VISIT…

O A P L
OX F O R D A M E R I C A N P S YC H I AT RY L I B R A RY

ADHD
O A P L
OXF OR D AM ER I C AN P S YC H I AT RY L I BR ARY

ADHD
James J. McGough, M.D., M.S.
Professor of Clinical Psychiatry and Biobehavioral Sciences
David Geffen School of Medicine and
Semel Institute for Neuroscience and Human Behavior at UCLA

1
1
Oxford University Press is a department of the University of
Oxford. It furthers the University’s objective of excellence in research,
scholarship, and education by publishing worldwide.
Oxford New York
Auckland  Cape Town  Dar es Salaam  Hong Kong  Karachi
Kuala Lumpur Madrid Melbourne Mexico City Nairobi
New Delhi Shanghai Taipei Toronto
With offices in
Argentina Austria Brazil Chile Czech Republic France Greece
Guatemala Hungary Italy Japan Poland Portugal Singapore
South Korea Switzerland Thailand Turkey Ukraine Vietnam
Oxford is a registered trademark of Oxford University Press
in the UK and certain other countries.
Published in the United States of America by
Oxford University Press
98 Madison Avenue, New York, NY 006
© Oxford University Press 204
All rights reserved. No part of this publication may be reproduced, stored in
a retrieval system, or transmitted, in any form or by any means, without the prior
permission in writing of Oxford University Press, or as expressly permitted by law,
by license, or under terms agreed with the appropriate reproduction rights organization.
Inquiries concerning reproduction outside the scope of the above should be sent to the
Rights Department, Oxford University Press, at the address above.
You must not circulate this work in any other form
and you must impose this same condition on any acquirer.
Library of Congress Cataloging-in-Publication Data
McGough, James J., author.
ADHD / James J. McGough.
  p. ; cm.—(Oxford American psychiatry library)
Attention deficit hyperactivity disorder
Includes bibliographical references.
ISBN 978–0–9–996990–6 (alk. paper)
I.  Title.  II.  Title: Attention deficit hyperactivity disorder.  III.  Series: Oxford American
psychiatry library. [DNLM: .  Attention Deficit Disorder with Hyperactivity. WS 350.8.A8]
RC394.A85
66.85′89—dc23
204006486
This material is not intended to be, and should not be considered, a substitute for medical
or other professional advice. Treatment for the conditions described in this material is highly
dependent on the individual circumstances. And, while this material is designed to offer accu-
rate information with respect to the subject matter covered and to be current as of the time
it was written, research and knowledge about medical and health issues is constantly evolving
and dose schedules for medications are being revised continually, with new side effects
recognized and accounted for regularly. Readers must therefore always check the product
information and clinical procedures with the most up-to-date published product information
and data sheets provided by the manufacturers and the most recent codes of conduct and
safety regulation. The publisher and the authors make no representations or warranties to
readers, express or implied, as to the accuracy or completeness of this material. Without
limiting the foregoing, the publisher and the authors make no representations or warranties
as to the accuracy or efficacy of the drug dosages mentioned in the material. The authors and
the publisher do not accept, and expressly disclaim, any responsibility for any liability, loss or
risk that may be claimed or incurred as a consequence of the use and/or application of any
of the contents of this material.

9 8 7 6 5 4 3 2 
Printed in the United States of America
on acid-free paper
For Caitlin and Daniel
 Contents

Acknowledgments╇ix
Disclosure╇ xi

. Introduction 
2. Historical Perspectives 3
3. Epidemiology and Burden 9
4. Etiology and Neurobiology 7
5. Diagnostic Criteria 27
6. Assessment 35
7. Treatment Planning: Children and
Adolescents 47
8. Treatment Planning: Adults 57

vii
9. Basic Pharmacology 67
0. Clinical Medication Management 79
. Comorbidity 89
2. Medication Controversies 0
3. Complementary and Alternative Medicine
Therapies 

Index╇ 121
 Acknowledgments

I wish to express appreciation to my students and colleagues, Drs. Peter

Chung, Carl Fleisher, Roya Ijadi-Maghsoodi, Jessica Jeffrey, Sandra Loo, Smitta
Patel, Gregory Sayer, Benjamin Schneider, Thomas Spencer, Mark Stein, and
Timothy Wilens, who helped guide my writing and provided comments on
earlier versions of this manuscript.
J.M.

ix
 Disclosure

The author has served on advisory boards or as a consultant to Akili

Interactive, Merck & Co., Neurovance, Shionogi & Co., Sunovion
Pharmaceuticals, Targacept, and Theravance, and has received research
support from NeuroSigma Inc., Purdue Pharma, Shionogi Pharmaceuticals,
Supurnus Pharmaceuticals, and Shire Pharmaceuticals.
Any discussion of off-label medication use contained herein is identified as
such.

xi
O A P L
OX F O R D A M E R I C A N P S YC H I AT RY L I B R A RY

ADHD
Chapter 

Introduction
Key Points
• Attention-deficit/hyperactivity disorder (ADHD) is a well-validated
and commonly occurring brain-based disorder with significant life
consequences.
• The scientific basis supporting our understanding and management of
ADHD is of the strongest demonstrated among mental and behav-
ioral disorders.

Attention-deficit/hyperactivity disorder (ADHD) is a frequently occur-

ring, brain-based, neurodevelopmental disorder with substantial negative
consequences for individual and public health. Once viewed as a childhood

1
condition, it is now recognized that a majority of cases persist throughout
adolescence and adulthood. The lifelong impact of ADHD often extends
beyond the disorder’s defining features of developmentally inappropriate
levels of inattention and/or hyperactivity and impulsivity. Having ADHD
is associated with significant added risk for developing other mental health
disorders, as well as functional impairments, across a range of life domains.
These include educational attainment, social skills, occupational success, per-
sonal relationships, parenting, personal safety, and general health. Societal
economic burdens associated with ADHD are considerable. The National
Institute of Mental Health (NIMH) has described ADHD as a major public
health concern.
The high community prevalence of ADHD suggests that there are
affected patients in virtually every clinical practice in every medical spe-
cialty. Nonetheless, comprehensive education about ADHD is largely
limited to specialized programs in child and adolescent psychiatry and
behavioral pediatrics. Other clinicians, notably some in general pedi-
atrics and other primary care disciplines, gain ADHD expertise through
self-initiated learning and patient-driven experience. The standard in most
general psychiatry and pediatric residency programs is to cover the topic
with a limited number of lectures, with few opportunities for comprehen-
sive and continuous clinical experience.
Misinformation about ADHD abounds. Some assert that ADHD is not
real. Critics variably maintain that childhood inattention and hyperactivity are
normal, the diagnosis is subjective, behaviors attributed to ADHD arise when
ADHD parents and teachers fail to maintain appropriate discipline, older students
fake symptoms to obtain academic advantages or performance-enhancing
drugs, adults are similarly drug seeking or looking to excuse various life fail-
ures, or that the condition represents a conspiracy by pharmaceutical compa-
nies and organized psychiatry to increase medication sales.
ADHD, in fact, is among the most scientifically validated psychiatric dis-
orders.2 Its diagnostic reliability is well demonstrated and on par with many
conditions in general medicine. The biological underpinnings of ADHD are
as well demonstrated, or better demonstrated, as any other psychiatric dis-
order. Similarly, the accumulated evidence base for its clinical management is
of the strongest in mental health. Medications for ADHD have been used for
over 70 years in millions of patients annually, creating an indisputable record
of real-world safety and positive benefit. There are more double-blind,
placebo-controlled medication studies in ADHD than for any other child-
hood condition. Treatment effect sizes are double those typically seen with
more widely prescribed medications for depression and schizophrenia.
The development of clinical acumen for management of any medical con-
dition is best achieved with supervised experience and long-term contact with
large numbers of patients. These cannot be replaced by any book or series
of lectures. This text is an introduction to the basic and clinical sciences of
ADHD. It is organized to inform on phenomenology, neurobiology, assess-
ment, and approaches to treatment that provide the necessary background
2

for optimal patient management. While primarily intended for students, train-
ees, and early-career clinicians, relevant information is succinctly summarized
in key points, boxes, tables, and figures for the benefit of the inexperienced
and experienced alike. Key references and suggestions for further reading are
provided for those seeking additional information or greater understanding
of presented topics.

References
. Diagnosis and treatment of attention deficit hyperactivity disorder. NIH
Consensus Statement. 998;6:–37.
2. Goldman LS, Genel M, Bezman RJ, Slanetz PJ. Diagnosis and treatment of
attention-deficit/hyperactivity disorder in children and adolescents. Council on
Scientific Affairs, American Medical Association. JAMA. 998;279:00–07.
Chapter 2

Historical Perspectives
Key Points
• Clinical descriptions consistent with ADHD have existed for over
200 years.
• Terms used to describe what we recognize as ADHD evolved in
response to emerging science and changing conceptions about mental
and behavioral disorders.
• For most of its history, ADHD has been recognized as largely brain
based and biologically driven.

Descriptions of behaviors that we would now recognize as ADHD have

existed for at least 200 years (Fig. 2.). The names given to this syndrome

3
have changed, generally in response to evolving conceptions about etiology
and phenomenology but also in response to shifting cultural and political
approaches to understanding emotional and behavioral disorders (Table 2.).
One consistent theme throughout most of this history is the view that ADHD
is a biologically driven, brain-based disorder.

