PMID:3928215.
Exclude: Insufficient detail of outcome data/not extractable
Borghi C, Brandolini C, Prandin MG, et al. Prevalence of tinnitus in patients with hypertension
and the impact of different antihypertensive drugs on the incidence of tinnitus: A prospective,
single-blind, observational study. Curr Ther Res. 2005;66(5):420-32.
Exclude: Only about prevalence
Borton TE, Clark SR. Electromyographic biofeedback for treatment of tinnitus. Am J Otol.
1988;9(1):23-30. PMID:3364533.
Exclude: Case study or series
Bovo R, Ciorba A, Martini A. Tinnitus and cochlear implants. Auris Nasus Larynx.
2011;38(1):14-20. PMID:20580171.
Exclude: Case study or series
Bradley WD. Management of tinnitus. Cranio. 1989;7(2):75.
Exclude: Not a primary study
Briner W, House J, O’Leary M. Synthetic prostaglandin E1 misoprostol as a treatment for
tinnitus. Arch Otolaryngol Head Neck Surg. 1993;119(6):652-4. PMID:8499097.
Exclude: Insufficient detail of outcome data/not extractable
Brookes GB. Vascular-decompression surgery for severe tinnitus. Am J Otol. 1996;17(4):569-
76. PMID:8841702.
Exclude: Case study or series
Brookler KH, Tanyeri H. Etidronate for the neurotologic symptoms of otosclerosis: Preliminary
study. Ear Nose Throat J. 1997;76(6):371-81.
Exclude: Tinnitus is somatic
Buechner A, Brendel M, Lesinski-Schiedat A, et al. Cochlear implantation in unilateral deaf
subjects associated with ipsilateral tinnitus. Otol Neurotol. 2010;31(9):1381-5. PMID:20729788.
Exclude: Case study or series
Bumby AF, Stephens SDG. Clonazepam in the treatment of tinnitus - A pilot study. J Audiol
Med. 1997;6(2):98-104.
Exclude: Insufficient detail of outcome data/not extractable
Burgos I, Feige B, Hornyak M, et al. Chronic tinnitus and associated sleep disturbances.
Somnologie. 2005;9(3):133-8.
Exclude: Only determined various effects
Busis SN. Treatment of tinnitus. JAMA. 1992;268(11):1467. PMID:1512918.
Exclude: Not a primary study
Cada DJ, Baker DE, Levien T. Gatifloxacin. Hosp Pharm. 2000;35(4):405-17.
Exclude: Article not available
Caffier PP, Haupt H, Scherer H, et al. Outcomes of long-term outpatient tinnitus-coping therapy:
Psychometric changes and value of tinnitus-control instruments. Ear Hear. 2006;27(6):619-27.
PMID:17086074.
Exclude: Insufficient detail of outcome data/not extractable
C-6
Caffier PP, Sedlmaier B, Haupt H, et al. Impact of laser eustachian tuboplasty on middle ear
ventilation, hearing, and tinnitus in chronic tube dysfunction. Ear Hear. 2011;32(1):132-9.
PMID:20585250.
Exclude: Non-randomized head-to-head
Campbell K. Tinnitus and vertigo. Arch Otolaryngol Head Neck Surg. 1993;119(4):474
PMID:8457316.
Exclude: Not a primary study
Canis M, Olzowy B, Welz C, et al. Simvastatin and Ginkgo biloba in the treatment of subacute
tinnitus: A retrospective study of 94 patients. Am J Otolaryngol. 2011;32(1):19-23.
PMID:20015810.
Exclude: Non-randomized head-to-head
Canlon B, Henderson D, Salvi R. Pharmacological strategies for prevention and treatment of
hearing loss and tinnitus. Hear Res. 2007;226(1-2):1-2.
Exclude: Not a primary study
Carbary LJ. Tuning out tinnitus. J Nurs Care. 1980;13(8):8-11. PMID:6904524.
Exclude: Not a primary study
Carlsson SG, Erlandsson SI. Habituation and tinnitus: An experimental study. J Psychosom Res.
1991;35(4-5):509-14. PMID:1920181.
Exclude: Only determined various effects
Carmen R, Svihovec D. Relaxation-biofeedback in the treatment of tinnitus. Am J Otol.
1984;5(5):376-81. PMID:6383065.
Exclude: Case study or series
Caro AZ. Dimethyl sulfoxide therapy in subjective tinnitus of unknown origin. Ann New York
Acad Sci. 1975;243:468-74. PMID:1055561.
Exclude: Case study or series
Carrick DG, Davies WM, Fielder CP, et al. Low-powered ultrasound in the treatment of tinnitus:
A pilot study. Br J Audiol. 1986;20(2):153-5. PMID:3719163.
Exclude: Insufficient detail of outcome data/not extractable
Catalano GB, Di Mauro A., Vancheri M. Tinnitus: Analysis of failures with Vernon treatment.
Rivista Italiana di Otorinolaringologia Audiologia e Foniatria. 1982;2(1):60-2.
Exclude: Article not available
Cathcart JM. Assessment of the value of tocainide hydrochloride in the treatment of tinnitus. J
Laryngol Otol. 1982;96(11):981-4. PMID:6813410.
Exclude: Case study or series
Cazals Y, Negrevergne M, Aran JM. Electrical stimulation of the cochlea in man: Hearing
induction and tinnitus suppression. J Am Audiol Soc. 1978;3(5):209-13. PMID:306987.
Exclude: Case study or series
Cesarani A, Capobianco S, Soi D, et al. Intratympanic dexamethasone treatment for control of
subjective idiopathic tinnitus: Our clinical experience. Int Tinnitus J. 2002;8(2):111-4.
PMID:14763222.
Exclude: Case study or series
C-7
Chole RA, Parker WS. Tinnitus and vertigo in patients with temporomandibular disorder. Arch
Otolaryngol Head Neck Surg. 1992;118(8):817-21. PMID:1642833.
Exclude: Not a primary study
Chopra H, Munjal M, Khurana AS, et al. Comparative study of lignocaine instillation (2% and
4%) and hydrocortisone through ventilation tubes in subjective tinnitus. Indian J Otol.
2002;8(2):63-5.
Exclude: Article not available
Chouard CH, Meyer B, Maridat D. Transcutaneous electrotherapy for severe tinnitus. Acta
Otolaryngol. 1981;91(5-6):415-22. PMID:6973909.
Exclude: Insufficient detail of outcome data/not extractable
Choy DS, Lipman RA, Tassi GP. Worldwide experience with sequential phase-shift sound
cancellation treatment of predominant tone tinnitus. J Laryngol Otol. 2010;124(4):366-9.
PMID:20067647.
Exclude: Insufficient detail of outcome data/not extractable
Christensen RC. Paroxetine in the treatment of tinnitus. Otolaryngol Head Neck Surg.
2001;125(4):436-8. PMID:11593197.
Exclude: Not a primary study
Claire LS, Stothart G, McKenna L, et al. Caffeine abstinence: An ineffective and potentially
distressing tinnitus therapy. Int J Audiol. 2010;49(1):24-9. PMID:20053154.
Exclude: Insufficient detail of outcome data/not extractable
Claussen CF. Industrial medicine: The future for vertigo and tinnitus patients. Int Tinnitus J.
2004;10(1):87-90. PMID:15379357.
Exclude: Not a primary study
Coad C. Nutritional supplement for Meniere’s disease and tinnitus. Positive Health.
2008;(151):1.
Exclude: Not a primary study
Coles R, Bradley P, Donaldson I, et al. A trial of tinnitus therapy with ear-canal magnets. Clin
Otolaryngol Allied Sci. 1991;16(4):371-2. PMID:1934552.
Exclude: Non-randomized head-to-head
Coles R. Trial of an extract of Ginkgo biloba (EGB) for tinnitus and hearing loss. Clin
Otolaryngol Allied Sci. 1988;13(6):501-2. PMID:3228994.
Exclude: Not a primary study
Coles RR, Baskill JL, Sheldrake JB. Measurement and management of tinnitus. Part II.
Management. J Laryngol Otol. 1985;99(1):1-10. PMID:2578535.
Exclude: Not a primary study
Coles RR, Hallam RS. Tinnitus and its management. Br Med Bull. 1987;43(4):983-98.
PMID:3329937.
Exclude: Not a primary study
Coles RR, Thompson AC, O’Donoghue GM. Intra-tympanic injections in the treatment of
tinnitus. Clin Otolaryngol Allied Sci. 1992;17(3):240-2. PMID:1505091.
Exclude: Case study or series
C-8
Collet L, Moussu MF, Dubreuil C, et al. Psychological factors affecting outcome of treatment
after transcutaneous electrotherapy for persistent tinnitus. Arch Oto-Rhino-Laryngol.
1987;244(1):20-2. PMID:3497623.
Exclude: Insufficient detail of outcome data/not extractable
Coping with tinnitus. ASHA. 1990;32(5):61. PMID:2337425.
Exclude: Not a primary study
Crocetti A, Forti S, Del BL. Neurofeedback for subjective tinnitus patients. Auris Nasus Larynx.
2011;38(6):735-8.
Exclude: Non-randomized head-to-head
Cronlein T, Langguth B, Geisler P, et al. Tinnitus and insomnia. Progr Brain Res. 2007;166:227-
33. PMID:17956787.
Exclude: Only determined various effects
Cummings M, Lundeberg T. Acupuncture for tinnitus. Complement Ther Med. 2006;14(4):290-
1. PMID:17105701.
Exclude: Not a primary study
Daneshi A, Mahmoudian S, Farhadi M, et al. Auditory electrical tinnitus suppression in patients
with and without implants. Int Tinnitus J. 2005;11(1):85-91. PMID:16419698.
Exclude: Non-randomized head-to-head
Daneshmend TK. Treatment of tinnitus. BMJ. 1979;1(6178):1628. PMID:466159.
Exclude: Not a primary study
Dauman R, Tyler RS. Tinnitus suppression in cochlear implant users. Adv Otorhinolaryngol.
1993;48:168-73. PMID:8273472.
Exclude: Case study or series
David J, Naftali A, Katz A. Tinntrain: A multifactorial treatment for tinnitus using binaural
beats. Hear J. 2010;63(11):25 .
Exclude: Not a primary study
Davies E, Donaldson I. Tinnitus, membrane stabilizers and taurine. Practitioner.
1988;232(1456:(Pt 2)):1139. PMID:3256861.
Exclude: Not a primary study
Davies E, Knox E, Donaldson I. The usefulness of nimodipine, an L-calcium channel antagonist,
in the treatment of tinnitus. Br J Audiol. 1994;28(3):125-9. PMID:7841896.
Exclude: Case study or series
Davies E. The pharmacological management of tinnitus. Audiol Med. 2004;2(1):26-8.
Exclude: Not a primary study
Davies S, McKenna L, and Hallam RS. Relaxation and cognitive therapy: A controlled trial in
chronic tinnitus. Psychol Health. 1995;10(2):129-43.
Exclude: Non-randomized head-to-head
Davis PB, Wilde RA, Steed LG, et al. Treatment of tinnitus with a customized acoustic neural
stimulus: A controlled clinical study. Ear Nose Throat J. 2008;87(6):330-9. PMID:18561116.
Exclude: Insufficient detail of outcome data/not extractable
C-9
Dawes PJ, Welch D. Childhood hearing and its relationship with tinnitus at thirty-two years of
age. Ann Otol Rhinol Laryngol. 2010;119(10):672-6. PMID:21049852.
Exclude: Only about prevalence
de Azevedo AA, Langguth B, de Oliveira PM, et al. Tinnitus treatment with piribedil guided by
electrocochleography and acoustic otoemissions. Otol Neurotol. 2009;30(5):676-80.
PMID:19574947.
Exclude: Insufficient detail of outcome data/not extractable
de Azevedo RF, Chiari BM, Okada DM, et al. Impact of acupuncture on otoacoustic emissions in
patients with tinnitus. Revista Brasileira de Otorrinolaringologia. 2007;73(5):599-607.
PMID:18094800.
Exclude: Non-randomized head-to-head
De Ridder D, Vanneste S, Kovacs S, et al. Transcranial magnetic stimulation and extradural
electrodes implanted on secondary auditory cortex for tinnitus suppression. J Neurosurg.
2011;114(4):903-11. PMID:21235318.
Exclude: Case study or series
De Ridder D., De Mulder G., Menovsky T, et al. Electrical stimulation of auditory and
somatosensory cortices for treatment of tinnitus and pain. Progr Brain Res. 2007;166:377-88.
PMID:17956802.
Exclude: Case study or series
De Ridder D., Menovsky T, Van de Heyning P. Auditory cortex stimulation for tinnitus
suppression. Otol Neurotol. 2008;29(4):574-5. PMID:18418286.
Exclude: Not a primary study
De Ridder D., Vanneste S, Adriaenssens I, et al. Microvascular decompression for tinnitus:
Significant improvement for tinnitus intensity without improvement for distress. A 4-year limit.
Neurosurg. 2010;66(4):656-60. PMID:20305490.
Exclude: Case study or series
De Ridder D., Vanneste S, van der Loo E, et al. Burst stimulation of the auditory cortex: A new
form of neurostimulation for noise-like tinnitus suppression. J Neurosurg. 2010;112(6):1289-94.
PMID:19911891.
Exclude: Case study or series
De Ridder D., Verstraeten E, Van der Kelen K, et al. Transcranial magnetic stimulation for
tinnitus: Influence of tinnitus duration on stimulation parameter choice and maximal tinnitus
suppression. Otol Neurotol. 2005;26(4):616-9. PMID:16015156.
Exclude: Insufficient detail of outcome data/not extractable
De Valck C., Van Rompaey V, Wuyts FL, et al. Tenotomy of the tensor tympani and stapedius
tendons in Meniere’s disease. B-ENT. 2009;5(1):1-6.
Exclude: Tinnitus is somatic
DeBartolo HM, Jr. Zinc and diet for tinnitus. Am J Otol. 1989;10(3):256. PMID:2750874.
Exclude: Not a primary study
DeBisschop M. Ginkgo ineffective for tinnitus. J Fam Pract. 2003;52(10):766. PMID:14529599.
Exclude: Not a primary study
C-10
DeCicco MJ, Hoffer ME, Kopke RD, et al. Round-Window Microcatheter-administered
microdose gentamicin: Results from treatment of tinnitus associated with Meniere’s disease. Int
Tinnitus J. 1998;4(2):141-3.
Exclude: Case study or series
Dehler R, Dehler F, Claussen CF, et al. Competitive-kinesthetic interaction therapy. Int Tinnitus
J. 2000;6(1):29-35. PMID:14689615.
Exclude: Case study or series
Dejonckere PH, Coryn C, Lebacq J. Experience with a medicolegal decision-making system for
occupational hearing loss-related tinnitus. Int Tinnitus J. 2009;15(2):185-92. PMID:20420345.
Exclude: Insufficient detail of outcome data/not extractable
DeLucchi E. Transtympanic pilocarpine in tinnitus. Int Tinnitus J. 2000;6(1):37-40.
PMID:14689616.
Exclude: Case study or series
Demajumdar R, Stoddart R, Donaldson I, et al. Tinnitus, cochlear implants and how they affect
patients. J Laryngol Otol Suppl. 1999;24:24-6. PMID:10664726.
Exclude: Non-randomized head-to-head
den Hartigh J., Hilders CG, Schoemaker RC, et al. Tinnitus suppression by intravenous lidocaine
in relation to its plasma concentration. Clin Pharmacol Therapeut. 1993;54(4):415-20.
PMID:8222484.
Exclude: Insufficient detail of outcome data/not extractable
Denk DM, Heinzl H, Franz P, et al. Caroverine in tinnitus treatment. A placebo-controlled blind
study. Acta Otolaryngol. 1997;117(6):825-30. PMID:9442821.
Exclude: Insufficient detail of outcome data/not extractable
Densert B, Densert O, Arlinger S, et al. Immediate effects of middle ear pressure changes on the
electrocochleographic recordings in patients with Meniere’s disease: A clinical placebo-
controlled study. Am J Otol. 1997;18(6):726-33.
Exclude: Tinnitus is somatic
Di Nardo W., Cantore I, Cianfrone F, et al. Tinnitus modifications after cochlear implantation.
Eur Arch Otorhinolaryngol. 2007;264(10):1145-9. PMID:17558507.
Exclude: Insufficient detail of outcome data/not extractable
Di Nardo W., Cianfrone F, Scorpecci A, et al. Transtympanic electrical stimulation for
immediate and long-term tinnitus suppression. Int Tinnitus J. 2009;15(1):100-6.
PMID:19842353.
Exclude: Case study or series
Dias A, Cordeiro R. Association between hearing loss level and degree of discomfort introduced
by tinnitus in workers exposed to noise. Revista Brasileira de Otorrinolaringologia.
2008;74(6):876-83. PMID:19582344.
Exclude: Non-randomized head-to-head
Dibb B, Yardley L. How does social comparison within a self-help group influence adjustment to
chronic illness? A longitudinal study. Soc Sci Med. 2006;63(6):1602-13.
Exclude: Insufficient detail of outcome data/not extractable
C-11
Dickter AE, Durrant JD, Ronis ML. Correlation of the complaint of tinnitus with central auditory
testing. J Laryngol Otol Suppl. 1981;(4):52-9. PMID:6946171.
Exclude: Case study or series
Dobie RA, Hoberg KE, Rees TS. Electrical tinnitus suppression: A double-blind crossover study.
Otolaryngol Head Neck Surg. 1986;95(3:Pt 1):319-23. PMID:3108780.
Exclude: Insufficient detail of outcome data/not extractable
Dobie RA, Sakai CS. Frusemide open trial for treatment of tinnitus. J Audiol Med.
1993;2(3):167-74.
Exclude: Insufficient detail of outcome data/not extractable
Dobie RA, Sullivan MD, Katon WJ, et al. Antidepressant treatment of tinnitus patients. Interim
report of a randomized clinical trial. Acta Otolaryngol. 1992;112(2):242-7. PMID:1604987.
Exclude: Insufficient detail of outcome data/not extractable
Dobie RA. Patients with tinnitus may benefit from antidepressant therapy. Am Fam Physician.
1992;46(1):241.
Exclude: Not a primary study
Domeisen H, Hotz MA, Hausler R. Caroverine in tinnitus treatment. Acta Otolaryngol.
1998;118(4):606-8. PMID:9726691.
Exclude: Not a primary study
Domenech J, Cuchi MA, Carulla M. High-frequency hearing loss in patients with tinnitus. Adv
Otorhinolaryngol. 1990;45:203-5. PMID:2077891.
Exclude: Non-randomized head-to-head
Donaldson I. Tinnitus: A theoretical view and a therapeutic study using amylobarbitone. J
Laryngol Otol. 1978;92(2):123-30. PMID:627765.
Exclude: Insufficient detail of outcome data/not extractable
Dong CH. Clinical observation of acupuncture on nervous tinnitus and deafness. Int J Clin
Acupuncture. 1996;7(4):469-71.
Exclude: Case study or series
Dong-Kee K, Shi-Nae P, Hyung Min K, et al. Prevalence and significance of high-frequency
hearing loss in subjectively normal-hearing patients with tinnitus. Ann Otol Rhinol Laryngol.
2011;120(8):523-8.
Exclude: Only about prevalence
Dornhoffer JL, Mennemeier M. Transcranial magnetic stimulation and tinnitus: Implications for
theory and practice. J Neurol Neurosurg Psychiatry. 2010;81(12):1414.
Exclude: Not a primary study
Dornhoffer JL, Mennemeier M. Transcranial magnetic stimulation and tinnitus: Implications for
theory and practice. J Neurol Neurosurg Psychiatry. 2010;81(1):126.
Exclude: Not a primary study
Duckert LG, Rees TS. Placebo effect in tinnitus management. Otolaryngol Head Neck Surg.
1984;92(6):697-9. PMID:6440090.
Exclude: Insufficient detail of outcome data/not extractable
C-12
Duckert LG, Rees TS. Treatment of tinnitus with intravenous lidocaine: A double-blind
randomized trial. Otolaryngol Head Neck Surg. 1983;91(5):550-5. PMID:6417606.
Exclude: Insufficient detail of outcome data/not extractable
Dyczek H. Tinnitus helped by chiropractic. Int J Alternat Complement Med. 1995;13(5):12.
Exclude: Not a primary study
Ehrenberger K. Topical administration of Caroverine in somatic tinnitus treatment: Proof-of-
concept study. Int Tinnitus J. 2005;11(1):34-7. PMID:16419686.
Exclude: Insufficient detail of outcome data/not extractable
Eklund S, Pyykko I, Aalto H, et al. Effect of intratympanic gentamicin on hearing and tinnitus in
Meniere’s disease. Am J Otol. 1999;20(3):350-6. PMID:10337977.
Exclude: Insufficient detail of outcome data/not extractable
El Refaie A., Davis A, Kayan A, et al. A questionnaire study of the quality of life and quality of
family life of individuals complaining of tinnitus pre- and post-attendance at a tinnitus clinic. Int
J Audiol. 2004;43(7):410-6. PMID:15515640.
Exclude: Insufficient detail of outcome data/not extractable
Electrical stimulation of the inner ear. J Laryngol Otol Suppl. 1984;9:121-44. PMID:6394678.
Exclude: Article not available
Emmett JR, Shea JJ. Medical treatment of tinnitus. J Laryngol Otol. 1983;97(Suppl. 9):264-70.
Exclude: Insufficient detail of outcome data/not extractable
Emmett JR, Shea JJ. Treatment of tinnitus aurium with Tocainide HCl. Otolaryngol Head Neck
Surg. 1979;87(4 II):196-7.
Exclude: Not a primary study
Emmett JR, Shea JJ. Treatment of tinnitus with tocainide hydrochloride. Otolaryngol Head Neck
Surg. 1980;88(4):442-6. PMID:6821429.
Exclude: Insufficient detail of outcome data/not extractable
Engelberg M, Bauer W. Transcutaneous electrical stimulation for tinnitus. Laryngoscope.
1985;95(10):1167-73. PMID:3900611.
Exclude: Insufficient detail of outcome data/not extractable
Erlandsson S, Ringdahl A, Hutchins T, et al. Treatment of tinnitus: A controlled comparison of
masking and placebo. Br J Audiol. 1987;21(1):37-44. PMID:3828583.
Exclude: Non-randomized head-to-head
Evans DL, Golden RN. Protriptyline and tinnitus. J Clin Psychopharmacol. 1981;1(6):404-6.
PMID:7334152.
Exclude: Case study or series
Evans RW, Ishiyama G. Migraine with transient unilateral hearing loss and tinnitus. Headache.
2009;49(5):756-8. PMID:19472451.
Exclude: Case study or series
Falkenberg E-S, Tungland OP, Skollerud S. Habituation therapy of chronic distressing tinnitus:
A presentation of a treatment programme and an evaluation study of its effects. Audiol Med.
2003;1(2):132-7.
Exclude: Non-randomized head-to-head
C-13
Farace E, Marshall LF, Betchen SA, et al. Quality of life in acoustics. J Neurosurg.
2003;99(5):807-9.
Exclude: Not a primary study
Fattori B, De Iaco G., Nacci A, et al. Alternobaric oxygen therapy in long-term treatment of
Meniere’s disease. Undersea Hyperb Med. 2002;29(4):260-70. PMID:12797667.
Exclude: Insufficient detail of outcome data/not extractable
Fattori B, De IG, Vannucci G, et al. Alternobaric and hyperbaric oxygen therapy in the
immediate and long-term treatment of Meniere’s disease. Audiology. 1996;35(6):322-34.
Exclude: Insufficient detail of outcome data/not extractable
Feldmann H. Homolateral and contralateral masking of tinnitus by noise-bands and by pure
tones. Audiology. 1971;10(3):138-44. PMID:5163656.
Exclude: Not a primary study
Feldmann H. Homolateral and contralateral masking of tinnitus. J Laryngol Otol Suppl.
1981;(4):60-70. PMID:6946172.
Exclude: Not a primary study
Figueiredo RR, Azevedo AA, Oliveira PM. Correlation analysis of the visual-analogue scale and
the Tinnitus Handicap Inventory in tinnitus patients. Revista Brasileira de Otorrinolaringologia.
2009;75(1):76-9. PMID:19488564.
Exclude: Non-randomized head-to-head
Figueiredo RR, Rates MA, Azevedo AA, et al. Correlation analysis of hearing thresholds,
validated questionnaires and psychoacoustic measurements in tinnitus patients. Revista Brasileira
de Otorrinolaringologia. 2010;76(4):522-6. PMID:20835541.
Exclude: Non-randomized head-to-head
Flor H, Hoffmann D, Struve M, et al. Auditory discrimination training for the treatment of
tinnitus. Appl Psychophysiol Biofeedback. 2004;29(2):113-20. PMID:15208974.
Exclude: Case study or series
Folmer RL, Carroll JR, Rahim A, et al. Effects of repetitive transcranial magnetic stimulation
(rTMS) on chronic tinnitus. Acta Otolaryngol Suppl. 2006;(556):96-101. PMID:17114152.
Exclude: Case study or series
Folmer RL, Carroll JR. Long-term effectiveness of ear-level devices for tinnitus. Otolaryngol
Head Neck Surg. 2006;134(1):132-7. PMID:16399193.
Exclude: Insufficient detail of outcome data/not extractable
Folmer RL, Griest SE, Martin WH. Chronic tinnitus as phantom auditory pain. Otolaryngol Head
Neck Surg. 2001;124(4):394-400. PMID:11283496.
Exclude: Only determined various effects
Folmer RL, Griest SE. Tinnitus and insomnia. Am J Otolaryngol. 2000;21(5):287-93.
PMID:11032291.
Exclude: Only determined various effects
Folmer RL, Shi YB. SSRI use by tinnitus patients: Interactions between depression and tinnitus
severity. Ear Nose Throat J. 110;83(2):107-8. PMID:15008444.
Exclude: Non-randomized head-to-head
C-14
Folmer RL. Long-term reductions in tinnitus severity. BMC Ear Nose Throat Disord. 2002;2:1-9.
Exclude: Non-randomized head-to-head
Folmer RL. Repetitive transcranial magnetic stimulation for tinnitus. Arch Otolaryngol Head
Neck Surg. 2011;137(7):730 .
Exclude: Not a primary study
Folmer RL. Transcranial magnetic stimulation for tinnitus. Otol Neurotol. 2005;26(6):1262-3.
PMID:16272954.
Exclude: Not a primary study
Formby C, Gold SL, Keaser ML, et al. Secondary benefits from tinnitus retraining therapy:
Clinically significant increases in loudness discomfort level and expansion of the auditory
dynamic range. Semin Hear. 2007;28(4):227-60.
Exclude: Non-randomized head-to-head
Formby C, Keaser ML. Secondary treatment benefits achieved by hearing-impaired tinnitus
patients using aided environmental sound therapy for tinnitus retraining therapy: Comparisons
with matched groups of tinnitus patients using noise generators for sound therapy. Semin Hear.
2007;28(4):276-94.
Exclude: Insufficient detail of outcome data/not extractable
Forti S, Costanzo S, Crocetti A, et al. Are results of tinnitus retraining therapy maintained over
time? 18-month follow-up after completion of therapy. Audiol Neuro Otol. 2009;14(5):286-9.
PMID:19372645.
Exclude: Non-randomized head-to-head
Forti S, Crocetti A, Scotti A, et al. Tinnitus sound therapy with open ear canal hearing aids. B-
ENT. 2010;6(3):195-9. PMID:21090162.
Exclude: Insufficient detail of outcome data/not extractable
Fortnum HM, Coles RR. Trial of flecainide acetate in the management of tinnitus. Clin
Otolaryngol Allied Sci. 1991;16(1):93-6. PMID:1903336.
Exclude: Case study or series
Fradis M, Podoshin L, Ben-David J, et al. Treatment of Meniere’s disease by intratympanic
injection with lidocaine. Arch Otolaryngol. 1985;111(8):491-3.
Exclude: Tinnitus is somatic
Frank E, Landgrebe M, Kleinjung T, et al. Burst transcranial magnetic stimulation for the
treatment of tinnitus. CNS Spect. 2010;15(8):536-7.
Exclude: Not a primary study
Frank G, Kleinjung T, Landgrebe M, et al. Left temporal low-frequency rTMS for the treatment
of tinnitus: Clinical predictors of treatment outcome--a retrospective study. Eur J Neurol.
2010;17(7):951-6. PMID:20158510.
Exclude: Non-randomized head-to-head
Frankenburg FR, Hegarty JD. Tinnitus, psychosis, and suicide. Arch Intern Med.
1994;154(20):2371. PMID:7944860.
Exclude: Not a primary study
C-15
Franz B, Collis-Brown G, Altidis P, et al. Cervical trauma and tinnitus. Int Tinnitus J.
1998;4(1):31-3.
Exclude: Case study or series
Franz B, Offutt G. Tinnitus suppression with threshold and subthreshold sound stimuli. Int
Tinnitus J. 2003;9(1):11-6. PMID:14763323.
Exclude: Case study or series
Fregni F, Marcondes R, Boggio PS, et al. Transient tinnitus suppression induced by repetitive
transcranial magnetic stimulation and transcranial direct current stimulation. Eur J Neurol.
2006;13(9):996-1001. PMID:16930367.
Exclude: Insufficient detail of outcome data/not extractable
Frew IJ, Menon GN. Betahistine hydrochloride in Meniere’s disease. Postgrad Med J.
1976;52(610):501-3. PMID:790351.
Exclude: Insufficient detail of outcome data/not extractable
Friedland DR, Gaggl W, Runge-Samuelson C, et al. Feasibility of auditory cortical stimulation
for the treatment of tinnitus. Otol Neurotol. 2007;28(8):1005-12. PMID:18043428.
Exclude: Case study or series
Fukuda S, Miyashita T, Inamoto R, et al. Tinnitus retraining therapy using portable music
players. Auris Nasus Larynx. 2011;38(6):692-6.
Exclude: Non-randomized head-to-head
Gabr TA, El-Hay MA, Badawy A. Electrophysiological and psychological studies in tinnitus.
Auris Nasus Larynx. 2011;38(6):678-83.
Exclude: Only determined various effects
Gananca MM, Caovilla HH, Gananca FF, et al. Clonazepam in the pharmacological treatment of
vertigo and tinnitus. Int Tinnitus J. 2002;8(1):50-3. PMID:14763236.
Exclude: Case study or series
Garduno-Anaya MA, De Toledo HC, Hinojosa-Gonzalez R, et al. Dexamethasone inner ear
perfusion by intratympanic injection in unilateral Meniere’s disease: A two-year prospective,
placebo-controlled, double-blind, randomized trial. Otolaryngol Head Neck Surg.
2005;133(2):285-94.
Exclude: Insufficient detail of outcome data/not extractable
Garin P, Gilain C, Van Damme JP, et al. Short- and long-lasting tinnitus relief induced by
transcranial direct current stimulation. Journal of Neurology. 2011;258(11):1940-8.
PMID:21509429.
Exclude: Insufficient detail of outcome data/not extractable
Gavilan J, Gavilan C. Middle fossa vestibular neurectomy. Long-term results. Arch Otolaryngol.
1984;110(12):785-7. PMID:6508626.
Exclude: Non-randomized head-to-head
Gerber KE, Nehemkis AM, Charter RA, et al. Is tinnitus a psychological disorder? Int J
Psychiatr Med. 1985;15(1):81-7. PMID:4055250.
Exclude: Article not available
C-16
Gersdorff M, Nouwen J, Gilain C, et al. Tinnitus and otosclerosis. Eur Arch Otorhinolaryngol.
2000;257(6):314-6. PMID:10993550.
Exclude: Case study or series
Geven LI, de Kleine E., Free RH, et al. Contralateral suppression of otoacoustic emissions in
tinnitus patients. Otol Neurotol. 2011;32(2):315-21. PMID:20962699.
Exclude: Only determined various effects
Giannasi LC, Almeida FR, Magini M, et al. Systematic assessment of the impact of oral
appliance therapy on the temporomandibular joint during treatment of obstructive sleep apnea:
Long-term evaluation. Sleep and Breathing. 2009;13(4):375-81.
Exclude: Only about prevalence
Ginsberg DL. Sertraline for severe tinnitus. Prim Psychiatr. 2006;13(3):32-3.
Exclude: Not a primary study
Giridharan W, Papanikolou V, Knight L. ‘Buzz’ in the ear. Ear Nose Throat J. 2004;83(2):83.
PMID:15008436.
Exclude: Case study or series
Goddard JC, Berliner K, Luxford WM. Recent experience with the neuromonics tinnitus
treatment. Int Tinnitus J. 2009;15(2):168-73. PMID:20420343.
Exclude: Non-randomized head-to-head
Goebel G, Kahl M, Arnold W, et al. 15-year prospective follow-up study of behavioral therapy
in a large sample of inpatients with chronic tinnitus. Acta Otolaryngol Suppl. 2006;(556):70-9.
PMID:17114147.
Exclude: Insufficient detail of outcome data/not extractable
Golden RN, Evans DL. Antidepressants and tinnitus. Arch Intern Med. 1994;154(12):1411
PMID:8002694.
Exclude: Not a primary study
Goldstein B, Shulman A, Avitable MJ. Clear Tinnitus, middle-ear pressure, and tinnitus relief: A
prospective trial. Int Tinnitus J. 2007;13(1):29-39. PMID:17691660.
Exclude: Tinnitus is somatic
Goldstein BA, Lenhardt ML, Shulman A. Tinnitus improvement with ultra-high-frequency
vibration therapy. Int Tinnitus J. 2005;11(1):14-22. PMID:16419683.
Exclude: Non-randomized head-to-head
Goldstein BA, Shulman A, Lenhardt ML, et al. Long-term inhibition of tinnitus by UltraQuiet
therapy: Preliminary report. Int Tinnitus J. 2001;7(2):122-7. PMID:14689651.
Exclude: Case study or series
Goldstein BA, Shulman A, Lenhardt ML. Ultra-high-frequency ultrasonic external acoustic
stimulation for tinnitus relief: A method for patient selection. Int Tinnitus J. 2005;11(2):111-4.
PMID:16639909.
Exclude: Non-randomized head-to-head
Goldstein BA, Shulman A. Tinnitus outcome profile and tinnitus control. Int Tinnitus J.
2003;9(1):26-31. PMID:14763326.
Exclude: Non-randomized head-to-head
C-17
Goodwin PE, Johnson RM. The loudness of tinnitus. Acta Otolaryngol. 1980;90(5-6):353-9.
PMID:7211329.
Exclude: Case study or series
Göörtelmeyer R, Schmidt J, Suckfüüll M, et al. Assessment of tinnitus-related impairments and
disabilities using the German THI-12: Sensitivity and stability of the scale over time. Int J
Audiol. 2011;50(8):523-9.
Exclude: Insufficient detail of outcome data/not extractable
Gopinath B, McMahon CM, Rochtchina E, et al. Incidence, persistence, and progression of
tinnitus symptoms in older adults: The Blue Mountains Hearing Study. Ear Hear.
2010;31(3):407-12. PMID:20124901.
Exclude: Only about prevalence
Gopinath B, McMahon CM, Rochtchina E, et al. Risk factors and impacts of incident tinnitus in
older adults. Ann Epidemiol. 2010;20(2):129-35. PMID:20123163.
Exclude: Only determined various effects
Gordon AG. Tinnitus and hallucinations. J Am Acad Child Adolesc Psychiatr. 1988;27(1):140-1.
PMID:3343202.
Exclude: Not a primary study
Graham JM, Hazell JW. Electrical stimulation of the human cochlea using a transtympanic
electrode. Br J Audiol. 1977;11(2):59-62. PMID:922226.
Exclude: Non-randomized head-to-head
Graham MD, Sataloff RT, Kemink JL. Tinnitus in Meniere’s disease: Response to titration
streptomycin therapy. J Laryngol Otol. 1983;97(Suppl. 9):281-6.
Exclude: Case study or series
Graul J, Klinger R, Greimel KV, et al. Differential outcome of a multimodal cognitive-
behavioral inpatient treatment for patients with chronic decompensated tinnitus. Int Tinnitus J.
2008;14(1):73-81. PMID:18616090.
Exclude: Non-randomized head-to-head
Griffitts TM, Collins CP, Collins PC, et al. Walker repair of the temporomandibular joint: A
retrospective evaluation of 117 patients. J Oral Maxillofac Surg. 2007;65(10):1958-62.
Exclude: Case study or series
Grossan M. Treatment of subjective tinnitus with biofeedback. Ear Nose Throat J.
1976;55(10):314-8. PMID:991780.
Exclude: Case study or series
Grossi MG, Belcaro G, Cesarone MR, et al. Improvement in cochlear flow with Pycnogenol® in
patients with tinnitus: A pilot evaluation. Panminerva Medica. 2010;52(2:Suppl 1):63-7.
