The British Journal of Psychiatry (2018)

212, 333–338. doi: 10.1192/bjp.2018.49

Review article

Enduring effects of psychological

treatments for anxiety disorders: meta-
analysis of follow-up studies
Borwin Bandelow, Anne Sagebiel, Michael Belz, Yvonne Görlich, Sophie Michaelis and Dirk Wedekind

Background significant difference when compared with psychotherapy.

It is a widespread opinion that after treatment with psychother- Patients in the placebo group did not deteriorate during follow-
apy, patients with anxiety disorders maintain their gains beyond up, but showed significantly worse outcomes than patients in
the active treatment period, whereas patients treated with cognitive–behavioural therapy.
medication soon experience a relapse after treatment termination.
Conclusions
Aims Not only psychotherapy, but also medications and, to a lesser
We aimed to provide evidence on whether enduring effects of extent, placebo conditions have enduring effects. Long-lasting
psychotherapy differ from control groups. treatment effects observed in the follow-up period may be
superimposed by effects of spontaneous remission or regres-
Method sion to the mean.
We searched 93 randomised controlled studies with 152 study
arms of psychological treatment (cognitive–behavioural therapy Declaration of interest
or other psychotherapies) for panic disorder, generalised anxiety In the past 12 months and in the near future, Dr Bandelow has
disorder and social anxiety disorder that included follow-up been/will be on the speakers/advisory board for Hexal,
assessments. In a meta-analysis, pre-post effect sizes for end- Mundipharma, Lilly, Lundbeck, Pfizer and Servier. Dr Wedekind
point and all follow-up periods were calculated and compared was on the speakers’ board of AstraZeneca, Essex Pharma,
with control groups (medication: n = 16 study arms; pill and Lundbeck and Servier. All other authors have nothing to declare.
psychological placebo groups: n = 17 study arms).
Keywords
Results Anxiety disorders; psychotherapy; drugs; follow-up;
Gains with psychotherapy were maintained for up to 24 months. meta-analysis.
For cognitive–behavioural therapy, we observed a significant
improvement over time. However, patients in the medication Copyright and usage
group remained stable during the treatment-free period, with no © The Royal College of Psychiatrists 2018.

According to treatment guidelines,1–3 psychological therapies and as to whether it is an oversimplification to assume that the differ-
psychopharmacological drugs have shown efficacy for the treatment ences in relapse rates between drug treatment and psychotherapy
of the three major anxiety disorders: panic disorder with or without are substantial. In naturalistic studies following up patients with
agoraphobia (PDA), generalised anxiety disorder (GAD) and social anxiety, considerable relapse rates were found years after CBT treat-
anxiety disorder (SAD). Among psychotherapies, cognitive–behav- ment. For example, in an analysis of 8 controlled studies of CBT
ioural therapy (CBT) is the method studied most, but some trials for anxiety disorders, 48% of patients were still symptomatic after
have also investigated applied relaxation, psychodynamic therapy, 2–14 years of follow-up.7 On the other hand, in relapse prevention
interpersonal therapy, mindfulness meditation and therapies con- studies1,8 in which treatment responders to open drug treat-
ducted via the internet. Medications used for anxiety disorders ment for 8–12 weeks were re-randomised to long-term treatment
include selective serotonin reuptake inhibitors, serotonin–nor- (24–52 months) with the same drug or placebo, the relapse rates
adrenaline reuptake inhibitors, pregabalin, tricyclic antidepressants, of patients randomised to placebo ranged from 8 to 56%.
benzodiazepines and others.1 Available follow-up studies directly comparing the durability of
In a recent meta-analysis of 234 acute treatment studies for CBT with drug therapy did not show clearly longer-lasting effects of
anxiety disorders involving 37 333 patients, we had shown that CBT: in only one9 of one studies of PDA, a longer-lasting effect of
medications were associated with significantly higher average pre- CBT could be demonstrated.10–13 Likewise, in SAD, only two14,15
post effect sizes (Cohen’s d = 2.02) than psychotherapies (Cohen’s of four studies have shown longer-lasting effects for CBT than for
d = 1.22).4 We did not find evidence that this result was influenced medication, whereas two did not.16,17
by heterogeneity, publication bias or allegiance effects.