Pre-20th-Century Descriptions
The earliest known clinical description of what is now understood as ADHD
might be found in an 8th-century medical text authored by the German
physician Melchior Adam Weikard. Published no later than 775, Weikard’s
textbook Der Philosophische Arzt broke with prevailing opinion in suggesting
that disorders of emotion and behavior arose from medical and physiological
causes, not from astrological influences of the moon, stars, and planets. In his
chapter on attention problems, Weikard characterized patients with attention
deficits as “unwary, careless, and flighty.” Additionally, these patients were
jumpy, impulsive, highly distractible, and deficient in completing tasks. Much
of this anticipates ADHD symptoms described in the Diagnostic and Statistical
Manual of Mental Disorders, fourth edition (DSM-IV). Weikard speculated that
these behaviors were due to either dysregulation of cerebral fibers resulting
from overstimulation or a general lack of discipline early in childhood. He fur-
ther observed that attention problems appeared to decrease with age.
A second 8th-century reference published in 795 by the Scottish physi-
cian Sir Alexander Crichton described a syndrome characterized by abnormal
degrees of inattention and distractibility.2 These problems began early in life,
interfered with education, diminished with age, and were believed to result
ADHD
1957 Laufer 1994 DSM-IV
Hyperkinesis and Attention-deficit/Hyperactivity
17th Century Developmental Delay Disorder
Weikard and 1902 Still Monograph
Chrichton texts Defect in “Moral Control”
“dysregulated 2013 DSM-5
nerves” 1968 DSM-II Attention-deficit/
Minimal Brain Hyperkinetic Reaction of Hyperactivity Disorder
Dysfunction Childhood

Pre 1900 1900 1930 1960 1990 2010

1844 Heinrich Hoffman Minimal Brain

“Fidgety Phil” Damage 1987 DSM-III-R Attention Deficit
Hyperactivity Disorder
1939
Bradley introduces
stimulant treatment
1918
Postinfluenza
encephalitis 1980 DSM-III
Attention Deficit Disorder

Figure 2.  ADHD timeline.

4

Table 2.  Changing Terms That Describe ADHD

Time Period Classification Term Defining Features
920s–930s Minimal brain Behavior caused by
damage structural brain lesions
930s–940s Minimal brain Behavior caused
dysfunction by functional brain
impairment
950s Hyperkinesis/ Brain-based
hyperkinetic developmental delay
syndrome usually outgrown by
adolescence
960s DSM-II Hyperkinetic Behavioral reaction
reaction of to unsupportive
childhood environments
980s DSM-III Attention-deficit Symptoms of inattention,
disorder (ADD) impulsivity, hyperactivity.
Could be diagnosed with
(ADD/H) or without
(ADD/WO) hyperactivity
DSM-III-R Attention-deficit/ Minimum number of
hyperactivity combined inattentive,
disorder (ADHD) impulsive, hyperactive
symptoms
990s DSM-IV Attention-deficit/ Predominately inattentive,
hyperactivity hyperactive/impulsive,
disorder (ADHD) and combined subtypes
200s DSM-5 Attention-deficit/ Criteria more
hyperactivity developmentally sensitive
disorder (ADHD) for older patients.
from dysregulated “sensibility of the nerves.” Associated difficulties included

Historical Perspectives
unusual levels of impulsivity, restlessness, and emotional reactivity.
In 844 the German pediatrician Heinrich Hoffman published an illus-
trated storybook for children titled Struwelpeter, which contained a series of
stories and pictures originally created to amuse crying children during physi-
cal examinations. One of these, “Fidgety Phil,” depicted disruption at a fam-
ily’s dinner due to a boy’s restlessness and lack of attention. The parent’s
angry response to their son’s disruptions reflects family conflicts typically
seen with an ADHD-affected child. “Fidgety Phil” suggests that observant
clinicians have long recognized ADHD-like behaviors and related effects.2

Chapter 2
Early 20th Century: Defects of Moral
Control, Postencephalitic Behavior, and
Minimal Brain Disorder

The first modern medical description of what is probably ADHD is attributed

to the physician Sir George Frederick Still, regarded as the father of British
pediatrics. In a series of lectures in 902, Still discussed emotional and behav-
ioral disorders of childhood in terms of “an abnormal defect of moral control”
thought to reflect some level of physical brain damage.3 Still viewed “moral

5
control” as an intellectual capacity that restrained an individual’s actions in the
service of overall societal well-being. He described a group of children whose
difficulties with inattention and impulsivity occurred without any specific intel-
lectual or physical impairment. These children exhibited additional behaviors
commonly associated with ADHD, including emotional reactivity and rage
attacks, low frustration tolerance, and aggression. While some of these fea-
tures are also consistent with oppositional defiant disorder, conduct disorder,
or antisocial personality, the general consensus is that some cases had clear
ADHD. Still’s most significant contributions to our historical understanding
of ADHD were his emphasis on a child-specific category of mental illness
and the attribution of these behavioral difficulties to brain-based dysfunction.
Other early 20th-century events further contributed to an emerging view
that problems with inattention and impulse control resulted from physical brain
damage.2 The first was an observed correlation between perinatal events, such
as anoxia or birth defects, and subsequent behavioral and learning difficulties.
Secondly, problems with inattention, distractibility, and mood lability were seen
in soldiers who sustained head injuries during World War I, further illustrat-
ing the perceived link between brain injury and abnormal behavior. Additional
evidence was seen in children who survived the flu pandemic of 98 and
subsequently developed a postencephalitic behavioral syndrome typified by
inattention, poor motor control, moodiness, and restlessness. Building on
Still’s earlier work, these and other events contributed to an emerging view
in the 930s and 940s that deviant behavior resulted from subtle damage to
the brain. Children with long-standing and pervasive problems with attention
and behavior were increasingly seen as suffering from minimal brain damage.
ADHD Although early 20th-century scientific investigations failed to identify specific
areas of brain damage that led to inattention and overactivity, one research
effort led to the serendipitous discovery of the positive effects of stimulant
medications on hyperactive children. In the late 930s, Dr. Charles Bradley,
medical director of the Emma Pendleton Bradley Home in East Providence,
Rhode Island, identified a group of youth with “emotional problems” and
other learning and behavioral difficulties that were not explained by distinct
neurological disorders. In investigating these children, Bradley obtained pneu-
moencephalograms to assess possible structural brain lesions. Bradley believed
he could possibly reduce development of postprocedure headaches with
amphetamine (Benzedrine®) administration, which he felt might stimulate the
choroid plexus to replace lost cerebrospinal fluid. Amphetamine had a negli-
gible impact on headaches, but teachers in the hospital’s school observed strik-
ing behavioral improvements in some children. Bradley subsequently initiated a
prospective trial, and in 937 he reported significant behavioral and academic
improvements in a majority of the children given amphetamine treatment.4
One unfortunate consequence of this discovery was development of the mis-
taken belief that stimulants led to “paradoxical calming” in hyperactive chil-
dren. This idea was later proven false when research showed that stimulants
improved attention and motor restlessness in almost everyone. Bradley’s dis-
covery ultimately led to introduction in the 950s and 960s of other ADHD
stimulants, including methamphetamine (Desoxyn®), dextroamphetamine
6

(Dexedrine®), and the nonamphetamine methylphenidate (Ritalin®).

950s: Minimal Brain Dysfunction, Hyperkinesis,

and Developmental Delay
Emerging investigations in the 950s questioned whether all children with
abnormal behavior had underlying brain damage, even in the absence of
demonstrated neurological lesions. New views suggested that functional as
opposed to structural brain deficits caused behavioral difficulties, leading to a
redefinition of “minimal brain damage” as “minimal brain dysfunction (MBD).”2
The concept of MBD also proved unsatisfactory, as the category was too het-
erogeneous and likely to subsume a range of various behavioral, learning, and
language disorders. In 957, Laufer and Denhoff proposed that hyperactivity
was the defining characteristic of the syndrome and introduced terms such as
“hyperkinetic impulse disorder,” “hyperkinesis,” or a “hyperkinetic syndrome.”5
While still viewed as resulting from underlying brain pathology, the hyperkinetic
syndrome was conceptualized as a developmental delay generally outgrown
by adolescence. This remained the prevailing view well into the 990s when
evidence on the adult persistence of ADHD gained wide acceptance.

960s–970s: DSM-II Hyperkinetic Reaction of

Childhood
The original DSM was published in 952 to provide a common nomenclature
for psychiatric illness. The manual contained only one childhood diagnosis,
“adjustment reaction of childhood/adolescence.” A second edition (DSM-II),

Historical Perspectives
published in 968, described a categorical grouping “behavior disorders of
childhood-adolescence,” which included the diagnosis “hyperkinetic reaction of
childhood.” This disorder was characterized by a short attention span, restless-
ness, and hyperactivity. The clear implication was that these behaviors arose in
reaction to unsupportive social environments, particularly caused by inadequate
parenting or other parental conflict. This idea was consistent with prevailing
views of the time that attributed most psychopathology to early developmental
and social causes. This is the only period when ADHD behaviors were ascribed
more to environmental and social causes rather than biological ones.

Chapter 2
980s: DSM-III Attention-Deficit Disorder
and DSM-III-R Attention-Deficit/
Hyperactivity Disorder
The third edition of the DSM (DSM-III) was the first classification system devel-
oped on broad-based scientific evidence. A major goal of DSM-III was to improve
the reliability of psychiatric diagnoses, with an expectation that this would
enhance research and standardize approaches to treatment. Expert panels in
each diagnostic area proposed criteria that defined the various conditions. Some

7
experts in childhood psychopathology noted that problems with attention some-
times occurred independently from hyperactive and impulsive symptoms, and
they argued that the disorder is more a problem of inattention than hyperactivity.
The previously named “hyperkinetic reaction” was redefined as attention-deficit
disorder (ADD). Two subtypes were defined, that is, either with hyperactivity
(ADD/H) or without it (ADD/WO). DSM-III proposed separate symptom lists
for problems with inattention, impulsivity, and hyperactivity, and required some
symptoms from each group for a diagnosis of ADD/H or from inattention and
impulsivity only for those diagnosed with ADD/WO. In the 987 revision of
DSM-III (DSM-III-R), these symptoms were combined into a single set and diagno-
sis was determined by meeting a minimum number of total symptoms. DSM-III-R
also reemphasized problems with hyperactivity and renamed the condition
attention-deficit/hyperactivity disorder (ADHD). The name ADHD continues
today as the official designation of this syndrome, but it is the cause of endless
confusion when individuals lack hyperactive or impulsive symptoms.