PMID:20657537.
Exclude: Non-randomized head-to-head
Gudex C, Skellgaard PH, West T, et al. Effectiveness of a tinnitus management programme: A 2-
year follow-up study. BMC Ear Nose Throat Disord. 2009;9(1):6.
Exclude: Non-randomized head-to-head
C-18
Gul H, Nowak R, Buchner FA, et al. Different treatment modalities of tinnitus at the
EuromedClinic. Int Tinnitus J. 2000;6(1):50-3. PMID:14689618.
Exclude: Case study or series
Gurr P, Owen G, Reid A, et al. Tinnitus in pregnancy. Clin Otolaryngol Allied Sci.
1993;18(4):294-7. PMID:8877189.
Exclude: Only about prevalence
Guth PS, Risey J, Briner W, et al. Evaluation of amino-oxyacetic acid as a palliative in tinnitus.
Ann Otol Rhinol Laryngol. 1990;99(1):74-9. PMID:1688487.
Exclude: Insufficient detail of outcome data/not extractable
Haginomori S, Makimoto K, Araki M, et al. Effect of lidocaine injection of EOAE in patients
with tinnitus. Acta Otolaryngol. 1995;115(4):488-92. PMID:7572122.
Exclude: Insufficient detail of outcome data/not extractable
Hahn A, Radkova L, Achiemere G, et al. Multimodal therapy for chronic tinnitus. Int Tinnitus J.
2008;14(1):69-72. PMID:18616089.
Exclude: Insufficient detail of outcome data/not extractable
Halford JB, Anderson SD. Anxiety and depression in tinnitus sufferers. J Psychosom Res.
1991;35(4-5):383-90. PMID:1920169.
Exclude: Only determined various effects
Halford JB, Anderson SD. Tinnitus severity measured by a subjective scale, audiometry and
clinical judgement. J Laryngol Otol. 1991;105(2):89-93. PMID:2013737.
Exclude: Non-randomized head-to-head
Hallam RS, Jakes SC, Chambers C, et al. A comparison of different methods for assessing the
‘intensity’ of tinnitus. Acta Otolaryngol. 1985;99(5-6):501-8. PMID:4024897.
Exclude: Non-randomized head-to-head
Haller S, Birbaumer N, Veit R. Real-time fMRI feedback training may improve chronic tinnitus.
Eur Radiol. 2010;20(3):696-703. PMID:19760238.
Exclude: Case study or series
Halmos P, Molnar L, Kormos M. Experiences made with anticonvulsiva in the therapy of
tinnitus. HNO-Praxis. 1982;7(1):59-61.
Exclude: Article not available
Hammami B, Chakroun A, Achour I, et al. Transmission deafness and tinnitus: What diagnosis?
Eur Ann Otorhinolaryngol Head Neck Dis. 2010;127(5):193-6. PMID:21035422.
Exclude: Case study or series
Handscomb L. Analysis of responses to individual items on the tinnitus handicap inventory
according to severity of tinnitus handicap. Am J Audiol. 2006;15(2):102-7. PMID:17182874.
Exclude: Only determined various effects
Handscomb L. Use of bedside sound generators by patients with tinnitus-related sleeping
difficulty: Which sounds are preferred and why? Acta Otolaryngol Suppl. 2006;(556):59-63.
PMID:17114145.
Exclude: Insufficient detail of outcome data/not extractable
C-19
Hanley PJ, Davis PB, Paki B, et al. Treatment of tinnitus with a customized, dynamic acoustic
neural stimulus: Clinical outcomes in general private practice. Ann Otol Rhinol Laryngol.
2008;117(11):791-9. PMID:19102123.
Exclude: Non-randomized head-to-head
Hann D, Searchfield GD, Sanders M, et al. Strategies for the selection of music in the short-term
management of mild tinnitus. Aust NZ J Audiol. 2008;30(2):129-40.
Exclude: Insufficient detail of outcome data/not extractable
Hansen PE, Hansen JH, Bentzen O. Acupuncture treatment of chronic unilateral tinnitus--A
double-blind cross-over trial. Clin Otolaryngol Allied Sci. 1982;7(5):325-9. PMID:6756709.
Exclude: Non-randomized head-to-head
Hansen PE, Hansen JH, Bentzen O. Acupuncture treatment of chronic unilateral tinnitus. A
double-blind cross-over investigation. Ugeskr-Laeg. 1981;143(44):2888-90.
Exclude: Insufficient detail of outcome data/not extractable
Happich M, Moock J, von LT. Health state valuation methods and reference points: The case of
tinnitus. Value Health. 2009;12(1):88-95. PMID:19911443.
Exclude: Non-randomized head-to-head
Haralambous G, Wilson PH, Platt-Hepworth S, et al. EMG biofeedback in the treatment of
tinnitus: An experimental evaluation. Behav Res Ther. 1987;25(1):49-55. PMID:3593161.
Exclude: Non-randomized head-to-head
Harrop-Griffiths J, Katon W, Dobie R, et al. Chronic tinnitus: Association with psychiatric
diagnoses. J Psychosom Res. 1987;31(5):613-21. PMID:3430424.
Exclude: Only determined various effects
Hastak SM. Treatment of memory impairment, vertigo and tinnitus in the elderly with piribedil
in an Indian general practice setting. J Indian Med Assoc. 2003;101(8):500-1. PMID:15071809.
Exclude: Case study or series
Hatanaka A, Ariizumi Y, Kitamura K. Pros and cons of tinnitus retraining therapy. Acta
Otolaryngol. 2008;128(4):365-8. PMID:18368566.
Exclude: Non-randomized head-to-head
Hawthorne M, O’Connor S. The psychological side of tinnitus. BMJ Clin Res Ed.
1987;294(6585):1441-2. PMID:3111582.
Exclude: Not a primary study
Hawthorne MR, Britten SR, O’Connor S, et al. The management of a population of tinnitus
sufferers in a specialized clinic: Part III. The evaluation of psychiatric intervention. J Laryngol
Otol. 1987;101(8):795-9. PMID:3655532.
Exclude: Not a primary study
Hayes R. On helping people with tinnitus to help themselves. Br J Audiol. 1987;21(4):327-8.
PMID:3690071.
Exclude: Not a primary study
Hazell JW, Jastreboff PJ, Meerton LE, et al. Electrical tinnitus suppression: Frequency
dependence of effects. Audiology. 1993;32(1):68-77. PMID:8447763.
Exclude: Case study or series
C-20
Hazell JW, McKinney CJ, Aleksy W. Mechanisms of tinnitus in profound deafness. Ann Otol
Rhinol Laryngol Suppl. 1995;166:418-20. PMID:7668731.
Exclude: Non-randomized head-to-head
Hazell JW, Wood S. Tinnitus masking-A significant contribution to tinnitus management. Br J
Audiol. 1981;15(4):223-30. PMID:7296101.
Exclude: Not a primary study
Hazell JW, Wood SM, Cooper HR, et al. A clinical study of tinnitus maskers. Br J Audiol.
1985;19(2):65-146. PMID:3896355.
Exclude: Insufficient detail of outcome data/not extractable
Hazell JW. Tinnitus. Practitioner. 1981;225(1361):1577-85. PMID:7335587.
Exclude: Article not available
Hazell JWP, Wood SM. Drug therapy and tinnitus: The UK experience. J Laryngol Otol.
1983;97(Suppl. 9):277-80.
Exclude: Not a primary study
Hebert S, Carrier J. Sleep complaints in elderly tinnitus patients: A controlled study. Ear Hear.
2007;28(5):649-55. PMID:17804979.
Exclude: Only determined various effects
Hebert S, Fullum S, Carrier J. Polysomnographic and quantitative electroencephalographic
correlates of subjective sleep complaints in chronic tinnitus. J Sleep Res. 2011;20(1:Pt 1):38-44.
PMID:20561177.
Exclude: Only determined various effects
Hebert S, Lupien SJ. Salivary cortisol levels, subjective stress, and tinnitus intensity in tinnitus
sufferers during noise exposure in the laboratory. Int J Hyg Environ Health. 2009;212(1):37-44.
PMID:18243788.
Exclude: Only determined various effects
Henry JA, James KE, Owens K, et al. Auditory test result characteristics of subjects with and
without tinnitus. J Rehab Res Dev. 2009;46(5):619-32. PMID:19882495.
Exclude: Only determined various effects
Henry JA, Rheinsburg B, Owens KK, et al. New instrumentation for automated tinnitus
psychoacoustic assessment. Acta Otolaryngol Suppl. 2006;(556):34-8. PMID:17114140.
Exclude: Non-randomized head-to-head
Henry JA, Rheinsburg B, Zaugg T. Comparison of custom sounds for achieving tinnitus relief. J
Am Acad Audiol. 2004;15(8):585-98. PMID:15553658.
Exclude: Insufficient detail of outcome data/not extractable
Henry JA, Schechter MA, Zaugg TL, et al. Clinical trial to compare tinnitus masking and tinnitus
retraining therapy. Acta Otolaryngol Suppl. 2006;(556):64-9. PMID:17114146.
Exclude: Insufficient detail of outcome data/not extractable
Henry JA, Schechter MA, Zaugg TL, et al. Outcomes of clinical trial: Tinnitus masking versus
tinnitus retraining therapy. J Am Acad Audiol. 2006;17(2):104-32. PMID:16640064.
Exclude: Non-randomized head-to-head
C-21
Henry JL, Kangas M, Wilson PH. Development of the psychological impact of tinnitus
interview: A clinician-administered measure of tinnitus-related distress. Int Tinnitus J.
2001;7(1):20-6. PMID:14964950.
Exclude: Non-randomized head-to-head
Henry JL, Wilson PH. The psychometric properties of two measures of tinnitus complaint and
handicap. Int Tinnitus J. 1998;4(2):114-21.
Exclude: Insufficient detail of outcome data/not extractable
Herraiz C, Diges I, Cobo P, et al. Auditory discrimination therapy (ADT) for tinnitus
managment: Preliminary results. Acta Otolaryngol Suppl. 2006;(556):80-3. PMID:17114148.
Exclude: Insufficient detail of outcome data/not extractable
Herraiz C, Diges I, Cobo P. Auditory discrimination therapy (ADT) for tinnitus management.
Progr Brain Res. 2007;166:467-71. PMID:17956811.
Exclude: Insufficient detail of outcome data/not extractable
Herraiz C, Hernandez FJ, Plaza G, et al. Long-term clinical trial of tinnitus retraining therapy.
Otolaryngol Head Neck Surg. 2005;133(5):774-9. PMID:16274808.
Exclude: Insufficient detail of outcome data/not extractable
Herraiz C, Hernandez FJ, Toledano A, et al. Tinnitus retraining therapy: Prognosis factors. Am J
Otolaryngol. 2007;28(4):225-9. PMID:17606035.
Exclude: Insufficient detail of outcome data/not extractable
Herraiz C, Plaza F, de los SG. Tinnitus retraining therapy in Meniere disease. Acta
Otorrinolaringol Espanola. 2006;57(2):96-100.
Exclude: Case study or series
Herraiz C, Plaza G, Aparicio JM, et al. Transtympanic steroids for Meniere’s disease. Otol
Neurotol. 2010;31(1):162-7. PMID:19924013.
Exclude: Insufficient detail of outcome data/not extractable
Herraiz C, Toledano A, Diges I. Trans-electrical nerve stimulation (TENS) for somatic tinnitus.
Progr Brain Res. 2007;166:389-94. PMID:17956803.
Exclude: Insufficient detail of outcome data/not extractable
Hesser H, Andersson G. The role of anxiety sensitivity and behavioral avoidance in tinnitus
disability. Int J Audiol. 2009;48(5):295-9. PMID:19842804.
Exclude: Only determined various effects
Hesser H, Pereswetoff-Morath CE, Andersson G. Consequences of controlling background
sounds: The effect of experiential avoidance on tinnitus interference. Rehabil Psychol.
2009;54(4):381-9. PMID:19929119.
Exclude: Insufficient detail of outcome data/not extractable
Hesser H, Westin V, Hayes SC, et al. Clients’ in-session acceptance and cognitive defusion
behaviors in acceptance-based treatment of tinnitus distress. Behav Res Ther. 2009;47(6):523-8.
PMID:19268281.
Exclude: Non-randomized head-to-head
C-22
Hester TO, Theilman G, Green W, et al. Cyclandelate in the management of tinnitus: A
randomized, placebo-controlled study. Otolaryngol Head Neck Surg. 1998;118(3:Pt 1):t-32
PMID:9527112.
Exclude: Insufficient detail of outcome data/not extractable
Hicks GW. Intratympanic and round-window drug therapy: Effect on cochlear tinnitus. Int
Tinnitus J. 1998;4(2):144-7.
Exclude: Tinnitus is somatic
Higgins KM, Chen JM, Nedzelski JM, et al. A matched-pair comparison of two cochlear implant
systems. J Otolaryngol. 2002;31(2):97-105. PMID:12019751.
Exclude: Non-randomized head-to-head
Hikita-Watanabe N, Kitahara T, Horii A, et al. Tinnitus as a prognostic factor of sudden
deafness. Acta Otolaryngol. 2010;130(1):79-83. PMID:19437168.
Exclude: Only determined various effects
Hiller W, Goebel G. Assessing audiological, pathophysiological, and psychological variables in
chronic tinnitus: A study of reliability and search for prognostic factors. Int J Behav Med.
1999;6(4):312-30.
Exclude: Non-randomized head-to-head
Hiller W, Goebel G. Rapid assessment of tinnitus-related psychological distress using the Mini-
TQ. Int J Audiol. 2004;43(10):600-4. PMID:15724525.
Exclude: Non-randomized head-to-head
Hiller W, Goebel G. When tinnitus loudness and annoyance are discrepant: Audiological
characteristics and psychological profile. Audiol Neuro Otol. 2007;12(6):391-400.
PMID:17664870.
Exclude: Only determined various effects
Hinchcliffe R, Chambers C. Loudness of tinnitus: An approach to measurement. Adv
Otorhinolaryngol. 1983;29:163-73. PMID:6837369.
Exclude: Non-randomized head-to-head
Hochberg I, Waltzman S. Comparison of pulsed and continuous tone thresholds in patients with
tinnitus. Audiology. 1972;11(5):337-42. PMID:4671203.
Exclude: Only determined various effects
Holdefer L, Oliveira CA, Venosa AR. Group therapy for patients with tinnitus at the University
of Brasilia Medical School. Revista Brasileira de Otorrinolaringologia. 2010;76(1):102-6.
PMID:20339697.
Exclude: Non-randomized head-to-head
Holgers KM, Axelsson A, Pringle I. Ginkgo biloba extract for the treatment of tinnitus.
Audiology. 1994;33(2):85-92. PMID:8179518.
Exclude: Insufficient detail of outcome data/not extractable
Holgers KM, Erlandsson SI, Barrenas ML. Predictive factors for the severity of tinnitus.
Audiology. 2000;39(5):284-91. PMID:11093613.
Exclude: Only determined various effects
C-23
Holgers KM, Hakansson BE. Sound stimulation via bone conduction for tinnitus relief: A pilot
study. Int J Audiol. 2002;41(5):293-300. PMID:12166689.
Exclude: Case study or series
Holgers KM, Zoger S, Svedlund K. Predictive factors for development of severe tinnitus
suffering-further characterisation. Int J Audiol. 2005;44(10):584-92. PMID:16315449.
Exclude: Non-randomized head-to-head
Holm AF, Staal MJ, Mooij JJ, et al. Neurostimulation as a new treatment for severe tinnitus: A
pilot study. Otol Neurotol. 428;26(3):425-8. PMID:15891644.
Exclude: Case study or series
Holmes S, Padgham ND. The incidence, management and consequence of tinnitus in older
adults. Rev Clin Gerontol. 2008;18(4):269-85.
Exclude: Not a primary study
House JW, Miller L, House PR. Severe tinnitus: Treatment with biofeedback training (results in
41 cases). Transactions. 1977;84(4 Pt 1):697-703. PMID:898522.
Exclude: Case study or series
House JW. Management of the tinnitus patient. Ann Otol Rhinol Laryngol. 1981;90(6:Pt 1):597-
601. PMID:7316384.
Exclude: Not a primary study
House JW. Therapies for tinnitus. Am J Otol. 1989;10(3):163-5. PMID:2665506.
Exclude: Not a primary study
House JW. Tinnitus: Evaluation and treatment. Am J Otol. 1984;5(6):472-5. PMID:6334995.
Exclude: Not a primary study
House JW. Treatment of severe tinnitus with biofeedback training. Laryngoscope.
1978;88(3):406-12. PMID:628294.
Exclude: Case study or series
House PR, House JW. The tinnitus patient: Personality and biofeedback treatment. Semin Hear.
1987;8(1):15-9.
Exclude: Not a primary study
Hu J. Acupuncture treatment of tinnitus. J Tradit Chin Med. 2004;24(3):238-40.
PMID:15510810.
Exclude: Case study or series
Hulshof JH, Vermeij P. The effect of intra-venous lidocaine and several different doses oral
tocainide HCl on tinnitus. A dose-finding study. Acta Otolaryngol. 1984;98(3-4):231-8.
PMID:6437131.
Exclude: Insufficient detail of outcome data/not extractable
Hulshof JH, Vermeij P. The effect of nicotinamide on tinnitus: A double-blind controlled study.
Clin Otolaryngol Allied Sci. 1987;12(3):211-4. PMID:2955964.
Exclude: Insufficient detail of outcome data/not extractable
Hulshof JH, Vermeij P. The value of carbamazepine in the treatment of tinnitus. ORL.
1985;47(5):262-6. PMID:3900856.
Exclude: Insufficient detail of outcome data/not extractable
C-24
Hulshof JH, Vermeij P. The value of flunarizine in the treatment of tinnitus. ORL.
1986;48(1):33-6. PMID:3513083.
Exclude: Insufficient detail of outcome data/not extractable
Hulshof JH, Vermeij P. The value of tocainide in the treatment of tinnitus. A double-blind
controlled study. Arch Oto-Rhino-Laryngol. 1985;241(3):279-83. PMID:3161487.
Exclude: Insufficient detail of outcome data/not extractable
Hulshof JH, Vermey P. Section 2: Medical treatment. The effect of several doses of oral
tocainide HCl on tinnitus: A dose-finding study. J Laryngol Otol. 1983;97(Suppl. 9):257-8.
Exclude: Not a primary study
Hulshof JH. The loudness of tinnitus. Acta Otolaryngol. 1986;102(1-2):40-3. PMID:3739691.
Exclude: Non-randomized head-to-head
Hurtuk A, Dome C, Holloman CH, et al. Melatonin: Can it stop the ringing? Ann Otol Rhinol
Laryngol. 2011;120(7):433-40. PMID:21859051.
Exclude: Insufficient detail of outcome data/not extractable
Hutter HP, Moshammer H, Wallner P, et al. Tinnitus and mobile phone use. Occup Environ
Med. 2010;67(12):804-8. PMID:20573849.
Exclude: Only about prevalence
Imipramine and tinnitus. J Clin Psychiatry. 1987;48(12):496-7. PMID:3693337.
Exclude: Not a primary study
Ince LP, Greene RY, Alba A, et al. A matching-to-sample feedback technique for training self-
control of tinnitus. Health Psychol. 1987;6(2):173-82. PMID:3830120.
Exclude: Case study or series
Israel JM, Connelly JS, McTigue ST, et al. Lidocaine in the treatment of tinnitus aurium. A
double-blind study. Arch Otolaryngol. 1982;108(8):471-3. PMID:7049137.
Exclude: Insufficient detail of outcome data/not extractable
Ito J, Sakakihara J. Suppression of tinnitus by cochlear implantation. Am J Otolaryngol.
1994;15(2):145-8. PMID:8179106.
Exclude: Case study or series
Ito J, Sakakihara J. Tinnitus suppression by electrical stimulation of the cochlear wall and by
cochlear implantation. Laryngoscope. 1994;104(6:Pt 1):752-4. PMID:8196452.
Exclude: Insufficient detail of outcome data/not extractable
Ito J. Tinnitus suppression in cochlear implant patients. Otolaryngol Head Neck Surg.
1997;117(6):701-3. PMID:9419102.
Exclude: Insufficient detail of outcome data/not extractable
Ito M, Soma K, Ando R. Association between tinnitus retraining therapy and a tinnitus control
instrument. Auris Nasus Larynx. 2009;36(5):536-40. PMID:19269119.
Exclude: Non-randomized head-to-head
Jackson A, MacPherson H, Hahn S. Acupuncture for tinnitus: A series of six n = 1 controlled
trials. Complement Ther Med. 2006;14(1):39-46. PMID:16473752.
Exclude: Case study or series
C-25
Jackson P. A comparison of the effects of eighth nerve section with lidocaine on tinnitus. J
Laryngol Otol. 1985;99(7):663-6. PMID:4020258.
Exclude: Case study or series
Jacobson GP, McCaslin DL. Clinical forum. A search for evidence of a direct relationship
between tinnitus and suicide. J Am Acad Audiol. 2001;12(10):493-6.
Exclude: Not a primary study
Jakes S, Stephens SD. Multivariate analyses of tinnitus complaint and change in tinnitus
complaint: A masker study. Br J Audiol. 1987;21(4):259-72. PMID:3690065.
Exclude: Tinnitus is somatic
Jakes SC, Hallam RS, Rachman S, et al. The effects of reassurance, relaxation training and
distraction on chronic tinnitus sufferers. Behav Res Ther. 1986;24(5):497-507. PMID:3530238.
Exclude: Case study or series
Jalali MM, Kousha A, Naghavi SE, et al. The effects of alprazolam on tinnitus: A cross-over
randomized clinical trial. Med Sci Monitor. 2009;15(11):I55-I60 PMID:19865063.
Exclude: Insufficient detail of outcome data/not extractable
Jang DW, Johnson E, Chandrasekhar SS. NeuromonicsTM Tinnitus Treatment: Preliminary
experience in a private practice setting. Laryngoscope. 2010;120(Suppl 4):S208.
PMID:21225806.
Exclude: Not a primary study
Jastreboff PJ, Gray WC, Gold SL. Neurophysiological approach to tinnitus patients. Am J Otol.
1996;17(2):236-40. PMID:8723954.
Exclude: Not a primary study
Jastreboff PJ. Tinnitus retraining therapy. Br J Audiol. 1999;33(1):68-70. PMID:10219725.
Exclude: Not a primary study
Javaheri S, Cohen V, Libman I, et al. Life-threatening tinnitus. Lancet. 2000;356(9226):308.
PMID:11071187.
Exclude: Case study or series
Jayarajan V, Coles R. Treatment of tinnitus with frusemide. J Audiol Med. 1993;2(2):114-9.
Exclude: Case study or series
Jerger J. Does tinnitus actually affect quality of life? J Am Acad Audiol. 2007;18(3):196.
PMID:17479612.
Exclude: Not a primary study
Jerger J. Sound-based relief. J Am Acad Audiol. 2004;15(8):540 PMID:15553653.
Exclude: Not a primary study
Joachim S, Kronau S, Moshovel N. Test-dependent osteopathic treatment of patients suffering
from craniomandibular disorders (CMD) and tinnitus. A pre-post pilot trial. Osteopathische
Medizin. 2009;10(1):34.
Exclude: Not a primary study
C-26
Job A, Raynal M, Kossowski M. Susceptibility to tinnitus revealed at 2 kHz range by bilateral
lower DPOAEs in normal hearing subjects with noise exposure. Audiol Neuro Otol.
2007;12(3):137-44. PMID:17259699.
Exclude: Non-randomized head-to-head
Johnson RM, Goodwin P. The use of audiometric tests in the management of the tinnitus patient.
J Laryngol Otol Suppl. 1981;(4):48-51. PMID:6946170.
Exclude: Not a primary study
Jozefowicz-Korczynska M, Ciechomska EA, Pajor AM. Electronystagmography outcome and
neuropsychological findings in tinnitus patients. Int Tinnitus J. 2005;11(1):54-7.
PMID:16419691.
Exclude: Only determined various effects
Jung S, Wermker K, Poetschik H, et al. The impact of hyperbaric oxygen therapy on serological
values of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).
Head Face Med. 2010;6:29. PMID:21176170.
Exclude: Non-randomized head-to-head
Kaada B, Hognestad S, Havstad J. Transcutaneous nerve stimulation (TNS) in tinnitus. Scand
Audiol. 1989;18(4):211-7. PMID:2609098.
Exclude: Insufficient detail of outcome data/not extractable
Kaasinen S, Pyykko I, Ishizaki H, et al. Effect of intratympanically administered gentamicin on
hearing and tinnitus in Meniere’s disease. Acta Otolaryngol Suppl. 1995;520:184-5.
PMID:8749114.
Exclude: Insufficient detail of outcome data/not extractable
Kalcioglu MT, Bayindir T, Erdem T, et al. Objective evaluation of the effects of intravenous
lidocaine on tinnitus. Hear Res. 2005;199(1-2):81-8. PMID:15574302.
Exclude: Insufficient detail of outcome data/not extractable
Kaldo V, Richards J, Andersson G. Tinnitus Stages of Change Questionnaire: Psychometric
development and validation. Psychol Health Med. 2006;11(4):483-97. PMID:17129924.
Exclude: Non-randomized head-to-head
Kaldo-Sandstrom V, Larsen HC, Andersson G. Internet-based cognitive-behavioral self-help
treatment of tinnitus: Clinical effectiveness and predictors of outcome. Am J Audiol.
2004;13(2):185-92. PMID:15903144.
Exclude: Non-randomized head-to-head
Kallio H, Niskanen ML, Havia M, et al. I.V. ropivacaine compared with lidocaine for the
treatment of tinnitus. Br J Anaesth. 2008;101(2):261-5. PMID:18522937.
Exclude: Insufficient detail of outcome data/not extractable
Kapkin O, Satar B, Yetiser S. Transcutaneous electrical stimulation of subjective tinnitus. A
placebo-controlled, randomized and comparative analysis. ORL. 2008;70(3):156-61.
PMID:18401195.
Exclude: Insufficient detail of outcome data/not extractable
Kasemsuwan L, Jariengprasert C, Chaturapatranont S. Transtympanic gentamicin treatment in
Meniere’s disease: A preliminary report. J Med Assoc Thai. 2006;89(7):979-85.
Exclude: Case study or series
C-27
Katon W, Sullivan M, Russo J, et al. Depressive symptoms and measures of disability: A
prospective study. J Affect Disord. 1993;27(4):245-54. PMID:8509525.
Exclude: Non-randomized head-to-head
Kaufman A, I, Gibson SA, Van de Water SM, et al. The effect of endolymphatic system surgery
on tinnitus in Meniere’s disease and hydrops. J Laryngol Otol. 1983;97(Suppl. 9):299-310.
Exclude: Case study or series
Kay NJ. Oral chemotherapy in tinnitus. Br J Audiol. 1981;15(2):123-4. PMID:7225648.
Exclude: Case study or series
Kearney BG, Wilson PH, Haralambous G. Stress appraisal and personality characteristics of
headache patients: Comparisons with tinnitus and normal control groups. Behav Change.
1987;4(2):25-31.
Exclude: Only determined various effects
Kemp S, George RN. Masking of tinnitus induced by sound. J Speech Hear Res.
1992;35(5):1169-79. PMID:1447927.
Exclude: Non-randomized head-to-head
Khan M, Gross J, Haupt H, et al. A pilot clinical trial of the effects of coenzyme Q10 on chronic
tinnitus aurium. Otolaryngol Head Neck Surg. 2007;136(1):72-7. PMID:17210337.
Exclude: Insufficient detail of outcome data/not extractable
Khedr EM, Abo-Elfetoh N, Rothwell JC, et al. Contralateral versus ipsilateral rTMS of
temporoparietal cortex for the treatment of chronic unilateral tinnitus: Comparative study. Eur J
Neurol. 2010;17(7):976-83. PMID:20236173.
Exclude: Insufficient detail of outcome data/not extractable
Khedr EM, Rothwell JC, El-Atar A. One-year follow up of patients with chronic tinnitus treated
with left temporoparietal rTMS. Eur J Neurol. 2009;16(3):404-8. PMID:19175380.
Exclude: Insufficient detail of outcome data/not extractable
Kilpatrick JK, Sismanis A, Spencer RF, et al. Low-dose oral methotrexate management of
patients with bilateral Meniere’s disease. Ear Nose Throat J. 2000;79(2):82-3, 86-8, 91-2.
PMID:10697931.
Exclude: Case study or series
Kim DK, Park SN, Park KH, et al. Clinical characteristics and audiological significance of
spontaneous otoacoustic emissions in tinnitus patients with normal hearing. J Laryngol Otol.
2011;125(3):246-50. PMID:21054911.
Exclude: Insufficient detail of outcome data/not extractable
Kim NK, Lee DH, Lee JH, et al. Bojungikgitang and banhabaekchulchonmatang in adult patients
with tinnitus, a randomized, double-blind, three-arm, placebo-controlled trial--study protocol.
Trials. 2010;11:34. PMID:20346181.
Exclude: Not a primary study
Kirsch CA, Blanchard EB, Parnes SM. A multiple-baseline evaluation of the treatment of
subjective tinnitus with relaxation training and biofeedback. Biofeedback Self Regul.
1987;12(4):295-312. PMID:3331298.
Exclude: Case study or series
C-28
Kirsch CA, Blanchard EB, Parnes SM. Psychological characteristics of individuals high and low
in their ability to cope with tinnitus. Psychosom Med. 1989;51(2):209-17. PMID:2710911.
Exclude: Only determined various effects
Kleinjung T, Eichhammer P, Landgrebe M, et al. Combined temporal and prefrontal transcranial
magnetic stimulation for tinnitus treatment: A pilot study. Otolaryngol Head Neck Surg.
2008;138(4):497-501. PMID:18359361.
Exclude: Non-randomized head-to-head
Kleinjung T, Eichhammer P, Langguth B, et al. Long-term effects of repetitive transcranial
magnetic stimulation (rTMS) in patients with chronic tinnitus. Otolaryngol Head Neck Surg.
2005;132(4):566-9. PMID:15806046.
Exclude: Insufficient detail of outcome data/not extractable
Kleinjung T, Steffens T, Landgrebe M, et al. Levodopa does not enhance the effect of low-
frequency repetitive transcranial magnetic stimulation in tinnitus treatment. Otolaryngol Head
Neck Surg. 2009;140(1):92-5. PMID:19130969.
Exclude: Non-randomized head-to-head
Kleinjung T, Steffens T, Landgrebe M, et al. Repetitive transcranial magnetic stimulation for
tinnitus treatment: No enhancement by the dopamine and noradrenaline reuptake inhibitor
bupropion. Brain Stimulation. 2011;4(2):65-70. PMID:21511205.
Exclude: Insufficient detail of outcome data/not extractable
Kleinjung T, Steffens T, Sand P, et al. Which tinnitus patients benefit from transcranial magnetic
stimulation? Otolaryngol Head Neck Surg. 2007;137(4):589-95. PMID:17903575.
Exclude: Insufficient detail of outcome data/not extractable
Ko Y, Park CW. Microvascular decompression for tinnitus. Stereotact Funct Neurosurg.
1997;68(1-4:Pt 1):266-9. PMID:9711727.
Exclude: Non-randomized head-to-head
Koefoed-Nielsen B, Tos M. Posttraumatic sensorineural hearing loss. A prospective long-term
study. ORL. 1982;44(4):206-15. PMID:7110669.
Exclude: Only about prevalence
Koh TC, Fung KT. Acupuncture therapy for tinnitus. Am J Acupuncture. 1983;11(1):59-61.
Exclude: Case study or series
Koizumi T, Nishimura T, Sakaguchi T, et al. Estimation of factors influencing the results of
tinnitus retraining therapy. Acta Otolaryngol Suppl. 2009;(562):40-5. PMID:19848238.
Exclude: Non-randomized head-to-head
Konopka W, Zalewski P, Olszewski J, et al. Tinnitus suppression by electrical promontory
stimulation (EPS) in patients with sensorineural hearing loss. Auris Nasus Larynx.
2001;28(1):35-40. PMID:11137361.
Exclude: Insufficient detail of outcome data/not extractable
Korres S, Mountricha A, Balatsouras D, et al. Tinnitus Retraining Therapy (TRT): Outcomes
after one-year treatment. Int Tinnitus J. 2010;16(1):55-9. PMID:21609915.
Exclude: Non-randomized head-to-head
C-29
Krog NH, Engdahl B, Tambs K. The association between tinnitus and mental health in a general
population sample: Results from the HUNT Study. J Psychosom Res. 2010;69(3):289-98.
PMID:20708451.
Exclude: Only determined various effects
Kroner-Herwig B, Hebing G, van Rijn-Kalkmann U, et al. The management of chronic tinnitus--
Comparison of a cognitive-behavioural group training with yoga. J Psychosom Res.
1995;39(2):153-65. PMID:7595873.
Exclude: Non-randomized head-to-head
Kroner-Herwig B, Zachriat C, Weigand D. Do patient characterisics predict outcome in the
outpatient treatment of chronic tinnitus? GMS Psycho-Social-Medicine. 2006;3:1-15.
Exclude: Insufficient detail of outcome data/not extractable
Kuk FK, Tyler RS, Rustad N, et al. Alternating current at the eardrum for tinnitus reduction. J
Speech Hear Res. 1989;32(2):393-400. PMID:2786979.
Exclude: Case study or series
Kunkle EC. Movement-induced transient tinnitus. Ann Otol Rhinol Laryngol. 2001;110(5:Pt
1):494. PMID:11372937.
Exclude: Not a primary study
Kusatz M, Ostermann T, Aldridge D. Auditive stimulation therapy as an intervention in subacute
and chronic tinnitus: A prospective observational study. Int Tinnitus J. 2005;11(2):163-9.
PMID:16639917.
Exclude: Insufficient detail of outcome data/not extractable
Kvestad E, Czajkowski N, Engdahl B, et al. Low heritability of tinnitus: Results from the second
Nord-Trondelag health study. Arch Otolaryngol Head Neck Surg. 2010;136(2):178-82.
PMID:20157066.
Exclude: Only about prevalence
Kwee HL, Struben WH. Tinnitus and myoclonus. J Laryngol Otol. 1972;86(3):237-41.
PMID:5014915.
Exclude: Case study or series
Labassi S, Beliaeff M. Retrospective of 1000 patients implanted with a Vibrant Soundbridge
middle-ear implant. Cochlear Implants Int. 2005;6(Suppl. 1):74-7.
Exclude: Not a primary study
Laffree JB, Vermeij P, Hulshof JH. The effect of iontophoresis of lignocaine in the treatment of
tinnitus. Clin Otolaryngol Allied Sci. 1989;14(5):401-4. PMID:2684451.
Exclude: Insufficient detail of outcome data/not extractable
Lam SYR. A comparative study of acupuncture treatment in bilateral sensory deafness and
tinnitus. Pac J Orient Med. 1999;(14):8-12.
Exclude: Article not available
LaMarte FP, Tyler RS. Noise-induced tinnitus. AAOHN J. 1987;35(9):403-6. PMID:3650081.
Exclude: Not a primary study
C-30
Lamm K. Hyperbaric oxygen therapy for the treatment of acute cochlear disorders and tinnitus.
ORL. 2003;65(6):315-6. PMID:14981322.
Exclude: Not a primary study
Landgrebe M, Frick U, Hauser S, et al. Association of tinnitus and electromagnetic
hypersensitivity: Hints for a shared pathophysiology? PLoS ONE. 2009;4(3):e5026.
PMID:19325894.
Exclude: Only about prevalence
Landis B, Landis E. Is biofeedback effective for chronic tinnitus? An intensive study with seven
subjects. Am J Otolaryngol. 1992;13(6):349-56. PMID:1443390.
Exclude: Case study or series
Langenbach M, Olderog M, Michel O, et al. Psychosocial and personality predictors of tinnitus-
related distress. Gen Hosp Psychiatry. 2005;27(1):73-7. PMID:15694221.
Exclude: Only determined various effects
Langguth B, Eichhammer P, Kreutzer A, et al. The impact of auditory cortex activity on
characterizing and treating patients with chronic tinnitus--first results from a PET study. Acta
Otolaryngol Suppl. 2006;(556):84-8. PMID:17114149.
Exclude: Insufficient detail of outcome data/not extractable
Langguth B, Kleinjung T, Fischer B, et al. Tinnitus severity, depression, and the big five
personality traits. Progr Brain Res. 2007;166:221-5. PMID:17956786.
Exclude: Only determined various effects
Langguth B, Kleinjung T, Marienhagen J, et al. Transcranial magnetic stimulation for the
treatment of tinnitus: Effects on cortical excitability. BMC Neurosci. 2007;8:45.