Lack of controlled follow-up studies

Enduring effects There is a lack of controlled follow-up studies for psychotherapy, as
It is a common opinion that patients treated with drugs show imme- 70–75% randomised controlled studies for anxiety disorders use a
diate relapse after stopping medication, whereas gains of psycho- waitlist as a control condition during the acute treatment period.4,18
logical therapies are maintained for months or years after For follow-up assessments, the waitlist patients cannot be used
treatment termination. This would offer psychological therapies anymore as a control group because they are assigned to active treat-
considerable advantage over drug treatment, and in some guidelines ment after their waiting period. When no deterioration is observed
(e.g. the UK National Institute for Health and Care Excellence guide- during follow-up after treatment discontinuation, we have to disen-
lines5,6), CBT is preferred over medication because of the assumed tangle whether this is attributable to a true enduring effect of the treat-
longer duration of effect. However, there have always been doubts ment or simply to spontaneous remission or regression to the mean.

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 Bandelow et al

To our knowledge, no previous meta-analysis has studied For every follow-up week, we pooled all available studies for the
whether psychological therapies have longer-lasting effects than three anxiety disorders for this time point. We only included studies
control conditions. Therefore, we used studies involving a drug with up to 24 months duration, as there was only one evaluable
treatment arm and studies using a pill placebo or a psychological study with one CBT arm using a longer follow-up period
(attention) placebo as a control to see if there was a significantly (36 months), and no further eligible studies with longer follow-up
larger decline of effect size after termination of drug treatment com- intervals.
pared with psychological therapies. A ‘psychological placebo’ is
defined as conversation of the same length as a psychotherapy
session, in which study staff who do not necessarily have psycho- Meta-analytical procedure
therapeutic training establish a supportive, listening and nondirec- Outcome measures
tive relationship without applying specific techniques. Three reviewers (B.B., Y.G., and A.S.) independently extracted all
The meta-analytic procedure has the advantage that all of the data. Any discrepancy was resolved by consensus. To limit hetero-
many available follow-up studies can be included in the analysis geneity and to achieve maximum comparability, we preferably used
and not only the few head-to-head comparisons of psychotherapy the most commonly applied scales: the Hamilton Rating Scale for
and drug or placebo conditions. Anxiety21 for PDA and GAD and the Liebowitz Social Anxiety
Scale22 for SAD. If these were not available for the follow-up time
points, we chose other scales following an algorithm described in
Method
Bandelow et al.4
Effect sizes (Cohen’s d) were calculated from the differences
Selection of studies between baseline and end-point or follow-up time point by sub-
The present study extends a comprehensive meta-analysis on effi- tracting the post-treatment mean from the pre-treatment mean
cacy of treatments for anxiety disorders in short-term studies to and dividing the difference by the pre-treatment s.d. of the
follow-up studies.4 measure.23 If there was more than two treatment groups in a
Randomised treatment studies from 1980 to 2016 for PDA, study, a pooled baseline s.d. based on all treatment arms in the
GAD and SAD were found by electronic and hand search. Study study was used.
quality was assessed with the Scottish Intercollegiate Guidelines Whenever available, intention-to-treat data were used. Where a
Network statement.19 Reasons for exclusion were missing informa- study only reported data from dichotomous outcomes (the propor-
tion making it impossible to compute effect sizes, a sample size of tion of responders to treatment, e.g. defined by a 50% reduction on
any of the treatment arms at inclusion less than ten, reports that the Hamilton Anxiety Scale), it was assumed that participants who
were restricted to subsamples (e.g. only elderly patients) and ceased to engage in the study from whatever group had an unfavour-
studies that included children and/or adolescents. We did not able outcome. Odds ratios were transformed to Cohen’s d.24
include open studies because these may have been influenced by We calculated the effect sizes for all three anxiety disorders
expectation effects. Drugs were included that had been shown to together, as effect size did not differ significantly between the differ-