990s: DSM-IV Attention-Deficit/Hyperactivity
Disorder
The fourth edition of the DSM (DSM-IV) was based in part on clinical field tri-
als of proposed diagnostic criteria that demonstrated that ADHD symptoms
appeared to separate into two domains, that is, inattentive and hyperactive/
impulsive. This led to creation of the predominately inattentive, predomi-
nately hyperactive/impulsive, and combined ADHD subtypes. The minimal
number of symptoms required for diagnosis was set at the 93rd percentile
of symptom counts among school-aged children, which approximated two
ADHD standard deviations above the mean for that group. Other DSM-IV criteria
established that ADHD symptoms and related impairments must have been
present by age 7, were evident in multiple settings, and were not better
explained by other psychiatric disorders.
DSM-IV ADHD criteria provided a basis for significant advances in phe-
nomenological and neurobiological research (see Chapter 4). Numerous
investigations based on DSM-IV demonstrated that the disorder is largely heri-
table with clear genetic underpinnings. Both structural and functional imaging
studies repeatedly revealed consistent differences between groups with and
without the disorder. Longitudinal and phenomenological studies increasingly
demonstrated that in a majority of cases ADHD persists into adulthood.

2st Century: DSM-5
The fifth edition of the DSM (DSM-5) made slight revisions to existing diag-
nostic criteria, primarily in response to an abundance of scientific findings (see
Chapter 5). The syndrome name remained unchanged. Symptom descrip-
tions were similarly unchanged, although clarifications were made to capture
developmental changes with increasing age. The age of onset criterion was
modified to require recognition of some symptoms prior to age 2, instead
of the age 7 requirement for onset of symptoms and impairment described
8

in DSM-IV. The number of symptoms necessary for diagnosis was reduced

for older individuals to improve the criteria’s developmental sensitivity. There
was clear recognition that ADHD frequently occurs in adults, and descrip-
tions of associated impairments were expanded to reflect more accurately
the problems and concerns of older patients. Slight modifications were made
to subtype definitions in favor of current symptom presentations. While the
biological basis of ADHD was increasingly appreciated, diagnosis of the dis-
order remained dependent on careful assessment of clinical symptoms.

References
. Barkley RA, Peters H. The earliest reference to ADHD in the medical literature?
Melchior Adam Weikard’s description in 775 of “attention deficit” (Mangel
der Aufmerksamkeit, Attentio Volubilis). J Atten Disord. 202;6:623–630.
2. Lang KW, Reichl S, Lange KM, Tucha L, Tucha O. The history of attention deficit
hyperactivity disorder. Atten Defic Hyperact Disord. 200;2:24–255.
3. Still GF. Some abnormal psychical conditions in children: the Goulstonian lec-
tures. Lancet. 902;:008–02.
4. Bradley C. The behavior of children receiving benzedrine. Am J Psychiatry.
937;94:577–585.
5. Laufer MW, Denhoff E. Hyperkinetic behavior syndrome in children. J Pediatr.
957:50:463–474.
Chapter 3

Epidemiology and Burden

Key Points
• Worldwide prevalence estimates for ADHD range from 3% to 0%
for school-age children and 4% to 5% for adults.
• ADHD is associated with increased lifetime risk for anxiety, depres-
sion, substance abuse, and impulse control disorders.
• Individuals with ADHD suffer greater numbers of accidents and
other medical difficulties, and they also exhibit higher levels of risky
behavior, particularly with driving and sexual activity.
• ADHD creates substantial economic costs for affected individuals,
families, and society.

9
ADHD is the most common behavioral disorder of childhood and in the
majority of cases persists into adolescence and adulthood. Across the life
span, ADHD is associated significant comorbidity, functional impairments,
and increased economic burden. Key demographic facts for ADHD are sum-
marized in Box 3..

Prevalence
The estimated prevalence of ADHD among school-age children ranges from
3% to 0%, with a 5.3% estimated worldwide mean. Variability among esti-
mates is due in part to differences in approaches to data collection, which
include structured diagnostic interviews, parent or teacher rating scales, or
parent histories that their child has received a clinician’s diagnosis. One study
from the US Centers for Disease Control and based on parent reports found
that 9.5% of children and adolescents between ages 4 and 7 years had been
given clinical diagnoses of ADHD.2
The prevalence of ADHD is higher in boys than in girls, with ratios of 9
to  and 3 to  in clinic and community samples, respectively. Boys might
be overrepresented in clinics because they more frequently exhibit hyper-
active/impulsive symptoms that create overt difficulties in school and with
peers. Girls with fewer hyperactive/impulsive symptoms might have equal
or greater impairments from inattention, but they are less likely to disturb
parents and teachers and be referred for clinical evaluation. Boys are almost
three times as likely as girls to receive a prescription.
ADHD occurs in all racial, ethnic, and socioeconomic groups and is not a
function of intellectual ability.2 Reported rates are somewhat higher in poorer
ADHD
Box 3.  ADHD: Key Demographics
Prevalence estimates School-age children 3%–0%
Adults 2%–7%
Male/female ratios School-age clinic samples 9:
School-age community 3:
samples
Adult clinic samples :
Adult community samples 3:2
2007 estimate of affected youth ages 4–7 years 5.4 million
(9.5%)
2007 estimate of youth ages 4–7 years on ADHD 2.2 million
medication
200 estimate of total cost of ADHD to US economy $43–$266
billion

families and those headed by single mothers. Hispanic families are less likely
to report that a child has been diagnosed, although it is unclear whether
this reflects lower ADHD prevalence or cultural bias against evaluation and
treatment.
ADHD symptoms often decrease as affected individuals enter adoles-
10

cence. Point prevalence estimates suggest that rates of ADHD are lower in
adolescents than in prepubertal children. However, methodological limita-
tions in available epidemiological studies preclude clear determination of
prevalence among older youth.3
In 2007, 2.2 million children and adolescents were taking medication for
ADHD, far less than expected given disorder prevalence estimates of 5.4 mil-
lion in the same age group.2 This contradicts suggestions by some that ADHD
medications are overprescribed.
Adult ADHD prevalence rates were at one time extrapolated from lon-
gitudinal studies of grown-up children previously diagnosed with the disor-
der. These suggested that more than half of ADHD-affected children have
ongoing symptoms and related impairment as adults. In 2006, the National
Comorbidity Survey Replication estimated the adult prevalence of ADHD
at 4.4%.4 A similar international study found a slightly lower but comparable
rate.5 These findings are consistent with, and provide support for, estimates
suggested by longitudinal follow-up studies. Unlike generally episodic condi-
tions such as mood and anxiety disorders, adults with ADHD typically have
unremitting symptoms that require ongoing management.

Psychiatric Comorbidity
ADHD creates substantial risk for additional psychopathology (see Chapter
). Over two thirds of children with ADHD have at least one additional
psychiatric disorder and 8% have three or more other disorders.6 The risk
for having three or more additional disorders is higher in children from poorer
families. Children with ADHD have increased rates of learning disabilities,
oppositional defiant disorder, conduct disorder, depression, anxiety, and

Epidemiology and Burden

other conditions, compared with unaffected children (Fig. 3.).
Adults with ADHD also demonstrate higher rates of co-occurring psy-
chiatric disorders (Fig. 3.2). In particular, adults with ADHD have difficul-
ties with other disorders of impulse control, including antisocial personality,

80
70 RR 5.1
Percent Prevalence (%)

60

Chapter 3
50 RR 7.8
40
30 RR 12.6
20 RR 7.5
RR 8.0 RR 4.4
10 RR 8.7
RR 10.7
0
y

ty

lem

m
r

er

er
e
it

io
xie

tru
rd

rd

rd
bil

ss

ob
iso

iso

iso
isa

An

ec
re

Pr
ep

Sp
tD

yD
gD

11
ch
D

’s
m
uc

An
nin

te
ee

tis
nd

et
ar

Sp

Au

ur
Co
Le

To

Figure 3.  Prevalence of comorbid disorders in children with ADHD. RR, relative

risks compared to unaffected children and corrected for age, sex, race/ethnicity, family
structure, and household income. All differences significant, p <.05. (Adapted from
Larson et al.6)

50 OR 3.7
45
OR 5.0
40
Percent Prevalence (%)

35
30
25
OR 3.7
20
OR 3.0
15
10
5
0
Any Mood Disorder Any Anxiety Any Substance Use Intermittent
Disorder Disorder Explosive Disorder

Figure 3.2  Past 2-month comorbidity of other psychiatric disorders in adults with

ADHD. OR, odds ratio. All differences significant compared with non-ADHD compari-
sons, p <.05. (Adapted from Kessler et al.4)
ADHD intermittent explosive disorder, and gambling, as well as increased lifetime
histories of mood, anxiety, and substance use disorders.4 Increased risks for
substance use disorders and antisocial traits in adults with ADHD are gener-
ally mediated by a history of juvenile conduct disorder.
Although often unrecognized, ADHD similarly co-occurs at increased rates
in individuals diagnosed with other emotional and behavioral disorders (Table
3.). The degree to which untreated ADHD contributes to additional impair-
ment and poorer outcomes in these patients has not been established.