PMID:17605764.
Exclude: Insufficient detail of outcome data/not extractable
Langguth B, Zowe M, Landgrebe M, et al. Transcranial magnetic stimulation for the treatment of
tinnitus: A new coil positioning method and first results. Brain Topogr. 2006;18(4):241-7.
PMID:16845596.
Exclude: Insufficient detail of outcome data/not extractable
Larsson B, Lyttkens L, Wasterstrom SA. Tocainide and tinnitus. Clinical effect and site of
action. ORL. 1984;46(1):24-33. PMID:6422376.
Exclude: Case study or series
Lasisi AO, Abiona T, Gureje O. Tinnitus in the elderly: Profile, correlates, and impact in the
Nigerian Study of Ageing. Otolaryngol Head Neck Surg. 2010;143(4):510-5. PMID:20869560.
Exclude: Only about prevalence
Laurikainen E, Johansson R, Akaan-Penttila E, et al. Treatment of severe tinnitus. Acta
Otolaryngol Suppl. 2000;543:77-8. PMID:10908984.
Exclude: Case study or series
Laurikainen EA, Johansson RK, Kileny PR. Effects of intratympanically delivered lidocaine on
the auditory system in humans. Ear Hear. 1996;17(1):49-54. PMID:8741967.
Exclude: Case study or series
C-31
Lavinsky L, Oliveira MW, Bassanesi HJ, et al. Hyperinsulinemia and tinnitus: A historical
cohort. Int Tinnitus J. 2004;10(1):24-30. PMID:15379344.
Exclude: Insufficient detail of outcome data/not extractable
Lechtenberg R, Shulman A. Benzodiazepines in the treatment of tinnitus. J Laryngol Otol.
1983;97(Suppl. 9):271-6.
Exclude: Insufficient detail of outcome data/not extractable
Lee SL, Abraham M, Cacace AT, et al. Repetitive transcranial magnetic stimulation in veterans
with debilitating tinnitus: A pilot study. Otolaryngol Head Neck Surg. 2008;138(3):398-9.
PMID:18312892.
Exclude: Case study or series
Lehner A, Schecklemann M, Landgrebe M, et al. Predictors for rTMS response in chronic
tinnitus. Frontiers in Systems Neuroscience. 2012;(FEBRUARY 2012).
Exclude: Non-randomized head-to-head
Lenarz T, Gulzow J. Treatment of tinnitus with lidocaine and tocainide. Laryngol-Rhinol-Otol.
1985;64(12):49-51.
Exclude: Insufficient detail of outcome data/not extractable
Lenarz T. Treatment of tinnitus with lidocaine and tocainide. Scand Audiol Suppl. 1987;26:49-
51.
Exclude: Article not available
Lenhardt ML, Goldstein BA, Shulman A, et al. Use of high-frequency and muscle vibration in
the treatment of tinnitus. Int Tinnitus J. 2003;9(1):32-6. PMID:14763327.
Exclude: Non-randomized head-to-head
Letowski TR, Thompson MV. Interrupted noise as a tinnitus masker: An annoyance study. Ear
Hear. 1985;6(2):65-70. PMID:3996786.
Exclude: Non-randomized head-to-head
Levi H, Chisin R. Can tinnitus mask hearing? A comparison between subjective audiometric and
objective electrophysiological thresholds in patients with tinnitus. Audiology. 1987;26(3):153-7.
PMID:3662938.
Exclude: Only determined various effects
Lew HL, Jerger JF, Guillory SB, et al. Auditory dysfunction in traumatic brain injury. J Rehab
Res Dev. 2007;44(7):921-8. PMID:18075949.
Exclude: Only about prevalence
Lewis JE. Tinnitus and suicide. J Am Acad Audiol. 2002;13(6):339-41. PMID:12141391.
Exclude: Not a primary study
Lima AS, Sanchez TG, Bonadia Moraes MF, et al. The effect of timpanoplasty on tinnitus in
patients with conductive hearing loss: A six month follow-up. Revista Brasileira de
Otorrinolaringologia. 2007;73(3):384-9. PMID:17684660.
Exclude: Non-randomized head-to-head
Lima AS, Sanchez TG, Marcondes R, et al. The effect of stapedotomy on tinnitus in patients
with otospongiosis. Ear Nose Throat J. 2005;84(7):412-4. PMID:16813029.
Exclude: Insufficient detail of outcome data/not extractable
C-32
Lindberg P, Scott B, Melin L, et al. Behavioural therapy in the clinical management of tinnitus.
Br J Audiol. 1988;22(4):265-72. PMID:3242716.
Exclude: Non-randomized head-to-head
Lindberg P, Scott B, Melin L, et al. Long-term effects of psychological treatment of tinnitus.
Scand Audiol. 1987;16(3):167-72. PMID:3432995.
Exclude: Non-randomized head-to-head
Lindberg P, Scott B, Melin L, et al. Matching tinnitus in natural environments with portable
equipment. A new methodological approach. J Audiol Med. 1995;4(3):143-59.
Exclude: Case study or series
Lindsay M. The roaring deafness. Nurs Times. 1983;79(5):61-3. PMID:6550312.
Exclude: Not a primary study
Lipman RI, Lipman SP. Phase-shift treatment for predominant tone tinnitus. Otolaryngol Head
Neck Surg. 2007;136(5):763-8. PMID:17478212.
Exclude: Insufficient detail of outcome data/not extractable
Loavenbruck A. Tinnitus masking devices: Safe and effective? ASHA. 1980;22(10):857-61.
PMID:7437091.
Exclude: Not a primary study
Long-standing adverse reactions. Med J Aust. 1993;159(9):621. PMID:7901742.
Exclude: Not a primary study
Lopez Gonzalez MA, Lopez FR. Sequential sound therapy in tinnitus. Acta Otorrinolaringol
Espanola. 2004;55(1):2-8.
Exclude: Case study or series
Lopez-Gonzalez MA, Lopez-Fernandez R. Sequential sound therapy in tinnitus. Int Tinnitus J.
2004;10(2):150-5. PMID:15732513.
Exclude: Insufficient detail of outcome data/not extractable
Lopez-Gonzalez MA, Moliner-Peiro F, Alfaro-Garcia J, et al. Sulpiride plus hydroxyzine
decrease tinnitus perception. Auris Nasus Larynx. 2007;34(1):23-7. PMID:17118597.
Exclude: Insufficient detail of outcome data/not extractable
Lopez-Gonzalez MA, Santiago AM, Esteban-Ortega F. Sulpiride and melatonin decrease tinnitus
perception modulating the auditolimbic dopaminergic pathway. J Otolaryngol. 2007;36(4):213-9.
PMID:17942035.
Exclude: Insufficient detail of outcome data/not extractable
Lorenz I, Muller N, Schlee W, et al. Short-term effects of single repetitive TMS sessions on
auditory evoked activity in patients with chronic tinnitus. J Neurophysiol. 2010;104(3):1497-
505. PMID:20592125.
Exclude: Non-randomized head-to-head
Loumidis KS, Hallam RS, Cadge B. The effect of written reassuring information on out-patients
complaining of tinnitus. Br J Audiol. 1991;25(2):105-9. PMID:2054540.
Exclude: Insufficient detail of outcome data/not extractable
C-33
Lugli M, Romani R, Ponzi S, et al. The windowed sound therapy: A new empirical approach for
an effectiv personalized treatment of tinnitus. Int Tinnitus J. 2009;15(1):51-61. PMID:19842347.
Exclude: Insufficient detail of outcome data/not extractable
Luxon LM. Tinnitus: Its causes, diagnosis, and treatment. BMJ. 1993;306(6891):1490-1.
PMID:8518671.
Exclude: Not a primary study
Lyttkens L, Larsson B, Wasterstrom SA. Local anaesthetics and tinnitus. Proposed peripheral
mechanism of action of lidocaine. ORL. 1984;46(1):17-23. PMID:6700953.
Exclude: Case study or series
Lyttkens L, Lindberg P, Scott B, et al. Treatment of tinnitus by external electrical stimulation.
Scand Audiol. 1986;15(3):157-64. PMID:3492030.
Exclude: Case study or series
Mackenzie I, Young C, Fraser WD. Tinnitus and Paget’s disease of bone. J Laryngol Otol.
2006;120(11):899-902. PMID:17040597.
Exclude: Only about prevalence
Macrae J. Tinnitus and workers compensation. Aust J Audiol. 1988;10(1):17-20.
Exclude: Not a primary study
Macrae JH. Tinnitus and percentage loss of hearing. Aust J Audiol. 1992;14(1):19-23.
Exclude: Not a primary study
Maddox HE, III, Porter TH. Evaluation of the tinnitus masker. Am J Otol. 1981;2(3):199-203.
PMID:7282889.
Exclude: Case study or series
Maes IH, Joore MA, Cima RF, et al. Assessment of health state in patients with Tinnitus: A
comparison of the EQ-5D and HUI Mark III. Ear Hear. 2011;32(4):428-35.
Exclude: Non-randomized head-to-head
Majumdar B, Mason SM, Gibbin KP. An electrocochleographic study of the effects of lignocaine
on patients with tinnitus. Clin Otolaryngol Allied Sci. 1983;8(3):175-80. PMID:6883780.
Exclude: Tinnitus is somatic
Makishima K, Yasuda K, Myahara T, et al. Treatment of sensory-neural deafness and tinnitus
with a nucleic acid derivative. Arzneimittel-Forschung. 1971;21(9):1343-9. PMID:4944968.
Exclude: Insufficient detail of outcome data/not extractable
Man A, Naggan L. Characteristics of tinnitus in acoustic trauma. Audiology. 1981;20(1):72-8.
PMID:7213203.
Exclude: Non-randomized head-to-head
Manage tinnitus with techniques used to treat chronic pain. Geriatrics. 2000;55(12):16.
PMID:11131847.
Exclude: Not a primary study
Marc I. Integrative approach for tinnitus: Potential for qigong. Focus Alt Complement Ther.
2011;16(1):58.
Exclude: Not a primary study
C-34
Mardini MK. Ear-clicking “tinnitus” responding to carbamazepine. N Engl J Med.
1987;317(24):1542. PMID:3683492.
Exclude: Not a primary study
Markou K, Lalaki P, Barbetakis N, et al. The efficacy of medication on tinnitus due to acute
acoustic trauma. Scand Audiol Suppl. 2001;52:180-4. PMID:11318462.
Exclude: Insufficient detail of outcome data/not extractable
Markou K, Nikolaou A, Petridis DG, et al. Evaluation of various therapeutic schemes in the
treatment of tinnitus due to acute acoustic trauma. J Ear Nose Throat Kbb. 2004;12(5-6):107-14.
PMID:16020985.
Exclude: Insufficient detail of outcome data/not extractable
Marks NJ, Emery P, Onisiphorou C. A controlled trial of acupuncture in tinnitus. J Laryngol
Otol. 1984;98(11):1103-9. PMID:6387018.
Exclude: Insufficient detail of outcome data/not extractable
Marks NJ, Karl H, Onisiphorou C. A controlled trial of hypnotherapy in tinnitus. Clin
Otolaryngol Allied Sci. 1985;10(1):43-6. PMID:3891159.
Exclude: Insufficient detail of outcome data/not extractable
Marks NJ, Onisiphorou C, Trounce JR. The effect of single doses of amylobarbitone sodium and
carbamazepine in tinnitus. J Laryngol Otol. 1981;95(9):941-5. PMID:7026706.
Exclude: Insufficient detail of outcome data/not extractable
Marlowe FI. Effective treatment of tinnitus through hypnotherapy. Am J Clin Hypnos.
1973;15(3):162-5. PMID:4780115.
Exclude: Case study or series
Martin FW, Colman BH. Tinnitus: A double-blind crossover controlled trial to evaluate the use
of lignocaine. Clin Otolaryngol Allied Sci. 1980;5(1):3-11. PMID:6988115.
Exclude: Insufficient detail of outcome data/not extractable
Martines F, Bentivegna D, Martines E, et al. Assessing audiological, pathophysiological and
psychological variables in tinnitus patients with or without hearing loss. Eur Arch
Otorhinolaryngol. 2010;267(11):1685-93. PMID:20577754.
Exclude: Only determined various effects
Mason J, Rogerson D. Client-centered hypnotherapy for tinnitus: Who is likely to benefit? Am J
Clin Hypnos. 1995;37(4):294-9. PMID:7741085.
Exclude: Insufficient detail of outcome data/not extractable
Matsushima J, Kumagai M, Kamada T, et al. Preliminary study of improved perception of words
with the same sound but different intonation in tinnitus patients following electrical stimulation
of the ear. Acta Otolaryngol Suppl. 1997;532:112-4. PMID:9442856.
Exclude: Only determined various effects
Matsushima J, Kumagai M, Takeichi N, et al. Improved word perception in tinnitus patients
following electrical stimulation of the ear: A preliminary report. Acta Otolaryngol Suppl.
1997;532:115-8. PMID:9442857.
Exclude: Non-randomized head-to-head
C-35
Matsushima J, Sakai N, Sakajiri M, et al. An experience of the usage of electrical tinnitus
suppressor. Artif Organs. 1996;20(8):955-8. PMID:8853814.
Exclude: Case study or series
Matsushima JI, Fujimura H, Sakai N, et al. A study of electrical promontory stimulation in
tinnitus patients. Auris Nasus Larynx. 1994;21(1):17-24. PMID:7980190.
Exclude: Non-randomized head-to-head
Maudoux A, Bonnet S, Lhonneux-Ledoux F, et al. Ericksonian hypnosis in tinnitus therapy. B-
ENT. 2007;3:75-7. PMID:18225612.
Exclude: Insufficient detail of outcome data/not extractable
Mazurek B, Fischer F, Haupt H, et al. A modified version of tinnitus retraining therapy:
Observing long-term outcome and predictors. Audiol Neuro Otol. 2006;11(5):276-86.
PMID:16717441.
Exclude: Non-randomized head-to-head
McCormick MS, Thomas JN. Mexiletine in the relief of tinnitus: A report on a sequential
double-blind crossover trial. Clin Otolaryngol Allied Sci. 1981;6(4):255-8. PMID:7026090.
Exclude: Insufficient detail of outcome data/not extractable
McIlwain JC. Glutamic acid in the treatment of tinnitus. J Laryngol Otol. 1987;101(6):552-4.
PMID:2885386.
Exclude: Tinnitus is somatic
McKerrow WS, Schreiner CE, Snyder RL, et al. Tinnitus suppression by cochlear implants. Ann
Otol Rhinol Laryngol. 1991;100(7):552-8. PMID:2064266.
Exclude: Case study or series
McShane DP, Hyde ML, Alberti PW. Tinnitus prevalence in industrial hearing loss
compensation claimants. Clin Otolaryngol Allied Sci. 1988;13(5):323-30. PMID:2977306.
Exclude: Only about prevalence
Meehan T, Stephens D, Wilson C, et al. Aromatherapy in tinnitus: A pilot study. Audiol Med.
2003;1(2):144-7.
Exclude: Case study or series
Meeus O, Blaivie C, Ost J, et al. Influence of tonic and burst transcranial magnetic stimulation
characteristics on acute inhibition of subjective tinnitus. Otol Neurotol. 2009;30(6):697-703.
PMID:19623097.
Exclude: Insufficient detail of outcome data/not extractable
Meeus O, Heyndrickx K, Lambrechts P, et al. Phase-shift treatment for tinnitus of cochlear
origin. Eur Arch Otorhinolaryngol. 2010;267(6):881-8. PMID:19937045.
Exclude: Insufficient detail of outcome data/not extractable
Megwalu UC, Finnell JE, Piccirillo JF. The effects of melatonin on tinnitus and sleep.
Otolaryngol Head Neck Surg. 2006;134(2):210-3. PMID:16455366.
Exclude: Non-randomized head-to-head
C-36
Mehlum D, Grasel G, Fankhauser C. Prospective crossover evaluation of four methods of
clinical management of tinnitus. Otolaryngol Head Neck Surg. 1984;92(4):448-53.
PMID:6435067.
Exclude: Case study or series
Melding PS, Goodey RJ, Thorne PR. The use of intravenous lignocaine in the diagnosis and
treatment of tinnitus. J Laryngol Otol. 1978;92(2):115-21. PMID:627764.
Exclude: Non-randomized head-to-head
Melding PS, Goodey RJ. The treatment of tinnitus with oral anticonvulsants. J Laryngol Otol.
1979;93(2):111-22. PMID:429894.
Exclude: Non-randomized head-to-head
Melin L, Scott B, Lindberg P, et al. Hearing aids and tinnitus--An experimental group study. Br J
Audiol. 1987;21(2):91-7. PMID:3594019.
Exclude: Insufficient detail of outcome data/not extractable
Memin Y. Perceived efficacy of cyclandelate in the treatment of cochleovestibular and retinal
disturbances related to cerebrovascular insufficiency. A study in general practice comprising
2772 patients. Drugs. 1987;33(Suppl. 2):120-4.
Exclude: Insufficient detail of outcome data/not extractable
Menkes DB, Larson PM. Sodium valproate for tinnitus. J Neurol Neurosurg Psychiatry.
1998;65(5):803. PMID:9810969.
Exclude: Not a primary study
Mennemeier M, Chelette KC, Allen S, et al. Variable changes in PET activity before and after
rTMS treatment for tinnitus. Laryngoscope. 2011;121(4):815-22. PMID:21287564.
Exclude: Insufficient detail of outcome data/not extractable
Merchant SN, Merchant N. Intravenous lignocaine in tinnitus. J Postgrad Med. 1985;31(2):80-2.
PMID:4057118.
Exclude: Insufficient detail of outcome data/not extractable
Mielczarek M, Konopka W, and OJ. Tinnitus treatment by using electrical stimulation.
Otolaryngol Pol. 2007;61(5):902-4.
Exclude: Article not available
Miguel Ramirez AL, Pablo Sandoval OG, Ernesto BL, et al. Treatment and follow-up of referred
otic symptomatology in 23 patients with diagnosed temporomandibular disorders. Audiol Med.
2006;4(2):73-81.
Exclude: Case study or series
Mihail RC, Crowley JM, Walden BE, et al. The tricyclic trimipramine in the treatment of
subjective tinnitus. Ann Otol Rhinol Laryngol. 1988;97(2:Pt 1):120-3. PMID:3355041.
Exclude: Insufficient detail of outcome data/not extractable
Mineau SM, Schlauch RS. Threshold measurement for patients with tinnitus: Pulsed or
continuous tones. Am J Audiol. 1997;6(1):52-6.
Exclude: Article not available
C-37
Mitchell CR, Vernon JA, Creedon TA. Measuring tinnitus parameters: Loudness, pitch, and
maskability. J Am Acad Audiol. 1993;4(3):139-51. PMID:8318704.
Exclude: Article not available
Miyano K. Tinnitus and bruxing. J Am Dent Assoc. 1038;134(8):1036 PMID:12956337.
Exclude: Not a primary study
Mo B, Harris S, Lindbaek M. Tinnitus in cochlear implant patients--A comparison with other
hearing-impaired patients. Int J Audiol. 2002;41(8):527-34. PMID:12477173.
Exclude: Only about prevalence
Moffat G, Adjout K, Gallego S, et al. Effects of hearing aid fitting on the perceptual
characteristics of tinnitus. Hear Res. 2009;254(1-2):82-91. PMID:19409969.
Exclude: Insufficient detail of outcome data/not extractable
Molini E, Faralli M, Calenti C, et al. Personal experience with tinnitus retraining therapy. Eur
Arch Otorhinolaryngol. 2010;267(1):51-6. PMID:19543742.
Exclude: Case study or series
Moller AR. A double-blind placebo-controlled trial of baclofen in the treatment of tinnitus. Am J
Otol. 1997;18(2):268-9. PMID:9093691.
Exclude: Not a primary study
Moller C, Odkvist LM, Thell J, et al. Vestibular and audiologic functions in gentamicin-treated
Meniere’s disease. Am J Otol. 1988;9(5):383-91.
Exclude: Case study or series
Moller MB, Moller AR, Jannetta PJ, et al. Vascular decompression surgery for severe tinnitus:
Selection criteria and results. Laryngoscope. 1993;103(4:Pt 1):421-7. PMID:8459751.
Exclude: Case study or series
Moody-Antonio S, House JW. Hearing outcome after concurrent endolymphatic shunt and
vestibular nerve section. Otol Neurotol. 2003;24(3):453-9. PMID:12806298.
Exclude: Non-randomized head-to-head
Mora R, Salami A, Barbieri M, et al. The use of sodium enoxaparin in the treatment of tinnitus.
Int Tinnitus J. 2003;9(2):109-11. PMID:15106284.
Exclude: Non-randomized head-to-head
Morales-Garcia C, Quiroz G, Matamala JM, et al. Neuro-otological findings in tinnitus patients
with normal hearing. J Laryngol Otol. 2010;124(5):474-6. PMID:20003596.
Exclude: Only determined various effects
Morgan DH. Dysfunction, pain, tinnitus, vertigo corrected by mandibular joint surgery. J South
Calif Dent Assoc. 1971;39(7):505-34. PMID:5314744.
Exclude: Not a primary study
Morgenstern C, Biermann E. The efficacy of Ginkgo special extract EGb 761 in patients with
tinnitus. Int J Clin Pharmacol Ther. 2002;40(5):188-97. PMID:12051570.
Exclude: Insufficient detail of outcome data/not extractable
C-38
Mrena R, Savolainen S, Kiukaanniemi H, et al. The effect of tightened hearing protection
regulations on military noise-induced tinnitus. Int J Audiol. 2009;48(6):394-400.
PMID:19925346.
Exclude: Non-randomized head-to-head
Mrena R, Ylikoski M, Makitie A, et al. Occupational noise-induced hearing loss reports and
tinnitus in Finland. Acta Otolaryngol. 2007;127(7):729-35. PMID:17573569.
Exclude: Only about prevalence
Muhammad Gadit AA. Transcranial magnetic stimulation (TMS): Should we officially include
this form of treatment? J Pakistan Med Assoc. 2008;58(7):413-4.
Exclude: Not a primary study
Muluk NB, Oguzturk O. Occupational noise-induced tinnitus: Does it affect workers’ quality of
life? J Otolaryngol Head Neck Surg. 2008;37(1):65-71. PMID:18479630.
Exclude: Only determined various effects
Muluk NB, Tuna E, Arikan OK. Effects of subjective tinnitus on sleep quality and Mini Mental
Status Examination scores. B-ENT. 2010;6(4):271-80. PMID:21302690.
Exclude: Only determined various effects
Muluk NB. The SF-36 Health Survey in tinnitus patients with a high jugular bulb. J Otolaryngol
Head Neck Surg. 2009;38(2):166-71. PMID:19442364.
Exclude: Only determined various effects
Murata Y. Treatment of cochlear-tinnitus with dexamethasone infusion into the tympanic cavity
as steroid targeting therapy. J Saitama Med Sch. 1997;24(4):201-10.
Exclude: Article not available
Muroi M, Ito F. Patients exhibiting tinnitus aurium with a history of cerebral infarction clinical
characteristics and pathogenesis. Kitakanto Med J. 1998;48(1):45-8.
Exclude: Tinnitus is somatic
Murtagh J. Patient education. Tinnitus. Aust Fam Physician. 1994;23(6):1102 PMID:8053844.
Exclude: Not a primary study
Nageris BI, Attias J, Raveh E. Test-retest tinnitus characteristics in patients with noise-induced
hearing loss. Am J Otolaryngol. 2010;31(3):181-4. PMID:20015738.
Exclude: Non-randomized head-to-head
Nagler S. Lemonade out of lemons--Tinnitus retraining therapy. J Med Assoc Ga.
1998;87(3):220-3. PMID:9747080.
Exclude: Not a primary study
Narozny W, Kuczkowski J, Mikaszewski B. Measuring severity of tinnitus with a visual analog
scale. Am Fam Physician. 2005;71(5):855-6. PMID:15768613.
Exclude: Not a primary study
Neher A. Tinnitus. South Med J. 1989;82(12):1589. PMID:2595438.
Exclude: Not a primary study
Neher A. Tracking tinnitus hunches. Am Fam Physician. 1989;40(6):48. PMID:2589150.
Exclude: Not a primary study
C-39
Neher A. Treatment for tinnitus. J Gen Intern Med. 1990;5(1):93. PMID:2299434.
Exclude: Not a primary study
Newman CW, Sandridge SA, Bolek L. Development and psychometric adequacy of the
screening version of the tinnitus handicap inventory. Otol Neurotol. 2008;29(3):276-81.
PMID:18277308.
Exclude: Non-randomized head-to-head
Newman CW, Sandridge SA, Jacobson GP. Psychometric adequacy of the Tinnitus Handicap
Inventory (THI) for evaluating treatment outcome. J Am Acad Audiol. 1998;9(2):153-60.
PMID:9564679.
Exclude: Non-randomized head-to-head
Newman CW, Sandridge SA. A comparison of benefit and economic value between two sound
therapy tinnitus management options. J Am Acad Audiol. 2012;23(2):126-38. PMID:22353681.
Exclude: Non-randomized head-to-head
Newman CW, Wharton JA, Shivapuja BG, et al. Relationships among psychoacoustic
judgments, speech understanding ability and self-perceived handicap in tinnitus subjects.
Audiology. 1994;33(1):47-60. PMID:8129680.
Exclude: Only determined various effects
Nilsson S, Axelsson A, Li DG. Acupuncture for tinnitus management. Scand Audiol.
1992;21(4):245-51. PMID:1488611.
Exclude: Non-randomized head-to-head
Nissen AJ. Medical and surgical management of tinnitus. Semin Hear. 1987;8(1):1-5.
Exclude: Not a primary study
Noble W. Tinnitus self-assessment scales: Domains of coverage and psychometric properties.
Hear J. 2001;54(11):20-5.
Exclude: Not a primary study
Nodar RH, Lovering LJ. Subjective and objective measurement of vibratory tinnitus. Eye Ear
Nose Throat Mo. 1971;50(8):302-5. PMID:5565014.
Exclude: Tinnitus is somatic
Nondahl DM, Cruickshanks KJ, Wiley TL, et al. Prevalence and 5-year incidence of tinnitus
among older adults: The epidemiology of hearing loss study. J Am Acad Audiol.
2002;13(6):323-31. PMID:12141389.
Exclude: Only about prevalence
Nondahl DM, Klein BE, Klein R, et al. Factors predicting severity of tinnitus: A population-
based assessment. J Am Acad Audiol. 2005;16(3):196. PMID:15844744.
Exclude: Not a primary study
Nottet JB, Moulin A, Brossard N, et al. Otoacoustic emissions and persistent tinnitus after acute
acoustic trauma. Laryngoscope. 2006;116(6):970-5. PMID:16735910.
Exclude: Insufficient detail of outcome data/not extractable
Novotny M, Kostrica R, Cirek Z. The efficacy of Arlevert therapy for vertigo and tinnitus. Int
Tinnitus J. 1999;5(1):60-2. PMID:10753423.
Exclude: Non-randomized head-to-head
C-40
Nozawa I, Nakayama H, Hashimoto K, et al. Efficacy of long-term administration of isosorbide
for Meniere’s disease. ORL. 1995;57(3):135-40.
Exclude: Case study or series
Objective evaluation: Quantitative assessment and measurement of tinnitus; Clinical experience.
J Laryngol Otol Suppl. 1984;9:145-92. PMID:6596357.
Exclude: Article not available
O’Connor S, Hawthorne M, Britten SR, et al. The management of a population of tinnitus
sufferers in a specialized clinic: Part II. Identification of psychiatric morbidity in a population of
tinnitus sufferers. J Laryngol Otol. 1987;101(8):791-4. PMID:3655531.
Exclude: Non-randomized head-to-head
Odkvist LM. Middle ear ototoxic treatment for inner ear disease. Acta Otolaryngol Suppl.
1989;107(457):83-6.
Exclude: Tinnitus is somatic
Ogata Y, Sekitani T, Moriya K, et al. Biofeedback therapy in the treatment of tinnitus. Auris
Nasus Larynx. 1993;20(2):95-101. PMID:8216052.
Exclude: Case study or series
Ogawa K, Takei S, Inoue Y, et al. Effect of prostaglandin E1 on idiopathic sudden sensorineural
hearing loss: A double-blinded clinical study. Otol Neurotol. 2002;23(5):665-8.
PMID:12218617.
Exclude: Non-randomized head-to-head
Ohsaki K, Ueno M, Zheng HX, et al. Evaluation of tinnitus patients by peroral multi-drug
treatment. Auris Nasus Larynx. 1998;25(2):149-54. PMID:9673727.
Exclude: Case study or series
Oishi N, Kanzaki S, Shinden S, et al. Effects of selective serotonin reuptake inhibitor on treating
tinnitus in patients stratified for presence of depression or anxiety. Audiol Neuro Otol.
2010;15(3):187-93. PMID:19851065.
Exclude: Non-randomized head-to-head
Okada DM, Onishi ET, Chami FI, et al. Acupuncture for tinnitus immediate relief. Revista
Brasileira de Otorrinolaringologia. 2006;72(2):182-6. PMID:16951850.
Exclude: Insufficient detail of outcome data/not extractable
Okamoto H, Stracke H, Stoll W, et al. Listening to tailor-made notched music reduces tinnitus
loudness and tinnitus-related auditory cortex activity. Proceedings of the National Academy of
Sciences of the United States of America. 2010;107(3):1207-10. PMID:20080545.
Excluded at Title & Abstract, reconsidered at request of Peer Reviewer, not eligible for this
report
Okhovat A, Berjis N, Okhovat H, et al. Low-level laser for treatment of tinnitus: A self-
controlled clinical trial. J Res Med Sci. 2011;16(1):33-8.
Exclude: Insufficient detail of outcome data/not extractable
Okusa M, Shiraishi T, Kubo T, et al. Tinnitus suppression by electrical promontory stimulation
in sensorineural deaf patients. Acta Otolaryngol Suppl. 1993;501:54-8. PMID:8447227.
Exclude: Case study or series
C-41
Oliveira CA, Venosa A, Araujo MF. Tinnitus program at Brasilia University Medical School. Int
Tinnitus J. 1999;5(2):141-3. PMID:10753434.
Exclude: Only about prevalence
Oliveira CA. How does stapes surgery influence severe disabling tinnitus in otosclerosis
patients? Adv Otorhinolaryngol. 2007;65:343-7. PMID:17245070.
Exclude: Non-randomized head-to-head
Olivier J, Plath P. Combined low power laser therapy and extracts of Ginkgo biloba in a blind
trial of treatment for tinnitus. Laser Ther. 1993;5(3):137-9.
Exclude: Insufficient detail of outcome data/not extractable
Omura Y. Simple custom-made disposable surface electrode system for non-invasive “electro-
acupuncture” or TNS and its clinical applications including treatment of cephalic hypertension
and hypotension syndromes as well as temporo-mandibular joint problems, tinnitus, shoulder and
lower back pain, etc. Acupuncture Eletctro Ther Res. 1981;6(2-3):109-34. PMID:6120617.
Exclude: Not a primary study
Oosterveld WJ. Flunarizine in vertigo. A double-blind placebo-controlled cross-over evaluation
of a constant-dose schedule. ORL. 1982;44(2):72-80. PMID:7041040.
Exclude: Tinnitus is somatic
Otsuka K, Pulec JL, Suzuki M. Assessment of intravenous lidocaine for the treatment of
subjective tinnitus. Ear Nose Throat J. 2003;82(10):781-4. PMID:14606175.
Exclude: Case study or series
Ozcankaya R, Dogru H. Depression and anxiety symptoms in tinnitus patients. Biomed Res.
2001;12(3):221-4.
Exclude: Only determined various effects
Paaske PB, Pedersen CB, Kjems G, et al. Zinc in the management of tinnitus. Placebo-controlled
trial. Ann Otol Rhinol Laryngol. 1991;100(8):647-9. PMID:1872515.
Exclude: Insufficient detail of outcome data/not extractable
Pan T, Tyler RS, Ji H, et al. Changes in the tinnitus handicap questionnaire after cochlear
implantation. Am J Audiol. 2009;18(2):144-51. PMID:19949236.
Exclude: Non-randomized head-to-head
Pang LQ, Pang MK, Takumi MM. A new method of managing subjective tinnitus. Hawaii Med
J. 1979;38(8):235-9. PMID:511527.
Exclude: Case study or series
Parker WS, Chole RA. Tinnitus, vertigo, and temporomandibular disorders. Am J Orthod
Dentofacial Orthop. 1995;107(2):153-8. PMID:7847272.
Exclude: Only about prevalence
Parkin JL. Tinnitus evaluation. Am Fam Physician. 1973;8(3):151-5. PMID:4542333.
Exclude: Not a primary study
Paul J, Brown NM. Tinnitus and ciprofloxacin. BMJ. 1995;311(6999):232. PMID:7627041.
Exclude: Case study or series
Paul RG, Dennis KC. Face-to-face. What about tinnitus? Am J Audiol. 1996;5(1):5-8.
Exclude: Article not available
C-42
Pawlak-Osinska K, Kazmierczak H, Kazmierczak W, et al. Ozone therapy and pressure-pulse
therapy in Meniere’s disease. Int Tinnitus J. 2004;10(1):54-7.
Exclude: Case study or series
Penner MJ. Judgments and measurements of the loudness of tinnitus before and after masking. J
Speech Hear Res. 1988;31(4):582-7. PMID:3230887.
Exclude: Case study or series
Perrin E, Degive C, Kos I, et al. Follow-up of a cohort of tinnitus patients attending a medical-
psychological joint consultation. Oto-Rhino-Laryngol Nova. 2000;10(1):28-31.
Exclude: Case study or series
Perucca E, Jackson P. A controlled study of the suppression of tinnitus by lidocaine infusion:
(Relationship of therapeutic effect with serum lidocaine levels). J Laryngol Otol.
1985;99(7):657-61. PMID:4020257.
Exclude: Insufficient detail of outcome data/not extractable
Piccirillo JF, Garcia KS, Nicklaus J, et al. Low-frequency repetitive transcranial magnetic
stimulation to the temporoparietal junction for tinnitus. Arch Otolaryngol Head Neck Surg.
2011;137(3):221-8. PMID:21422304.
Exclude: Insufficient detail of outcome data/not extractable
Pilgramm M, Schumann K. Hyperbaric oxygen therapy for acute acoustic trauma. Arch Oto-
Rhino-Laryngol. 1985;241(3):247-57. PMID:4026691.
Exclude: Tinnitus is somatic
Pineda JA, Moore FR, Viirre E. Tinnitus treatment with customized sounds. Int Tinnitus J.
2008;14(1):17-25. PMID:18616082.
Exclude: Insufficient detail of outcome data/not extractable
Pinto PC, Sanchez TG, Tomita S. The impact of gender, age and hearing loss on tinnitus
severity. Revista Brasileira de Otorrinolaringologia. 2010;76(1):18-24. PMID:20339684.
Exclude: Only about prevalence
Plath P, Olivier J. Results of combined low-power laser therapy and extracts of Ginkgo biloba in
cases of sensorineural hearing loss and tinnitus. Adv Otorhinolaryngol. 1995;49:101-4.
PMID:7653339.
Exclude: Not a primary study
Plewnia C, Bartels M, Gerloff C. Transient suppression of tinnitus by transcranial magnetic
stimulation. Ann Neurol. 2003;53(2):263-6. PMID:12557296.
Exclude: Non-randomized head-to-head
Plewnia C, Reimold M, Najib A, et al. Dose-dependent attenuation of auditory phantom
perception (tinnitus) by PET-guided repetitive transcranial magnetic stimulation. Hum Brain
Mapp. 2007;28(3):238-46. PMID:16773635.
Exclude: Insufficient detail of outcome data/not extractable
Plewnia C, Reimold M, Najib A, et al. Moderate therapeutic efficacy of positron emission
tomography-navigated repetitive transcranial magnetic stimulation for chronic tinnitus: A
randomised, controlled pilot study. J Neurol Neurosurg Psychiatry. 2007;78(2):152-6.
PMID:16891384.
Exclude: Insufficient detail of outcome data/not extractable
C-43
Podoshin L, Ben-David Y, Fradis M, et al. Idiopathic subjective tinnitus treated by amitriptyline
hydrochloride/biofeedback. Int Tinnitus J. 1995;1(1):54-60.
Exclude: Insufficient detail of outcome data/not extractable
Podoshin L, Fradis M, David YB. Treatment of tinnitus by intratympanic instillation of
lignocaine (lidocaine) 2 per cent through ventilation tubes. J Laryngol Otol. 1992;106(7):603-6.
PMID:1527456.
Exclude: Case study or series
Poreisz C, Boros K, Antal A, et al. Safety aspects of transcranial direct current stimulation
concerning healthy subjects and patients. Brain Res Bull. 2007;72(4-6):208-14.