be effective in randomised controlled studies and are licensed in ent disorders in our first study.4
at least some countries for the treatment of anxiety disorders.1
Psychological therapies were categorised as follows: ‘CBT’ included
individual or group CBT or exposure techniques or a combination Analysis
of both, as well as CBT treatments conducted via the internet; ‘other Meta-analyses were done by Comprehensive Meta-Analysis
psychotherapies’ comprised psychodynamic therapy (n = 5), inter- Version 3.0 (Biostat, USA). IBM SPSS Statistics 24 was used to
personal therapy (n = 2), relaxation (n = 16), mindfulness therapy conduct further analyses. Because most studies differed consider-
(n = 2) and bibliotherapy (n = 7). Drugs used in the studies were ably in scheduling follow-up assessments, including intervals
alprazolam, citalopram, clomipramine, fluoxetine, fluvoxamine, between 4 and 104 weeks (see online Table DS2 for an overview),
imipramine, lorazepam, moclobemide, paroxetine, phenelzine and we interpolated missing data linearly between the nearest empirical
sertraline. Control conditions included pill placebo (n = 7 studies) follow-up assessments by calculating the mean of the available
and ‘psychological placebo’ (n = 8), and a combination of both follow-up scores before and after the interpolated follow-up time
(n = 2). None of the included control conditions involved treatment point. If no further follow-up scores were available, we used the
as usual. Because of the small sample sizes in the different placebo last-observation-carried-forward (LOCF) method. We preferred
groups, we did not analyse the placebo conditions separately. In this combined model, as solely using the LOCF method can lead
the psychological placebo studies, the number and length of the ses- to an inappropriate bias.25 We chose a general linear model for
sions were the same as in the experimental conditions, except in two repeated measures, as this fits best to analyse the variance
studies, in which patients in the psychological placebo condition for within-subject measurements (follow-up assessments) and for
had fewer sessions than the psychotherapy group. between-subject factors (treatments) within the same model.
From the original database of 234 eligible studies used in the Follow-up effect sizes were added as 13-stage within-subject factor,
meta-analysis, 91 studies with 180 study arms were chosen that also including the interpolated and LOCF scores. Treatment arms
had investigated psychological therapies, medications or a psycho- were included as a four-stage between-subject factor. For multiple
logical placebo and had included at least one follow-up assessment. comparisons, P values were corrected by the Bonferroni method (sig-
In addition, two new follow-up studies that appeared since nificance was set at P < 0.05, two-tailed).
1 October 2013 were added.15,20 Heterogeneity was assessed with the Q statistic and the I2 metric
A total of 93 studies with 185 study arms were included in the with 95% confidence intervals.26 Because moderate (I2 > 50%) to
analysis (CBT, n = 120 study arms; other psychotherapies, n = 32 high (I2 > 75%) heterogeneity27 was found for most comparisons
study arms; medications, n = 16 study arms and placebo conditions, (online Table DS2), the random effects model in which studies
n = 17 study arms). The selection of studies is displayed in a are weighted based on the inverse variances and an additional vari-
Preferred Reporting Items for Systematic Reviews and Meta- ance component reflecting the observed heterogeneity was applied
Analyses statement (Fig. 1). All studies are listed in online in all analyses. In general, including a random effect will lead to
Table DS3. more conservative results than the fixed effects model.

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 Enduring effects of psychological treatments for anxiety disorders

Time span: 1980–2013 (Database closed: 10 June 2017)

Identification

1031 records identified in PUB MED

Search algorithm: (((”panic disorder”[Title]) OR (”agoraphobia”[Title])) OR (”generalized anxiety disorder”[Title]) OR ((”social anxiety disorder “[Title])
OR (”social phobics”[Title]) OR (”social phobia”[Title]))) AND (”randomized”[All fields]) AND (”treatment”[All fields]). No language restrictions

768 records identified in Web of Science

Search algorithm: Title=((panic disorder OR agoraphobia) OR (generalized anxiety disorder) OR (social anxiety disorder) OR (social phobics) OR
(social phobia)) AND Topic=(randomized) AND ((therapy) OR (treatment))

Total: 1799 records

1420 records after duplicates removed 1175 eliminated; reasons: meeting abstract; no full-text available;
Screening