Accidents, Risk Taking, and Medical Outcomes

Children with ADHD are more likely to have nonfatal accidental injuries,
increased emergency room and hospital admissions, more major accidents,
and higher rates of sexually transmitted disease (Fig. 3.3).7 Older youth with
ADHD have more motor vehicle accidents, traffic citations, and incidents of
driving while intoxicated. Studies of children with ADHD followed as adults
reveal increased rates of risky driving and sexual behaviors, increased non-
alcohol substance use disorders and nicotine dependence, and increased
difficulties with traffic accidents and speeding tickets (Fig. 3.4). Individuals
12

Table 3.  Percentages of Patients with Other Psychiatric

Conditions and Comorbid ADHD
Psychiatric Disorder % With ADHD
Major depression 3%
Anxiety disorders 0%
Substance use disorders %
Impulse control disorders 2%

60
p = .0001
50
p = .004
40 p = .004 Mean Age = 16.4 years
% Reporting

30

20 p = .03
p = .04
10

0
Emergency At fault 2 or Someone Head injury Sexually
room visits 3 more car injured in transmitted
or more accidents accident disease
ADHD Non-ADHD

Figure 3.3  Medical outcomes with ADHD versus non-ADHD. (Adapted from

Olazagasti et al.7)
 Epidemiology and Burden
2.5

2
Fitted Risk Ratio

1.5

0.5

Chapter 3
ed

ng

ns

15

’s

’s

s
er
or

20

30
io
i
nd

riv

rtn
e
m

lat

ag

l in

l in
pe

sd

pa
or

io

by
s

ro

ro
les
su

gv

al
5

nt

nt
x

xu
s

ck

in
se

Se

co

co
et

ov

se
Re
en

ick

th

th
m
Lic

26
gt

bir

bir
er

>
din

th

o
N

N
ee

O
Sp

Figure 3.4  Increased risky behaviors in adults with ADHD compared with

non-ADHD. All comparisons significant, p <.05. (Adapted from Olazagasti et al.7)

13
with ADHD are more likely to have earlier initiation of sexual activity, more
lifetime sexual partners, and decreased contraception use. These risks are
particularly prominent in children with ADHD who also develop associated
problems with conduct and antisocial personality disorder.

Functional Impairments
ADHD is associated over the life span with impairments in family, academic,
social, and occupational functioning.6 Families exhibit increased parental con-
flict and aggravation. Academic underperformance and other school-related
problems are typical. Children with ADHD are almost 0 times more likely
to have difficulties with making or keeping friends. 2 Childhood ADHD
leads to greater occurrence of adolescent and adult criminal behaviors. 7
These risks are most evident in the third of ADHD-affected children who
also develop secondary conduct disorder. Children with ADHD have
higher rates of lifetime arrests, criminal convictions, and incarcerations.
Adolescents with ADHD are more likely than typically developing youth to
have spent time on probation or in jail, and to have been assigned by a court
to a clinical social worker.
Adults with ADHD consistently demonstrate difficulties with academic
and occupational achievement.8 Those who enroll in college and succeed
in obtaining degrees often require 5 to 6 years to complete their studies,
compared with the usual 4 years. Increased substance abuse, early and
risky sexual behavior, and poor adaptive skills often lead to personal insta-
bility with concomitant demoralization and low self-esteem.7 It is unclear
whether equal risk for these negative outcomes exists for women or those
ADHD with a predominance of inattentive symptoms. Adults who seek treat-
ment for school, work, or personal difficulties exhibit poor academic and
occupational performance, dissatisfaction with friendships and intimate
relationships, low self-esteem, substance abuse, and antisocial behaviors. 8
Employees with ADHD take more frequent sick days from work. 2 Other
discrepancies in ADHD-affected adults include lower levels of education
compared to cognitively matched peers, poor management of personal
finances, more divorces and other relationship failures, and higher degrees
of personal chaos.8

Economic Burden
Individual and social costs associated with ADHD are substantial and last-
ing.9 The financial consequences of ADHD are borne by affected individuals,
their families, and broader society in terms of lost productivity and income,
health costs, educational failures, substance abuse, and increased criminality.
Total estimated annual costs of ADHD in the United States in 200 dollars
range from $43 to $266 billion. Per-person costs are estimated to range
from $62 to $2,720 for children and adolescents, and $37 to $4,20 for
adults. Almost 75% of costs associated with ADHD are related to adults
with ADHD or adult family members who miss work to take care of their
14

affected children. Child and adolescent costs are mostly attributable to

health care and education expense, while adult costs are mainly due to losses
in income and productivity.
Average annual medical costs for children and adolescents with ADHD
are three times higher than for typically developing youth.0 Medical costs
for non-ADHD family members of ADHD patients are more than double
those in families without ADHD. These increased costs result from inpatient
hospital expense, primary care visits, mental and behavioral health visits, and
prescription medications, and are comparable to those seen with children
suffering from other chronic medical conditions, such as asthma. Similarly,
adults with ADHD have annual medical costs two to three times higher than
matched non-ADHD comparisons.
Direct medical costs for the management of ADHD usually range from
$,000 to $5,000 per person annually.9 This includes clinic visits, prescrip-
tion medications, and other adjunctive therapies such as parent management
training. It does not include additional expenses associated with academic
accommodations, tutoring, or other specialized school services.
Additional indirect costs are borne by the parents of children and
employers of adults. 9 Childhood ADHD increases the strain in parent–
child relationships and heightens parental conflict. Parents of children with
ADHD have .6 times as many claims for their own medical care com-
pared with controls. Similarly, indirect costs due to parental disability and
work absenteeism result from the need to miss work for direct child care,
meeting with teachers, and bringing children to medical and other service
appointments. On average, adults with ADHD are less productive at work
and are more likely to take sick days or exhibit repeated absenteeism.
Adult professionals with ADHD who have obtained college degrees on

Epidemiology and Burden

average earn $40,000 less per year than similarly matched comparisons
without the disorder.
Criminal behaviors associated with ADHD create added societal eco-
nomic burdens. Total costs for criminal behavior among juveniles is three
times higher for youth with ADHD compared with controls.0
ADHD is associated with increased costs for management of other
comorbid psychiatric and general medical conditions. One study demon-
strated average increased costs of $358 per patient per year for manage-
ment of depression, $258 for oppositional defiant disorder, $54 for bipolar
disorder, $488 for anxiety, $868 for substance abuse, $98 for tics, and $247
for personality disorders.0 Costs also increased for several general medica-

Chapter 3
tion conditions, including $630 for respiratory illness, $670 for acute sinusitis,
$972 for general injuries, and $507 for allergies. Whether these expenses can
be reduced with aggressive ADHD management is not presently known and
requires additional research.

References
. Polanczyk G, Silva de Lima M. Horta BL, Biederman J, Rohde LA. The world-
wide prevalence of ADHD: a systematic review and metaregression analysis.
Am J Psychiatry. 2007;64:942–948.

15
2. Centers for Disease Control and Prevention. Increasing prevalence of
parent-reported attention-deficit/hyperactivity disorder among children—
United States, 2003 and 2007. MMWR. 200;59:439–443.
3. Kessler RC, Avenevoli S, McLaughlin KA, et  al. Lifetime co-morbidity
of DSM-IV disorders in the US National Survey Replication Adolescent
Supplement (NCS-A). Psychol Med. 202;42:997–200.
4. Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult
ADHD in the United States: results from the National Comorbidity Survey
Replication. Am J Psychiatry. 2006;63:76–723.
5. Fayyad J, De Graaf R, Kessler R, et  al. Cross-national prevalence
and correlates of adult attention-deficit hyperactivity disorder. BJP.
2007;90:402–409.
6. Larson K, Russ SA, Kahn RS, Halfon N. Patterns of comorbidity, functioning, and
service use for US children with ADHD, 2007. Pediatrics. 20;27:462–470.
7. Olazagasti MA, Klein RG, Mannuzza S, et al. Does childhood attention-deficit/
hyperactivity disorder predict risk-taking and medical illnesses in adulthood? J
Am Acad Child Adolesc Psychiatry. 203;52:53–62.
8. Barkley RA, Murphy KR, Smallish L, Fletcher K. Young adult outcomes of
hyperactive children: adaptive functioning in major life activities. J Am Acad
Child Adolesc Psychiatry. 2006;45:9–202.
9. Doshi JA, Hodgkins P, Kahle J, et al. Economic impact of childhood and adult
attention-deficit/hyperactivity disorder in the United Stats. J Am Acad Child
Adolesc Psychiatry. 202;5:990–002.
0. Matza LS, Paramore C, Prasad M. A review of the economic burden of ADHD.
Cost Eff Resour Alloc. 2005;3:5.
. Biederman J, Faraone SV. The effects of attention-deficit/hyperactivity disor-
der on employment and household income. Med Gen Med. 2006:8:2.
ADHD Further Reading
Nigg J. Attention-deficit/hyperactivity disorder and adverse health outcomes. Clin
Psychol Rev. 203;33:25–228.
Pelham WE, Foster EM, Robb JA. The economic impact of attention-deficit/hyper-
activity disorder in children and adolescents. Ambul Pediatr. 2007;7:2–3.
Willcutt EG. The prevalence of DSM-IV attention-deficit/hyperactivity disorder: a
meta-analytic review. Neurotherapeutics. 202;9:490–499.
16
Chapter 4

Etiology and Neurobiology

Key Points
• The biological basis of ADHD is strongly evidenced in genetic and
brain imaging studies.
• ADHD is a complex trait likely to arise from the interactions of mul-
tiple genes and environmental factors.
• Neuropsychological models emphasize deficits in executive function
and reward pathways that likely represent dysfunction in multiple
brain circuits.
• Despite demonstrated biological difference in groups with and with-
out ADHD, the disorder remains a behaviorally defined syndrome
diagnosed by careful assessment of symptoms and clinical history, not
by laboratory tests or brain imaging.