Exclude: Non-randomized head-to-head
Poreisz C, Paulus W, Moser T, et al. Does a single session of theta-burst transcranial magnetic
stimulation of inferior temporal cortex affect tinnitus perception? BMC Neurosci. 2009;10:54.
PMID:19480651.
Exclude: Insufficient detail of outcome data/not extractable
Portmann M, Cazals Y, Negrevergne M, et al. Temporary tinnitus suppression in man through
electrical stimulation of the cochlea. Acta Otolaryngol. 1979;87(3-4):294-9. PMID:312586.
Exclude: Case study or series
Pothier DD, Bredenkamp CL. The placebo effect of transcutaneous electrical nerve stimulation. J
Laryngol Otol 2006;120:442-5. J Laryngol Otol. 2008;122(2):217. PMID:18252020.
Exclude: Not a primary study
Prestes R, Daniela G. Impact of tinnitus on quality of life, loudness and pitch match, and high-
frequency audiometry. Int Tinnitus J. 2009;15(2):134-8. PMID:20420337.
Exclude: Only determined various effects
Prinz RJ. Assessment of treatments for subjective phenomena. Semin Hear. 1987;8(1):63-9.
Exclude: Not a primary study
Protheroe D, House A. Treatments for tinnitus. BMJ. 1993;307(6902):505. PMID:8400956.
Exclude: Not a primary study
Pugh RS, Stephens D, Budd R. The contribution of spouse responses and marital satisfaction to
the experience of chronic tinnitus. Audiol Med. 2004;2(1):60-73.
Exclude: Only determined various effects
Pulec JL. Cochlear nerve section for intractable tinnitus. Ear Nose Throat J. 1995;74(7):468-6.
PMID:7671835.
Exclude: Case study or series
Qian X. Experience in the clinical application of zhongzhu (TE 3). J Tradit Chin Med.
2004;24(4):282-3. PMID:15688696.
Exclude: Not a primary study
Quaranta A, Scaringi A, Aloisi A, et al. Intratympanic therapy for Meniere’s disease: Effect of
administration of low concentration of gentamicin. Acta Otolaryngol. 2001;121(3):387-92.
Exclude: Tinnitus is somatic
C-44
Quaranta N, Fernandez-Vega S, D’elia C, et al. The effect of unilateral multichannel cochlear
implant on bilaterally perceived tinnitus. Acta Otolaryngol. 2008;128(2):159-63.
PMID:17851950.
Exclude: Non-randomized head-to-head
Rahko T, Kotti V. Tinnitus treatment by transcutaneous nerve stimulation (TNS). Acta
Otolaryngol Suppl. 1997;529:88-9. PMID:9288279.
Exclude: Insufficient detail of outcome data/not extractable
Ramkumar V, Rangasayee R. Studying tinnitus in the ICF framework. Int J Audiol.
2010;49(9):645-50. PMID:20707669.
Exclude: Only determined various effects
Rask-Andersen H, Friberg U, Johansson M, et al. Effects of intratympanic injection of
latanoprost in Meniere’s disease: A randomized, placebo-controlled, double-blind, pilot study.
Otolaryngol Head Neck Surg. 2005;133(3):441-3.
Exclude: Insufficient detail of outcome data/not extractable
Ratnayake SA, Jayarajan V, Bartlett J. Could an underlying hearing loss be a significant factor in
the handicap caused by tinnitus? Noise Health. 2009;11(44):156-60. PMID:19602769.
Exclude: Non-randomized head-to-head
Raza SA, Phillipps JJ. Vertigo, hearing loss, and tinnitus. Postgrad Med J. 1998;74(872):375-7.
PMID:9799900.
Exclude: Not a primary study
Reed HT, Meltzer J, Crews P, et al. Amino-oxyacetic acid as a palliative in tinnitus. Arch
Otolaryngol. 1985;111(12):803-5. PMID:2415097.
Exclude: Tinnitus is somatic
Reich GE, Johnson RM. Personality characteristics of tinnitus patients. J Laryngol Otol.
1983;97(Suppl. 9):228-32.
Exclude: Non-randomized head-to-head
Reisser CH, Weidauer H. Ginkgo biloba extract EGb 761 or pentoxifylline for the treatment of
sudden deafness: A randomized, reference-controlled, double-blind study. Acta Otolaryngol.
2001;121(5):579-84. PMID:11583389.
Exclude: Insufficient detail of outcome data/not extractable
Rendell RJ, Carrick DG, Fielder CP, et al. Low-powered ultrasound in the inhibition of tinnitus.
Br J Audiol. 1987;21(4):289-93. PMID:3318977.
Exclude: Insufficient detail of outcome data/not extractable
Riihikangas P, Anttonen H, Hassi J, et al. Hearing loss and impulse noise during military service.
Scand Audiol Suppl. 1980;Suppl 12:292-7. PMID:6939100.
Exclude: Only about prevalence
Risey J, Briner W, Guth PS, et al. The superiority of the Goodwin procedure over the traditional
procedure in measuring the loudness level of tinnitus. Ear Hear. 1989;10(5):318-22.
PMID:2792585.
Exclude: Non-randomized head-to-head
C-45
Roberts C, Inamdar A, Koch A, et al. A randomized, controlled study comparing the effects of
vestipitant or vestipitant and paroxetine combination in subjects with tinnitus. Otol Neurotol.
2011;32(5):721-7. PMID:21646935.
Exclude: Insufficient detail of outcome data/not extractable
Robinson M. Tinnitus and otosclerosis surgery. J Laryngol Otol. 1983;97(Suppl. 9):294-8.
Exclude: Tinnitus is somatic
Robinson SK, McQuaid JR, Viirre ES, et al. Relationship of tinnitus questionnaires to depressive
symptoms, quality of well-being, and internal focus. Int Tinnitus J. 2003;9(2):97-103.
PMID:15106282.
Exclude: Only determined various effects
Robinson SK, Viirre ES, Bailey KA, et al. A randomized controlled trial of cognitive-behavior
therapy for tinnitus. Int Tinnitus J. 2008;14(2):119-26. PMID:19205162.
Exclude: Insufficient detail of outcome data/not extractable
Rocha CA, Sanchez TG. Myofascial trigger points: Another way of modulating tinnitus. Progr
Brain Res. 2007;166:209-14. PMID:17956784.
Exclude: Not a primary study
Roeser RJ, Price DR. Clinical experience with tinnitus maskers. Ear Hear. 1980;1(2):63-8.
PMID:7372018.
Exclude: Case study or series
Rosenberg SI, Silverstein H, Rowan PT, et al. Effect of melatonin on tinnitus. Laryngoscope.
1998;108(3):305-10. PMID:9504599.
Exclude: Insufficient detail of outcome data/not extractable
Rosenhall U, Karlsson AK. Tinnitus in old age. Scand Audiol. 1991;20(3):165-71.
PMID:1842285.
Exclude: Only about prevalence
Ross UH, Lange O, Unterrainer J, et al. Ericksonian hypnosis in tinnitus therapy: Effects of a 28-
day inpatient multimodal treatment concept measured by Tinnitus-Questionnaire and Health
Survey SF-36. Eur Arch Otorhinolaryngol. 2007;264(5):483-8. PMID:17206402.
Exclude: Non-randomized head-to-head
Rossi S, De CA, Ulivelli M, et al. Effects of repetitive transcranial magnetic stimulation on
chronic tinnitus: A randomised, crossover, double blind, placebo controlled study. J Neurol
Neurosurg Psychiatry. 2007;78(8):857-63. PMID:17314192.
Exclude: Insufficient detail of outcome data/not extractable
Rossiter S, Stevens C, Walker G. Tinnitus and its effect on working memory and attention. J
Speech Lang Hear Res. 2006;49(1):150-60. PMID:16533080.
Exclude: Only determined various effects
Roydhouse N. Multiple tinnitus. NZ Med J. 1989;102(879):594. PMID:2812600.
Exclude: Case study or series
C-46
Rubak T, Kock S, Koefoed-Nielsen B, et al. The risk of tinnitus following occupational noise
exposure in workers with hearing loss or normal hearing. Int J Audiol. 2008;47(3):109-14.
PMID:18307090.
Exclude: Only about prevalence
Rubin W. Tinnitus evaluations: Aids to diagnosis and treatment. J Laryngol Otol. 1983;97(Suppl.
9):178-80.
Exclude: Not a primary study
Rubinstein B, Carlsson GE. Effects of stomatognathic treatment on tinnitus: A retrospective
study. Cranio. 1987;5(3):254-9. PMID:3476212.
Exclude: Non-randomized head-to-head
Ruckenstein MJ, Hedgepeth C, Rafter KO, et al. Tinnitus suppression in patients with cochlear
implants. Otol Neurotol. 2001;22(2):200-4. PMID:11300269.
Exclude: Insufficient detail of outcome data/not extractable
Sadlier M, Stephens SD, Kennedy V. Tinnitus rehabilitation: A mindfulness meditation cognitive
behavioural therapy approach. J Laryngol Otol. 2008;122(1):31-7. PMID:17451612.
Exclude: Insufficient detail of outcome data/not extractable
Sadlier M, Stephens SD. An approach to the audit of tinnitus management. J Laryngol Otol.
1995;109(9):826-9. PMID:7494113.
Exclude: Non-randomized head-to-head
Sakai M, Sato M, Iida M, et al. The effect on tinnitus of stapes surgery for otosclerosis. Rev
Laryngol Otol Rhinol. 1995;116(1):27-30. PMID:7644843.
Exclude: Tinnitus is somatic
Sakaki T, Morimoto T, Miyamoto S, et al. Microsurgical treatment of patients with vestibular
and cochlear symptoms. Surg Neurol. 1987;27(2):141-6. PMID:3492773.
Exclude: Tinnitus is somatic
Sakata H, Kojima Y, Koyama S, et al. Treatment of cochlear tinnitus with transtympanic
infusion of 4% lidocaine into the tympanic cavity. Int Tinnitus J. 2001;7(1):46-50.
PMID:14964956.
Exclude: Article not available
Sala T. Transtympanic administration of aminoglycosides in patients with Meniere’s disease.
Arch Oto-Rhino-Laryngol. 1988;245(5):293-6.
Exclude: Non-randomized head-to-head
Salama NY, Bhatia P, Robb PJ. Efficacy of oral oxpentifylline in the management of idiopathic
tinnitus. ORL. 1989;51(5):300-4. PMID:2682431.
Exclude: Insufficient detail of outcome data/not extractable
Salembier L, De RD, Van de Heyning PH. The use of flupirtine in treatment of tinnitus. Acta
Otolaryngol Suppl. 2006;(556):93-5. PMID:17114151.
Exclude: Non-randomized head-to-head
C-47
Salley LH, Jr., Grimm M, Sismanis A, et al. Methotrexate in the management of immune
mediated cochleovestibular disorders: Clinical experience with 53 patients. J Rheumatol.
2001;28(5):1037-40.
Exclude: Case study or series
Salonen J, Johansson R, Joukamaa M. Alexithymia, depression and tinnitus in elderly people.
Gen Hosp Psychiatry. 2007;29(5):431-5. PMID:17888810.
Exclude: Only about prevalence
Salvi R, Sun W, Lobarinas E. Clinical and scientific aspects of tinnitus: Part II. Semin Hear.
2008;29(4):311.
Exclude: Not a primary study
Salvi R, Sun W, Lobarinas E. Clinical and scientific aspects of tinnitus. Semin Hear.
2008;29(3):229-30.
Exclude: Not a primary study
Sanches SG, Samelli AG, Nishiyama AK, et al. GIN Test (Gaps-in-Noise) in normal listeners
with and without tinnitus. Profono. 2010;22(3):257-62. PMID:21103715.
Exclude: Only determined various effects
Sanchez L, Stephens SDG. Perceived problems of tinnitus clinic clients at long-term follow up. J
Audiol Med. 2000;9(2):94-103.
Exclude: Non-randomized head-to-head
Sanchez TG, Balbani AP, Bittar RS, et al. Lidocaine test in patients with tinnitus: Rationale of
accomplishment and relation to the treatment with carbamazepine. Auris Nasus Larynx.
1999;26(4):411-7. PMID:10530736.
Exclude: Insufficient detail of outcome data/not extractable
Sanchez TG, da Silva LA, Brandao AL, et al. Somatic modulation of tinnitus: Test reliability and
results after repetitive muscle contraction training. Ann Otol Rhinol Laryngol. 2007;116(1):30-5.
PMID:17305275.
Exclude: Insufficient detail of outcome data/not extractable
Sanchez TG, Medeiros IR, Levy CP, et al. Tinnitus in normally hearing patients: Clinical aspects
and repercussions. Revista Brasileira de Otorrinolaringologia. 2005;71(4):427-31.
PMID:16446955.
Exclude: Only determined various effects
Santoni CB, Fiorini AC. Pop-rock musicians: Assessment of their satisfaction provided by
hearing protectors. Revista Brasileira de Otorrinolaringologia. 2010;76(4):454-61.
PMID:20835532.
Exclude: Non-randomized head-to-head
Savastano M, Brescia G, Marioni G. Antioxidant therapy in idiopathic tinnitus: Preliminary
outcomes. Arch Med Res. 2007;38(4):456-9. PMID:17416295.
Exclude: Non-randomized head-to-head
Savastano M. Lidocaine intradermal injection--a new approach in tinnitus therapy: Preliminary
report. Adv Ther. 2004;21(1):13-20. PMID:15191153.
Exclude: Insufficient detail of outcome data/not extractable
C-48
Schaette R, Konig O, Hornig D, et al. Acoustic stimulation treatments against tinnitus could be
most effective when tinnitus pitch is within the stimulated frequency range. Hear Res.
2010;269(1-2):95-101. PMID:20619332.
Exclude: Non-randomized head-to-head
Schleuning AJ, Johnson RM, Vernon JA. Evaluation of a tinnitus masking program: A follow-up
study of 598 patients. Ear Hear. 1980;1(2):71-4. PMID:7372020.
Exclude: Case study or series
Schmitt C, Patak M, Kroner-Herwig B. Stress and the onset of sudden hearing loss and tinnitus.
Int Tinnitus J. 2000;6(1):41-9. PMID:14689617.
Exclude: Non-randomized head-to-head
Schmuziger N, Patscheke J, Probst R. Hearing in nonprofessional pop/rock musicians. Ear Hear.
2006;27(4):321-30. PMID:16825883.
Exclude: Only about prevalence
Scholz BA, Holmes HM, Marcus DM. Use of herbal medications in elderly patients. Ann Long
Term Care. 2008;16(12):24-8.
Exclude: Not a primary study
Schutte NS, Noble W, Malouff JM, et al. Evaluation of a model of distress related to tinnitus. Int
J Audiol. 2009;48(7):428-32. PMID:19925329.
Exclude: Case study or series
Scott B, Larsen HC, Lyttkens L, et al. An experimental evaluation of the effects of
transcutaneous nerve stimulation (TNS) and applied relaxation (AR) on hearing ability, tinnitus
and dizziness in patients with Meniere’s disease. Br J Audiol. 1994;28(3):131-40.
PMID:7841897.
Exclude: Insufficient detail of outcome data/not extractable
Scott B, Lindberg P, Lyttkens L, et al. Psychological treatment of tinnitus. An experimental
group study. Scand Audiol. 1985;14(4):223-30. PMID:3912955.
Exclude: Insufficient detail of outcome data/not extractable
Searchfield GD, Jerram C, Wise K, et al. The impact of hearing loss on tinnitus severity. Aust
NZ J Audiol. 2007;29(2):67-76.
Exclude: Insufficient detail of outcome data/not extractable
Searchfield GD, Morrison-Low J, Wise K. Object identification and attention training for
treating tinnitus. Progr Brain Res. 2007;166:441-60. PMID:17956809.
Exclude: Insufficient detail of outcome data/not extractable
Segal NT, Puterman M, Shkolnik M, et al. The role of tinnitus evaluation tests in differentiating
functional versus organic tinnitus. Otolaryngol Head Neck Surg. 2007;137(5):772-5.
PMID:17967644.
Exclude: Insufficient detail of outcome data/not extractable
Seidman MD, Ridder DD, Elisevich K, et al. Direct electrical stimulation of Heschl’s gyrus for
tinnitus treatment. Laryngoscope. 2008;118(3):491-500. PMID:18094653.
Exclude: Case study or series
C-49
Seydel C, Haupt H, Szczepek AJ, et al. Long-term improvement in tinnitus after modified
tinnitus retraining therapy enhanced by a variety of psychological approaches. Audiol Neuro
Otol. 2010;15(2):69-80. PMID:19657182.
Exclude: Insufficient detail of outcome data/not extractable
Shaladi AM, Crestani F, Saltari R. Auricular acupuncture plus antioxidants in the treatment of
subjective tinnitus: A case series. Med Acupuncture. 2009;21(2):131-4.
Exclude: Case study or series
Shambaugh GE, Jr. Zinc for tinnitus, imbalance, and hearing loss in the elderly. Am J Otol.
1986;7(6):476-7. PMID:3492920.
Exclude: Not a primary study
She W, Dai Y, Du X, et al. Treatment of subjective tinnitus: A comparative clinical study of
intratympanic steroid injection vs. oral carbamazepine. Med Sci Monitor. 2009;15(6):I35-I39.
PMID:19478715.
Exclude: Insufficient detail of outcome data/not extractable
Shea JJ, Emmett JR, Orchik DJ, et al. Medical treatment of tinnitus. Ann Otol Rhinol Laryngol.
1981;90(6:Pt 1):264-70. PMID:7032398.
Exclude: Not a primary study
Shea JJ, Harell M. Management of tinnitus aurium with lidocaine and carbamazepine.
Laryngoscope. 1978;88(9:Pt 1):1477-84. PMID:682804.
Exclude: Case study or series
Shemen L. Fluoxetine for treatment of tinnitus. Otolaryngol Head Neck Surg. 1998;118(3:Pt
1):421. PMID:9527133.
Exclude: Not a primary study
Shiomi Y, Takahashi H, Honjo I, et al. Efficacy of transmeatal low power laser irradiation on
tinnitus: A preliminary report. Auris Nasus Larynx. 1997;24(1):39-42. PMID:9148726.
Exclude: Insufficient detail of outcome data/not extractable
Shulman A, Ballantyne JC, Shea J. Section 1: Tinnitus masking. J Laryngol Otol.
1983;97(Suppl. 9):249-56.
Exclude: Not a primary study
Shulman A, Goldstein B. Intratympanic drug therapy with steroids for tinnitus control: A
preliminary report. Int Tinnitus J. 2000;6(1):10-20. PMID:14689612.
Exclude: Case study or series
Shulman A, Strashun AM, Goldstein BA. GABAA-benzodiazepine-chloride receptor-targeted
therapy for tinnitus control: Preliminary report. Int Tinnitus J. 2002;8(1):30-6. PMID:14763233.
Exclude: Insufficient detail of outcome data/not extractable
Shulman A. Clinical classification of subjective idiopathic tinnitus. J Laryngol Otol Suppl.
1981;(4):102-6. PMID:6946157.
Exclude: Not a primary study
Shulman A. External electrical stimulation in tinnitus control. Am J Otol. 1985;6(1):110-5.
PMID:3872077.
Exclude: Case study or series
C-50
Shulman A. External electrical stimulation. Tinnitus suppression-hearing preliminary results. J
Laryngol Otol. 1983;97(Suppl. 9):141-4.
Exclude: Case study or series
Shulman A. Gabapentin and tinnitus relief. Int Tinnitus J. 2008;14(1):1-5. PMID:18616079.
Exclude: Not a primary study
Shulman A. Medical audiological evaluation of the tinnitus patient. Semin Hear. 1987;8(1):7-14.
Exclude: Not a primary study
Shulman A. Secondary endolymphatic hydrops--tinnitus. Otolaryngol Head Neck Surg.
1991;104(1):146-7. PMID:1900621.
Exclude: Article not available
Shulman A. Tinnitology, tinnitogenesis, nuclear medicine, and tinnitus patients. Int Tinnitus J.
1998;4(2):102-8.
Exclude: Not a primary study
Shulman A. Tinnitus suppression. Laryngoscope. 1987;97(9):1109-10. PMID:3498105.
Exclude: Not a primary study
Shulman A. Vasodilator-antihistamine therapy and tinnitus control. J Laryngol Otol Suppl.
1981;(4):123-9. PMID:6117599.
Exclude: Case study or series
Silverstein H, Choo D, Rosenberg SI, et al. Intratympanic steroid treatment of inner ear disease
and tinnitus (preliminary report). Ear Nose Throat J. 1996;75(8):468-71. PMID:8828271.
Exclude: Insufficient detail of outcome data/not extractable
Silverstein H, Isaacson JE, Olds MJ, et al. Dexamethasone inner ear perfusion for the treatment
of Meniere’s disease: A prospective, randomized, double-blind, crossover trial. Am J Otol.
1998;19(2):196-201. PMID:9520056.
Exclude: Non-randomized head-to-head
Simpson JJ, Donaldson I, Davies WE. Use of homeopathy in the treatment of tinnitus. Br J
Audiol. 1998;32(4):227-33. PMID:9923984.
Exclude: Non-randomized head-to-head
Simpson JJ, Donaldson I, Gilbert AM, et al. The assessment of lamotrigine, an anti-epileptic
drug, in the treatment of tinnitus. Br J Audiol. 1997;31(2):118.
Exclude: Not a primary study
Simpson JJ, Gilbert AM, Weiner GM, et al. The assessment of lamotrigine, an antiepileptic drug,
in the treatment of tinnitus. Am J Otol. 1999;20(5):627-31. PMID:10503585.
Exclude: Insufficient detail of outcome data/not extractable
Singhal S, Sharma SC, Singhal KC. Adverse reactions to gentamycin in patients with ear, nose
or throat infections. Indian J Physiol Pharmacol. 1992;36(3):189-92.
Exclude: Tinnitus is somatic
Sirimanna T, Stephens D. Coping with tinnitus. Practitioner. 1992;236(1518):821-6.
PMID:1461881.
Exclude: Not a primary study
C-51
Sismanis A. Tinnitus. Advances in evaluation and management. Otolaryngol Clin North Am.
2003;36(2):xi-xii. PMID:12856292.
Exclude: Not a primary study
Slater R. On helping people with tinnitus to help themselves. Br J Audiol. 1987;21(2):87-90.
PMID:3594018.
Exclude: Not a primary study
Smith JA, Mennemeier M, Bartel T, et al. Repetitive transcranial magnetic stimulation for
tinnitus: A pilot study. Laryngoscope. 2007;117(3):529-34. PMID:17334317.
Exclude: Case study or series
Smith PA, Parr VM, Lutman ME, et al. Comparative study of four noise spectra as potential
tinnitus maskers. Br J Audiol. 1991;25(1):25-34. PMID:2012900.
Exclude: Non-randomized head-to-head
Sobhy OA, Koutb AR, Abdel-Baki FA, et al. Evaluation of aural manifestations in temporo-
mandibular joint dysfunction. Clin Otolaryngol Allied Sci. 2004;29(4):382-5. PMID:15270827.
Exclude: Non-randomized head-to-head
Sobrinho PG, Oliveira CA, Venosa AR. Long-term follow-up of tinnitus in patients with
otosclerosis after stapes surgery. Int Tinnitus J. 2004;10(2):197-201. PMID:15732523.
Exclude: Tinnitus is somatic
Sockalingam R, Dunphy L, Nam K-E, et al. Effectiveness of frequency-matched masking and
residual inhibition in tinnitus therapy: A preliminary study. Audiol Med. 2007;5(2):92-102.
Exclude: Insufficient detail of outcome data/not extractable
Sockalingam R, Gulliford K, Gulliver M, et al. Effectiveness of frequency-matched masking and
residual inhibition in tinnitus therapy. Asia Pac J Speech Lang Hear. 2006;10(2):87-103.
Exclude: Insufficient detail of outcome data/not extractable
Souliere CR, Jr., Kileny PR, Zwolan TA, et al. Tinnitus suppression following cochlear
implantation. A multifactorial investigation. Arch Otolaryngol Head Neck Surg.
1992;118(12):1291-7. PMID:1449687.
Exclude: Insufficient detail of outcome data/not extractable
Sparano A, Leonetti JP, Marzo S, et al. Effects of stapedectomy on tinnitus in patients with
otosclerosis. Int Tinnitus J. 2004;10(1):73-7. PMID:15379354.
Exclude: Tinnitus is somatic
Spitzer JB, Goldstein BA, Salzbrenner LG, et al. Effect of tinnitus masker noise on speech
discrimination in quiet and two noise backgrounds. Scand Audiol. 1983;12(3):197-200.
PMID:6648316.
Exclude: Non-randomized head-to-head
Stacey JS. Apparent total control of severe bilateral tinnitus by masking, using hearing aids. Br J
Audiol. 1980;14(2):59-60. PMID:7388189.
Exclude: Case study or series
Staecker H. Tinnitus evaluation and treatment: Assessment of quality of life indicators. Acta
Otorhinolaryngol Belgica. 2002;56(4):355-6. PMID:12674089.
Exclude: Not a primary study
C-52
Stanaway RG, Morley T, Anstis SM. Tinnitus not a reference signal in judgments of absolute
pitch. Q J Exp Psychol. 1970;22(2):230-8. PMID:5431399.
Exclude: Case study or series
Steenerson RL, Cronin GW. Treatment of tinnitus with electrical stimulation. Otolaryngol Head
Neck Surg. 1999;121(5):511-3. PMID:10547461.
Exclude: Insufficient detail of outcome data/not extractable
Steiger JR, Hamill TA. A proposed clinical pathway for tinnitus evaluation and management.
Hear J. 2004;57(7):26-8.
Exclude: Not a primary study
Steigerwald DP, Verne SV, Young D. A retrospective evaluation of the impact of
temporomandibular joint arthroscopy on the symptoms of headache, neck pain, shoulder pain,
dizziness, and tinnitus. Cranio. 1996;14(1):46-54. PMID:9086876.
Exclude: Non-randomized head-to-head
Steinmetz LG, Zeigelboim BS, Lacerda AB, et al. The characteristics of tinnitus in workers
exposed to noise. Revista Brasileira de Otorrinolaringologia. 2009;75(1):7-14. PMID:19488554.
Exclude: Case study or series
Stephens D, Jaworski A, Kerr P, et al. Use of patient-specific estimates in patient evaluation and
rehabilitation. Scand Audiol Suppl. 1998;27(49):61-8.
Exclude: Not a primary study
Stephens SD, Corcoran AL. A controlled study of tinnitus masking. Br J Audiol.
1985;19(2):159-67. PMID:3896354.
Exclude: Insufficient detail of outcome data/not extractable
Stevinson C. Negative trial of ginkgo for tinnitus. Focus Alt Complement Ther. 2001;6(2):121.
Exclude: Not a primary study
Stidham KR, Solomon PH, Roberson JB. Evaluation of botulinum toxin A in treatment of
tinnitus. Otolaryngol Head Neck Surg. 2005;132(6):883-9. PMID:15944559.
Exclude: Insufficient detail of outcome data/not extractable
Stiegler P, Matzi V, Lipp C, et al. Hyperbaric oxygen (HBO2) in tinnitus: influence of
psychological factors on treatment results? Undersea Hyperb Med. 2006;33(6):429-37.
PMID:17274312.
Exclude: Insufficient detail of outcome data/not extractable
Stoney PJ, Callaghan DE, Walker FS, et al. A controlled trial of azapropazone in tinnitus. Br J
Audiol. 1991;25(6):415-7. PMID:1773202.
Exclude: Non-randomized head-to-head
Stuerz K, Lafenthaler M, Pfaffenberger N, et al. Body image and body concept in patients with
chronic tinnitus. Eur Arch Otorhinolaryngol. 2009;266(7):961-5. PMID:18941764.
Exclude: Only determined various effects
Suchova L. Tinnitus retraining therapy--The experiences in Slovakia. Bratisl Lek Listy.
2005;106(2):79-82. PMID:16026138.
Exclude: Case study or series
C-53
Sulkowski W, Kowalska S, Lipowczan A, et al. Tinnitus and impulse noise-induced hearing loss
in drop-forge operators. Int J Occup Med Environ Health. 1999;12(2):177-82. PMID:10465907.
Exclude: Only about prevalence
Sullivan MD, Dobie RA, Sakai CS, et al. Treatment of depressed tinnitus patients with
nortriptyline. Ann Otol Rhinol Laryngol. 1989;98(11):867-72. PMID:2817678.
Exclude: Insufficient detail of outcome data/not extractable
Sullivan MD, Katon W, Dobie R, et al. Disabling tinnitus. Association with affective disorder.
Gen Hosp Psychiatry. 1988;10(4):285-91. PMID:3417130.
Exclude: Only determined various effects
Surr RK, Kolb JA, Cord MT, et al. Tinnitus Handicap Inventory (THI) as a hearing aid outcome
measure. J Am Acad Audiol. 1999;10(9):489-95. PMID:10522622.
Exclude: Insufficient detail of outcome data/not extractable
Sutbas A, Yetiser S, Satar B, et al. Low-cholesterol diet and antilipid therapy in managing
tinnitus and hearing loss in patients with noise-induced hearing loss and hyperlipidemia. Int
Tinnitus J. 2007;13(2):143-9. PMID:18229794.
Exclude: Non-randomized head-to-head
Sweetow R. Counseling the patient with tinnitus. Arch Otolaryngol. 1985;111(5):283-4.
PMID:3985848.
Exclude: Not a primary study
Sweetow RW, Mraz NR. Providing audiology services to tinnitus patients. Audiol Today.
2004;16(1):33-5.
Exclude: Article not available
Sweetow RW, Sabes JH. Effects of acoustical stimuli delivered through hearing aids on tinnitus.
J Am Acad Audiol. 2010;21(7):461-73. PMID:20807482.
Exclude: Insufficient detail of outcome data/not extractable
Sweetow RW. Comprehensive tinnitus patient management. Semin Hear. 1987;8(1):71-4.
Exclude: Not a primary study
Sziklai I, Komora V, Ribari O. Double-blind study on the effectiveness of a bioflavonoid in the
control of tinnitus in otosclerosis. Acta Chir Hung. 1992;33(1-2):101-7. PMID:1343452.
Exclude: Tinnitus is somatic
Sziklai I, Szilvassy J, Szilvassy Z. Tinnitus control by dopamine agonist pramipexole in
presbycusis patients: A randomized, placebo-controlled, double-blind study. Laryngoscope.
2011;121(4):888-93. PMID:21433025.
Exclude: Insufficient detail of outcome data/not extractable
Szymanski M, Golabek W, Mills R. Effect of stapedectomy on subjective tinnitus. J Laryngol
Otol. 2003;117(4):261-4. PMID:12816213.
Exclude: Case study or series
Tan J, Tange RA, Dreschler WA, et al. Long-term effect of hyperbaric oxygenation treatment on
chronic distressing tinnitus. Scand Audiol. 1999;28(2):91-6. PMID:10384896.
Exclude: Case study or series
C-54
Tauber S, Schorn K, Beyer W, et al. Transmeatal cochlear laser (TCL) treatment of cochlear
dysfunction: A feasibility study for chronic tinnitus. Lasers Med Sci. 2003;18(3):154-61.
PMID:14505199.
Exclude: Insufficient detail of outcome data/not extractable
Terry AM, Jones DM, Davis BR, et al. Parametric studies of tinnitus masking and residual
inhibition. Br J Audiol. 1983;17(4):245-56. PMID:6667357.
Exclude: Insufficient detail of outcome data/not extractable
Terry AM, Jones DM. Preference for potential tinnitus maskers: Results from annoyance ratings.
Br J Audiol. 1986;20(4):277-97. PMID:3790773.
Exclude: Non-randomized head-to-head
Test T, Canfi A, Eyal A, et al. The influence of hearing impairment on sleep quality among
workers exposed to harmful noise. Sleep. 2011;34(1):25-30. PMID:21203368.
Exclude: Only determined various effects
Tewfik S. Phonocephalography. An objective diagnosis of tinnitus. J Laryngol Otol.
1974;88(9):869-75. PMID:4430868.
Exclude: Tinnitus is somatic
The treatment of tinnitus. Clin Otolaryngol Allied Sci. 1980;5(1):1-2. PMID:7363488.
Exclude: Not a primary study
Thedinger BS, Karlsen E, Schack SH. Treatment of tinnitus with electrical stimulation: An
evaluation of the Audimax Theraband. Laryngoscope. 1987;97(1):33-7. PMID:3491942.
Exclude: Insufficient detail of outcome data/not extractable
Thomas M, Laurell G, Lundeberg T. Acupuncture for the alleviation of tinnitus. Laryngoscope.
1988;98(6:Pt 1):664-7. PMID:3374243.
Exclude: Case study or series
Thomas M, Laurell G, Lundeberg T. Vibratory stimulation as a treatment alternative in patients
with tinnitus. Ear Nose Throat J. 817;68(11):810-4. PMID:2693064.
Exclude: Insufficient detail of outcome data/not extractable
Ting SKS, Chan YM, Cheong PWT, et al. Short duration repetitive transcranial magnetic
stimulation for tinnitus treatment: A prospective Asian study. Clin Neurol Neurosurg.
2011;113(7):556-8.
Exclude: Non-randomized head-to-head
Tinnitus: Treatment methods and results. J Laryngol Otol Suppl. 1984;9:247-318.
PMID:6440940.
Exclude: Article not available
Tonkin JP. Tinnitus. Clinical approaches to management. Curr Ther. 1985;26(1):37-40.
Exclude: Not a primary study
Trotter MI, Donaldson I. Hearing aids and tinnitus therapy: A 25-year experience. J Laryngol
Otol. 2008;122(10):1052-6. PMID:18353195.
Exclude: Insufficient detail of outcome data/not extractable
C-55
Tullberg M, Ernberg M. Long-term effect on tinnitus by treatment of temporomandibular
disorders: A two-year follow-up by questionnaire. Acta Odontol Scand. 2006;64(2):89-96.
PMID:16546850.
Exclude: Non-randomized head-to-head
Turner JS, Jr. Treatment of hearing loss, ear pain, and tinnitus in older patients. Geriatrics.
116;37(8):107-11. PMID:7095424.
Exclude: Not a primary study
Tyler RS, Babin RW, Niebuhr DP. Some observations on the masking and post-masking effects
of tinnitus. J Laryngol Otol. 1983;97(Suppl. 9):150-6.
Exclude: Not a primary study
Tyler RS, Bentler RA. Tinnitus maskers and hearing aids for tinnitus. Semin Hear. 1987;8(1):49-
61.
Exclude: Not a primary study
Tyler RS. Tinnitus in the profoundly hearing-impaired and the effects of cochlear implants. Ann
Otol Rhinol Laryngol Suppl. 1995;165:25-30. PMID:7717631.
Exclude: Case study or series
Uri N, Doweck I, Cohen-Kerem R, et al. Acyclovir in the treatment of idiopathic sudden
sensorineural hearing loss. Otolaryngol Head Neck Surg. 2003;128(4):544-9.
Exclude: Insufficient detail of outcome data/not extractable
Van de Heyning P, Vermeire K, Diebl M, et al. Incapacitating unilateral tinnitus in single-sided
deafness treated by cochlear implantation. Ann Otol Rhinol Laryngol. 2008;117(9):645-52.
PMID:18834065.
Exclude: Non-randomized head-to-head
Van Deelen GW, Huizing EH. Use of a diuretic (Dyazide) in the treatment of Meniere’s disease.
A double-blind cross-over placebo-controlled study. ORL. 1986;48(5):287-92.
Exclude: Insufficient detail of outcome data/not extractable
Van Deelen GW, Hulk J, Huizing EH. The use of the underpressure chamber in the treatment of
patients with Meniere’s disease. J Laryngol Otol. 1987;101(3):229-35.
Exclude: Insufficient detail of outcome data/not extractable
Vanneste S, Figueiredo R, De RD. Treatment of tinnitus with cyclobenzaprine: An open-label
study. Int J Clin Pharmacol Ther. 2012;50(5):338-44.
Exclude: Insufficient detail of outcome data/not extractable
Vanneste S, Plazier M, Ost J, et al. Bilateral dorsolateral prefrontal cortex modulation for tinnitus
by transcranial direct current stimulation: A preliminary clinical study. Exp Brain Res.
2010;202(4):779-85. PMID:20186404.
Exclude: Insufficient detail of outcome data/not extractable
Vanneste S, Plazier M, P, et al. Repetitive transcranial magnetic stimulation frequency dependent
tinnitus improvement by double cone coil prefrontal stimulation. J Neurol Neurosurg Psychiatry.
2011;82(10):1160-4.