Screened by title and abstract letter; review; meta-analysis; pooled study; double publication;
secondary analyses; open study; naturalistic; case reports; case
series; no randomisation; drug/herbal preparation not licensed;
no DSM/ICD anxiety disorder diagnosis/patients with more than
one anxiety disorder/comorbid patients; treatment of subgroups
(e.g., only students; only elderly patients; children/adolescents
<18 etc.); treatment of non-responders/adjunctive treatment of non-
responders/augmentation/drug combination treatments; long-term;
maintenance; relapse prevention studies; sample size of any of the
arms in a study of <10 at baseline
Eligibility

245 full-text articles assessed for 30 eliminated after reading full-text; reasons: double publication
eligibility (4); scores necessary to calculate effect sizes not presented (8);
data only presented as a graph (6); only subgroups analysed (3);
n<10 at baseline in one of the study arms (2); no adequate control
group (2); methodological flaws (5)
Included

215 records included

234 studies published in 232 papers 26 additional records indentified through seven eliminated; reasons: scores necessary to
included in qualitative synthesis hand search calculate effect sizes not presented (three); data
only presented as a graph (one); methodological
flaws (three)

91 papers with follow-up assessments two studies added that appeared after
extracted original meta-analysis

93 studies included

Fig. 1 Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.28

The analysis of publication bias has been described in a previous The general linear model for repeated measures showed a sig-
publication.4 Possible allegiance effects for all study arms were ana- nificant difference between the four treatment arms (F(3, 181) =
lysed by two independent raters and were assumed when a medica- 3.268; P = 0.023; see Fig. 2). However, post hoc analyses revealed
tion study was sponsored by the current manufacturer of the that only the difference between CBT and placebo was significant
investigated drug, when authors disclosed financial support from (P = 0.021). The medication arms did not differ significantly from
the manufacturer or when one of the authors was a staff member the CBT and other psychotherapies arms, demonstrating that
of the manufacturer. For psychological treatments, allegiance patients who stopped taking a drug showed the same durable
effects were assumed when authors had developed the treatment, improvement as patients who stopped psychotherapy.
contributed to an aetiological model or published manuals for the Substantial heterogeneity was found in all three conditions, with
treatment. moderate to high I2 values (online Table DS2), indicating that the
distribution did not estimate a common population mean. For 40
(26.3%) of the psychotherapy arms and 5 (31.1%) of the drug
arms, allegiance effects were assumed.
Results

After termination of treatment, we observed no significant deterior-

ation in any of the four conditions during the follow-up period (all
Bonferroni-corrected pairwise comparisons were not significant; see Discussion
Fig. 2) (Table 1 and Fig. 2). Raw scores for Cohen’s d for all studies at
the different follow-up time points are shown in online Table DS2. In the present meta-analysis, we could demonstrate that patients
Post hoc analyses revealed that patients in the CBT group even treated with psychological therapies (CBT and other psychothera-
showed a significant improvement over time for all follow-ups from pies) maintained their gains for up to 2 years after treatment was
26 weeks onwards (P-value between 0.05 and 0.003), as measured stopped. In the CBT group, patients even improved relative to
from end-point. However, this improvement was moderate. their values at treatment termination.

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 Bandelow et al

1.8

1.6
Effect size (Cohen's d)

1.4

1.2

0.8

0.6
Placebo

0.4 CBT

Other psychotherapy
0.2
Drugs

0
0 468 13 16 26 35 39 52 65 78 104
FU week

Fig. 2 Outcome during follow-up period. Error bars indicate 95% CI.
CBT, cognitive–behavioural therapy; FU, follow-up.