17
17
Evidence supporting the biological underpinnings of ADHD is of the strongest
of any psychiatric disorder. Earliest conceptualizations of the disorder were
informed by observations of behavioral sequelae of the influenza pandemic
of 97 that suggested both inattention and overactive behavior resulted
from brain pathology (see Chapter 2). This preliminary view has evolved in
tandem with other advances in neuroscience that demonstrate relationships
between brain functioning, cognition, and behavior. ADHD remains a clinical
syndrome defined by clinical criteria. However, a century of research reveals
that ADHD is a complex, brain-based, neurodevelopmental disorder likely
arising from the interplay of numerous social, developmental, environmental,
and genetic risk factors (Fig. 4.).

Psychosocial Risk
Psychosocial factors such as parenting style, parental conflict, or family stress
do not appear to be primary causes of ADHD. Although families with one
or more ADHD-affected members often exhibit higher levels of conflict, this
usually results from the parents’ need to manage children’s oppositional or
other problematic behaviors. Decreases in parental conflict and stress typi-
cally follow successful management of ADHD symptoms.
Although not causal, psychosocial adversity appears to exacerbate the
ADHD symptom severity and clinical presentation.2 Risk factors include
severe marital discord, low socioeconomic status, economic stress, large
ADHD
Genetic Risk Environmental Risk

ADHD

Brain Brain
Structure Function

Figure 4.  Biological basis of ADHD. (Adapted from Purper-Ouakil et al.)

family size, paternal criminality, maternal mental illness, abuse, and foster
care placement. Aggregation of several risk factors rather than any one factor
predicts greater ADHD severity. Conclusions about chronic family conflict,
decreased family cohesion, and exposure to parental mental illness are dif-
ficult to untangle as these both result from ADHD and simultaneously appear
to worsen ADHD-related difficulties.
ADHD-affected children often elicit parental interactions that com-
pound rather than reduce the disorder’s negative effects.3 Children with
ADHD are more frequently off task, more active, less compliant, and less
18

responsive to discipline. Fathers of boys with ADHD are likely to be more

demanding, aversive, and prone to use physical discipline. Mothers tend
to be more disapproving, negative, inappropriately involved, and critical.
This negative cycle of parent–child interaction worsens family, marital, and
personal difficulties.
The negative effects of ineffective parenting are further exacerbated when
one or both parents have ADHD. Children with ADHD have an estimated
30% chance of having at least one parent with the disorder. Parents with
ADHD are often lax and inconsistent disciplinarians and have greater difficulty
implementing recommended approaches to parenting.3

Prenatal and Perinatal Risk Factors

Prenatal factors associated with increased risk include maternal use of nico-
tine or alcohol during pregnancy, fetal exposure to other drugs or environ-
mental factors, notably polychlorinated biphenyls (PCBs) and the insecticide
DDT, and intrauterine growth delay.4 Perinatal risks include poor maternal
health, increased maternal age, prematurity, toxemia, preeclampsia, long
labor, and fetal distress.2 Particularly high risk is evident with births before 32
weeks gestation. Risk is even higher with births earlier than 28 weeks gesta-
tion, very low birth weight, particularly for newborns weighing ,500 g (3 lb
5 oz) or less, and births later then 42 weeks gestation. Early postnatal risks
include neonatal anoxia, seizures, and brain hemorrhage. Children exposed
to early and severe institutional deprivation, such as seen in certain orphan-
ages, often have ADHD symptoms, although these might be better corre-
lated with attachment disorders.
 Controversy persists regarding the relationship of maternal nicotine

Etiology and Neurobiology

and alcohol consumption during gestation and subsequent ADHD risk. 2
Laboratory animal studies demonstrate increased hyperactivity with ges-
tational nicotine exposure. However, since mothers with ADHD have
increased risk for nicotine addiction and are less likely to quit or cut down
use while pregnant, it remains unclear whether increased ADHD in their
children results directly from in utero nicotine exposure or is due to inher-
ited maternal genetic risks for the disorder. Preliminary research suggests
that the link between maternal smoking and ADHD persists but is dimin-
ished after controlling for genetic and other environmental factors. This
speaks to the public health benefit of reducing maternal nicotine and alco-
hol use during pregnancy.

Chapter 4
Environmental Risk Factors
Elevated serum lead is associated with increased ADHD risk.5 Symptom
increases attributed to even miniscule lead levels are far lower than estab-
lished safety thresholds. Direct causality, however, is difficult to demon-
strate. Many individuals with elevated lead levels do not have ADHD, and
lead exposure does not account for a substantial percentage of ADHD cases.

19
Individuals with elevated lead levels frequently have other ADHD risk fac-
tors, including poverty and low parental educational attainment. Laboratory
screening for serum lead is appropriate when clinical history raises concerns
about possible lead ingestion. Chelation therapy can reduce ADHD symp-
toms in individuals positive for serum lead.
There are persistent assertions that dietary sugar, food additives, and/
or deficits in vitamins and other micronutrients cause ADHD (see Chapter
3).3 None of these claims has substantial support. Most studies examining a
potential relationship between diet and ADHD suffer many methodological
limitations, including very small sample sizes. Many parents have hard-held
beliefs that chocolate or other foods high in refined sugar cause their children
to be hyperactive due to an excess of energy. This opinion is not supported
by controlled research and is not consistent with known physical effects of
sugar ingestion. There is some evidence that artificial food additives might
be associated with very small increased risk, but this might be true only in
individuals with certain genotypes. If there is any causal relationship between
diet and ADHD, the contribution of dietary factors to overall occurrence of
ADHD is likely to be almost negligible.

ADHD Genetics
Initial interest in possible genetic underpinnings of ADHD emerged from fam-
ily studies that began in the 970s and demonstrated increased frequency of
the disorder in first-degree relatives of ADHD-affected youth. Specifically,
20% to 30% of children with ADHD had at least one additional affected family
member, suggesting a familial basis for the disorder.6 Adoption studies revealed
ADHD that adopted children with ADHD had similarly increased rates among their
biological, but not adopted, relatives. Examinations of concordance rates in
monozygotic and dizygotic twins consistently estimate that ADHD heritability
approximates 74%, which suggests that 74% of the symptom variability in a
population is due to genetic causes.7 ADHD is about as heritable as height
and is one of the most heritable psychiatric disorders (Fig. 4.2).
Early ADHD molecular genetics investigations were influenced by the
idea that common disorders were caused by common genetic variants.6
These studies were typically case-control and family-based investigations of
candidate genes that were selected based on known targets and metabolic
pathways of stimulant medications proven useful in ADHD treatment. Most
emphasized allele variants in the dopamine and norepinephrine transmitter
systems. There was initially great excitement surrounding two dopamine
system variants, the variable number tandem repeat (VNTR) polymorphism
found in the 3' untranslated region (UTR) region of the dopamine transporter
(SLC6A3) and the 7-repeat allele of the 48-base pair VNTR found in exon 3 of
the dopamine D4 receptor (DRD4). Other candidate genes also showed posi-
tive associations. However, findings from many of these early studies were
not replicated in later investigations and were often limited by false-positive
results, small sample sizes, and failures to consider population differences.
Meta-analyses confirm positive findings for several candidate genes, but none
of these is causal for ADHD and none, either alone or in combination, pre-
20

dicts substantial risk for the disorder.6

Genetic linkage studies in families with multiple affected members were
conducted to assess cosegregation of genetic markers that could sug-
gest certain genomic regions with high probability of harboring risk genes.
Linkage studies examine the entire genome and do not require preconceived

1
0.9
Heritability Estimate Percent (%)

0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
es

IQ

HD

ia

m
er

igh
io

en

tru
et

rd

ss

He

AD

hr
iab

iso

ec
re

op
D

ep

Sp
D

hiz
II

D
nic

m
pe

Sc

tis
Pa
Ty

Au

Figure 4.2  Heritability of ADHD and other complex traits. (Adapted from

Purper-Ouakil et al.)
hypotheses about particular genes. These studies are limited to finding genes

Etiology and Neurobiology

of larger effect, specifically genes that can account for more than 0% of
symptom variance. A meta-analysis of seven ADHD linkage studies identified
one significant peak on the long arm of chromosome 6, but no genes in that
region have been implicated in candidate gene investigations.8
Genome-wide association studies (GWAS) compare single-nucleotide
polymorphisms (SNPs) across the genome in individuals with and without
disorders. Increased frequencies of particular SNPs identify genomic regions
that likely contain genes related to the disorder of interest. Due to the high
number of SNP comparisons, very stringent significance levels (p < 0-8) are
required to minimize false-positive findings. In initial ADHD GWAS, no find-
ings attained statistical significance, but trends implicated multiple regions

Chapter 4
containing genes involved in directing cell architecture and communication.6
A related GWAS of multiple psychiatric disorders identified four genomic
regions likely to harbor common risk alleles for ADHD, depression, bipolar
disorder, autism spectrum disorder, and schizophrenia.9
GWAS failed to support the idea that ADHD is substantially caused by
common genetic variants or major risk genes. More recent studies suggest
that individuals with ADHD have higher numbers of rare copy number vari-
ants (CNVs) across their genomes compared with unaffected individuals.0
CNVs are insertion or deletion mutations that persist in the genome over
time. Some CNVs associated with ADHD involve genes that regulate learn-

21
ing, behavior, synaptic transmission, and neural development, but overall
CNV burden appears to be more important for ADHD risk than which genes
are affected. CNVs might account for a substantial proportion of ADHD her-
itability in some families, but given that the variants are by definition rare they
do not explain substantial overall population risk.