Exclude: Insufficient detail of outcome data/not extractable
C-56
Vanneste S, Plazier M, Van de Heyning P, et al. Transcutaneous electrical nerve stimulation
(TENS) of upper cervical nerve (C2) for the treatment of somatic tinnitus. Exp Brain Res.
2010;204(2):283-7. PMID:20505927.
Exclude: Non-randomized head-to-head
Vanneste S, Plazier M, van der Loo E, et al. Burst transcranial magnetic stimulation: Which
tinnitus characteristics influence the amount of transient tinnitus suppression? Eur J Neurol.
2010;17(9):1141-7. PMID:20374277.
Exclude: Insufficient detail of outcome data/not extractable
Vasama JP, Moller MB, Moller AR. Microvascular decompression of the cochlear nerve in
patients with severe tinnitus. Preoperative findings and operative outcome in 22 patients. Neurol
Res. 1998;20(3):242-8. PMID:9583586.
Exclude: Case study or series
Vermeij P, Hulshof JH, Hilders CGJM, et al. Lidocaine in the treatment of tinnitus. Eur J
Pharmacol. 1990;183(3):1021.
Exclude: Not a primary study
Vermeij P, Hulshof JH. Dose finding of tocainide in the treatment of tinnitus. Int J Clin
Pharmacol Ther Toxicol. 1986;24(4):207-12. PMID:3086242.
Exclude: Insufficient detail of outcome data/not extractable
Vermeire K, Heyndrickx K, De RD, et al. Phase-shift tinnitus treatment: An open prospective
clinical trial. B-ENT. 2007;3(Suppl 7):65-9. PMID:18225610.
Exclude: Non-randomized head-to-head
Vermeire K, Van de Heyning P. Binaural hearing after cochlear implantation in subjects with
unilateral sensorineural deafness and tinnitus. Audiol Neuro Otol. 2009;14(3):163-71.
PMID:19005250.
Exclude: Non-randomized head-to-head
Vernon J, Press L, McLaughlin T. Magnetic resonance imaging and tinnitus. Otolaryngol Head
Neck Surg. 1996;115(6):587-8. PMID:8969772.
Exclude: Not a primary study
Vernon J, Schleuning A. Tinnitus: A new management. Laryngoscope. 1978;88(3):413-9.
PMID:628295.
Exclude: Not a primary study
Vernon J. Use of electricity to suppress tinnitus. Semin Hear. 1987;8(1):29-48.
Exclude: Not a primary study
Vernon JA, Fenwick JA. Attempts to suppress tinnitus with transcutaneous electrical stimulation.
Otolaryngol Head Neck Surg. 1985;93(3):385-9. PMID:3927235.
Exclude: Insufficient detail of outcome data/not extractable
Vernon JA, Press LS. Characteristics of tinnitus induced by head injury. Arch Otolaryngol Head
Neck Surg. 1994;120(5):547-51. PMID:8172707.
Exclude: Non-randomized head-to-head
C-57
Vesterager V. Combined psychological and prosthetic management of tinnitus: A cross-sectional
study of patients with severe tinnitus. Br J Audiol. 1994;28(1):1-11. PMID:7987267.
Exclude: Insufficient detail of outcome data/not extractable
Vierstraete K, Debruyne F, Vantrappen G, et al. Tinnitus maskers in the treatment of tinnitus.
The MICROTEK 321Q. Acta Otorhinolaryngol Belgica. 1996;50(3):211-20. PMID:8888905.
Exclude: Case study or series
von Wedel H., Calero L, Walger M, et al. Soft-laser/Ginkgo therapy in chronic tinnitus. A
placebo-controlled study. Adv Otorhinolaryngol. 1995;49:105-8. PMID:7653340.
Exclude: Insufficient detail of outcome data/not extractable
von Wedel H., von Wedel UC, Zorowka P. Tinnitus diagnosis and therapy in the aged. Acta
Otolaryngol Suppl. 1990;476:195-201. PMID:2087963.
Exclude: Insufficient detail of outcome data/not extractable
Voroba B. Tinnitus research frontiers. Acta Phoniatrica Latina. 1981;3(Suppl.):9-17.
Exclude: Not a primary study
Waddell A, Canter R. Tinnitus. Clin Evid. 2002;(7):481-9. PMID:12230674.
Exclude: Article not available
Walsh WM, Gerley PP. Thermal biofeedback and the treatment of tinnitus. Laryngoscope.
1985;95(8):987-9. PMID:3894844.
Exclude: Insufficient detail of outcome data/not extractable
Wang K, Bugge J, Bugge S. A randomised, placebo-controlled trial of manual and electrical
acupuncture for the treatment of tinnitus. Complement Ther Med. 2010;18(6):249-55.
PMID:21130361.
Exclude: Insufficient detail of outcome data/not extractable
Wang L, Wu P, and Ju YL. Observation on the effect of acupoint Iinjection for sensorineural
hearing loss and tinnitus. J Tradit Chin Med. 2008;49(1):47-9.
Exclude: Article not available
Ward LM, Baumann M. Measuring tinnitus loudness using constrained psychophysical scaling.
Am J Audiol. 2009;18(2):119-28. PMID:19638478.
Exclude: Non-randomized head-to-head
Ward WD. General auditory effects of noise. Otolaryngol Clin North Am. 1979;12(3):473-92.
PMID:471497.
Exclude: Not a primary study
Weiler EW, Brill K, Tachiki KH, et al. Neurofeedback and quantitative electroencephalography.
Int Tinnitus J. 2002;8(2):87-93. PMID:14763216.
Exclude: Case study or series
Weise C, Heinecke K, Rief W. Stability of physiological variables in chronic tinnitus sufferers.
Appl Psychophysiol Biofeedback. 2008;33(3):149-59. PMID:18600443.
Exclude: Only determined various effects
Welch D, Dawes PJ. Personality and perception of tinnitus. Ear Hear. 2008;29(5):684-92.
PMID:18596645.
Exclude: Non-randomized head-to-head
C-58
West PDB. Effective treatment for tinnitus: Audit of a district general hospital service. J Audiol
Med. 1999;8(2):92-100.
Exclude: Insufficient detail of outcome data/not extractable
Westerlaken BO, de Kleine E., van der Laan B, et al. The treatment of idiopathic sudden
sensorineural hearing loss using pulse therapy: A prospective, randomized, double-blind clinical
trial. Laryngoscope. 2007;117(4):684-90. PMID:17415139.
Exclude: Non-randomized head-to-head
Westin V, Hayes SC, Andersson G. Is it the sound or your relationship to it? The role of
acceptance in predicting tinnitus impact. Behav Res Ther. 2008;46(12):1259-65.
PMID:18926522.
Exclude: Only determined various effects
Westin V, Ostergren R, Andersson G. The effects of acceptance versus thought suppression for
dealing with the intrusiveness of tinnitus. Int J Audiol. 2008;47:112-8. PMID:19012119.
Exclude: Non-randomized head-to-head
White TP, Hoffman SR, Gale EN. Psychophysiological therapy for tinnitus. Ear Hear.
1986;7(6):397-9. PMID:3539680.
Exclude: Insufficient detail of outcome data/not extractable
Wilmot TJ, Menon GN. Betahistine in Meniere’s disease. J Laryngol Otol. 1976;90(9):833-40.
PMID:787460.
Exclude: Insufficient detail of outcome data/not extractable
Wilson PH, Henry J, Bowen M, et al. Tinnitus reaction questionnaire: Psychometric properties of
a measure of distress associated with tinnitus. J Speech Hear Res. 1991;34(1):197-201.
PMID:2008074.
Exclude: Not a primary study
Wilson PH, Henry JL. Psychological approaches in the management of tinnitus. Aust J
Otolaryngol. 1993;1(4):296-302.
Exclude: Not a primary study
Wilson PH, Henry JL. Tinnitus cognitions questionnaire: Development and psychometric
properties of a measure of dysfunctional cognitions associated with tinnitus. Int Tinnitus J.
1998;4(1):23-30.
Exclude: Non-randomized head-to-head
Wise K, Rief W, Goebel G. Meeting the expectations of chronic tinnitus patients: Comparison of
a structured group therapy program for tinnitus management with a problem-solving group. J
Psychosom Res. 1998;44(6):681-5. PMID:9678749.
Exclude: Insufficient detail of outcome data/not extractable
Witsell DL, Hannley MT, Stinnet S, et al. Treatment of tinnitus with gabapentin: A pilot study.
Otol Neurotol. 2007;28(1):11-5. PMID:17106432.
Exclude: Insufficient detail of outcome data/not extractable
Wood KA, Webb WL, Jr., Orchik DJ, et al. Intractable tinnitus: Psychiatric aspects of treatment.
Psychosomatics. 565;24(6):559-61. PMID:6878604.
Exclude: Case study or series
C-59
Wright EF, Bifano SL. Tinnitus improvement through TMD therapy. J Am Dent Assoc.
1997;128(10):1424-32. PMID:9332144.
Exclude: Non-randomized head-to-head
Yamada Y, Tomita H. Influences on taste in the area of chorda tympani nerve after
transtympanic injection of local anesthetic (4% lidocaine). Auris Nasus Larynx. 1989;16:41-6.
PMID:2604615.
Exclude: Non-randomized head-to-head
Yanick J. Dietary and lifestyle influences on cochlear disorders and biochemical status: A 12-
month study. J Appl Nutr. 1988;40(2):75-84.
Exclude: Insufficient detail of outcome data/not extractable
Yetiser S, Kertmen M. Intratympanic gentamicin in Meniere’s disease: The impact on tinnitus.
Int J Audiol. 2002;41(6):363-70. PMID:12353609.
Exclude: Insufficient detail of outcome data/not extractable
Yetiser S, Tosun F, Satar B, et al. The role of zinc in management of tinnitus. Auris Nasus
Larynx. 2002;29(4):329-33. PMID:12393036.
Exclude: Insufficient detail of outcome data/not extractable
Ylikoski J, Mrena R, Makitie A, et al. Hyperbaric oxygen therapy seems to enhance recovery
from acute acoustic trauma. Acta Otolaryngol. 2008;128(10):1110-5. PMID:18607951.
Exclude: Insufficient detail of outcome data/not extractable
Yonehara E, Mezzalira R, Porto PR, et al. Can cochlear implants decrease tinnitus? Int Tinnitus
J. 2006;12(2):172-4. PMID:17260883.
Exclude: Case study or series
Young IM, Lowry LD. Incurrence and alterations in contralateral tinnitus following monaural
exposure to a pure tone. J Acoust Soc Am. 1983;73(6):2219-21. PMID:6875103.
Exclude: Case study or series
Zagolski O. Management of tinnitus in patients with presbycusis. Int Tinnitus J. 2006;12(2):175-
8. PMID:17260884.
Exclude: Insufficient detail of outcome data/not extractable
Zenner HP, De Maddalena H. Validity and reliability study of three tinnitus self-assessment
scales: Loudness, annoyance and change. Acta Otolaryngol. 2005;125(11):1184-8.
PMID:16353397.
Exclude: Insufficient detail of outcome data/not extractable
Zenner HP. A totally implantable drug delivery system for local therapy of tinnitus. Int Tinnitus
J. 2001;7(1):40. PMID:14964954.
Exclude: Article not available
Zhou F, Wu P, Wang L, et al. The NGF point-injection for treatment of the sound-perceiving
nerve deafness and tinnitus in 68 cases. J Tradit Chin Med. 2009;29(1):39-42. PMID:19514187.
Exclude: Case study or series
Zhou Y, Wei W. Clinical experience in application of the point zhongzhu. J Tradit Chin Med.
2002;22(4):294-5. PMID:16579098.
Exclude: Case study or series
C-60
Zimbabwean people with head noises are offered help. Cent Afr J Med. 1998;44(11):296.
PMID:10189754.
Exclude: Not a primary study
Zoger S, Svedlund J, Holgers KM. Relationship between tinnitus severity and psychiatric
disorders. Psychosomatics. 2006;47(4):282-8. PMID:16844885.
Exclude: Only about prevalence
C-61
Appendix D. Publications Not Eligible for Extraction
Table D1. Pharmacological or food supplement interventions and outcomes: Honorable mention group (n=10)
Pharm/Food # Specific Intervention Tinnitus- Loudnes Anxiety Depression Global Adverse
Sleep
Intervention Specific QoL s Symptoms Symptoms QoL Effects
Anti- INACTIVE COMPARATOR
depressant 1 Amitriptyline vs. Placebo
drugs 1 ATA-Q
Bayar, 2001
2 Nortriptyline vs. Placebo HAS,
2 IOWA, Tinnitus
Dobie, 1993 Self- HDS sub- Sheehan’s
interference BDI, HDS
reported scale Disability
(self-report),
Scale
Psychoactiv INACTIVE COMPARATOR
e 1 Gabapentin (GABA analogue – GABAergic) vs.
(Neurotrans- placebo Dehkordi, 2011
3
TSI subjective
mitter) drugs
Other drugs INACTIVE COMPARATOR
1 Melatonin and Sulodexide vs. control group
4,5 THI
Neri, 2009
2 Melatonin alone vs. control group
4,5 THI
Neri, 2009
3 Memantine vs. Placebo
6 THI
Figueiredo, 2008
4 Atorvastatin vs. Placebo
7 Tinnitus Score
Olzowy, 2007
5 Misoprostol vs. Placebo Self- Self-
8 Self-reported
Akkuzu, 2004 reported reported
6 Cinnarizine vs. Placebo
9 Self-reported
Podoshin, 1991
7 Neramexane vs. Placebo THI, TA Likert- Likert-
10
Suckfüll, 2011 (annoyance) scale scale
8 AM-101 injection vs. Placebo
11 THI subjective
Muehlmeier, 2011
D-1
Table D1. Pharmacological or food supplement interventions and outcomes: Honorable mention group (n=10) (continued)
# Specific Intervention
Tinnitus- Anxiety Depression Global Adverse
Pharm/Food Loudness Sleep
Specific QoL Symptoms Symptoms QoL Effects
Intervention
Other drugs HEAD TO HEAD
(cont’d) 1 Melatonin and Sulodexide vs. Melatonin alone
THI
Neri, 20094,5
2 Cinnarizine vs. Biofeedback
Self-reported
Podoshin, 19919
3 Cinnarizine vs. Acupuncture
Self-reported
Podoshin, 19919
Abbreviations: GABAB1 = gamma-aminobutyric acid B1; gen = generation; med/surg = medical/surgical; PDE5 = phosphodiesterase type 5; QoL = quality of life; rTMS =
repetitive transcranial magnetic stimulation; SARI = serotonin antagonist reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor; vs. = versus
D-2
Table D2. Medical interventions and outcomes: Honorable mention group (n=4)
Medical # Specific Intervention Tinnitus- Loudnes Anxiety Depression Global Adverse
Sleep
Intervention Specific QoL s Symptoms Symptoms QoL Events
RTMS INACTIVE COMPARATOR
1 1Hz rTMS vs. sham THI, self-
12
Khedr, 2007 reported
2 10Hz rTMS vs. sham THI, self-
12
Khedr, 2007 reported
3 25Hz rTMS vs. sham THI, self-
12
Khedr, 2007 reported
4 Electromagnetic stimulation vs. Placebo
13 Self-reported
Roland, 1993
HEAD TO HEAD
1 1Hz rTMS vs. 10Hz rTMS THI, self-
12
Khedr, 2007 reported
2 1Hz rTMS vs. 25Hz rTMS THI, self-
12
Khedr, 2007 reported
3 10Hz rTMS vs. 25Hz rTMS THI, self-
12
Khedr, 2007 reported
Neuromodulation HEAD TO HEAD
1 InterX (electrical neuro stimulation) vs.
THI,
Osteopathic manipulations
14 VAS
Bonaconsa, 2010
Laser INACTIVE COMPARATOR
1 Laser therapy vs. Placebo Self-
15 Self-reported
Gungor, 2008 reported
D-3
Table D3. Sound treatments/technologies interventions and outcomes: Honorable mention group (n=4)
Sound # Specific Intervention
Tinnitus- Loudnes Anxiety Depression Global Adverse
Treatment/ Sleep
Specific QoL s Symptoms Symptoms QoL Events
Technology
INACTIVE COMPARATOR
1 HLSAME ADT vs. WLG
16 THI VAS
Herraiz, 2010,
2 HLNONSAME ADT vs. WLG
16 THI VAS
Herraiz, 2010,
3 Aural masker vs. placebo masker TEQ, IWDA, TEQ- sub
17
Jakes, 1992, CCEI scale
4 Group cognitive therapy + aural masker
TEQ, IWDA, TEQ- sub
vs. placebo masker
17 CCEI scale
Jakes, 1992,
HEAD TO HEAD
1 HLSAME ADT vs. HLNONSAME ADT
16 THI VAS
Herraiz, 2010,
2 Hearing aid plus counselling vs. counselling
only THQ
18
Searchfield, 2010,
3 Tinnitus Masking vs. pharmacotherapy
19 THI HAS HAD
Pandey, 2010,
4 Tinnitus Masking vs. yoga (Bhramari
Pranayama) THI HAS HAD
19
Pandey, 2010,
5 Tinnitus Masking vs. combination therapy
19 THI HAS HAD
Pandey, 2010,
6 Aural masker vs. Group cognitive therapy +
TEQ, IWDA, TEQ- sub
aural masker
17 CCEI scale
Jakes, 1992,
D-4
Table D4. Psychological/behavioral interventions and outcome measures: Honorable mention group (n=6)
Psych/Beh # Specific Intervention Tinnitus- Loudnes Anxiety Depression Global Adverse
Sleep
Intervention Specific QoL s Symptoms Symptoms QoL Events
CBT / CBT INACTIVE COMPARISONS
combination 1 Group cognitive therapy vs. WLC TEQ, IWDA, TEQ- sub
17
Jakes, 1992, CCEI scale
2 Group cognitive therapy + aural masker vs.
TEQ, IWDA, TEQ- sub
WLC
17 CCEI scale
Jakes, 1992,
HEAD TO HEAD COMPARISONS
Group cognitive therapy vs. Group cognitive
TEQ, IWDA, TEQ- sub
therapy + aural masker
17 CCEI scale
Jakes, 1992,
Relaxation INACTIVE COMPARATOR
1 Relaxation & exposure vs. WLC Tinnitus control
20
Lindberg, 1989, (VAS),
VAS
discomfort
(VAS)
2 Relaxation & distraction vs. WLC Tinnitus control
20
Lindberg, 1989, (VAS),
VAS
discomfort
(VAS)
HEAD to HEAD
D-5
Table D4. Psychological/behavioral interventions and outcome measures: Honorable mention group (n=6) (continued)
Psych/Beh # Specific Intervention Tinnitus- Loudnes Anxiety Depression Global Adverse
Sleep
Intervention Specific QoL s Symptoms Symptoms QoL Events
Other HEAD TO HEAD
psych/ beh 1 yoga (Bhramari Pranayama) vs.
(cont’d) pharmacotherapy THI HAS HAD
19
Pandey, 2010,
2 yoga (Bhramari Pranayama) vs. combination
therapy THI HAS HAD
19
Pandey, 2010,
3 Client centered hypnotherapy vs. counseling
21 TSSS
Mason, 1996,
4 Biofeedback vs. Stomatognathic treatment
22 Self-reported
Erlandsson, 1991,
Abbreviations: ACT = acceptance and commitment therapy; CBT = cognitive behavioral training; psych/beh = psychological/behavioral; EMG = electromyography; TCT tinnitus
coping therapy; TRT = tinnitus retraining therapy; vs. = versus; WLC = wait list control
D-6
Appendix D. References
1. Bayar N, Boke B, Turan E, et al. Efficacy of 10. Suckfüll M, Althaus M, Ellers-Lenz B, et al.
amitriptyline in the treatment of subjective A randomized, double-blind, placebo-
tinnitus. J Otolaryngol. 2001;30(5):300-3. controlled clinical trial to evaluate the
PMID:11771024 efficacy and safety of neramexane in
patients with moderate to severe subjective
2. Dobie RA, Sakai CS, Sullivan MD, et al.
tinnitus. BMC Ear Nose Throat Disord.
Antidepressant treatment of tinnitus patients:
2011;11(1):1.
Report of a randomized clinical trial and
clinical prediction of benefit. Am J Otol. 11. Muehlmeier G, Biesinger E, Maier H. Safety
1993;14(1):18-23. PMID:8424470 of intratympanic injection of AM-101 in
patients with acute inner ear tinnitus. Audiol
3. Dehkordi MA, Abolbashari S, Taheri R, et
Neuro Otol. 2011;16(6):388-97.
al. Efficacy of gabapentin on subjective
PMID:21252501
sidiopathic tinnitus: A randomized, double-
blind, placebo-controlled trial. Ear Nose 12. Khedr EM, Rothwell JC, Ahmed MA, et al.
Throat J. 2011;90(4):150-8. Effect of daily repetitive transcranial
magnetic stimulation for treatment of
4. Neri G, De SA, Baffa C, et al. Treatment of
tinnitus: Comparison of different stimulus
central and sensorineural tinnitus with orally
frequencies. J Neurol Neurosurg Psychiatry.
administered Melatonin and Sulodexide:
2008;79(2):212-5. PMID:18202212
Personal experience from a randomized
controlled study. Acta Otorhinolaryngol Ital. 13. Roland NJ, Hughes JB, Daley MB, et al.
2009;29(2):86-91. PMID:20111618 Electromagnetic stimulation as a treatment
of tinnitus: A pilot study. Clin Otolaryngol
5. Neri G, Baffa C, De SA, et al. Management
Allied Sci. 1993;18(4):278-81.
of tinnitus: Oral treatment with melatonin
PMID:8877185
and sulodexide. Journal of Biological
Regulators & Homeostatic Agents. 14. Bonaconsa A, Mazzoli MM, Antonia M, et
2009;23(2):103-10. PMID:19589291 al. Posturography measures and efficacy of
different physical treatments in somatic
6. Figueiredo RR, Langguth B, Mello de OP, et
tinnitus. Int Tinnitus J. 2010;16(1):44-50.
al. Tinnitus treatment with memantine.
PMID:21609913
Otolaryngol Head Neck Surg.
2008;138(4):492-6. PMID:18359360 15. Gungor A, Dogru S, Cincik H, et al.
Effectiveness of transmeatal low power laser
7. Olzowy B, Canis M, Hempel JM, et al.
irradiation for chronic tinnitus. J Laryngol
Effect of atorvastatin on progression of
Otol. 2008;122(5):447-51. PMID:17625032
sensorineural hearing loss and tinnitus in the
elderly: Results of a prospective, 16. Herraiz C, Diges I, Cobo P, et al. Auditory
randomized, double-blind clinical trial. Otol discrimination training for tinnitus
Neurotol. 2007;28(4):455-8. treatment: The effect of different paradigms.
PMID:17529847 Eur Arch Otorhinolaryngol.
2010;267(7):1067-74. PMID:20044759
8. Akkuzu B, Yilmaz I, Cakmak O, et al.
Efficacy of misoprostol in the treatment of 17. Jakes SC, Hallam RS, McKenna L, et al.
tinnitus in patients with diabetes and/or Group cognitive therapy for medical
hypertension. Auris Nasus Larynx. patients: An application to tinnitus. Cognit
2004;31(3):226-32. PMID:15364356 Ther Res. 1992;16(1):67-82.
9. Podoshin L, Ben-David Y, Fradis M, et al. 18. Searchfield GD, Kaur M, Martin WH.
Idiopathic subjective tinnitus treated by Hearing aids as an adjunct to counseling:
biofeedback, acupuncture and drug therapy. Tinnitus patients who choose amplification
Ear Nose Throat J. 1991;70(5):284-9. do better than those that don’t. Int J Audiol.
PMID:1914952 2010;49(8):574-9. PMID:20500032
D-7
19. Pandey S, Mahato NK, Navale R. Role of
self-induced sound therapy: Bhramari
Pranayama in Tinnitus. Audiol Med.
2010;8(3):137-41.
20. Lindberg P, Scott B, Melin L, et al. The
psychological treatment of tinnitus: An
experimental evaluation. Behav Res Ther.
1989;27(6):593-603. PMID:2692553
21. Mason JD, Rogerson DR, Butler JD. Client
centred hypnotherapy in the management of
tinnitus--Is it better than counselling? J
Laryngol Otol. 1996;110(2):117-20.
PMID:8729491
22. Erlandsson SI, Rubinstein B, Carlsson SG.
Tinnitus: Evaluation of biofeedback and
stomatognathic treatment. Br J Audiol.
1991;25(3):151-61. PMID:1873582
D-8
Appendix E. Characteristics of Included Studies Evidence Tables
Table E1. Pharmacological or food supplement interventions and outcomes (n=16)
Author Population Intervention Outcome Results
Year Measures
Setting
76
Aoki, Baseline sample: Total n = 60; Lyophilized powder of enzymolyzed Depression The lyophilized powder of enzymolyzed
2012 Interven: n = 30; Cntrl: n = 30 honeybee larvae (720 mg/4 capsules/day) (THI-sub) honeybee larvae was not superior to placebo
Setting: Department of Otolaryngology with regard to the total score on the Tinnitus
Japan Mean age (SD): Comparator: Placebo (hydrogenated TS-QOL Handicap Inventory and the visual analog
Interven: 64.9y (11.3); dextrin; (THI*, VAS) scale.
Cntrl: 61.6y (11.1) 720 mg/4 capsules/day) indistinguishable
Gender: 20.7% male in appearance or odor Adverse Events: “experienced discomfort
after taking the capsules” (1 Interven; 1 Cntrl)
Presumed etiology of tinnitus: Idiopathic Duration of treatment: 12 weeks
Duration of tinnitus: > 6 months Number of follow ups: 3 (4, 8 and 12
Severity of tinnitus: unilateral chronic weeks)
Number of dropouts: 2 Duration of study: November 2009 to
Reasons for dropouts: Adverse events October 2010
Audiological factors: 4-tone average
better ear (dB)
Interven: 31.8 +/-18.5; Cntrl 31.3 +/-20.4.
Four-tone average worse ear (dB):
Interven: 60.7+/-23.6; Cntrl: 56.8+/-22.8
Comorbidities: NR
E-1
Table E1. Pharmacological or food supplement interventions and outcomes (n=16) (continued)
Author Population Intervention Outcome Results
Year Measures
Setting
77
Arda, 2003 Baseline sample: Total n = 50; Zinc Loudness Clinically favorable progress was detected in
Interven n = 30; Cntrl n = 20 Interven: 28 patients in the zinc group were (Subjective 46.4% of patients given zinc.
Turkey Setting: ENT Clinic given 50 mg zinc per day for 2 months score 0-7) The severity of subjective tinnitus decreased in
Mean age (SD): Total range: 21-74 y; (Zinco 220, 50 mg). 82% of the patients receiving zinc (NS).
Interven: 55 y (14.3); Cntrl: 51.2 y (12.8) The mean of subjective tinnitus decreased from
Gender: Comparator: Placebo – 1 starch tablet 5.25 ± 1.08 to 2.82 ± 1.81 (P < 0.001).
Interven: 42.8% male; Cntrl: 30.7% male daily for 2 months
Adverse Events: 2 patients in the zinc group
Presumed etiology of tinnitus: Idiopathic Duration of treatment: 2 months had minor gastric disturbances
Duration of tinnitus: Interven: 39.39 Number of follow-ups: 1
months (±34.30); Cntrl: 26.08 months Duration of study: April 2000 to May 2001
(±21.32)
Severity of tinnitus: unilateral chronic
Number of dropouts: 9
Interven n = 2; Cntrl n = 7
Reasons for dropouts: Non-compliance
Interven n = 2; Cntrl n = 7
Audiological factors: Continuous tinnitus
Interven 10 (35.7%); Cntrl 6 (46.2%)
Comorbidities: Not reported
E-2
Table E1. Pharmacological or food supplement interventions and outcomes (n=16) (continued)
Author Population Intervention Outcome Results
Year Measures
Setting
72
Azevedo, Baseline sample: Total n = 50 Double Blind RCT TS-QOL A high index of success in the relief of tinnitus,
2005 Interven n = 25; Cntrl n = 25 Acamprosate 333mg, TID (subjective) about 86.9%.n 47.8% of the cases, more than
Setting: Otorhinology Hospital clinic 50% relief was found.
Brazil Mean age (SD): 60 y; range 35y to 82y Comparator: Placebo, TID
Gender: 58% male Authors conclude that Acamprosate, a drug
Duration of treatment: 90 days used in the treatment of alcoholism, is a safe
Presumed etiology of tinnitus: Number of followups: 3 at 30 days, 60 and successful alternative for sensorineural
sensorineural days, 90 days tinnitus’ treatment.
Duration of tinnitus: 9.8% <1y; 53.7% 1 to Duration of study: October 2003 to October
7y; 36.6% >7y 2004 Adverse events: The incidence of side effects
Severity of tinnitus: NR was low, 12%, all of them mild (epigastralgia,
Number of dropouts: choking).
Interven n = 2; Cntrl n = 7
Reasons for dropouts:
Side effects: Interven (1); Cntrl (5)
Family pressures: Interven (1); Cntrl (2)
Audiological factors: conductive and
mixed hearing loss were excluded
Comorbidities: Hearing loss (59.4%);
Dizziness (46.9%); Hyperacusis (9.3%)
81
Dib, Baseline sample: Total n = 85 Trazodone (antidepressant) G-QOL (VAS) There was a significant improvement in
2007 Interven n = 43; Cntrl n = 42 50mg per tablet, single night dose for 60 intensity, discomfort and life quality in both
Setting: NR continuous days. If important side effects TS-QOL groups after treatment; however, there was
Brazil Age Range: 45 to 80 y were seen, the medication was (VAS-s*; VAS- no significant difference between the drug
Gender: discontinued. d) and placebo groups.
Interven: 41.9% male;
Cntrl: 26.2% male Comparator: Placebo Trazodone was not efficient in Cntrlling
tinnitus in the patients evaluated under the
Presumed etiology of tinnitus: no defined Only the pharmacist knew what drug was
doses utilized.
etiology disease in the middle ear being given to which patient.
Duration of tinnitus: 1 yr
Adverse Events: No AEs in 83.7% of the
Severity of tinnitus: NR Duration of treatment: 60 days
Treatment group. AEs included: apathy,
Number of dropouts: 0 Number of follow ups: 1
hypertensive crisis, epigastralgia, nausea,
Reasons for dropouts: N/A Duration of study: February to June (2005)
sleepiness
Audiological factors: Normal audiograms,
mild/moderate sensorineural hearing loss
Sleepiness Interven = 3 (7%); Cntrl = 1 (2.4%)
Comorbidities: NR
E-3
Table E1. Pharmacological or food supplement interventions and outcomes (n=16) (continued)
Author Population Intervention Outcome Results
Year Measures
Setting
84
Drew, Baseline sample: Total n = 1,121 Ginkgo Biloba: 252 tablets containing 50 TS-QOL (TSQ- 50 mg Ginkgo biloba extract LI 1370 given 3
2001 Interven n = 559; Cntrl n = 562 mg standardized extract LI 1370 21) times daily for 12 weeks is no more effective
Setting: mail and telephone (containing 25% flavonoids, 3% than placebo in treating tinnitus.
United Mean age (SD): ginkgolides, and 5% bilobalides) – Loudness
Kingdom Int: 52.9y (9.3); Cntrl: 53.0y (9.3) instructed to take 3 tablets daily (VAS) Adverse events: The incidence of AEs was
Gender: similar between the treatment groups.
Int 69% male; Cntrl 69% male Comparator: Placebo tablets identical to AEs included: gastrointestinal upset, dizziness,
the active tables in shape, size, color and headache, mouth ulcer, sleep problems,
Presumed etiology of tinnitus: NR packaging. redness of face, awareness of heartbeat,
Duration of tinnitus: >12 months; ≤5 y effects on hearing, hyperacusis.
Int: 10.0y (8.3); Cntrl: 10.1y (8.3) Duration of treatment: 12 weeks More than 1 AE: Interven: 2.0% Cntrl: 1.6%
Severity of tinnitus: NR Number of followups: 3 (4, 12, 14 weeks)
Number of dropouts: Duration of study: NR
Interven: 99 (17.7%); Cntrl: 87 (15.5%)
Reasons for dropouts: didn’t return
questionnaires
Audiological factors: NR
Comorbidities: NR
24
Johnson, Baseline sample: Total n = 40 Interven n Interven: Alprazolam Loudness Of the 17 patients receiving alprazolam,
1993 = 20; Cntrl n = 20 Subjects given a 9-day supply of (VAS) 13 (76%) had a reduction in the loudness of
Setting: University clinic Alprazolam, 1 per day, return to the clinic their tinnitus when measurements were made
United Mean age: NR for a reevaluation of their tinnitus. Subjects using a tinnitus synthesizer and a visual analog
States Gender: NR interviewed for adverse reaction to drugs, scale.
and loudness of tinnitus evaluated with
Presumed etiology of tinnitus: Idiopathic synthesizer. If no AE for the first week, Alprazolam is a drug that will provide
Duration of tinnitus: >1 year received an appropriate amount of therapeutic relief for some patients with
Severity of tinnitus: Constant and not medication for the next 23 days and asked tinnitus.
fluctuant in nature, sufficient severity to to return to clinic. Followup at 21 days, if
disrupt daily activities (greater than 600 tolerated well, were given a final supply of Adverse Events: excessive drowsiness (2);
on the disability sub-scale of the IOWA the drug for 58 days, and scheduled for a mild withdrawal symptoms (1); more dreams
THQ return visit in 56 days. (4); unfocussed (1)
Number of dropouts:
Interven n = 3, Cntrl n = 1 Comparator: Placebo
Reasons for dropouts:
Excessive drowsiness (2); not attend 2nd Duration of treatment: 12 weeks
appointment (1); noncompliance (1) Number of follow-ups: 3 (1, 4, 12 weeks)
Audiological factors: NR Duration of study: NR
Comorbidities: NR
E-4
Table E1. Pharmacological or food supplement interventions and outcomes (n=16) (continued)
Author Population Intervention Outcome Results
Year Measures
Setting
97
Mazurek, Baseline sample: Total n=42 Vardenafil G-QOL Vardenafil had no superior efficacy over
2009 Setting: Tinnitus Centre Interven: 10 mg vardenafil administered (SF-36) placebo in the treatment of chronic tinnitus
orally twice a day over a period of 12 during this study.
Germany Mean age (SD): week, dosing interval approx.12 hours. TS-QOL
Total=49.0 y (10.2) Non-medicated follow-up for another 4 (TQ) Within- and between-groups differences on the
Gender: 71.4% male weeks. TQ were clinically not relevant.
Sleep
Presumed etiology of tinnitus: Idiopathic Comparator: Matching placebo tablets (TQ-subscale) There was a tendency on the TQ subscales for
Duration of tinnitus: administered orally twice a day over a minor deteriorations under Vardenafil
> 3 months period of 12 week medication. All differences in changes from
Severity of tinnitus: “chronic” (excluded baseline were statistically not significant.
acute or intermittent) Duration of treatment: 12 weeks
Number of dropouts: Interven=5; Cntrl=2 Number of follow ups: Measured at Adverse Events: There were no serious or fatal
Reasons for dropouts: drug-related baseline (V2), 4 weeks into treatment (V3), AEs. 6 subjects (28.5%) in the Vardenafil group
adverse events: Interven=4; Cntrl=1; poor at the end of treatment (V4), and 4 weeks reported drug-related AEs of headache,
compliance: Interven=1; Cntrl=1 after treatment (V5). diarrhea, nasal congestion or prolonged penile
Audiological factors: NR erection
Comorbidities: NR Duration of study: 16 weeks
98
Meeus, Baseline sample: Total n = 35 Double-blind crossover trial – data Loudness Significant tinnitus reduction was seen after
2011 Interven n = 13; Cntrl n = 15 extracted from end of first period only (VAS) intake of the combination clonazepam-Deanxit,
Setting: Multidisciplinary Tinnitus Clinic whereas no differences in tinnitus could be
Belgium Mean age (SD): 55.4y (9.1) Interven: Additional effect of Deanxit Sleep demonstrated after the administration of
Int: 57.9y ; Cntrl: 53.2y (Flupentixol 0.5 mg + melitracen 10 mg) on (TQ-sub) clonazepam-placebo. This was true for all
Gender: 89.3% male clonazepam (Rivotril) 1 mg patients according to the following parameters:
Int: 76.9%male; Cntrl 100% male Depression time patients are annoyed by the tinnitus (p =
Comparator: Placebo (BDI) 0.026) and the VAS for tinnitus annoyance (p =
Presumed etiology of tinnitus: unilateral or 0.024).
bilateral tinnitus Duration of treatment: 3 weeks TS-QOL
Duration of tinnitus: > 3m Number of followups: 1 week washout, (TQ*, VAS) Adverse events: extrapyramidal syndromes
Severity of tinnitus: primary complaint of switch to treatment and tardive dyskinesia are known side effects
chronic tinnitus Duration of study: NR of Deanxit – not observed in this study
Number of dropouts: 7 population
Reasons for dropouts: NR
Audiological factors: normal MRI pontine
angle
Comorbidities: none
E-5
Table E1. Pharmacological or food supplement interventions and outcomes (n=16) (continued)
Author Population Intervention Outcome Results
Year Measures
Setting
101
Piccirillo, Baseline sample: Total n=115 Gabapentin (Neurontin) TS-QOL (THI) The change among the 59 subjects
2007 Interven=70; Cntrl=65; Interven: Patients in gabapentin arm randomized to the gabapentin arm was 11.3
Setting: Dept of Otolaryngology received gradually titrated dosages of and the change among the 56 subjects in the
United Mean age (SD): NR gabapentin (week 1, 900 mg/d; week 2, placebo arm was 11.0. The difference was 0.03
States Gender: 1800 mg/d; week 3, 2700 mg/d; and week (95% confidence interval, −5.5 to 6.2; P=.91).