The enduring effect of drug treatment was not significantly patients take their medication only for some months and stop the
smaller than the one obtained with psychotherapy. Our study drug soon after remission has occurred, although guidelines recom-
casts doubt on the widespread assumption that only psychological mend a treatment duration of 121 or 62 months after remission.
treatments have enduring effects and gains achieved with medica- Also, the effect sizes in the placebo conditions did not show a
tions are lost soon after they are stopped. However, the good significant decline during the follow-up period. However, in con-
news for patients with anxiety disorders is that the chance of deteri- trast to the other psychotherapies, CBT showed significantly
oration within 2 years after treatment termination is low, and inde- higher effect sizes than the placebo arms, which may have been a
pendent from previous treatment. result of the large number of study arms in this condition. No dif-
We know from relapse prevention studies that drugs may have ferences were found between CBT and the other psychotherapies;
long-lasting effects. These enduring effects may have a neurobio- however, as the latter group comprised various forms of psychother-
logical background. For example, serotonergic drugs may exert sus- apy, no conclusions can be drawn from this finding.
taining effects on serotonin neurotransmitter systems in the brain, Our results will have to be reconciled with relapse prevention
which last longer than the actual treatment period. However, expect- drug studies, which mostly show some deterioration in the drug
ancy effects may also take effect, as patients who have experienced arm and a significantly greater deterioration in the placebo arms.
improvement with a drug know that they can restart the drug at Also, psychotherapy is associated with substantial relapse rates, as
any time in case a relapse occurs. Many patients with anxiety disor- has been shown in naturalistic studies. The most probable explan-
ders have concerns that they ‘will have to take the drug forever’, once ation for this lack of deterioration during the treatment-free
a medication has been started. In clinical practice, however, many period in our meta-analysis is that the long-lasting effects seen in

Table 1 Pre-post effect sizes effect sizes during follow-up period (Cohen’s d).

Treatment Other
All Psychological Psychotherapies Psychological or pill
therapies (n = 152) CBT (n = 120) (n = 32) Medication (n = 16) placebo (n = 17)
d 95% CI d 95% CI d 95% CI d 95% CI d 95% CI
End-point 1.362 1.247–1.477 1.370 1.242–1.499 1.332 1.076–1.587 1.379 0.994–1.764 0.885 0.566–1.204
Follow-up
4 weeks 1.397 1.285–1.509 1.404 1.280–1.528 1.371 1.115–1.627 1.321 0.983–1.659 0.908 0.601–1.215
6 weeks 1.406 1.296–1.516 1.412 1.290–1.534 1.384 1.126–1.642 1.292 0.972–1.612 0.914 0.607–1.220
8 weeks 1.415 1·306–1.524 1.421 1.300–1.541 1.397 1.136–1.657 1.263 0.957–1.569 0.917 0.609–1.224
13 weeks 1.439 1.331–1.547 1.442 1.324–1.559 1.430 1.163–1.697 1.220 0.946–1.494 0.946 0.633–1.258
16 weeks 1.450 1.341–1.559 1.453 1.335–1.570 1.439 1.171–1.707 1.215 0.939–1.491 0.954 0.634–1.274
26 weeks 1.485 1.374–1.596 1.489 1.368–1.610 1.468 1.194–1.743 1.199 0.897–1.501 0.982 0.626–1.338
35 weeks 1.501 1.389–1.613 1.508 1.385–1.630 1.476 1.203–1.749 1.195 0.902–1.489 0.989 0.634–1.344
39 weeks 1.508 1.395–1.621 1.515 1.392–1.638 1.480 1.208–1.753 1.194 0.903–1.485 0.992 0.638–1.347
52 weeks 1.527 1.413–1.641 1.536 1.410–1.662 1.492 1.219–1.764 1.197 0.907–1.487 0.993 0.641–1.346
65 weeks 1.528 1.418–1.648 1.543 1.416–1.669 1.497 1.222–1.771 1.211 0.921–1.501 0.989 0.641–1.337
78 weeks 1.539 1.423–1.655 1.549 1.422–1.676 1.502 1.224–1.779 1.219 0.926–1.512 0.982 0.637–1.327
104 weeks 1.544 1.427–1.661 1.555 1.427–1.683 1.501 1.224–1.779 1.234 0.933–1.535 0.966 0.625–1.308
CBT, cognitive–behavioural therapy; d, Cohen’s d; n = number of study arms.
Missing values were interpolated.

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 Enduring effects of psychological treatments for anxiety disorders

all four conditions may be superimposed by effects of spontaneous

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