Gene–Environment Interactions
There is growing appreciation of the extent to which interactions between
genetic and environmental factors increase disease risk. Although both
genetic and environmental ADHD risk factors are identified, none is causal
and many individuals with them do not develop the disorder. Evidence sug-
gests that underlying ADHD genetic risks have greater expression in the
context of high environmental adversity and are attenuated with increased
psychosocial stability.
Several small studies suggest that specific gene–environment interactions
are causal for ADHD. 6 One study demonstrated that maternal smoking
during pregnancy was associated with increased risk for subsequent ADHD
only when the child had specific risk alleles, specifically the 7-repeat of
the DRD4 exon III VNTR or the 0-repeat of the SCL6A3 3' UTR VNTR.
Children lacking these exhibited much lower ADHD rates regardless
of whether their mothers smoked. Similarly, it has been suggested that
increased ADHD risk from certain food additives is influenced by the pres-
ence or absence of variants in histaminergic and dopaminergic genes. If vali-
dated in large samples, an increased understanding of gene–environment
ADHD interactions and ADHD risk raises the possibility of primary prevention or
symptom reduction through targeted environmental interventions for those
with increased genetic risk.

Brain Imaging
Brain imaging is not useful or appropriate for ADHD diagnosis. There is a
great range of variability and overlap in individuals with and without the disor-
der, such that imaging studies lack the predictive power that is necessary for
a diagnostic test. Nonetheless, research on groups with and without ADHD
has consistently demonstrated measurable differences in brain structure and
function that provide a basis for understanding areas of brain dysfunction
associated with the disorder.
Structural imaging studies using computerized tomography (CT)
and magnetic resonance imaging (MRI) consistently find evidence of
brain abnormalities, most commonly smaller total brain and white mat-
ter volumes with particular decreases in frontal cortex, cerebellum,
and subcortical structures.2 Caudate nucleus differences seem to disap-
pear by adolescence. Differences in other brain structures appear fixed.
Normalization in areas such as the parietal cortex and hippocampus are
associated with symptom reduction, whereas ongoing volume loss is typi-
22

cally seen with symptom persistence. Longitudinal studies suggest that

ADHD-affected groups have parallel but delayed patterns of brain devel-
opment, with approximately 3-year delays in cortical maturation.  This
suggests that early genetic and environmental effects on brain develop-
ment are nonprogressive and stable.
Positron emission tomography (PET) in adult parents of children with
ADHD revealed decreased glucose metabolism in the premotor and supe-
rior prefrontal cortices.2 Studies using single-photon emission computerized
tomography (SPECT) in ADHD diagnosed adults found decreased perfusion
and underactivation in prefrontal regions, consistent with measured executive
function deficits, as well as striatal regions.2 Adult radioligand binding stud-
ies revealed decreased blood flow and increased density of dopamine trans-
porters (DATs) in striatal regions.2 Functional MRI (fMRI) studies in children
and adolescents showed patterns of hypoactivation with ADHD, primarily in
frontostriatal and parietal areas.3
Early imaging findings emphasized abnormalities in discrete brain regions
and prefrontal-striatal circuits. More recently, the research emphasis has
shifted toward examining patterns of dysfunction and altered connectiv-
ity across multiple neuronal systems that involve both higher level cognitive
and sensorimotor processes (Fig. 4.3).3 ADHD is associated with abnormal
activation in large-scale brain systems. Children with ADHD exhibit hypo-
activation in brain regions associated with executive function and attention,
specifically the frontoparietal and ventral attentional networks, respectively,
and hyperactivation in the default, ventral attentional and somatomotor net-
works. Adults demonstrate hypoactivation in the frontoparietal and hyperac-
tivation in the visual, dorsal attention, and default networks.
 Etiology and Neurobiology
SMC

FC

PC

T
AN

Chapter 4
BG

FC Frontal Cortex
PC Parietal Cortex Fronto-cerebellar network
SMC Supplementary Motor Cortex
Reward network
AN Accumbens Nucleus

23
T Thalamus Fronto-striatal network
BG Basal Ganglia Executive function network
C Cerebellum Attentional network

Figure 4.3  ADHD functional circuits. (Adapted from Purper-Ouakil et al.)

Neuropsychological Models
Neuropsychological tests identify patterns of cognitive dysfunction in ADHD
that are often consistent with brain imaging abnormalities.4 As with neuro-
imaging, neuropsychological tests detect group effects that are not helpful
in making ADHD diagnoses due to the high degree of variability exhibited
by affected and unaffected individuals. Neuropsychological findings provide
a basis for several models that help elucidate dysfunctional brain processes
associated with the disorder. Abnormalities in brain function identified by
neuropsychological testing have been proposed as ADHD endophenotypes,
that is, more homogeneous subgroups within the broader DSM-defined
behavioral syndrome that are attributable to more easily identified genetic
underpinnings.
One popular neuropsychological model suggests that ADHD arises from
primary deficits in executive functions (EFs), generally defined as cognitive
processes that support appropriate problem-solving skills aimed toward
achieving future goals.5 Specifically, EFs maintain information about pos-
sible choices in working memory and facilitate integration with other rele-
vant information from the current environmental context in order to make
ADHD optimal choices in a given situation. EF deficits in ADHD include working
memory, response inhibition, and general weaknesses in executive control. EF
processes are largely functions of the prefrontal lobes, which are implicated
further with behavioral hyperactivity, impulsivity, and inattention. Impaired EF
appears to play an important role in the complex neuropsychology of ADHD,
but it does not adequately explain all cases of the disorder.
The dual-pathway model of ADHD suggests that inattention and EF
deficits result from impaired prefrontal-striatal circuits, while hyperactivity
results from frontal-limbic dysfunctions that regulate motivation and reward
response. Another model proposes that impaired signaling in the prefrontal
cortex leads to failures in detecting differences between actual and expected
environmental inputs, which results in inappropriate behavioral responses.
Ongoing work is required to elucidate specific relationships between ADHD
symptoms and dysfunction in specific neural networks.

Clinical Implications
Our understanding of ADHD neurobiology provides biological validation of
the disorder and reduces social stigma that results from those who deny the
legitimacy of the condition or argue that it is merely a relative social construct.
Increased knowledge about biological mechanisms associated with ADHD
24

and related cognitive and behavioral impairment provides a foundation for

development of new medication and psychosocial treatment strategies, as
well as the targeting of specific interventions designed for optimized treat-
ment of individual patients.

References
. Purper-Ouakil D, Ramoz N, Lepagnol-Bestel A, Gorwood P, Simonneau
M. Neurobiology of attention deficit/hyperactivity disorder. Pediatr Res.
20;69:69R-76R.
2. Spencer T, Biederman J, Mick E. Attention-deficit/hyperactivity disor-
der:  diagnosis, lifespan, comorbidities, and neurobiology. J Pediatr Psychol.
2007;32:63–642.
3. Daley D. Attention deficit hyperactivity disorder: a review of the essential facts.
Child Care Health Dev. 2006;32:93–204.
4. Banerjee TD, Middleton F, Faraone SV. Environmental risk factors for
attention-deficit/hyperactivity disorder. Acta Paediatr. 2007;96:269–274.
5. Nigg JT, Nikolas M, Mark Knottnerus M, Cavanagh K, Friderici K. Confirmation
and extension of association of blood lead with attention-deficit/hyperactivity
disorder (ADHD) and ADHD symptom domains at population-typical expo-
sure levels. J Child Psychol Psychiatry. 200;5:58–65.
6. Faraone SV, Mick E. Molecular genetics of attention deficit hyperactivity disor-
der. Psychiatr Clin N Am. 200;33:59–80.
7. Faraone SV, Doyle AE. The nature and heritability of attention-deficit/hyperac-
tivity disorder. Child Adolesc Psychiatr Clin N Am. 200;0:299–36.
  8. Zhou K, Dempfle A, Arcos-Burgos M, et al. Meta-analysis of genome-side

Etiology and Neurobiology

linkage scans of attention deficit hyperactivity disorder. Am J Med Genet B
Neuropyschiatr Genet. 2008;t47B:392–398.
  9. Cross-Disorder Group of the Psychiatric Genomics Consortium. Genetic
relationships between five psychiatric disorders estimated from genome-wide
SNPs. Nat Genet. 203;45:984–994.
0. Yang L, Neale BM, Liu L, et al. Polygenic transmission and complex neuro-
developmental network for attention deficit hyperactivity disorder: genome
wide association study of both common and rare variants. Am J Med Gen B
Neuropyschiatr Genet. 203;62B:49–430.
. Shaw P, Eckstrand K, Sharp W, et al. Attention-deficit/hyperactivity disor-
der is characterized by a delay in cortical maturation. Proc Natl Acad Sci USA.
2007;04:9649–9654.

Chapter 4
2. C ubilla A, Rubia K. Structural and functional brain imaging in adults
with attention-deficit/hyperactivity disorder. Expert Rev Neurother.
200;0:603–620.
3. Cortese S, Kelly C, Chabernaud C, et  al. Towards systems neurosci-
ence of ADHD:  a meta-analysis of 55 fMRI studies. Am J Psychiatry.
202;69:038–055.
4. Tripp G, Wickens JR. Neurobiology of ADHD. Neuropharmacol.
2009;57:579–589.
5. Willcutt EG, Doyle AE, Nigg JT, Faraone SV, Pennington BF. Validity of execu-
tive function theory of attention-deficit/hyperactivity disorder: a meta-analytic

25
review. Biol Psychiatry. 2005;57:336–346.

Further Reading
Sonuga-Barke EJ. The dual pathway model of AD/HD:  an elaboration of
neuro-developmental characteristics. Neuro Sci Biobev Rev. 2003;27:593–604.
Weyandt L, Swentosky A, Gudmundsdottir BG. Neuroimaging and ADHD,
PET, DTI findings, and methodological limitations. Dev Neuropsychol. 203;38:
2–225.
Chapter 5

Diagnostic Criteria
Key Points
• ADHD is diagnosed on the basis of persistent difficulties from symp-
toms of inattention and/or hyperactivity-impulsivity that occur to a
greater degree than expected for an individual’s developmental level.
• Diagnosis is based on clinical criteria as currently defined in the DSM-5.
• DSM-5 criteria incorporate a developmental perspective that recog-
nizes symptom changes and thresholds for diagnosis as individuals
become older adolescents and adults.