Interven: 35.6% male; Cntrl: 44.6% males 4, 3600 mg/d). All subjects were provided
an equal number of capsules (300 mg The response to gabapentin, as measured by
Presumed etiology of tinnitus: NR each) and instructed to follow a dosing the THI score, does not reflect a true effect.
Duration of Tinnitus: >6m schedule of 3 times per day. If intolerable
Severity of tinnitus: Sufficient to disrupt adverse reactions occurred, the dosage Adverse Events: 9/153 (7%) withdrew owing to
daily activities, THI score ≥38 was decreased in 1-dose (300 mg) steps AEs. Nausea (3); Weight gain (2); Sleep
Number of dropouts: until the drug could be tolerated. The dose disturbance (2); dizziness (2). All AEs ceased
Interven: 11; Cntrl: 9 established during the titration period was on discontinuation of the study medication.
Reasons for dropouts: maintained throughout the additional 4
Lack of results(9); Nausea(3); Weight week fixed-dose period afterwards
gain(2); sleep disturbance(2);
Dizziness(1); Other(2) Comparator: Placebo
Audiological factors: NR
Comorbidities: TMJ Duration of treatment: 8 weeks
Interven: 86%; Cntrl: 77% Number of follow-ups: 2 (4 weeks; 8
weeks)
Duration of study: 8 weeks
E-6
Table E1. Pharmacological or food supplement interventions and outcomes (n=16) (continued)
Author Population Intervention Outcome Results
Year Measures
Setting
103
Rejali, Baseline sample: Total n = 66 Gingko Biloba TS-QOL Ginkgo biloba does not benefit patients with
2004 Interven n = 33; Cntrl n = 33 Interven: Patients received 120 mg once (THI) tinnitus
Setting: Otolaryngology clinic daily sustained release formulation of G.
United Mean age (SD): biloba G-QOL Adverse Events:
Kingdom Interven: 60 y (11.4); Cntrl: 59 y (10.4) Comparator: Placebo (GHSI) diarrhea (6% in placebo and 3% in active
Gender: group) and headache (3% in each group).
Interven: 55% male; Cntrl: 59% male Duration of treatment: 12 weeks
Presumed etiology: noise exposure Number of follow-ups: 1
(55%); middle ear disease (22%); Duration of study: NR
idiopathic (43%)
Duration of tinnitus: Duration of tinnitus:
Interven: 4.4 y; Cntrl: 5.9 y
E-7
Table E1. Pharmacological or food supplement interventions and outcomes (n=16) (continued)
Author Population Intervention Outcome Results
Year Measures
Setting
105
Robinson, Baseline sample: Total: n = 115; Paroxetine: Treatment 10 mg of paroxetine Depression Majority of individuals did not benefit from
2005 Interven n = 57; Cntrl n = 58 (or placebo) per day for the first week. (HADS-D, paroxetine in a consistent fashion.
Setting: Otolaryngology clinic Dose increased to 20 mg per day for 2 BDI*)
United weeks. Dose was increased in 10-mg Adverse Events:
States Mean age: 57 y increments every 2 weeks to a maximum Anxiety Significantly more participants in the paroxetine
Gender: 58% male of 50 mg per day. (HADS-A, group (n =17) dropped out because of adverse
Presumed etiology of tinnitus: BAI*) events than those in the placebo group (n =5),
Comparator: Placebo p <.05).
Duration of tinnitus: >6m TS-QOL Significantly more participants in the paroxetine
Severity of tinnitus: NR Duration of treatment: 100 days (THQ*, Likert 0 group reported moderate or severe sexual
Number of dropouts: 26 Number of follow-ups: 1 (1 month post- to 7) dysfunction, drowsiness, and dry mouth than in
Interven n = 17; Cntrl n = 5 treatment) the placebo group at follow-up.
Reasons for dropouts: adverse events Duration of study: (mean) 100 days Sleep (PSQI)
(side effect, perceived increase in tinnitus)
Audiological factors: NR NOTE: 21 participants who withdrew from G-QOL (QWB)
Comorbidities: Major depression (n=1) the study had their last observation carried
Number of dropouts: 26 (Interven=17; forward, resulting in a total of 115
Cntrl=5) Reasons for dropouts: adverse participants with follow-up data, used in the
events (side effect, perceived increase in ITT analysis
tinnitus)
E-8
Table E1. Pharmacological or food supplement interventions and outcomes (n=16) (continued)
Author Population Intervention Outcome Results
Year Measures
Setting
106
Sharma, Baseline sample: Total n = 40 Acamprosate G-QOL The drug had shown a statistically significant
2012 Setting: Outpatient Department of ENT (Subjective) improvement in reducing the tinnitus score in
Hospital Interven: tab. acamprosate 333 mg 1 tab 92.5% of the patients and placebo with an
India Mean age (SD): 53 years TID for 45 days; then washout period of 7 Loudness improvement in 12.5% of the patients.
Gender: NR days; crossed over to matched placebo 1 (VAS)
tab orally TID for next 45 days Adverse Events: The drug was well tolerated
Presumed etiology of tinnitus: Idiopathic Cntrl: matched placebo 1 tab TID for next without any serious drug reactions
Duration of tinnitus: NR 45 days; then washout period of 7 days;
Severity of tinnitus: NR crossed over to tab acamprosate 333 mg 1
Number of dropouts: 5 tab orally TID for 45 days
Reasons for dropouts: worsening of Comparator: Placebo
condition (n=2); left treatment at
crossover and could not complete the Duration of treatment: 45 days
study (n=3) Number of follow-ups: 3 (45 days, 7 day
Audiological factors: varying degrees of washout, 45 day)
sensorineural hearing loss; 65% of Duration of study: NR
patients had bilateral hearing loss; 35%
had bilateral tinnitus
Comorbidities: NR
E-9
Table E1. Pharmacological or food supplement interventions and outcomes (n=16) (continued)
Author Population Intervention Outcome Results
Year Measures
Setting
107
Sullivan, Baseline sample: Total n = 117: Nortriptyline Depression The antidepressant Nortriptyline decreases
1993 Interven n = 63, Cntrl n = 54 Intervention: Treatment initiated at 25 mg (HDS) depression, functional disability, and tinnitus
Setting: University otolaryngology clinic at bedtime and titrated upward 25 mg per loudness associated with severe chronic
United Mean age (SD): 62.1 y (8.0) week. When therapeutic or side effects Anxiety tinnitus.
States Gender: 52% male were evident or when 100 mg was (Sheehans’
Interven: 61% male; Cntrl: 42% male reached, blood level was assessed. Disability Separate analysis demonstrates that
Dosage adjusted to a therapeutic level Scale) decreases in tinnitus disability closely parallel
Presumed etiology of tinnitus: Idiopathic between 50 and 150 mg/mL and decreases in depression severity.
Duration of tinnitus: ≥ 6 months maintained there for 6 weeks. TS-QOL
Severity of tinnitus: sufficient severity to Comparator: Placebo (IOWA*, Likert Adverse Events: anticholinergic side effects
disrupt daily activities (score ≥600 THQ scale) and sedation (n=11)
disability subscale) Nortriptyline and placebo groups received
Number of drop outs: same number of capsules and same
Interven n = 14; Cntrl n = 11 titration protocol.
Reasons for dropouts:
Interven: Anticholinergic side effects, Duration of treatment:12 weeks
sedation; Number of follow ups: 1
Cntrl: Unsatisfactory therapeutic response Duration of study: NR
and scheduling conflicts
Audiological factors: Treatable otologic
disorder related to the tinnitus excluded
Comorbidities: 28 participants had current
major comorbid depression and 54 were
depression-NOS subjects
E-10
Table E1. Pharmacological or food supplement interventions and outcomes (n=16) (continued)
Author Population Intervention Outcome Results
Year Measures
Setting
109
Topak, Setting and subject recruitment: Hospital Methylprednisolone (by intratympanic TS-QOL (TSI) No significant post-treatment changes in the
2009 Baseline Sample: Total n=69 injection). Patients were randomized to tinnitus severity index individual and total
Mean age (SD): receive one of two treatments: 0.3 to 0.4 Loudness scores were observed in either group.
Turkey Interven: 49.9 y; Cntrl: 55.3 y ml intratympanic injections of either a (Self-rated)
Gender: Interven: 66.7% male; 6.25mg methylprednisolone solution or The results of this study indicate that
Cntrl: 58.6% male placebo (saline solution). The treatment intratympanic methylprednisolone has no
protocol comprised 3 intratympanic benefit, compared with placebo, for the
Presumed etiology of tinnitus: Subjective injections, 1 per week for 3 weeks. treatment of subjective tinnitus of cochlear
tinnitus of cochlear origin origin refractory to medical treatment.
Duration of tinnitus: NR Comparator: Placebo
Severity of tinnitus: Only subjects for Adverse Events: pain during injection, vertigo,
whom drug treatment had failed Duration of treatment: 3 weeks a burning sensation around the ear and in the
Number of dropouts: 11 Number of follow ups: 1 throat, and a bitter taste
Reasons for dropouts: Failed to return for Duration of study: 30 months
follow-up
Audiological factors: Patients with sudden
sensorineural hearing loss excluded
Comorbidities: NR
1
Westerberg, Baseline sample: Total n = 63 Baclofen vs Placebo TS-QOL (THI) Reports of subjective improvement occurred in
11
Interven n = 31;Cntrl n = 32 only 9.7% of the baclofen vs 3.4% of the
1996 Setting: ear institute Baclofen: Three weeks of baclofen (10 mg Self-reported placebo groups (NS).
nd
Mean age (SD): Total: 51.2 y BID for 1 week, 20 mg BID 2 week and Loudness
rd
United Gender: 57% male 30 mg BID 3 week) were given to drug (Subjective 0- Adverse Events: 26% withdrawals from the
States Interven: 58% male; Cntrl: 56% male group. Drug was tapered before 10) baclofen arm due to AEs. None were severe or
discontinuation life threatening and all resolved with stopping
Presumed etiology of tinnitus: Idiopathic the medication or by study’s end.
Duration of tinnitus: NR Comparator: Placebo designed to mimic
Severity of tinnitus: NR baclofen capsules in route, schedule
Number of dropouts: 11 appearance and taste
Reasons for dropouts: side effects (n=9);
unknown (n=2) Duration of treatment: 3 weeks
Audiological factors: Only constant, non- Number of follow-ups: 1 (3 weeks)
pulsatile included Duration of Study: NR
Comorbidities: NR
E-11
Table E1. Pharmacological or food supplement interventions and outcomes (n=16) (continued)
Author Population Intervention Outcome Results
Year Measures
Setting
114
Zoger, Baseline sample: Total n = 76; Sertraline TS-QOL Individuals in the Interven condition who
2006 Interven n = 38; Cntrl n = 38 Interven: During the first week, 25mg/d of (TSQ*, VAS) completed the post-assessment experienced a
Setting: Audiology department, university sertraline; 50 mg/d thereafter. To alleviate significant reduction in tinnitus distress from
Companion: hospital an expected initial worsening of Loudness pre-Interven to post-Interven (p =.0001].
90
Holgers, Mean age (SD): psychological distress, all patients offered (VAS)
2011 Interven: 40 y; Cntrl: 46 y oxazepam 10mg during first 2 weeks of the The between-groups difference in the rates of
Gender: study. Limit 3 tablets of oxazepam10mg reliable change, although in the hypothesized
Sweden Interven: 51.7% male; daily to maximum of 25 tablets Anxiety (HAS*, direction, was not statistically significant (p
Cntrl: 61.8% male CPRS-S-A, =.15).
Comparator: Placebo PGWB sub)
Presumed etiology of tinnitus: Idiopathic Adverse Events: Sexual side effects (1
Duration of tinnitus: NR Duration of treatment: 16 weeks Depression Interven; 2 Cntrl)
Severity of tinnitus: major complaint Number of follow-ups: (HDS*, CPRS-
Number of drop outs: 2 (16 weeks and 28 weeks) S-A, PGWB
Interven n = 9; Cntrl n = 4 Duration of study: 28 weeks sub)
Reasons for drop outs:
90
Interven; A/E (2), moved (1), stress (2), All patients were offered an open trial of G-QOL
other (4) sertraline at week 16 for another 12 weeks (PGWB)
Cntrl: changed psychiatric condition (2), (post-data is taken before crossover
moved (1); other (1) portion of this study).
Audiological factors: Pure-tone averages
better than 50dB HL in the worse hearing
ear; positive answer on at least one of
NHP items
Comorbidities: excluded psychiatrically
severe condition in need of acute
treatment
*Indicates the test used to measure outcomes which were selected to represent the domain in the forest plots (and subsequent SOE decisions)
Abbreviations: A/E = Adverse events; AMT = active motor threshold; CBT = cognitive behavioral treatment; ENT = ear, nose and throat; grp = group; G-QOL = global quality of
life; HADS = Hospital Anxiety and Depression Scale; HDS = Hamilton Depression Rating Scale; interven = intervention; month = month; N/A = not applicable; NR = not
reported; QOL = quality of life; RCT = randomized controlled trial; SD = standard deviation; TCT = Tinnitus Coping Therapy; THI = Tinnitus Handicap Inventory; TMJ =
temporal mandibular joint; TS = tinnitus specific; TSQ = Tinnitus Severity Questionnaire; VAS = visual analog scale; week = week; WLC = wait list Cntrl; yr = year
E-12
Table E2. Medical interventions and outcomes (n=11)
Author Population Description Intervention Outcome Results
Year Measures
Setting
73
Anders, Baseline sample: Total n = 52; Repetitive Transcranial Magnetic TS-QOL The ability to reduce the symptoms of the
2010 Interven n = 26; Cntrl n = 26 Stimulation (rTMS) (THI*, TQ-mod, tinnitus appeared in both randomized groups
Setting: Outpatient Otorhinolaryngology Patients were treated with either real or VAS) immediately after the 1 Hz rTMS and sham
Czech clinic sham low frequency rTMS over a period of stimulation phase. There was a significant
Republic Mean age (SD): 2 weeks. Blinding design applied. reduction in both groups of the tinnitus total
Interven: 48.1y (14.86); score on the Tinnitus Handicap Inventory (THI)
Cntrl: 50.1y (13.97) Comparator: Placebo (real rTMS p=0.00t; sham rTMS p=0.049).
Gender: 69% male Reduction of symptoms as evaluated using the
Duration of treatment: 2 weeks TQ was significant compared to baseline in the
Presumed etiology of tinnitus: Idiopathic Number of follow ups: 4 real rTMS group at week 2, 6 and 14 (p=0.003;
Duration of tinnitus: > 6 months Duration of study: 6 months p=0.024; p=0.022).
Severity of tinnitus: Uni- or bilateral
tinnitus according to KD-10, no response Real 1 Hz rTMS treatment was capable of
to >3 months of pharmacological significantly reducing the total baseline score of
treatment basic scales that measure tinnitus severity.
Number of dropouts: 10 Important for patients with long-term symptoms
Reasons for dropouts: Treatment n = 4; resistant to pharmacological treatment.
worsening of tinnitus (2); adverse
events(2) Adverse Events: unacceptable pain in
Cntrl n = 6; lack of efficacy (3); adverse stimulation area, headache, lack of efficacy and
events (2); unknown (1) subjective worsening of tinnitus
Audiological factors: Included age-
adjusted normal sensorineural hearing.
Excluded profound hearing loss or
Meniere’s disease
Comorbidities: NR
E-13
Table E2. Medical Interventions and outcomes (n=11) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
79
Chung, Baseline sample: Total n = 22 Intervention: rTMS coil was placed over the TS-QOL 9/12 patients (75%) in the active-stimulation group
2012 Intervention n = 12 auditory cortex with the intensity setting at 80% (THI*, TQ) reported tinnitus suppression following treatment
Cntrl n = 10 with rTMS.
China Setting: University medical Hospital
of the resting motor threshold. Continuous Loudness (VAS) TQ global scores averaged 8.58 points lower 1
Total Mean age: theta-burst rTMS (cTBS) was delivered at a week after treatment, a significant decrease
52.96 (range 20-76 yrs) burst frequency of 5 Hz (the theta rhythm in compared to the sham-stimulation group
Gender: the EEG); each burst consisted of 3 pulses (p <0.01).
Int 91.6% male Cntrl 90.0% male THI scores were, on average, 8.33 points lower
repeated at 50 Hz. We administered 900 pulses
after treatment, which were also significantly lower
Presumed etiology of tinnitus: (300 bursts) of stimulation once daily for 10 than those of patients in the sham-stimulation
Duration of tinnitus: : consecutive business days. group (p <0.01).
Int range 0.5 to 20 years Tinnitus loudness also decreased significantly
Cntrl: 2 to 10 years after delivering rTMS. (p<0.05)
Severity of tinnitus: Mean score on TQ and Comparator: Sham rTMS
THI Adverse Events: No patients experienced
Number of dropouts: 0 Duration of treatment: Once daily for 10 sustained side effects after the rTMS treatment.
Reasons for dropouts: NA consecutive days
Audiological factors: Most subjects had Number of followups: 1 week and 1 month
unilateral problems post treatment.
Comorbidities: Excluded subjects with Duration of study: NR
known history of metal implants, head injury,
stroke, epilepsy
80
Cuda, Baseline sample: Total n = 46 Low Level Laser Stimulation + combined TS-QOL Approximately 61% of irradiated patients had
2008 Interven n = 26; Cntrl n = 20 counseling protocol (LLS+). Emission power (THI) tinnitus severity decreased by one class, in
Setting: University Otolaryngolgy clinic was 5mW, and the wavelength was 650nm. comparison to 35% of the placebo group.
Italy Mean age (SD): 56.4y (13.6) Patients trained to use the device for 20
Int: 50.3y (9.8); Cntrl: 64.4y (14.1) minutes per day, each day for 3 months. This study confirmed a significant difference in the
Gender: 58.7 % male benefit of treatment between the LLS+ and LLS-
Comparator: combined counseling protocol groups.
Presumed etiology of tinnitus: non- with sham LLS (LLS-)
intermittent subjective tinnitus Combined Counseling consisted of a Adverse events: NR
Duration of tinnitus: mean 6.4 years (8.8) combination of hypnotic techniques with
Severity of tinnitus: ‘disturbing’ > 3 months relations techniques based on respiration,
Number of dropouts: None proprioception and insight
Reasons for dropouts: NA
Audiological factors: 60.9% had no clinically Duration of treatment: 3m
significant hearing impairment Number of followups: 10
Comorbidities: NR Duration of study: NR
E-14
Table E2. Medical Interventions and outcomes (n=11) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
85
Ghossaini, Baseline sample Total n = 29 High-Frequency Pulsed Electromagnetic TS-QOL There was no significant change in the pre-
2004 Interven n = 15; Cntrl n =14 Energy (Diapulse) (THI*, TMR) treatment and post-treatment audiometric
Setting: NR Patients received 30-minute treatments with thresholds in either group.
United States the Diapulse device (model D103) 3 times per
Age: Range 23 to 83 y week for 1 month. There were no significant differences between the
Gender: NR pretreatment and post-treatment THI scores or the
Etiology of tinnitus: cause/origin of tinnitus in Comparator: placebo (deactivated machine) tinnitus rating scores in either subject group
the study sample varied
Duration of tinnitus: 7 months to 60 y Duration of treatment: 1 month Adverse Events: tingling (Treatment) and
Severity of tinnitus: Chronic >6 months Number of follow-ups: NA worsening of tinnitus (5 Control; 4 Treatment)
Number of dropouts: 2 Duration of study: NR
Reasons for dropouts: Failure to return for
post-treatment testing (not included in
analysis)
Comorbidities: NR
94
Langguth, Baseline sample: Total n = 32 To investigate whether priming stimulation TS-QOL There was no significant difference between the
2008 Interven n = 16; Cntrl n = 16 enhances the efficacy of low-frequency rTMS. (TQ) standard protocol and the protocol involving
Setting: Dept. of Psychiatry Medtronic priming stimulation.
Germany Mean age (SD): 51.5y (11.6)
Int: 52.6y (12.6); Cntrl: 50.3y (10.8) Interven: Priming protocol (960 stimuli; 6 Hz + Data does not support an enhancing effect of
Gender: 71.8% male 1040 stimuli; 1 Hz) higher frequency priming on low-frequency rTMS
Int: 81.3% male; Cntrl: 62.5% male in the treatment of tinnitus.
Comparator: standard protocol (2000 stimuli;
Presumed etiology of tinnitus: NR 1 Hz) Adverse Events: No serious adverse or side
Duration of tinnitus: effects were observed
Int: 10.9y (10.1); Cntrl: 11.7y (10.9) Duration of treatment: 10 working days
Severity of tinnitus: ‘disturbing’ tinnitus Number of followups: 4 over 13 weeks
Number of dropouts: None Duration of study: NR
Reasons for dropouts: NA
Audiological factors: normal middle-ear
status
Comorbidities: all had tried several standard
treatment modalities
E-15
Table E2. Medical Interventions and outcomes (n=11) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
96
Marcondes, Baseline sample: Total n=19 Repetitive Transcranial Magnetic Stimulation: TS-QOL Significant improvement of the tinnitus score in the
2010 Interven=10 5 sessions of rTMS performed on 5 (THI) active rTMS group as compared to sham rTMS for
Cntrl=9 consecutive days up to 6 months after stimulation. SPECT
Spain Setting: Otohinolaryngology clinic measurements demonstrated a reduction of
Mean Age: NR Comparator: Placebo metabolic activity in the inferior left temporal lobe
Gender: NR after active rTMS.
Duration of treatment: 5 days Results demonstrate a significant reduction of
Presumed etiology of tinnitus: Idiopathic tinnitus complaints over a period of at least 6
Duration of tinnitus: > 3 months Number of follow ups: 10 months and significant reduction of neural activity
Severity of tinnitus: NR in the inferior temporal cortex.
Number of dropouts: 1 Duration of study: 6 months
Reasons for dropouts: 1 participant withdrew Adverse Events: no relevant side effects
consent before treatment began
Audiological factors: Hearing lever in tinnitus
ears – data presented by ear
Comorbidities: NR
99
Mirz, Baseline sample: Total n = 50 Laser Therapy vs Placebo Anxiety (STAI) The results showed only moderate (18%)
1999 Interven n = 25; Cntrl n = 25 The active laser applied 50mW (cw, 830 nm) subjective improvement with no statistically
Setting: otorhinolaryngology clinic over a period of 10 min per session. The laser Depression significant differences between the effects of the
Denmark Mean age (SD): treatment consisted of three periods of five (BDI) active laser and placebo treatment.
Interven n = 48.6 y; Cntrl n = 48.7 y consecutive days separated by weekends,
Gender: Total: 75.5% male totaling 15 treatment sessions. Loudness (VAS) There were no statistically significant differences
Interven: 64.0% male; Cntrl: 87.5% male in pre-post measurements of tinnitus loudness,
Comparator: Placebo – an identical looking TS-QOL VAS scores, THI scores, or TCSQ scores for
Presumed etiology of tinnitus: Idiopathic laser probe was inactivated by the producer (THI*, VAS-Ann, patients treated with active laser compared with
Duration of tinnitus: Mean 5.5y VAS-Att) those treated with placebo.
Severity of tinnitus: Disabling, chronic Duration of treatment: 5 week days
Number of dropouts: 1 Number of follow ups: 4 Adverse Events: No serious untoward adverse or
Reasons for dropouts: Unrelated illness Duration of study: side effects were noticed
Audiological factors: sensorineural hearing
loss
Comorbidities: NR
E-16
Table E2. Medical Interventions and outcomes (n=11) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
102
Plewnia, Baseline sample: Total n = 48 4 weeks of bilateral cTBS to the secondary TS-QOL (TQ) Tinnitus severity was slightly reduced from
2012 Interven1 (SAC) n = 16 auditory cortex (SAC) and temporoparietal baseline by a mean (SD) 2.6 (8.2) after sham, 2.4
Interven2 (TAC) n = 16 cortex (TAC) (8.0) after temporoparietal, 2.2 (8.3) after temporal
Germany Cntrl (PLC) n = 16 Stimulation (cTBS) intensity was standardized treatment of 16 patients each, but there was no
Setting: University Psychiatry and outpatient at 80% AMT significant difference between sham treatments
clinic Department of Otorhinolaryngology Each stimulation train (40 s) consisted of 600 and temporal (confidence interval [CI] -5.4 to +6.7)
Mean age (SD): stimuli applied in bursts of 3 pulses at 50 Hz or temporoparietal cTBS (CI -5.9 to +6.3) or real
SAC: 46.4y (13.0); TAC: 55.8y (9.7); given every 200 msec (i.e., at 5 Hz). Fifteen cTBS (CI -7 to +5.1).
PLC: 45.6y (10.3) minutes after the first 2 trains, a second pair
Gender: of cTBS trains was given (a total of 2,400 Patients’ global evaluation of tinnitus change after
SAC 10.5%male; TAC 43.8%male; stimuli/day). Patients received cTBS treatment did not indicate any effects.
PLC 50%male treatment each working day for 4 weeks (20
sessions) the 10–20 EEG electrode Adverse events:
Presumed etiology of tinnitus: NR placement system was used to localize Patients reported the following side effects:
Duration of tinnitus: < 5y chronic tinnitus Brodmann area 39 (TAC: halfway between headache (SAC: 2, TAC: 2, PLC: 3), worsening of
Severity of tinnitus: NR T5/P3 and T6/P4) and Brodmann area 42/22 tinnitus (SAC: 1, TAC: 2, PLC: 3), increased
Number of dropouts: total n = 8; (SAC: halfway between T3/C3 and T4/C4). sensitivity to noise (TAC: 1, PLC: 1), painful local
SAC n = 4; TAC n = 2; PLC n= 2 For adequate masking of the patients, sham sensation (SAC: 1), and sleep disturbance (SAC:
Reasons for dropouts: Tinnitus worsening stimulation (PLC) was performed behind the 1). An acute hearing loss associated with
(4); Patient decision (3); sudden hearing loss mastoid. increased tinnitus loudness was observed in 1
(1) Comparator: sham stimulation (PLC) patient after session 17 (SAC). In this patient,
Audiological factors: hearing thresholds and tinnitus returned to
Comorbidities: Duration of treatment: 4 weeks baseline after 3 weeks.
Number of followups: 1 (12 weeks)
Duration of study: Feb 2008 to May 2010
E-17
Table E2. Medical Interventions and outcomes (n=11) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
108
Tass, Baseline sample: Total n=63 Acoustic Coordinated Reset (CR) TS-QOL Strong and significant reduction of VAS loudness
2012 Interven (4 groups) G1 n = 22; G2 n = 12; neuromodulation: 4 stimulation groups. For (TQ*, VAS) in G1 and G3 in the on-stimulation condition
G3 n = 12; G4 n = 12 G1, G3 and G4 four tones (top, f1 to f4) are (p≤0.01)
Germany Cntrl (G5) n = 5 grouped around the tinnitus frequency (ft). G3 Loudness (VAS) G1 also significant compared to placebo (G5)
Setting: 2 treatment centers in Germany differs only in repetition rate F being adapted (p<0.05)
Mean age (SD): >18 to the individual EEG § -band peak.
G1: 45.7 (10.8); G2 47.7 (5.6); G3 50.0 For G2 each CR cycle is formed by a varying A reduction of at least 6 TQ points was obtained in
(14.7); G4 50.3 (11.8); G5 57.6 (6.3) composition of four tones (dark green: active) 75% of patients with a mean TQ reduction of 50%
Gender: chosen out of twelve tones (middle, f1 to f12) among responders.
G1: 72.7% male; G2: 83.3% male; G3: surrounding ft.
50.0% male; G4: 75.0% male; G5: 60.0% Adverse events – 15 AEs: 13 AEs during blinded
male Comparator: Placebo stimulation (G5) is phase, 2 AEs in LTE.
formed similar to G1 using a down-shifted 2 SAEs not associated with treatment were
Presumed etiology of tinnitus: chronic tonal stimulation-frequency fp (fp = 0.7071·ft/ (2n), reported; All other AEs were of mild to moderate
tinnitus fp within [300 Hz, 600 Hz]) outside the intensity and none was permanent.
Duration of tinnitus [years – Mean (SD)]: all synchronized tinnitus focus. 8 AEs were judged to be treatment related of
>6 months which 3 AEs were associated with a transient
G1: 5.7 (5.1); G2: 6.6 (6.0); G3: 5.4 (3.5); Duration of treatment: G1 to G3 received increase of tinnitus loudness
G4: 7.9 (9.8); G5: 11.3 (5.6) stimulation for 4 to 6 hours every day for 12
Severity of tinnitus: chronic weeks applied either continuously or split into
Number of dropouts: 0 several sessions not shorter than 1 hour
Reasons for dropouts: N/A G4 and G5 all received stimulation for 1 hour
Audiological factors: Morbus Meniere, TMJ, max. every day
psychiatric disorders and objective tinnitus
excluded Number of followups: 1,4,8, 12 and 16 weeks
Comorbidities: NR after beginning of treatment and every 4
weeks during optional 24 week LTE
Duration of study: NR
E-18
Table E2. Medical Interventions and outcomes (n=11) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
31
Teggi, Baseline sample Total n = 60 Laser Therapy TS-QOL No statistical difference was detected between the
2009 Interven: n = 30; Cntrl n = 30 All patients instructed to perform laser (THI) 2 groups in the THI total score (p = 0.97), and the
Setting: ENT department therapy with the TinniTool soft laser at home functional (p = 0.89), emotional (p = 0.89) and
Italy Mean age (SD): for 20 min a day for a period of 3 months; Loudness (VAS) catastrophic (p = 0.89) subscales. VAS for self-
Interven: 51.6y (11.3); patients in the first group (group L) received perceived loudness of the tinnitus showed no
Cntrl: 53.1y (12.9) an active laser difference between the groups (p = 0.69).
Gender:
Interven: 59.2% male; Comparator: Placebo - a dummy laser (group Soft laser therapy demonstrated no efficacy as a
Cntrl: 51.2% male C). therapeutic measure for tinnitus in this report.
Presumed etiology of tinnitus: NR Duration of treatment: 3 months Adverse Events: subjects with migraine presenting
Duration of Tinnitus: NR Number of follow ups: 1 hyperacusis (Treatment = 4; Control = 2).
Severity of tinnitus: NR Duration of study: NR Increase in loudness (Treatment = 1; Control = 1)
Number of dropouts: Interven n = 3; Cntrl n
=3
Reasons for dropouts: familial reasons (4),
increase in tinnitus loudness (2)
Audiological factors: NR
Comorbidities: NR
110
Vilholm, Baseline sample Total n = 54 Acupuncture vs Placebo TS-QOL No statistically significant differences were found
1998 Interven n = 29; Cntrl n = 25 Acupuncture group treated with traditional (VAS-Ann*, between the acupuncture group and the placebo
Setting: Department of Audiology Chinese acupuncture of 25 treatment VAS-Awr) group.
Denmark Mean Age (SD): 53.1 y sessions over 2 months. Sessions distributed
Gender: over 3 treatment periods of 10, 5 and 10 Loudness (VAS) Adverse Events: NR
Int: 68.9% male; Cntrl: 60.0% male treatments separated first by a pause of one
week, and then by a pause of two weeks.
Presumed etiology of tinnitus: Idiopathic Treatment given each day for 30 minutes.
Duration of tinnitus: ≥ 1 yr Comparator: Placebo group treated with
Severity of tinnitus: Severe treatment- placebo acupuncture.
resistant tinnitus
Number of dropouts: 0 Duration of treatment: 4 months
Reasons for dropouts: N/A Number of follow ups: 2
Audiological factors: NR Duration of study: NR
Comorbidities: NR
*Indicates the test used to measure outcomes which were selected to represent the domain in the forest plots (and subsequent SOE decisions)
Abbreviations: A/E = Adverse events; AMT = active motor threshold; CBT = cognitive behavioral treatment; ENT = ear, nose and throat; G1 to G5 = group; G-QOL = global
quality of life; HADS = Hospital Anxiety and Depression Scale; interven = Intervention; month = month; N/A = not applicable; NR = not reported; QOL = quality of life; RCT =
randomized Controlled trial; SD = standard deviation; TCT = Tinnitus Coping Therapy; THI = Tinnitus Handicap Inventory; TMJ = temporal mandibular joint; TS = tinnitus
specific; TSQ = Tinnitus Severity Questionnaire; VAS = visual analog scale; week = week; WLC = wait list Cntrl; yr = year
E-19
Table E3. Sound treatment/technologies intervention and outcomes (n=5)
Author Population Description Intervention Outcome Results
Year Measures
Setting
46
Davis, Baseline sample: Total n = 35 Participants were provided with a high fidelity TS-QOL Improvements increased with time over
2007 Stage1 n = 16; Stage2 n = 19 personal sound player with earphones and an (TRQ, VAS) the first 6 months of therapy, at which
Setting: Clinic acoustic stimulus that had been spectrally time 91% of all subjects across the two
Australia Mean age (SD): 58.5y(13.4) modified according to their individual Loudness groups reported an improvement in
Stage1: 61.3y(8.9): Stage2: 56.1y(16.2) audiometric profile. They were instructed to use (VAS) tinnitus disturbance (as measured by the
Gender: 74%male the acoustic stimulus for at least 2 hr per day, TRQ) of at least 40%, with a mean
particularly at those times when their tinnitus improvement of 65%.
Presumed etiology of tinnitus: NR was usually disturbing.
Duration of tinnitus: 11.0y (11.3) Each group had equal amounts of clinician time Inter-group differences were not
Severity of tinnitus: moderate to severe for education, monitoring, and support. statistically significant measuring tinnitus
Number of dropouts: 1 Complete covering of perception initially, then disturbance.
Reasons for dropouts: NR intermittent perception (Stage2)
Audiological factors: decreased sound tolerance Adverse events: NR
Comorbidities: NR Comparator: intermittent perception throughout
(Stage1)
E-20
Table E3. Sound treatment/technologies intervention and outcomes (n=5) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
89
Hiller, Baseline sample: Total n = 136 CBT: subjects score 40 or more on TQ TS-QOL No additive effects due to the NGs could
2005 Int1 (CBT+NG) n = 33; Cntrl1 (CBT only) n = 33 (severe), training consists of 10 120- minute (TQ, T-Cog) be demonstrated.
Setting: Outpatient Department, University sessions. Treatment was strictly manualized.