While much research demonstrates its biological correlates (see Chapter

4), ADHD remains a clinically defined syndrome diagnosed on the basis of

27
27
structured clinical criteria. ADHD is classified in the Neurodevelopmental
Disorders section of the Diagnostic and Statistical Manual of Mental Disorders,
fifth edition (DSM-5), which reflects its initial presentation in childhood and
frequent co-occurrence with other early-onset brain-based disorders. ADHD
diagnostic criteria are summarized in Box 5.

Historical Perspectives
Regardless of what it has been called, developmentally inappropriate levels
of inattention, impulsivity, and hyperactivity have always defined ADHD (see
Chapter 2). The Diagnostic and Statistical Manual of Mental Disorders, second
edition (DSM-II) broadly characterized the hyperkinetic reaction of childhood
(or adolescence) in those youth who exhibited difficulties due to overactivity,
restlessness, distractibility, and short attention span. DSM-II largely viewed
hyperkinetic reaction as a disorder of younger children with the expectation
that these behaviors diminished by adolescence.
The Diagnostic and Statistical Manual of Mental Disorders, third edition
(DSM-III) provided the first elucidation of specific symptom sets, which were
organized into three areas of inattention, impulsivity, and hyperactivity.
A panel of experts in childhood psychopathology proposed symptoms based
on their own clinical and research experience, but there were no attempts to
validate these diagnostic criteria. In DSM-III, the diagnosis of attention-deficit
disorder with hyperactivity (ADDH) required a minimum of three of five inat-
tentive, three of six impulsive, and two of six hyperactive symptoms, while
a diagnosis of attention-deficit disorder without hyperactivity (ADDWO)
ADHD
Box 5.  Summary of ADHD Diagnosis Criteria
According to the criteria in the DSM-5, persistent impaired behavior for
a minimum of 6 months that exceeds what is expected for an individual’s
developmental level and is characterized by at least 6 of 9 inattentive and/
or 6 of 9 hyperactive-impulsive symptoms is required in order to make an
ADHD diagnosis. If the patient is 7 or older, only 5 of 9 symptoms are
required.
The patient also must show some history of symptoms before age 2 and
at least several symptoms must occur in more than one setting (e.g., home,
school, social relations, work, recreational activities, etc.). The symptoms
also must result in clinically meaningful impairment in social, academic, or
occupational functioning; and the symptoms must not have occurred due to
schizophrenia or other psychotic illness and cannot be better explained by
conditions such as mood, anxiety, personality, or substance use disorders.

required only the minimum number of inattentive and impulsive symptoms.

The revised DSM-III (DSM-III-R) replaced the three separate symptom sets
with a single list of 4 symptoms, required a minimum of eight symptoms
for the diagnosis, and eliminated any distinction between individuals with and
28

without hyperactivity.
The single symptom list in DSM-III-R suggested that ADHD existed along
a single dimension, instead of the three originally conceived in DSM-III.
Subsequent analysis of several data sets revealed that ADHD appeared to
comprise two symptom dimensions, the inattentive and hyperactive-impulsive.
Some investigators voiced surprise that impulsive symptoms were associated
with hyperactivity, and not inattention, as originally thought. Recognition of
the two-dimensional structure of ADHD symptoms informed the conduct
of clinical field trials designed to provide an empirical basis for a revised clas-
sification system in the Diagnostic and Statistical Manual of Mental Disorders,
fourth edition (DSM-IV).

Symptoms
DSM-5 retains the same set of 8 ADHD symptoms used in DSM-IV,
nine inattentive (Table 5.) and nine hyperactive/impulsive (Table 5.2).
In field trials conducted for DSM-IV, the clinical utility of potential symp-
toms derived from DSM-III, DSM-III-R, and ICD-0 was assessed in several
hundred pediatric patients ages 4–7 years. Clinicians participating in the
trial designated which of these proposed symptoms characterized their
own patients diagnosed with ADHD. Investigators further assessed the
correlation of proposed symptoms with parent and teacher impairment
ratings. DSM-IV included those symptoms that best differentiated patients
with ADHD from other disorders and also best correlated with parent and
teacher ratings of impairment.
 Diagnostic Criteria
Table 5.  ADHD Inattentive Symptoms
Younger Individuals Older Individuals
 Fails to notice details, makes Careless or inaccurate work
careless errors
2 Trouble maintaining attention Trouble staying focused on boring
work, mind wanders, difficulty with
sustained reading
3 Appears not to listen even when Difficulty focusing on what people say,
spoken to directly even when addressed directly

Chapter 5
4 Trouble completing tasks or Has difficulty finishing tasks, easily
following through on instructions sidetracked
5 Difficulty with organization Procrastinates, trouble completing
tasks in order, messy, misses deadlines
6 Avoids activities that require Delays or avoids work or activities that
sustained attention are boring or repetitive
7 Loses or misplaces things Often misplaces things required at
work, home, or other activities
8 Distracted easily by extraneous Distracted by surrounding noises
stimuli or other activities, or by unrelated
thoughts
9 Forgets easily Trouble remembering appointments
and other obligations

29
Table 5.2  ADHD Hyperactive-Impulsive Symptoms
Younger Individuals Older Individuals
 Frequently fidgets, taps hands or feet, Often restless or fidgety
squirms when seated
2 Frequently gets out of seat Often leaves seats at meetings and
other times seating is required
3 Runs and climbs when inappropriate Feels internally restless
4 Unable to play quietly Often louder than appropriate for a
given situation
5 Frequently “on the go” as if “driven Has trouble unwinding or relaxing,
by a motor” always needs something to do
6 Talks to excess Talks too much in social situations
7 Blurts out answers before questions Finishes others’ sentences or
are completed answers questions before they are
finished
8 Trouble waiting turn or in line Difficulty standing in line or
waiting turn
9 Frequently interrupts or intrudes Interrupts others’ conversations
and activities, intrudes into what
others are doing

DSM-IV ADHD symptoms have proven useful in extensive research and

clinical practice. The decision to retain DSM-IV symptoms in DSM-5 allows
continuity in clinical diagnosis and the application of past research. A major
shortcoming of the DSM-IV ADHD field trial was its sole focus on school-age
children. Few older adolescents and no adults participated. Whether DSM-IV
ADHD symptoms were developmentally representative of older patients had never
been demonstrated. Some symptoms, such as “runs and climbs excessively”
and “has difficulty playing quietly,” were irrelevant in older persons. Although
DSM-5 includes the same set of DSM-IV ADHD symptoms, the text discus-
sion expands consideration of how they expressed in older individuals. This
approach places symptom assessment in a more appropriate developmental
context. Regardless of a person’s age, the diagnosis depends on symptom
frequency and severity that exceeds what is expected for the individual’s
developmental level.

Diagnostic Thresholds
There has been ongoing debate about whether ADHD is a categorical or
dimensional disorder. In a categorical disorder, individuals either have or do
not have the condition. Examples are pneumonia, otitis media, enuresis, and
anorexia nervosa. In a dimensional disorder, symptoms or laboratory values
exist in a continuum within the population, and one end of the distribution is
associated with increased risk for morbidity or other impairments. Examples
are blood pressure, cholesterol, intelligence, and possibly mood and anxiety
symptoms. Frequently within psychiatric classification, neither approach is
completely satisfactory in defining various conditions.
30

Symptoms of inattention, impulsivity, and hyperactivity clearly exist across

the population. Many have argued that these symptoms are quite normal for
certain ages and circumstances. In DSM-IV, cutoffs of six symptoms in either
the inattentive or hyperactive/impulsive dimension were based on field trial
data demonstrating that 50% of patients identified by clinicians as having
ADHD had six or more symptoms. The six-symptom cutoff also correlated
strongly with parent and teacher impairment ratings. Furthermore, this cutoff
falls approximately two standard deviations above the mean and at the 92nd
percentile for total number of symptoms for school-age children.
Many studies, including genetic and imaging studies, have demonstrated
significant differences in individuals with and without ADHD based on meet-
ing or failing to meet the categorical cutoff of six symptoms (see Chapter 4).
Other studies, particularly brain imaging studies, have demonstrated incre-
mental differences that correlate with increasing symptom number along a
dimension of symptom number, regardless of a discrete cutoff.
The mean number of ADHD symptoms exhibited at any given age
decreases over time.2 Requiring six symptoms for diagnosis in adults meant
that older patients had numbers of symptoms three to four standard devia-
tions greater than expected for their age, a much higher threshold than
required in children. Studies demonstrated that adults with as few as four
inattentive symptoms had significant impairments relative to their peers. This
suggested that the DSM-IV requirement for six symptoms was overly restric-
tive and failed to identify considerable numbers of older patients with mean-
ingful levels of clinical impairment.3
DSM-5 introduced a level of developmental sensitivity to the symptom
threshold required for diagnosis. The first criterion for ADHD continues
to require a minimum of six of nine inattentive and/or six of nine specified

Diagnostic Criteria
hyperactive-impulsive symptoms for diagnosis in children and younger ado-
lescents. However, only five symptoms in either category are sufficient when
patients are 7 years or older. This modification is consistent with the require-
ment for a persistent pattern of inattention and/or hyperactivity-impulsivity
that is developmentally inappropriate and meaningfully interferes with devel-
opment or functioning.