Germany Mean age (SD): Loudness Adverse Events: NR
Int1 (CBT+NG): 51.0y (13.2); All therapies conducted by two clinical (VAS)
Study 1 Cntrl1 (CBT only): 51.4y (10.9) psychologists
Gender: Int1 (CBT+NG): 68% male Anxiety (WI)
Cntrl1 (CBT only): 41% male Int1 = CBT + Noise generator
Cntrl1 = CBT only
Presumed etiology of tinnitus:
> 25% had sudden hearing loss Duration of treatment: up to 10 weeks
Duration of tinnitus: at least 6 months Number of followups: 6, 18m
Severity of tinnitus: chronic Duration of study: NR
Number of dropouts:
Int1 (CBT+NG)= 2; Cntrl1 (CBT only)= 4
Reasons for dropouts: external reasons; insufficient
motivation; unknown
Audiological factors: NR
Comorbidities: NR
89
Hiller, Baseline sample: Total n=136 Tinnitus Education (TE): patients with mild to TS-QOL No additive effects due to the NGs could
2005 Int2 (TE + NG)= 34; Cntrl2 (TE only) = 36 moderate distress as scored by the TQ – (TQ, T-Cog, be demonstrated.
Setting: Outpatient Department, University abridged version of CBT 4 90-minute weekly VAS, Diary)
Germany Mean age (SD): sessions Adverse Events; NR
Int2 (TE + NG)= 52.5y (15.3) Loudness
Study 2 Cntrl2 (TE only) = 45.2y (14.1) All therapies conducted by two clinical (VAS)
Gender: psychologists
Int2 (TE + NG)= 52% male Anxiety (WI)
Cntrl2 (TE only) = 61% male Int2 = TE + Noise generator
Cntrl2 = TE only G-QOL
Presumed etiology of tinnitus: (SCL-90R,
> 25% had sudden hearing loss PSDI)
Duration of tinnitus: at least 6 months Duration of treatment: up to 4 weeks
Severity of tinnitus: chronic, Number of followups: 6, 18m
Number of dropouts: Duration of study: NR
Int2 (TE + NG)= 3; Cntrl2 (TE only) = 3
Reasons for dropouts: external reasons; insufficient
motivation; unknown
Audiological factors: NR
Comorbidities: NR
E-21
Table E3. Sound treatment/technologies intervention and outcomes (n=5) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
100
Parazzini, Baseline sample: Total n=91 TRT with open hearing aids (OE-HA) G-QOL TRT was equally effective with sound
2011 Interven (OE-HA) n=49; (VAS) generator or open ear hearing aids: they
Cntrl (SG) n=42 Comparator: TRT with sound generator (SG) TS-QOL gave basically identical, statistically
Italy, United Setting: Tinnitus clinics in Milan, Baltimore (THI) indistinguishable results
States Mean age (SD): 38.8y (1.9) Duration of treatment: 1 year
Gender: 51/91 (56%) male Number of followups: 3 (3m, 6m, 12m) Loudness Adverse Events: NR
Int: 57.1%male; Cntrl: 54.7% male Duration of study: NR (subjective)
E-22
Table E4. Psychological/behavioral intervention and outcomes (n=19)
Author Population Description Intervention Outcome Results
Year Measures
Setting
71
Abbott, Baseline Sample: Total n = 56; Internet-based education Depression The CBT program was not found to be superior to
2009 Interven n = 32; Cntrl n = 24 Interven: 10 components, presented in six (DASS-D) the information program for treating tinnitus
Setting: Internet in 23 industrial settings, modules, and completed at the rate of one distress.
Australia Mean Age (SD): module per week. Modules included Anxiety (DASS- Participants who completed the program generally
Interven: 50.5 y (9.5); homework assignments and weekly diaries A) reported finding most aspects of it useful, but
Cntrl: 48.7 y (8.6) submitted electronically. Participants found the sound enrichment, sound sensitivity,
Gender: completed daily online registrations 1 week Loudness (VAS) and cognitive restructuring tools less useful.
Interven: 96% male before Interven (pre-assessment) and 1 week
Cntrl: 83% male immediately after Interven (post-assessment) Sleep Adverse Events: None
on VAS (range 0 to 10) (VAS)
Presumed etiology of tinnitus: idiopathic
Duration of tinnitus: > 3 months Comparator: Information only G-QOL (WHO-
Severity of tinnitus: NR Social)
Number of dropouts: Duration of treatment: 6 weeks
Interven N=4; Cntrl=1 Number of follow ups: 1 TS-QOL
Reasons for dropouts: most indicated Duration of study: June 2006 to March 2007 (TRQ*, VAS,
withdrawal by no response when contacted OSI-R)
Audiological factors: NR
Comorbidities: NR
75
Andersson, Baseline sample Total n = 23; CBT TS-QOL TS-QOL Results showed statistically significant
2005 Interven n = 12; Cntrl n = 11 Interven: Sessions covered information about (TRQ) reductions of tinnitus-related distress. F(1,21)=6.4,
Setting: web pages and newspaper articles tinnitus, applied relaxation, cognitive p=0.02
Sweden Mean age (SD): 70.1y (3.90) restructuring, behavioral activation, positive Depression
Gender: 52% male imagery, sound enrichment, exposure to (HADS-D) CBT was better than no treatment, but the
tinnitus, advice regarding hyperacusis, particular aspects of CBT that contributed to the
Presumed etiology of tinnitus: NR hearing tactics, and relapse prevention. Anxiety (HADS- effects can not be established.
Duration of tinnitus: Mean 13y (12.5) A*, ASI)
Severity of tinnitus: “problem with tinnitus” as Comparator: Wait list The findings give some support for the use of
inclusion criteria group CBT for elderly people with tinnitus.
Number of dropouts: None Duration of treatment: 6 weeks of 2 hour
Reasons for dropouts: N/A sessions Adverse Events: NR
Audiological factors: 22% previously fitted Number of follow-ups: 2 (immediately post-
with hearing aids treatment and 3 months post-treatment taken
Comorbidities: NR after crossover)
Duration of study: 19 weeks
E-23
Table E4. Psychological/behavioral intervention and outcomes (n=19) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
74
Andersson, Baseline sample Total n = 117; CBT TS-QOL TS-QOL: group effect on pre- vs. post-treatment
2002 Interven n = 53; Cntrl n = 64 Interven: Self-help manual constructed (TRQ*, VAS- change score: t(70)=3.99, p=0.002
Setting: web pages and newspaper articles following cognitive behavioral Ann, VAS-Ctrl) ITT analysis: NS
Sweden Mean age (SD): principles, consisting of 6 modules (1
Interven: 48.5y (12.3); Cntrl: 47.2y (15) module performed per week). Daily Anxiety (HADS- No significant differences between the groups
Gender: diary ratings were included for 1 week A*, ASI) were found at either post-treatment (p = 0.29) or
Interven: 54% male; Cntrl: 52% male before and 1 week following the at the 1-year follow-up (p= 0 .16).
treatment period. Depression
Presumed etiology of tinnitus: NR (HADS-D) CBT via the Internet can help individuals decrease
Severity of tinnitus: “severe problem” for which Comparator: Wait list annoyance associated with tinnitus.
patient has seen GP or ENT Sleep
Number of dropouts: Duration of treatment: 6 weeks (VAS) Adverse Events: NR
Interven n = 29; Cntrl n = 16 Number of follow-ups:1
Reasons for dropouts: Duration of study: 1 yr Loudness
Interven: 26 did not finish treatment; 4 incomplete (VAS)
questionnaire;
Cntrl: 16 incomplete questionnaire
Audiological factors: problems in 68%
Comorbidities: sleep problems, anxiety, depression
E-24
Table E4. Psychological/behavioral intervention and outcomes (n=19) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
78
Biesinger, Baseline sample Total: n = 40 Qigong Therapy is a set of breathing TS-QOL Qigong was completed by 80% of the assigned
2010 Interven: n = 20; Cntrl: n = 20 and movement exercises with possible (TBF-12*, VAS) patients.
Mean age(SD): benefits to health through stress Compared with the Cntrl group, Qigong
Germany Interven: 44.7y (10.9); reduction and body activity. Qigong participants experienced improvement in tinnitus
Cntrl: 39.9y (11.3) contains important principles severity, as reflected by a significant reduction in
Gender: 47.1% male of modern tinnitus therapy, such as both the VAS and the TBF-12 (group x time
relaxation, reduction of muscle interaction: F(3,66)=3.7, p=0.015)
Presumed etiology of tinnitus: tension, attention distraction, stress In the subgroup of patients with somatosensoric
Nonsomaterenic tinnitus reduction, activation, and tinnitus, Qigong effects were more pronounced,
Duration of tinnitus: >3 months communication, especially when resulting in a highly significant improvement in
Severity of tinnitus: Main complaint exercising in groups. both scales compared to the waiting-list group.
Number of dropouts: Qigong training program for 5 weeks,
Interven: 5; Cntrl: 1 2 hrs twice a week under professional Adverse events: No Qigong related reasons
Reasons for dropouts: Missed sessions- job-related, Qigong instructor. affected participation in the study. No relevant
personal, organizational reasons, incomplete data side effects were reported.
Audiological factors: Normal audiogram (LE 10dB or Comparator: Wait list
any frequency) as inclusion criteria
Comorbidities: NR Duration of treatment: 10 sessions, 5
weeks
Number of follow ups: 3
Duration of study: NR
54
Cima, Baseline sample Total: n = 492 Specialized care of CBT with sound- G-QOL Patients assigned to specialized care improved in
2012 Interven n = 245; Cntrl n = 247 focused tinnitus retraining therapy. (HUI) health-related QOL during a period of 12 months
Setting: Tinnitus Centre Comparator: Usual Care (between-group difference 0.059, 95% CI 0.025 to
Netherlands Mean age (SD): TS-QOL 0.094; p=0.0009);
Int: 53.74y (11.05); Cntrl: 54.63y (12.02) Duration of treatment: 8 months (TQ*, THI) Decreased tinnitus severity (between group
Gender: Number of follow ups: 2 difference –8.062, 95% CI –10.829 to –5.295;
Int: 65% male; Cntrl: 61% male Duration of study: September 2007 Depression p<0.0001) and tinnitus impairment (between
and January 2011 (HADS) group difference –7.506, 95% CI –10.661 to –
Presumed etiology of tinnitus: Idiopathic 4.352; p<0.0001).
Duration of tinnitus: >1 year 70% Specialized treatment of tinnitus based on CBT
Severity of tinnitus: primary complaint, 84% with could be suitable for widespread implementation
continuous tinnitus for patients with tinnitus of varying severity.
Number of dropouts:
Interven n=74 (30%); Cntrl n=86 (35%) Adverse Events: Adverse results as a result of
Reasons for dropouts: NR treatment or measurements did not occur
Audiological factors: 19% with hearing aid; 19%
with sound generator
Comorbidities: NR
E-25
Table E4. Psychological/behavioral intervention and outcomes (n=19) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
87
Henry, 1998 Baseline sample Total n = 54 CBT Depression The analyses revealed that the combined
Int Grp1: n = 12; Int Grp2: n = 14 ACI - Attention Cntrl and Imagery (BDI) treatment condition (ACI +CR) showed
Australia Int Grp3: n = 12; Cntrl: n = 14 Training: cognitive coping strategies to significantly greater improvement on a measure of
Setting: response to radio or newspaper help subject learn to shift attention to TS-QOL psychological distress and achieved a higher
announcements and from tinnitus and focus on (TRQ*, THQ clinical response rate compared to the two single
Mean age: 56.3 y (range 35 to 83) pleasant stimuli – all subjects provided handicap, treatments.
Gender: 62% male with a written educational manual TCSQ coping, Subjects in the CR condition improved
CR – Cognitive Restructuring –- all TEQ) significantly more than the ACI condition on the
Presumed etiology of tinnitus: idiopathic subjects provided with a written TRQ (F( 1,46) = 4.47, p <0.05)
Duration of tinnitus: >6 months educational manual based on case Subjects in the combined ACI + CR condition
Severity of tinnitus: primary complaint examples and educational materials improved significantly more than those subjects in
Number of dropouts: 4 ACI+CR – Combined Treatment – the ACI condition and CR condition on the TRQ
Reason for dropouts: NR condensed version of 2 treatments – (F( 1,46) = 4.38, p < 0.05).
Audiological factors: score 17+ on the TRQ subjects provided with treatment and There were no significant group by time effects for
Comorbidities: treatment resistant, 72% had education manuals any of the dependent variables at the six-month
subjective hearing loss 3 treatment programs consisted of 8 follow-up.
weekly group sessions lasting 90 Results were interpreted as supporting the
minutes practice of combining the two cognitive
approaches.
Comparator: Wait list Cntrl – treatment
provided after 8 weeks Adverse Events: NR
E-26
Table E4. Psychological/behavioral intervention and outcomes (n=19) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
86
Henry, 1996 Baseline sample: Total n = 60, CBT Depression TS-QOL: significant reduction in tinnitus distress
Int Grp1: n = 20, Int Grp2: n = 20, ACI - Attention Cntrl and Imagery (BDI) which was significantly greater when the cognitive
Australia Cntrl: n = 20 Training & CBT vs wait list coping training was combined with education than
Setting: Hospital Treatment groups involved 1 90- TS-QOL (TRQ*, when education alone was provided
Mean age: 64.6 y minute session per week for six TEQ, THQ- (F(1,57)=16.19, p <0.01)
Gender: 86.6% male weeks. Treatment conducted in handicap,
groups of 5 to 7 participants. All TCSQ coping, Subjects who received the combined
Presumed etiology of tinnitus: idiopathic psychological treatment was delivered TCQ cognitive/education intervention demonstrated
Duration of tinnitus: >6 months by a clinical psychologist. awareness) significantly greater reductions in distress and
Severity of tinnitus: score ≥17 points on the TRQ; Int Grp1: Cognitive coping skills handicaps associated with tinnitus and
unsuccessful previous treatments training plus education; Loudness (Self engagement in dysfunctional cognitions, than the
Number of dropouts: 0 Int Grp2: Education, reported) subjects who received education alone. No
Reasons for dropouts: NA significant effects were obtained on measures of
Audiological factors: no hearing aid, masker or Comparator: Wait List Cntrl depression or loudness.
tinnitus suppressive medication previous 6 months
Comorbidities: NR Duration of treatment: 6 weeks Adverse Events: NR
Number of follow ups: 2
Duration of study: 12 months
88
Henry, 2007 Baseline sample Total n = 268 Group Education Counseling (TRT TS-QOL (TSI) The educational counseling group showed a
Int Grp1 n = 94, Int Grp2 n = 84, principles) significant reduction in mean TSI score from
United States Cntrl n = 90 Interven group attended four 1.5 hour baseline to 6 months (p < 0.001) and baseline to
Setting: Hospital group sessions each week conducted 12 months (p < 0.001).
Mean age(SD): by audiologists. Assessed at baseline,
IntGrp1: 62.1y (8.9); IntGrp2: 60.8y (9.5); and at 1, 6, and 12 months after their The effect sizes for the educational counseling
Cntrl: 62.0y (11.3) last group session. Comparison group group were 0.59 at 6 months and 0.45 at 12
Gender: (traditional-support) subjects attended months, while the effect sizes for the traditional
IntGrp1: 96.8% male; IntGrp2: 96.4% male four weekly 1.5-hour discussion-type support and no treatment groups were 0.11 or
Cntrl: 96.7% male group sessions. Sessions were less at 6 and 12 months.
moderated by the project coordinator.
Presumed etiology: NR No education was provided in the Adverse Events: None
Duration of tinnitus: 87.7% GE 3 y support group.
Severity of tinnitus: Sufficiently bothersome to
warrant Interven Comparator: no treatment and
Number of dropouts: IntGrp1 n = 26, IntGrp2 n = 23, traditional support
Cntrl n = 15
Reasons for dropouts: NR Duration of treatment: 4 weeks
Audiological factors: 93% difficulty hearing at least Number of follow ups: 3
‘sometimes’ Duration of study: 12 months
Comorbidities: NR
E-27
Table E4. Psychological/behavioral intervention and outcomes (n=19) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
52
Ireland, Baseline sample: Total n =33 Relaxation Therapy vs wait list Anxiety (STAI) No significant effects for relaxation training were
1985 Setting: University clinic Int Grp1: Relaxation training; found on any measure.
Mean Age: 55.9 y Int Grp2: Counterdemand, Neutral Depression The BDI improved significantly from pretreatment
Australia Gender: 46.6% males Demand (BDI) to post-treatment, but the degree of change was
Int Grp1: 54.5% males Cntrl: Wait List Cntrl equivalent for both treated and untreated groups
Int Grp2: 44.4% males Loudness (Self-
Cntrl:40.0% males Duration of treatment: 6 weeks reported) Adverse Events: NR
Number of follow ups: 2
Presumed etiology of tinnitus: Idiopathic Duration of Duration of study: NR TS-QOL
tinnitus: NR Severity of tinnitus: Other traditional (Tinnitus
treatments not recommended or had failed interference
Number of drop outs: 3 self-report)
Reasons for drop outs: discontinued treatment
Audiological factors: NR
Comorbidities: NR
91
Kaldo, Baseline sample: Total n=72 CBT TS-QOL (THI, TS-QOL: group x time interaction: (F(1,70)=12.4,
2007 Interven=34; Cntrl=38 Self-help book and brief telephone TRQ*, VAS) p <0.001
Setting: phone calls and mailouts therapy Treatment group: read the
Sweden Mean age (SD): self-help book and had 7 weekly Loudness (VAS) On the TRQ, in the treatment group, 32% reached
Interven=45.9 y(13.0); phone calls from one of two therapists the criteria for clinical significance (at least 50%
Cntrl=48.5 y (15.7) over a period of 6 weeks (HIGH Depression reduction of the TRQ) compared to 5% in the wait-
Gender: therapist contact group) (HADS-D) list group.
Interven: 50% male; Cntrl group: Wait-list; received self-
Cntrl: 47.3% male help book and had one initial phone Anxiety (HADS- In the treatment group, 32% reached the criteria
call after treatment group finished A) for clinical significance (at least 50% reduction of
Presumed etiology of tinnitus: NR (LOW therapist contact group) the TRQ) compared to 5% in the wait-list group.
Duration of tinnitus: Measured pre-treatment, post- Sleep
>6 months treatment, extra 6 week post- (ISI) Adverse Events: NR
Severity of tinnitus: Score of 10 or above on TRQ treatment for LOW group, and follow-
Number of dropouts: 12 up 1 yr after LOW group’s post-
Reasons for dropouts: 4 ended treatment treatment measurement.
prematurely; 3 general reasons. 5 unclear
Audiological factors: NR Comparator: Wait list
Comorbidities: NR
Duration of treatment: 6 weeks
Number of follow ups: 3
Duration of study: 1 yr
E-28
Table E4. Psychological/behavioral intervention and outcomes (n=19) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
92
Kaldo, Baseline sample: Total n = 51 Recruited by advertisements in TS-QOL (THI, Both groups had improved, and there were few
2008 Interven n = 26; Cntrl n = 25 newspapers, Wait List Cntrl for TRQ, VAS) differences between them.
Setting: Audiology clinic, Internet psychological treatment at the local
Sweden Mean age (SD): Dept. of Audiology Depression The effect size for the Internet treatment was d =
Int: 47.4 (12.9); Cntrl: 45.0 (12.8) (HADS-D) 0.73 (95% CI = 0.16 to 1.30) and for the group
Gender: Internet-administered CBT self-help treatment was d = 0.64 (95% CI = 0.07 to 1.21).
Int 58% male; Cntrl 56% male Anxiety (HADS-
Comparator: traditional CBT group A) The Internet treatment consumed less therapist
Presumed etiology of tinnitus: Idiopathic treatment time and was 1.7 times as cost-effective as the
Duration of tinnitus: Sleep (ISI) group treatment.
Int: 9.9y(13.5); Cntrl: 5.6y (6.1) Both groups used the same treatment
Severity of tinnitus: primary problem; ≥10 TRQ manual Loudness (VAS) Adverse Events: NR
(Wilson et al., 1991)
Number of dropouts: 7 Duration of treatment: 7 weeks
Int n=4; Cntrl n=3 Number of followups: 1
Reasons for dropouts: NR Duration of study: 14 months
Audiological factors: 33% “Much” or “very much:
distressed by hearing deficit
Comorbidities: NR
Kröner- Baseline sample: Total n = 95; CBT Loudness TS-QOL: reduced psychological impairment
Herwig,
93
TCT1 n = 7;TCT2 n = 8; Tinnitus Coping Training: TCT1 and (Diary) German version of the TQ F(1,32)=4.43, p ≤0.04
1995 Yoga n = 9; WLC n = 19 TCT2 to Cntrl for therapist effect –
Setting: Dept. of Audiology training consisted of Patient Education Sleep Statistical analyses showed effects favoring the
Germany Mean age (SD): Total: 46.8y (11.5); (1 session); CBT (sessions 2 to 10) (Diary, TQ TCT treatment in comparison to the Cntrl and
TCT1: 44.7 y(12.7); TCT2: 48.5 y(10.6); Yoga (Hathayoga) – special yogic subscale*) yoga treatment. The TCT-treated patients
Yoga: 50.0 y (12.6); WLC: 47.3 y (7.9) exercises to foster relaxation and reported more satisfaction with the training than
Gender: adequate body perception G-QOL the yoga group.
TCT1: 57% male; TCT2: 50% male; Comparator: Wait List Cntrl (WLC) (TQ, Bef-Skala,
Yoga: 67% male; WLC: 63% male Bes-Liste*) Adverse Events: NR
Duration of treatment: 10- 2 hour
Presumed etiology of tinnitus: idiopathic sessions Depression
Duration of tinnitus: Mean 4.5 y (range 6m to 20y) Number of followups: end of (Dep-Skala)
Severity of tinnitus: >4 on a 10 point scale treatment, 3 month followup
Number of dropouts: Duration of study: 22 weeks TS-QOL
TCT1 n=3; TCT2 n=2; Yoga n=1; WLC n=3 (Diary, TQ*)
Reasons for dropouts: NR
Audiological factors: hearing ability enough to allow
communication in a group setting
Comorbidities: hearing deficits with 56%
E-29
Table E4. Psychological/behavioral intervention and outcomes (n=19) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
Kröner- Baseline sample: Total n = 95; CBT Depression TSQOL: WLC group (F(1,34)=6.79, p <0.01) on
13
Herwig, Int Grp1 n = 43;Int Grp2 n = 16; Tinnitus Coping Therapy (TCT); (ADS) the TEI; TQ=NS
2003 Int Grp3 n = 16; Cntrl n = 20 Education; Relaxation Therapy
Setting: varied by treatment arm Int Grp1: TCT= detailed training G-QOL There is no significant superiority of TCT relative
Germany Mean age (SD): Total: 46.8y (11.5); manual provided guidelines for 11 (SCL-90R) to the combined MC treatments in subjective
IntGrp1: 44.7 y(12.7); IntGrp2: 48.5 y(10.6); sessions change.
IntGrp3: 50.0 y (12.6); Cntrl: 47.3 y (7.9) Int Grp2: Minimal Contact-Education TS-QOL
Gender: Total: 48.4% male; (MC-E) comprised 2 education (TDI, TQ*, TC Concluded that the CBT outpatient group training
IntGrp1: 44.2% male; IntGrp2: 58.8% male; sessions regarding tinnitus etiology, 4 cope subscales) of tinnitus shows good efficacy in reducing the
IntGrp3: 46.7% male; Cntrl: 50% male weeks self-help exercise negative impact of tinnitus on the person’s life by
Int Grp3: Minimal Contact-Relaxation Loudness improving coping and reducing the threatening
Presumed etiology: Idiopathic, exclude Moribus (MC-R) 4 sessions; educational, (Diary) character of tinnitus.
Meniere verbal relaxation; discussions
Duration of tinnitus: NR Adverse Events: NR
Severity: Subjective annoyance >40 on 9 scales Comparator: Wait-list Cntrl
assessing disruptiveness of tinnitus Duration of treatment:
Number of dropouts: Int Grp1 n = 13; Int Grp2 n = 4; Int Grp1: 11 sessions 90-120 minutes;
Int Grp3 n = 4; Cntrl n = 0 Int Grp2: 2 sessions (4 weeks);
Reasons for dropouts: NR Int Grp3: 4 sessions
Comorbidities: NR
Number of followups:
Int Grp1: 3 followups (immediately
post-treatment 6 and 12 months after
treatment); Int Grp2 and Int Grp3: 1
followup (immediately post-treatment)
Duration of study: NR
E-30
Table E4. Psychological/behavioral intervention and outcomes (n=19) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
95
Malouff, Baseline sample: Total n = 162 Participants received a book based on G-QOL Individuals in the Interven condition who
2010 Interven n = 84; Cntrl n = 78 cognitive-behavioral principles, (GPQ-12) completed the post-assessment experienced a
Setting: Internet online participation including educational information on significant reduction in tinnitus distress from pre-
Australia Mean age (SD): tinnitus, cognitive reappraisal and TS-QOL Interven to post-Interven (p =.0001].
Interven 1: 57.3y (13.7); restructuring, relaxation and stress (TRQ) The between-groups difference in the rates of
Cntrl: 57.8y (13.3) management techniques, attention reliable change, although in the hypothesized
Gender: Cntrl techniques, use of self- direction, was not statistically significant (p =.15).
Interven: 51% male; Cntrl: 60.3% male instruction, making lifestyle changes,
and maintaining gains. A brief letter Intention-to-treat analyses showed no significant
Presumed etiology of tinnitus: Idiopathic asking participants to read the book effect for between-groups analyses, but did show
Duration of tinnitus: NR and to follow the suggestions it a significant effect for the 1-year follow-up pre–
Severity of tinnitus: NR contained in the subsequent 6 weeks. post analysis.
Number of dropouts n = 35;
Interven: n = 29 (35%); Cntrl n = 8 (10%) Comparator: WLC Adverse Events: None
Reasons for dropouts: NR
Audiological factors: NR Duration of Treatment: 2 months
Comorbidities: NR Number of followups: 2m, 4m, 12m
Duration of study: NR
104
Rief, Baseline sample: Total n= 42 CBT TS-QOL On most tinnitus specific variables, patients in the
2005 Interven n = 22; Cntrl n = 20 Training consisted of 1 pre- (TQ) treatment group improved significantly more than
Setting: University psychotherapy outpatient clinic assessment session, 7 treatment patients on the Wait List Cntrl.
Germany Mean age (SD): sessions, and a final session G-QOL
Interven: 45.5y (12.8); Cntrl: 48.0y (15.3) summarizing Interven strategies and (HRLS*, GSI, Main effect sizes for tinnitus-specific variables
Gender: conducting post-assessment.Training SCL-90R) were up to 0.89.
Interven: 59.1% male; Cntrl: 40.0% male was manual-guided, included
handouts (basic information on ear Loudness Adverse events: Participants did not report any
Presumed etiology of tinnitus: NR and the hearing system; information (diary) adverse events
Duration of tinnitus: processes involved in tinnitus; the
Interven: 4.5 y (5.3); Cntrl: 8.3 y (7.7) vicious circle of tinnitus annoyance,
Severity of tinnitus: (VAS out of 10) muscular reactivity, and selective
Interven: 6.5 (1.7); Cntrl: 5.9 (1.6) attention; and aspects of tinnitus
Number of dropouts: 1 maintenance, modulating factors,etc.).
Interven n = 0; Cntrl n = 1
Reasons for dropouts: discontinued Interven Comparator: Waiting-list Cntrl
Audiological factors: hearing problems (57%) Setting: outpatient clinic
Comorbidities: depressive disorder: 36.4% 1st Duration of Treatment: 8 weeks
Interven group; 35.0% wait list group Number of followups: 1 (6 months)
Duration of study: October 2002 to
November 2003
E-31
Table E4. Psychological/behavioral intervention and outcomes (n=19) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
7
Scott, Baseline sample: Relaxation Therapy vs wait list Depression TS-QOL: A significant effect on both direct (group
1985 Total n=24; Interven=12; Cntrl=12 The treatment comprised 10 one-hour (Self-report R) x time interaction: F(1,21)=6.01, p <0.05) and
Setting: Department of Audiology, Hospital sessions over 3 weeks: relaxation retrospective measures (group x time interaction:
Sweden Mean age: 52.6 training, training of self-control by TS-QOL (Self- F(1,21)=7.92, p <0.01)
Interven: 50.9 y; Cntrl: 54.3 y distraction exercises with the aim of report D)
Gender: Total: 43.4% male reducing the discomfort from tinnitus, Adverse Events: 8 (38%) reported an increase of
Interven: 41.6% male; Cntrl: 45.5% male and application of the method in Loudness negative effects of the intensive self-monitoring on
situations associated with tinnitus. (Self-report D) the loudness of and discomfort from their tinnitus.
Presumed etiology of tinnitus: Idiopathic 14/15 patients reported a general reduction of
Duration of tinnitus: mean 9.4y (1-23 years) Comparator: WLC dizziness, headache and troublesome muscle
Severity of tinnitus: grade 2 or 3 (Klockhoff & tension.
Lindblom) Duration of treatment; 10 to 11 weeks
Number of dropouts: 2 Cntrl group, women Number of follow ups: 1
Reasons for dropouts: NR Duration of study: NR
Audiological factors: All had some form of hearing
impairment
Comorbidities: no retrocochlear lesions suspected
14
Weise, Baseline sample: Total n = 111 Biofeedback-based CBT Loudness (VAS) For the TQ and the tinnitus diary, the MANOVA
2008 Setting: Outpatient treatment center for showed a statistically significant group effect,
psychological Intervens Interven: 12 sessions of 20 mins. of Sleep F(13, 97) = 2.84, p <.01; a significant time effect,
Germany Mean age (SD): biofeedback training combined with 20 (VAS*, TQ-sub) F(13, 97) = 14.75, p <.001; and a significant
Interven: 49.5 y (11.83); mins of CBT. Treatment over 3 interaction for Time x Group, F(13, 97) = 5.16, p
Cntrl: 52.9 y (11.92) months. G-QOL (GSI <.001 for the completer analysis.
Gender: SCL-90-R)
Interven: 55.8% male Comparator: Waitlist group measured Improvements were maintained over a 6-month
Cntrl: 55.9% male at initiation, 3 months later, then had Depression follow-up period in which medium-to-large effect
the Interven and measured again after (BDI) sizes were observed.
Presumed etiology: Idiopathic Interven (6 months).
Duration of tinnitus: >6 months TS-QOL (TQ*, Adverse Events: Majority of the patients did not
Severity of tinnitus: High tinnitus annoyance Duration of treatment: 3 months VAS, TRSS experience negative side effects caused by the
Number of dropouts: Number of follow ups: 1 (6 months) catastrophizing, treatment
Interven n = 15; Cntrl n= 20 Duration of study: 9 months TRCS
Reasons for dropouts: helplessness)
Interven: incomplete (4), discontinued Interven (7),
refused follow-up assessment (4);
Cntrl=1 incomplete (1), discontinued waiting period
(7), discontinued Interven (7), refused follow-up
assessment (5)
Comorbidities: Depression
E-32
Table E4. Psychological/behavioral intervention and outcomes (n=19) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
112
Westin, , Baseline sample: n = 64 CBT Sleep A comparison between the active treatments,
2011 Interven1 (ACT): n = 22; Cntrl (WLC): n = 22; Acceptance and Commitment Therapy (ISI) including all assessment points, revealed
Interven2 (TRT): n = 20 (ACT) significant differences in favor of ACT regarding
Sweden Setting: Audiology department TS-QOL tinnitus impact (Cohen’s d = 0.75) and problems
Mean age (SD): ACT: max 10 weekly individual (THI) with sleep.
Interven1: 53.5 years (12.84) sessions of 60 minutes No significant main effects were found. On QOL,
Cntrl: 49.59 years (11.86) TRT: one 2.5 hr individual consultation Anxiety (HADS- anxiety or depression no time, group or interaction
Interven2: 48.95 (14.3) session, 30 min follow-up session over A) effects were found.
Gender: 53.1% male telephone, wearable sound generators
used min 8 hrs/day for 18 months Depression .Adverse Events: None
Presumed etiology of tinnitus: Idiopathic WLC started CBT treatment after 10 (HADS-D)
Duration of tinnitus: Mean 8.3 y (SD 7.3) weeks
Severity of tinnitus: score ≥30 on THI G-QOL
Number of dropouts: 4 Duration of treatment: 10 weeks to 18 (QOLI)
Reasons for dropouts: NR months
Audiological factors: 12.8 dB hearing level (SD=7.1) Number of follow ups: 3
for better ear Duration of study: 18 months
Comorbidities: n=49:
rheumatological conditions (n=35), cardiovascular
conditions (n=10), respiratory conditions or allergy
(n=10), mild to moderate depression (n=9),
gastroenterological conditions (n=6), sleep
problems (n=6), cancer (n=5), endocrinological
conditions (n=6),
skin disease (n=2).
E-33
Table E4. Psychological/behavioral intervention and outcomes (n=19) (continued)
Author Population Description Intervention Outcome Results
Year Measures
Setting
113
Zachriat, Baseline sample: Total n = 77 HT: Habituation-based treatment, 5 G-QOL Findings reveal highly significant improvements in
2004 TCT n = 27; HT n = 30 sessions – counseling concentrating (VEV) both tinnitus coping training and habituation-based
EDU n = 20 on education of factors having an treatment in comparison with the Cntrl group.
Germany Setting: University Psychology department impact on tinnitus and training in TS-QOL
Mean age (SD): sound generator use for ≥6 hours per (TQ, TCQ, JQ, While tinnitus coping training and habituation-
TCT: 53.8y (11.8); HT: 51.6y (11.0); day Diary) based treatment do not differ significantly in
EDU: 56.1y(10.6) TCT: tinnitus coping training, 11 reduction of tinnitus disability, improvement in
Gender: sessions, 90 to 120 minutes in groups Loudness general well-being and adaptive behavior is
TCT: 59.3% male; HT: 66.7% male; of 6 to 8 – relaxation exercises, use of (Diary) greater in tinnitus coping training than habituation-
EDU: 74.0% male attention distraction strategies; coping based treatment.
techniques
Presumed etiology of tinnitus: idiopathic EDU: (Cntrl): educational Interven, 1 Adverse events: NR
Duration of tinnitus: ≥3 months (range 4 to 324 m) session informing about physiology
Severity of tinnitus: TQ ≥ 25 and psychology of tinnitus
Number of dropouts:
TCT n = 2; HCT n = 1; EDU n = 3 Duration of treatment: 15 weeks
Reasons for dropouts: NR Number of followups: 3 to 27 weeks,
Audiological factors: NR 53 weeks, 18 to 21 months
Comorbidities: no treatable organic disease Duration of study: NR
*Indicates the test used to measure outcomes which were selected to represent the domain in the forest plots (and subsequent SOE decisions)
Abbreviations: A/E = Adverse events; AMT = active motor threshold; Bef-Skala = Befindlichkeits-Skala; Bes-Liste = Beschwerden-Liste; CBT = cognitive behavioral treatment;
Ctrl = Control; Dep-Skala = Depressivitäts-Skala; ENT = ear, nose and throat; grp = group; G-QOL = global quality of life; HADS = Hospital Anxiety and Depression Scale;
interven = Intervention; month = month; ISI = Insomnia Severity Index; N/A = not applicable; NR = not reported; OSI-R = Occupational Stress Inventory- Revised; QOL = quality
of life; RCT = randomized controlled trial; SD = standard deviation; TCT = Tinnitus Coping Therapy; THI = Tinnitus Handicap Inventory; TMJ = temporal mandibular joint;
TRCS = Tinnitus-Related Control Scale; TRSS = Tinnitus-related Self-Statements Scale; TS = tinnitus specific; TSQ = Tinnitus Severity Questionnaire; VAS = visual analog
scale; week = week; WLC = wait list Cntrl; yr = year
E-34
Appendix E. References
1. American Tinnitus Association. Top 10 13. Kroner-Herwig B, Frenzel A, Fritsche G, et
most frequently asked questions. al. The management of chronic tinnitus:
www.ata.org/for-patients/faqs. Accessed Comparison of an outpatient cognitive-
January 10, 2011. behavioral group training to minimal-contact
interventions. J Psychosom Res.
2. Davis A, El Rafaie A. Epidemiology of
2003;54(4):381-9. PMID:12670617
tinnitus. In: Epidemiology of tinnitus, Tyler
RS,ed. San Diego,CA: Singular Publishing 14. Weise C, Heinecke K, Rief W. Biofeedback-
Group; 2000. 1 p. 1-24. based behavioral treatment for chronic
tinnitus: Results of a randomized controlled
3. Press release: Two ATA Scientific Advisory
trial. J Consult Clin Psychol.
Committee members receive Department of
2008;76(6):1046-57. PMID:19045972
Defense grant. www.ata.org/about-ata/news-
pubs/press-releases#DoDGrant. Accessed 15. Dobie RA. A review of randomized clinical
June 1, 2011. trials in tinnitus. Laryngoscope.
1999;109(8):1202-11. PMID:10443820
4. Savage J, Cook S, Wadell A. Tinnitus. Clin
Evid. 2007; PMID:19454115 16. McCombe A, Baguley D, Coles R, et al.
Guidelines for the grading of tinnitus
5. Shargorodsky J, Curhan GC, Farwell WR.
severity: The results of a working group
Prevalence and characteristics of tinnitus
commissioned by the British Association of
among US adults. Am J Med.
Otolaryngologists, Head and Neck
2010;123(8):711-8. PMID:20670725
Surgeons, 1999. Clin Otolaryngol Allied
6. Zoger S, Erlandsson S, Svedlund J, et al. Sci. 2001;26(5):388-93. PMID:11678946
Benefits from group psychotherapy in the
17. Erlandsson S. Psychological profiles of
treatment of severe refractory tinnitus.
tinnitus in patients. In: Tinnitus Handbook,
Audiol Med. 2008;6(1):62-72.
Tyler RS, ed. San Diego, CA: Singular
7. Scott B, Lindberg P, Lyttkens L, et al. Publishing Group; 2000. 2 p. 25-58.
Psychological treatment of tinnitus. Scand
18. Figueiredo RR, Azevedo AA, Oliveira PM.
Audiol. 1985;14(4):223-30.
Correlation analysis of the visual-analogue
8. Weber C, Arck P, Mazurek B, et al. Impact scale and the Tinnitus Handicap Inventory in
of a relaxation training on psychometric and tinnitus patients. Revista Brasil
immunologic parameters in tinnitus Otorrinolaringol. 2009;75(1):76-9.
sufferers. J Psychosom Res. 2002;52(1):29- PMID:19488564
33. PMID:11801262
19. Kamalski DM, Hoekstra CE, van Zanten
9. Henry, JA. 2011 Jul 26; Key informant BG, et al. Measuring disease-specific health-
interview. related quality of life to evaluate treatment
outcomes in tinnitus patients: A systematic
10. Henry JA, Zaugg TL, Myers PJ, et al. A
review. Otolaryngol Head Neck Surg.
triage guide for tinnitus. J Fam Pract.
2010;143(2):181-5.
2010;59(7):389-93. PMID:20625568
20. Lipsey MW. Design sensitivity: Statistical
11. Tinnitus: Guidelines for primary care.
power for experimental research. Newburry
British Tinnitus Association. 2009;
Park, CA: Sage Publications, Inc.; 1990.
http://tinnitus.demonweb.co.uk/files/Tinnitu
s%20%20Guidelines%20for%20Primary%2 21. Kazdin AE. Research design in clinical
0Care.pdf. Accessed September 19, 2012. psychology. 4th. Needham Heights, MA:
Allyn & Bacon; 2003.
12. Holgers K-M. Mechanisms and
classification of tinnitus: A discussion paper. 22. Meikle M, Henry JA, Griest S, et al. The
Audiol Med. 2003;1(4):238-41. Tinnitus Functional Index: Development of
a new clinical measure for chronic, intrusive
tinnitus. Ear Hear. 2011;32(5): PMID:
22156949
E-35
23. Baldo P, Doree C, Lazzarini R, et al. 34. Ash CM, Pinto OF. The TMJ and the middle
Antidepressants for patients with tinnitus. ear: Structural and functional correlates for
Cochrane Database Syst Rev. aural symptoms associated with
2006;(4):CD003853. PMID:17054188 temporomandibular joint dysfunction. Int J
Prosthodont. 1991;4(1):51-7. PM:2012671
24. Johnson RM, Brummett R, Schleuning A.
Use of alprazolam for relief of tinnitus. A 35. Langguth B, Hajak G, Kleinjung T, et al.
double-blind study. Arch Otolaryngol Head Repetitive transcranial magnetic stimulation
Neck Surg. 1993;119(8):842-5. and chronic tinnitus. Acta Otolaryngol
PMID:8343245 Suppl. 2006;(556):102-5. PMID:17114153
25. Jalali MM, Kousha A, Naghavi SE, et al. 36. Henry JA, Dennis KC, Schechter MA.
The effects of alprazolam on tinnitus: A General review of tinnitus: Prevalence,
cross-over randomized clinical trial. Med mechanisms, effects, and management. J
Sci Mon. 2009;15(11):I55-I60 Speech Lang Hear Res. 2005;48(5):1204-35.
PMID:19865063 PMID:16411806
26. Kalcioglu MT, Bayindir T, Erdem T, et al. 37. Park J, White AR, Ernst E. Efficacy of
Objective evaluation of the effects of acupuncture as a treatment for tinnitus: A
intravenous lidocaine on tinnitus. Hear Res. systematic review. Arch Otolaryngol Head
2005;199(1-2):81-8. PMID:15574302 Neck Surg. 2000;126(4):489-92.
PMID:10772302
27. Agarwal L, Pothier DD. Vasodilators and
vasoactive substances for idiopathic sudden 38. Bennett M, Kertesz T, Yeung P. Hyperbaric
sensorineural hearing loss. Cochrane oxygen therapy for idiopathic sudden
Database Syst Rev. 2009;(4):CD003422. sensorineural hearing loss and tinnitus: A
PM:19821308 systematic review of randomized controlled
trials. J Laryngol Otol. 2005;119(10):791-8.
28. Noble W. Treatments for tinnitus. Trends
PMID:16259656
Amplification. 2008;12(3):236-41.
PMID:18635586 39. Keate, B. Diet and tinnitus: What to eat …
and what not to eat. Tinnitus Library.
29. Sziklai I, Szilvassy J, Szilvassy Z. Tinnitus
www.tinnitusformula.com/infocenter/article
control by dopamine agonist pramipexole in
s/treatments/diet.aspx. Accessed June 10,
presbycusis patients: A randomized,
2011.
placebo-controlled, double-blind study.
Laryngoscope. 2011;121(4):888-93. 40. Tinnitus and your diet. New Tinnitus
PMID:21433025 Treatments Blog. 2011; www.tinnitus
treatments.org/tinnitus-and-your-diet.html.
30. Hilton M, Stuart E. Ginkgo biloba for
Accessed June 10, 2011.
tinnitus. Cochrane Database Syst Rev.
2004;(2):CD003852. PMID:15106224 41. Tinnitus relief through diet - Foods to avoid
to relieve tinnitus. Tinnitus Remedies Web
31. Teggi R, Bellini C, Piccioni LO, et al.
Site. 2011; www.thetinnitussite.info/
Transmeatal low-level laser therapy for
tinnitus-relief-2/tinnitus-relief-through-diet-
chronic tinnitus with cochlear dysfunction.
foods-to-avoid-to-relieve-tinnitus. Accessed
Audiol Neuro Otol. 2009;14(2):115-20.
June 10, 2011.
PMID:18843180
42. Henry JA, Zaugg TL, Myers PJ, et al.
32. Tuz HH, Onder EM, Kisnisci RS.
Progressive audiologic tinnitus management.
Prevalence of otologic complaints in patients
ASHA Leader. 2008;13(8):14-7.
with temporomandibular disorder. Am J
Orthod Dentofacial Orthop. 43. Hobson J, Chisholm E, El RA. Sound
2003;123(6):620-3. PMID:12806339 therapy (masking) in the management of
tinnitus in adults. Cochrane Database Syst
33. Wright EF, Syms CA, III, Bifano SL.
Rev. 2010;12:CD006371. PMID:21154366
Tinnitus, dizziness, and nonotologic otalgia
improvement through temporomandibular
disorder therapy. Milit Med.
2000;165(10):733-6. PMID:11050868
E-36
44. CIGNA medical coverage policy No. 0220. 55. Davis A, Smith P, Ferguson M, et al.
Tinnitus treatment services and devices. Acceptability, benefit and costs of early
www.cigna.com/assets/docs/health-care- screening for hearing disability: A study of
professionals/coverage_positions/mm_0220 potential screening tests and models. Health
_coveragepositioncriteria_tinnitus_instr_dev Technol Assess. 2007;11(42):iii-294
ices_retraining_ther.pdf. Accessed June 10, PMID:17927921
2011.
56. Searchfield G. A commentary on the
45. Davis PB, Wilde RA, Steed LG, et al. complexity of tinnitus management: Clinical
Treatment of tinnitus with a customized guidelines provide a path through the fog.
acoustic neural stimulus: A controlled Eval Health Prof. 2011; PM:21224266
clinical study. Ear Nose Throat J.
57. Hoare DJ, Gander PE, Collins L, et al.
2008;87(6):330-9. PMID:18561116
Management of tinnitus in English NHS
46. Davis PB, Paki B, Hanley PJ. Neuromonics audiology departments: An evaluation of
tinnitus treatment: Third clinical trial. Ear current practice. J Eval Clin Pract. 2010;
Hear. 2007;28(2):242-59. PMID:17496674 PM:21087449
47. Langguth B, Kleinjung T, Landgrebe M. 58. Henry JA, Schechter MA, Loovis CL, et al.
Tinnitus: The complexity of standardization. Clinical management of tinnitus using a
Eval Health Prof. 2011;34(4):429-33. “progressive intervention” approach. J
PMID:21224265 Rehabil Res Dev. 2005;42(4:Suppl 2):95-
116. PMID:16470467
48. Martinez-Devesa P, Perera R, Theodoulou
M, et al. Cognitive behavioural therapy for 59. Juni P, Holenstein F, Sterne J, et al.
tinnitus. Cochrane Database Syst Rev. Direction and impact of language bias in
2010;(9):CD005233. PMID:20824844 meta-analyses of controlled trials: Empirical
study. Int J Epidemiol. 2002;31(1):115-23.
49. Department of Health. Provision of services
for adults with tinnitus: A good practice 60. Moher D, Pham B, Klassen T, et al. What
guide. London: Central Office of contributions do languages other than
Information; 2009. English make on the results of meta-
analysis? J Clin Epidemiol. 2000;53(9):964-
50. Phillips JS, McFerran D. Tinnitus Retraining
72.
Therapy (TRT) for tinnitus. Cochrane
Database Syst Rev. 2010;(3):CD007330. 61. Wells, G. A., Shea, B., O’Connell, D. et al.
PMID:20238353 The Newcastle-Ottawa Scale (NOW) for
assessing the quality of nonrandomised
51. Jastreboff PJ, Hazell JW. A
studies in meta-analyses. www.ohri.ca/
neurophysiological approach to tinnitus:
programs/clinical_epidemiology/oxford.asp.
Clinical implications. Br J Audiol.
Accessed September 19, 2012.
1993;27(1):7-17. PMID:8339063
62. Jadad AR, Moore RA, Carroll D, et al.
52. Ireland CE, Wilson PH, Tonkin JP, et al. An
Assessing the quality of reports of
evaluation of relaxation training in the
randomized clinical trials: Is blinding
treatment of tinnitus. Behav Res Ther.
necessary? Control Clin Trials.
1985;23(4):423-30. PMID:3896227
1996;17(1):1-12. PM:8721797
53. Henry JA, Zaugg TL, Myers PJ, et al. The
63. Atkins D, Chang S, Gartlehner G, et al.
role of audiologic evaluation in progressive
Assessing applicability when comparing
audiologic tinnitus management. Trends
medical interventions: AHRQ and the
Amplification. 2008;12(3):170-87.
Effective Health Care Program. J Clin
PMID:18628281
Epidemiol. 2011;64(11):1198-207.
54. Cima RF, Maes IH, Joore MA, et al.
64. Guyatt GH, Oxman AD, Kunz R, et al.
Specialised treatment based on cognitive
GRADE guidelines: 7. Rating the quality of
behaviour therapy versus usual care for
evidence--inconsistency. J Clin Epidemiol.
tinnitus: A randomised controlled trial.
2011;64(12):1294-302. PM:21803546
Lancet. 2012;379(9830):1951-9.
PM:22633033
E-37
65. Martinez DP, Perera R, Theodoulou M, et al. 75. Andersson G, Porsaeus D, Wiklund M, et al.
Cognitive behavioural therapy for tinnitus. Treatment of tinnitus in the elderly: A
Cochrane Database Syst Rev. controlled trial of cognitive behavior
2010;(2):CD005233 PM:17253549 therapy. Int J Audiol. 2005;44(11):671-5.
PMID:16379495
66. Owens DK, Lohr KN, Atkins D, et al.
AHRQ series paper 5: Grading the strength 76. Aoki M, Wakaoka Y, Hayashi H, et al.
of a body of evidence when comparing Effect of lyophilized powder made from
medical interventions—Agency for enzymolyzed honeybee larvae on tinnitus-
Healthcare Research and Quality and the related symptoms, hearing levels, and
Effective Health-care program. J Clin hypothalamus-pituitary-adrenal axis-related
Epidemiol. 2010;63(5):513-23. hormones. Ear Hear. 2012;33(3):430-6.
PM:19595577 PMID:21971082
67. Grading the strength of a body of evidence 77. Arda HN, Tuncel U, Akdogan O, et al. The
when assessing health care interventions: An role of zinc in the treatment of tinnitus. Otol
update [Draft]. Rockville, MD: Agency for Neurotol. 2003;24(1):86-9. PMID:12544035
Healthcare Research and Quality; 2012.
78. Biesinger E, Kipman U, Schatz S, et al.
68. Hayden JA, Cote P, Bombardier C. Qigong for the treatment of tinnitus: A
Evaluation of the quality of prognosis prospective randomized controlled study. J
studies in systematic reviews. Ann Intern Psychosom Res. 2010;69(3):299-304.
Med. 2006;144(6):427-37. PM:16549855 PMID:20708452
69. Guyatt GH, Oxman AD, Montori V, et al. 79. Chung HK, Tsai CH, Lin YC, et al.
GRADE guidelines: 5. Rating the quality of Effectiveness of theta-burst repetitive
evidence--publication bias. J Clin transcranial magnetic stimulation for
Epidemiol. 2011;64(12):1277-82. treating chronic tinnitus. Audiol Neuro Otol.
PM:21802904 2012;17(2):112-20. PMID:21865723
70. Moher D, Liberati A, Tetzlaff J, et al. 80. Cuda D, De CA. Effectiveness of combined
Preferred reporting items for systematic counseling and low-level laser stimulation in
reviews and meta-analyses: The PRISMA the treatment of disturbing chronic tinnitus.
statement. Ann Intern Med. Int Tinnitus J. 2008;14(2):175-80.
2009;151(4):264-9, W64. PMID:19622511 PMID:19205171
71. Abbott JA, Kaldo V, Klein B, et al. A cluster 81. Dib GC, Kasse CA, Alves de AT, et al.
randomised trial of an internet-based Tinnitus treatment with Trazodone. Revista
intervention program for tinnitus distress in Brasil Otorrinolaringol. 2007;73(3):390-7.
an industrial setting. Cognit Behav Ther. PMID:17684661
2009;38(3):162-73. PMID:19675959
82. Dineen R, Doyle J, Bench J. Managing
72. Azevedo AA, Figueiredo RR. Tinnitus tinnitus: A comparison of different
treatment with acamprosate: Double-blind approaches to tinnitus management training.
study. Revista Brasil Otorrinolaringol. Br J Audiol. 1997;31(5):331-44.
2005;71(5):618-23. PMID:16612523 PMID:9373742
73. Anders M, Dvorakova J, Rathova L, et al. 83. Dineen R, Doyle J, Bench J, et al. The
Efficacy of repetitive transcranial magnetic influence of training on tinnitus perception:
stimulation for the treatment of refractory An evaluation 12 months after tinnitus
chronic tinnitus: A randomized, placebo management training. Br J Audiol.
controlled study. Neuroendocrinol Lett. 1999;33(1):29-51. PMID:10219721
2010;31(2):238-49. PMID:20424590
84. Drew S, Davies E. Effectiveness of Ginkgo
74. Andersson G, Stromgren T, Strom L, et al. biloba in treating tinnitus: Double blind,
Randomized controlled trial of internet- placebo controlled trial. BMJ.
based cognitive behavior therapy for distress 2001;322(7278):73 PMID:11154618
associated with tinnitus. Psychosom Med.
2002;64(5):810-6. PMID:12271112
E-38
85. Ghossaini SN, Spitzer JB, Mackins CC, et 95. Malouff JM, Noble W, Schutte NS, et al.
al. High-frequency pulsed electromagnetic The effectiveness of bibliotherapy in
energy in tinnitus treatment. Laryngoscope. alleviating tinnitus-related distress. J
2004;114(3):495-500. PMID:15091224 Psychosom Res. 2010;68(3):245-51.
PMID:20159209
86. Henry JL, Wilson PH. The psychological
management of tinnitus: Comparison of a 96. Marcondes RA, Sanchez TG, Kii MA, et al.
combined cognitive educational program, Repetitive transcranial magnetic stimulation
education alone and a waiting list control. improve tinnitus in normal hearing patients:
Int Tinnitus J. 1996;2:9-20. A double-blind controlled, clinical and
neuroimaging outcome study. Eur J Neurol.
87. Henry JL, Wilson PH. An evaluation of two
2010;17(1):38-44. PMID:19614962
types of cognitive intervention in the
management of chronic tinnitus. Scand J 97. Mazurek B, Haupt H, Szczepek AJ, et al.
Behav Ther. 1998;27(4):156-66. Evaluation of vardenafil for the treatment of
subjective tinnitus: A controlled pilot study.
88. Henry JA, Loovis C, Montero M, et al.
J Negative Results Biomed. 2009;8:3.
Randomized clinical trial: Group counseling
PMID:19222841
based on tinnitus retraining therapy. J
Rehabil Res Dev. 2007;44(1):21-32. 98. Meeus O, De RD, Van de Heyning P.
PMID:17551855 Administration of the combination
clonazepam-Deanxit as treatment for
89. Hiller W, Haerkotter C. Does sound
tinnitus. Otol Neurotol. 2011;32(4):701-9.
stimulation have additive effects on
PMID:21358561
cognitive-behavioral treatment of chronic
tinnitus? Behav Res Ther. 2005;43(5):595- 99. Mirz F, Zachariae R, Andersen SE, et al.
612. PMID:15865915 The low-power laser in the treatment of
tinnitus. Clin Otolaryngol Allied Sci.
90. Holgers K-M, Zoger S, Svedlund J. The
1999;24(4):346-54. PMID:10472473
impact of sertraline on health-related quality
of life in severe refractory tinnitus: A 100. Parazzini M, Del B, Jastreboff M, et al.
double-blind, randomized, placebo- Open ear hearing aids in tinnitus therapy: An
controlled study. Audiol Med. 2011;9(2):67- efficacy comparison with sound generators.
72. Int J Audiol. 2011;50(8):548-53.
www.cinahl.com/cgi-bin/refsvc?jid=
91. Kaldo V, Cars S, Rahnert M, et al. Use of a
2576&accno=2011208063
self-help book with weekly therapist contact
to reduce tinnitus distress: A randomized 101. Piccirillo JF, Finnell J, Vlahiotis A, et al.
controlled trial. J Psychosom Res. Relief of idiopathic subjective tinnitus: Is
2007;63(2):195-202. PMID:17662757 gabapentin effective? Arch Otolaryngol
Head Neck Surg. 2007;133(4):390-7.
92. Kaldo V, Levin S, Widarsson J, et al.
PMID:17438255
Internet versus group cognitive-behavioral
treatment of distress associated with tinnitus: 102. Plewnia C, Vonthein R, Wasserka B, et al.
A randomized controlled trial. Behav Ther. Treatment of chronic tinnitus with theta
2008;39(4):348-59. PMID:19027431 burst stimulation: A randomized controlled
trial. Neurology. 2012;78(21):1628-34.
93. Kroner-Herwig B, Hebing G, van Rijn-
PMID:22539568
Kalkmann U, et al. The management of
chronic tinnitus--Comparison of a cognitive- 103. Rejali D, Sivakumar A, Balaji N. Ginkgo
behavioural group training with yoga. J biloba does not benefit patients with
Psychosom Res. 1995;39(2):153-65. tinnitus: A randomized placebo-controlled
PMID:7595873 double-blind trial and meta-analysis of
randomized trials. Clin Otolaryngol Allied
94. Langguth B, Kleinjung T, Frank E, et al.
Sci. 2004;29(3):226-31. PMID:15142066
High-frequency priming stimulation does
not enhance the effect of low-frequency
rTMS in the treatment of tinnitus. Exp Brain
Res. 2008;184(4):587-91. PMID:18066684
E-39
104. Rief W, Weise C, Kley N, et al. 114. Zoger S, Svedlund J, Holgers KM. The
Psychophysiologic treatment of chronic effects of sertraline on severe tinnitus
tinnitus: A randomized clinical trial. suffering--A randomized, double-blind,
Psychosom Med. 2005;67(5):833-8. placebo-controlled study. J Clin
PMID:16204446 Psychopharmacol. 2006;26(1):32-9.
PMID:16415703
105. Robinson SK, Viirre ES, Bailey KA, et al.
Randomized placebo-controlled trial of a 115. Neri G, De SA, Baffa C, et al. Treatment of
selective serotonin reuptake inhibitor in the central and sensorineural tinnitus with orally
treatment of nondepressed tinnitus subjects. administered Melatonin and Sulodexide:
Psychosom Med. 2005;67(6):981-8. Personal experience from a randomized
PMID:16314604 controlled study. Acta Otorhinolaryngol Ital.
2009;29(2):86-91. PMID:20111618
106. Sharma DK, Kaur S, Singh J, et al. Role of
acamprosate in sensorineural tinnitus. Indian 116. Figueiredo RR, Langguth B, Mello de OP, et
J Pharmacol. 2012;44(1):93-6. al. Tinnitus treatment with memantine.
Otolaryngol Head Neck Surg.
107. Sullivan M, Katon W, Russo J, et al. A
2008;138(4):492-6. PMID:18359360
randomized trial of nortriptyline for severe
chronic tinnitus. Effects on depression, 117. Akkuzu B, Yilmaz I, Cakmak O, et al.
disability, and tinnitus symptoms. Arch Efficacy of misoprostol in the treatment of
Intern Med. 1993;153(19):2251-9. tinnitus in patients with diabetes and/or
PMID:8215728 hypertension. Auris Nasus Larynx.
2004;31(3):226-32. PMID:15364356
108. Tass PA, Adamchic I, Freund H-J, et al.
Counteracting tinnitus by acoustic 118. Bayar N, Boke B, Turan E, et al. Efficacy of
coordinated reset neuromodulation. Restor amitriptyline in the treatment of subjective
Neurol Neurosci. 2012;30(2):137-59. tinnitus. J Otolaryngol. 2001;30(5):300-3.
PMID:11771024
109. Topak M, Sahin-Yilmaz A, Ozdoganoglu T,
et al. Intratympanic methylprednisolone 119. Dobie RA, Sakai CS, Sullivan MD, et al.
injections for subjective tinnitus. J Laryngol Antidepressant treatment of tinnitus patients:
Otol. 2009;123(11):1221-5. Report of a randomized clinical trial and
PMID:19640315 clinical prediction of benefit. Am J Otol.
1993;14(1):18-23. PMID:8424470
110. Vilholm OJ, Moller K, Jorgensen K. Effect
of traditional Chinese acupuncture on severe 120. Suckfüll M, Althaus M, Ellers-Lenz B, et al.
tinnitus: A double-blind, placebo-controlled, A randomized, double-blind, placebo-
clinical investigation with open therapeutic controlled clinical trial to evaluate the
control. Br J Audiol. 1998;32(3):197-204. efficacy and safety of neramexane in
PMID:9710337 patients with moderate to severe subjective
tinnitus. BMC Ear Nose Throat Disord.
111. Westerberg BD, Roberson JB, Jr., Stach BA.
2011;11(1):
A double-blind placebo-controlled trial of
baclofen in the treatment of tinnitus. Am J 121. Dehkordi MA, Abolbashari S, Taheri R, et
Otol. 1996;17(6):896-903. PMID:8915419 al. Efficacy of gabapentin on subjective
idiopathic tinnitus: A randomized, double-
112. Westin VZ, Schulin M, Hesser H, et al.
blind, placebo-controlled trial. Ear Nose
Acceptance and commitment therapy versus
Throat J. 2011;90(4):
tinnitus retraining therapy in the treatment of
tinnitus: A randomised controlled trial. 122. Jakes SC, Hallam RS, McKenna L, et al.
Behav Res Ther. 2011;49(11):737-47. Group cognitive therapy for medical
PMID:21864830 patients: An application to tinnitus. Cognit
Ther Res. 1992;Vol16, pp67-82, 1992:67-
113. Zachriat C, Kroner-Herwig B. Treating
82.
chronic tinnitus: Comparison of cognitive-
behavioural and habituation-based
treatments. Cognit Behav Ther.
2004;33(4):187-98. PMID:15625793
E-40
123. Herraiz C, Diges I, Cobo P, et al. Auditory 133. Roland NJ, Hughes JB, Daley MB, et al.
discrimination training for tinnitus Electromagnetic stimulation as a treatment
treatment: The effect of different paradigms. of tinnitus: A pilot study. Clin Otolaryngol
Eur Arch Otorhinolaryngol. Allied Sci. 1993;18(4):278-81.
2010;267(7):1067-74. PMID:20044759 PMID:8877185
124. Olzowy B, Canis M, Hempel JM, et al. 134. Khedr EM, Rothwell JC, Ahmed MA, et al.
Effect of atorvastatin on progression of Effect of daily repetitive transcranial
sensorineural hearing loss and tinnitus in the magnetic stimulation for treatment of
elderly: Results of a prospective, tinnitus: Comparison of different stimulus
randomized, double-blind clinical trial. Otol frequencies. J Neurol Neurosurg Psychiatry.
Neurotol. 2007;28(4):455-8. 2008;79(2):212-5. PMID:18202212
PMID:17529847
135. Podoshin L, Ben-David Y, Fradis M, et al.
125. Searchfield GD, Kaur M, Martin WH. Idiopathic subjective tinnitus treated by
Hearing aids as an adjunct to counseling: biofeedback, acupuncture and drug therapy.
Tinnitus patients who choose amplification Ear Nose Throat J. 1991;70(5):284-9.
do better than those that don’t. Int J Audiol. PMID:1914952
2010;49(8):574-9. PMID:20500032
136. Loke YK, Price D, Herxheimer A.
126. Mason JD, Rogerson DR, Butler JD. Client Systematic reviews of adverse effects:
centred hypnotherapy in the management of Framework for a structured approach. BMC
tinnitus--Is it better than counselling? J Med Res Methodol. 2007;7:32.
Laryngol Otol. 1996;110(2):117-20. PM:17615054
PMID:8729491
137. Montori VM, Guyatt GH. Intention-to-treat
127. Pandey S, Mahato NK, Navale R. Role of principle. CMAJ. 2001;165(10):1339-41.
self-induced sound therapy: Bhramari PM:11760981
Pranayama in Tinnitus. Audiol Med.
138. Klockhoff I, Lindblom U. Meniere’s disease
2010;8(3):137-41.
and hydrochlorothiazide (Dichlotride)--A
128. Erlandsson SI, Rubinstein B, Carlsson SG. critical analysis of symptoms and
Tinnitus: Evaluation of biofeedback and therapeutic effects. Acta Otolaryngol.
stomatognathic treatment. Br J Audiol. 1967;63(4):347-65. PMID:6033658
1991;25(3):151-61. PMID:1873582
139. Geyh S, Cieza A, Schouten J, et al. ICF Core
129. Bonaconsa A, Mazzoli MM, Antonia M, et Sets for stroke. J Rehabil Med. 2004;(44
al. Posturography measures and efficacy of Suppl):135-41. PM:15370761
different physical treatments in somatic
140. Meng Z, Liu S, Zheng Y, et al. Repetitive
tinnitus. Int Tinnitus J. 2010;16(1):44-50.
transcranial magnetic stimulation for
PMID:21609913
tinnitus. Cochrane Database Syst Rev.
130. Neri G, Baffa C, De SA, et al. Management 2011;(10):CD007946 PMID:21975776
of tinnitus: Oral treatment with melatonin
141. Savage J, Waddell A. Tinnitus. Clinical
and sulodexide. Journal of Biological
Evidence. 2012;2012,2012 PMID:22331367
Regulators & Homeostatic Agents.
2009;23(2):103-10. PMID:19589291 142. Hoare DJ, Kowalkowski VL, Kang S, et al.
Systematic review and meta-analyses of
131. Lindberg P, Scott B, Melin L, et al. The
randomized controlled trials examining
psychological treatment of tinnitus: An
tinnitus management. Laryngoscope.
experimental evaluation. Behav Res Ther.
2011;121(7):1555-64. PMID:21671234
1989;27(6):593-603. PMID:2692553
143. Hesser H, Weise C, Westin VZ, et al. A
132. Gungor A, Dogru S, Cincik H, et al.
systematic review and meta-analysis of
Effectiveness of transmeatal low power laser
randomized controlled trials of cognitive-
irradiation for chronic tinnitus. J Laryngol
behavioral therapy for tinnitus distress.
Otol. 2008;122(5):447-51. PMID:17625032
Clinical Psychology Review.
2011;31(4):545-53. PMID:21237544
E-41
144. Kochkin S, Tyler R, Born J. MarkeTrak 147. Karkos PD, Leong SC, Arya AK, et al.
VIII: The prevalence of tinnitus in the ‘Complementary ENT’: A systematic review
United States and the self-reported efficacy of commonly used supplements. J Laryngol
of various treatments. Hear Rev. Otol. 2007;121(8):779-82. PMID:17125579
2011;18(12):10-27.
148. Hilton, Malcolm P, Stuart, et al. Ginkgo
145. Nondahl DM, Cruickshanks KJ, Huang GH, biloba for tinnitus. Cochrane Database Syst
et al. Generational differences in the Rev. 2010;(3):
reporting of tinnitus. Ear Hear.
149. Baldo, Paolo, Doree, et al. Antidepressants
2012;33(5):640-4. PM:22588269
for patients with tinnitus. Cochrane
146. Hoekstra CE, Rynja SP, van Zanten GA, et Database Syst Rev. 2009;(1):
al. Anticonvulsants for tinnitus. Cochrane
150. Ioannidis JPA, Evans SJW, Gotzsche PC, et
Database Syst Rev. 2011;(7):CD007960.
al. Better reporting of harms in randomized
PMID:21735419
trials: An extension of the CONSORT
statement. Ann Intern Med.
2004;141(10):781-8.
E-42
Appendix F. List of Ongoing Clinical Trials Evaluating
Interventions To Treat Idiopathic Tinnitus Registered
in Clinicaltrials.gov
F-1
Table F2. Ongoing clinical trials evaluating medical surgical interventions using rTMS or vagal
nerve stimulation
Med/Surg Study Title Intervention Sponsor
Intervention (NCT number)
Category Completion date
Device: Effect of rTMS on Resting State Device: Repetitive University of Arkansas; National
Repetitive Brain Activity in Tinnitus Transcranial Magnetic Institutes of Health (NIH)
Transcranial (NCT00926237) Stimulation (rTMS) -
Magnetic ACTIVE; Device: Repetitive March 2016
Stimulation Transcranial Magnetic
(rTMS) - Stimulation (rTMS) - SHAM
ACTIVE;
Device:
Repetitive
Transcranial
Magnetic
Stimulation
(rTMS) -
SHAM
Device: Transcranial Magnetic Device: repetitive Department of Veterans Affairs
repetitive Stimulation for Tinnitus transcranial magnetic
transcranial (NCT01104207) stimulation (rTMS); Device: December 2014
magnetic placebo rTMS
stimulation
(rTMS);
Device:
placebo rTMS
Device: rTMS Bimodal Treatment For Device: Bimodal Repetitive Washington University School of
Bimodal Tinnitus: A Pilot Study Transcranial Magnetic Medicine
Repetitive (NCT01590264) Stimulation
Transcranial November 2012
Magnetic
Stimulation
Device: Repetitive Transcranial Device: Repetitive Singapore General Hospital
Repetitive Magnetic Stimulation for Transcranial Magnetic
Transcranial Tinnitus Treatment Stimulation (rTMS) August 2013
Magnetic (NCT01093872)
Stimulation
(rTMS)
Device: tVNS- The Treatment of Tinnitus With Device: tVNS-Device cerbomed GmbH
Device Transcutaneous Non-invasive
Vagus Nerve Stimulation July 2012
(NCT01176734)
Device: vagus
nerve
stimulation
(VNS)
Device: rTMS Repetitive Transcranial Device: Medial Frontal rTMS University of Regensburg
Magnetic Stimulation With Double-Cone-Coil; Device:
Double Cone Coil in Chronic Left DLPFC Butterfly Coil December 2013
Tinnitus (Ti-CDC)
(NCT01663311)
Device: Low rTMS for the Treatment of Device: Magventure Mag University of Regensburg
frequency Chronic Tinnitus: Optimization Pro Option
rTMS by Simulation of the Cortical March 2014
Tinnitus Network (Triple)
(NCT01663324)
F-2
Table F3. Ongoing clinical trials evaluating psychological/behavioral interventions
Psych/Beh Study Title Intervention Sponsor
Intervention (NCT number)
Completion date
CBT/CBT Cognitive Behavioral Therapy CBT/Education Department of Veterans Affairs; Yale
combination (CBT) for Tinnitus Training/Usual Care University
(NCT00724152)
January 2013
Treatment of Chronic Behavioral: Cognitive Washington University School of
Bothersome Tinnitus Using Training; Drug: placebo Medicine
Cognitive Training and D-
cycloserine June 2012
(NCT01550796)
Other psych/ Cognitive Training for Brain Fitness Program - Washington University School of
behavioral Firefighters With Tinnitus Tinnitus Medicine; Federal Emergency
(NCT01458821) Management Agency
October 2013
Mindfulness Based Tinnitus Mindfulness Based Tinnitus University of California, San
Reduction (MBTR): A Symptom Reduction/Treatment as Francisco
Perception Shift Program Usual
(NCT01229709) January 2015
Multi-Site Evaluation of Progressive Tinnitus Department of Veterans Affairs
Progressive Tinnitus Management/Treatment as
Management Usual June 2013
(NCT01015781)
Telephone Tinnitus Education Telephone Tinnitus Department of Veterans Affairs
for Patients With Traumatic Education/Wait List Control
Brain Injury (TBI) September 2014
(NCT01129141)
Neuro-Music Therapy for Neuro-Music Therapy German Center for Music Therapy
Recent Onset Tinnitus: immediately/after waiting Research; University Hospital for
Evaluation of a Therapy time/Music-therapeutical Ear, Nose, and Throat, University of
Concept stress management Heidelberg, Germany; Clinic of
(NCT01566708) coaching Diagnostic and Interventional
Neuroradiology, Saarland University
Clinic, Homburg, Germany
July 2013
New Therapy for Patients With Other: Sound Based and Duke University; National Institutes
Severe Tinnitus Educational (SBE) of Health (NIH); National Institute on
(NCT01480193) Therapies; Other: Deafness and Other Communication
Integrated Medicine Disorders (NIDCD)
Therapies and Sound
Based Education October 2013
Therapies; Other:
Integrated Medicine
Therapies and SBE
Abbreviations: CBT = cognitive behavioural therapy
F-3
Table F4. Ongoing clinical trials evaluating sensory modulation or other devices
Devices Study Title Intervention Sponsor
Category (NCT number)
Completion date
Coventional/ Tinnitus Retraining Therapy Coventional/Placebo Sound Johns Hopkins Bloomberg School of
Placebo Sound Trial Generator (SG) Public Health; National Institute on
Generator (NCT01177137) Deafness and Other Communication
Disorders (NIDCD); University of
Alabama, Tuscaloosa; David Grant
U.S. Air Force Medical Center;
Wilford Hall Medical Center; United
States Naval Medical Center, San
Diego; United States Naval Medical
Center, Portsmouth; National Naval
Medical Center; Naval Hospital Camp
Pendleton
February 2015
Device: CR Evaluation of the CR Device: CR Nottingham University Hospitals NHS
Neuromodulation Neuromodulation Treatment for Neuromodulation Trust; University of Nottingham;
Tinnitus University College, London
(NCT01541969)
November 2013
Device: Transcranial Direct Current Device: BrainSTIM Centre Hospitalier Universitaire
BrainSTIM Stimulation (tDCS) for the Transcranial Stimulator Vaudois
Transcranial Treatment of Tinnitus
Stimulator (NCT01575496) January 2015
The Inhibitor™ Inhibitor Masking Device & Medical College of Wisconsin
The Inhibitor™ Tinnitus
Tinnitus SCN9 Gene Expression
Masking Device
Masking Device (NCT01412918) December 2016
Device: P-Stim Somatosensory Based Massachusetts Eye and Ear Infirmary
Treatments for Tinnitus Device: P-Stim
(NCT01066273) December 2015 - Withdrawn
Device: ANM Acoustic Coordinated Reset ANM Adaptive Neuromodulation
T30 CR®- (CR®) Neuromodulation for the GmbH; Ceres GmbH evaluation &
Device: ANM T30 CR®-
System Treatment of Chronic Tonal research
System
Tinnitus (“RESET Real Life”)
(NCT01435317) July 2013
Device: Customized Acoustic University of California, Irvine
Customized Stimulation for the Treatment of Device: Customized sound;
sound; Regular Tinnitus Device: Regular masker July 2012: this study is still recruiting
masker (NCT01487447) participants
Device: Efficacy of Internet and
Device: modified TRT using Seoul National University Hospital;
Smartphone and Smartphone Application-
smartphone and web based Soonchunhyang University Hospital
web based TRT delivered Tinnitus Retraining
materials; Drug: Gingko
Therapy
biloba December 2013
(NCT01663467)
Abbreviations: PSTIM = pulse stimulation treatment; TRT = Tinnitus Retraining Therapy
F-4