Chapter 5
Age of Onset
Some history of ADHD symptoms history prior to age 2 is required for diag-
nosis. This represents a change from previous DSM editions. In the early 980s,
investigators decided to require an age of symptom onset prior to 7 years
as a means to create more homogeneous research groups and ensure that
clinical subjects were suffering from a developmental, that is, early-onset, dis-
order. DSM-III incorporated the age of 7 onset criterion without any particular
scientific basis. DSM-IV further complicated matters in requiring that clinically
meaningful impairment as well as symptoms had to be evident before age 7.4
Recognition of the difficulties that arose from attempts to apply this crite-
rion retrospectively, particularly in adults, led to changing the required age of
onset from younger than age 7 to younger than age 2. The DSM-IV field trial

31
itself found a significant number of individuals assessed as having ADHD who
failed to have an age of onset or associated impairment prior to age 7.4 For
those with the predominately inattentive subtype, 5% and 43% failed to have
symptoms and impairment, respectively, by the age cutoff. Other studies
showed that no differences in patterns of comorbidity or impairment were
evident between those who did and did not report early onset. Adult stud-
ies, which generally relied on retrospective determination of age of onset,
had similar findings. As with children in the DSM-IV field trial, individuals with
early versus late onset had no differences in functional impairment, age, edu-
cation, psychological adjustment, or neuropsychiatric testing.5 Other studies
suggested that virtually all adults otherwise diagnosed with ADHD report age
of onset prior to age 2. Changing this criterion to require age of onset prior
to 2 resulted in virtually no additional persons being assigned the diagnosis.6
A related issue is the degree to which it is feasible to expect adults to
report reliably on childhood symptoms and impairments.3 In a longitudinal
study of school-age children diagnosed with ADHD, adult participants were
asked to recall the onset of their childhood symptoms and related difficul-
ties. Just over half accurately recounted an onset of symptoms prior to age
7. On average, the group recalled an age of onset 4 year later than described
by their parents in real time. This suggests that retrospectively adults tend
to report that problems related to ADHD emerged several years later than
described by their parents when they were children.
The unlinking of impairment from the age of onset criterion reflects grow-
ing recognition that some individuals with ADHD, particularly those with
higher intelligence or stronger support systems, are able to compensate
for the disorder and not exhibit meaningful difficulties. At times, clinically
ADHD significant impairment does not emerge until individuals face increased
demands of higher education or employment. In these cases, some history of
symptoms prior to age 2 is required, but the diagnosis is dependent on cur-
rent impairment and not retrospective recall of childhood difficulties.

Domains of Clinical Impairment

A history of ADHD symptoms and associated difficulties should be evident in
at least two settings. Common areas of impairment in children include fam-
ily life, school, and peer relationships. Additionally, older youth and adults
typically have problems with employment, driving, accidental injuries, gen-
eral health choices, and interpersonal conflicts. Some individuals, particularly
adults, acknowledge impairment in only one area, while exhibiting restrictive life
choices that suggest broader difficulties. Examples might be a single adult who
lives alone and denies difficulties outside of work, a chronically underemployed
actress waiting to be cast in a role, or a successful businessman threatened with
a divorce. It is expected that impairments in multiple areas should be evident
over an individual’s life history, even though an individual might only admit to
one current area of difficulty. Clinicians should assess functional impairment in
relation to social norms exhibited by the individual patient’s reference group.
32

Differential Diagnosis
ADHD is not diagnosed if symptoms occur solely during the course of schizo-
phrenia or another psychotic disorder, or if symptoms are better explained by
another mental disorder. The previous exclusion for pervasive developmental
disorders, now subsumed under autism spectrum disorder, has been elimi-
nated. An individual with autism spectrum disorder, intellectual disability, or
other developmental disorder should also be diagnosed with ADHD if he or
she meets criteria, with the caveat that symptom frequency and severity must
exceed what is expected generally for that person’s developmental level, not
chronological age.
Many mental disorders share ADHD features. The clinician must determine
if symptoms are better explained by other disorders or if other disorders are
comorbid with ADHD. Often a deciding feature in support of ADHD is a
persistent history of difficulties with inattentive and/or hyperactive-impulsive
symptoms that precede and continue outside of any discrete episode of mood,
anxiety, or behavioral difficulties. When symptoms are not persistent, they are
more likely to represent conditions other than ADHD. Other disorders should
be diagnosed as comorbid with ADHD when both sets of criteria are met.

Specifiers
DSM-IV created a great emphasis on ADHD subtypes. Patients with sufficient
symptoms in both the inattentive and hyperactive-impulsive categories were
deemed to have the Combined subtype. Those with six or more inattentive
but fewer than six hyperactive-impulsive were categorized by the predomi-

Diagnostic Criteria
nately Inattentive subtype. Those with six or more hyperactive-impulsive
symptoms but fewer than six inattentive were categorized as the predomi-
nately Hyperactive-impulsive subtype.
DSM-IV subtypes posed several difficulties.3 Subtypes were not stable over
time, and individuals often manifested different subtypes at different ages.
Genetic studies showed that while ADHD was highly heritable, subtypes
were not. Subtypes had no predictive value for treatment response.
DSM-5 eliminated subtypes and replaced them with specifiers that describe

Chapter 5
clinical presentation in the preceding 6 months. Patients meeting diagnostic
thresholds for both inattentive and hyperactive-impulsive symptoms are
specified as having the Combined presentation. Those meeting the diagnostic
threshold only for inattentive or hyperactive-impulsive symptoms are speci-
fied as having, respectively, either the Inattentive or Hyperactive-impulsive
presentation. Use of these specifiers allows greater descriptive characteriza-
tion of individual patients. Whether or not this added specification has any
other value is as yet unknown.
As with many disorders, ADHD severity can be specified based on the
number of presenting symptoms. Mild ADHD is specified when few, if any,
symptoms are present in excess of what is required and if there is no more
than minor functional difficulties. Severe ADHD is specified when many
symptoms in excess of what is required are present, or if there is marked

33
functional impairment in one or more settings. Moderate ADHD is speci-
fied when symptoms and impairment fall somewhere between “mild” and
“severe.”
ADHD can be specified “in partial remission” when a patient previously
met full criteria, currently has fewer than the necessary symptom number for
full diagnosis, but continues to exhibit clinically meaningful impairment due to
remaining symptoms.

Other Specified and Unspecified ADHD

Individuals who suffer clinically significant impairment due to ADHD symp-
toms but do not meet full diagnostic criteria can be assigned the diagnosis
“other specified ADHD.” The diagnosis should then specify the reason full
criteria were not met, such as “other specified ADHD with insufficient inat-
tentive and hyperactive-impulsive symptoms.” If a clinician chooses not to
specify which criteria are lacking, it is acceptable to assign a diagnosis of
“unspecified ADHD.”

References
. Lahey BB, Applegate B, McBurnett K, et al. DSM-IV field trials for attention
deficit hyperactivity disorder in children and adolescents. Am J Psychiatry.
994;5:673–685.
2. Biederman J, Mick E, Faraone SV. Age-dependent decline of symptoms of atten-
tion deficit hyperactivity disorder: impact of remission definition and symptom
type. Am J Psychiatry. 2000;57:88–88.
ADHD 3. McGough JJ, Barkley RA. Diagnostic controversies in adult attention deficit
hyperactivity disorder. Am J Psychiatry. 2004;6:948–956.
4. Applegate B, Lahey BB, Hart EL, et al. Validity of the age-of-onset criterion for
ADHD: a report from the DSM-IV field trials. J Am Acad Child Adolesc Psychiatry.
997;36:2–22.
5. Faraone SV, Biederman J, Spencer T, et al. Diagnosing adult attention deficit
hyperactivity disorder: are late onset and subthreshold diagnoses valid? Am J
Psychiatry. 2006;63:720–729.
6. Polanczyk G, Caspi A, Houts R, Kollins SH, Rohde LA, Moffitt TE. Implications
of extending the ADHD age-of-onset criterion to 2: results from a prospec-
tively studied birth cohort. J Am Acad Child Adolesc Psychiatry. 200;49:20–26.

Further Reading
American Psychiatric Association. Diagnostic and Statistical Manual of Mental
Disorders (5th ed.). Arlington, VA: American Psychiatric Association, 203.
Solanto MV, Wasserstein J, Marks DJ, Mitchell KJ. Diagnosis of ADHD in
adults: what is the appropriate DSM-5 symptom threshold for hyperactivity/
impulsivity? J Attent Disord. 202;6:63–634.
Willcutt EG, Nigg JT, Pennington BF, et al. Validity of DSM-IV attention deficit/
hyperactivity disorder symptom dimensions and subtypes. J Abnorm Psychol.
202:2:99–00.
34
Chapter 6

Assessment
Key Points
• ADHD is a behavioral syndrome diagnosed on the basis of clinical
criteria.
• ADHD assessment relies on careful integration of clinical information
derived from a wide variety of sources.
• Comorbidity is typical and should be considered in any ADHD
evaluation.
• ADHD is not diagnosed with neuropsychological tests, computer-
ized tests of attention, laboratory measures, EEG profiles, or brain
imaging.

35
35
ADHD should be assessed in any child or adolescent exhibiting academic
or behavioral difficulties or any adult with long-standing problems due
to inattention or distractibility. The diagnosis reflects a clinical picture
that generally begins before or during grade school, persists over time,
manifests in different settings, and is associated with clinically significant
impairment in a range of life activities, including family, school, social, and
occupational functioning.
ADHD is most reliably assessed by careful review and integration of
clinical information obtained from multiple sources. These include parent,
teacher, and other third-party reports, patient self-report rating scales, past
psychiatric and medical histories, educational and occupational records,
clinical interviews, direct observation, and, in some cases, psychoeducational
testing (Fig. 6.). Diagnosis cannot rely on any individual rating scale or bit of
clinical information.
For children and adolescents, the most critical aspect of the evaluation is
a face-to-face interview with one or both parents and the child. For adults,
the patient is usually the primary informant, but family members, partners,
employers, and others can provide helpful supplemental data. In all cases,
review and documentation of ADHD symptoms as defined by DSM-5 is para-
mount (see Chapter 5). ADHD is a clinical syndrome. Although neuropsy-
chological testing can be valuable in assessing particular cases, ADHD is not
diagnosed on the basis of any distinct neuropsychological profile. There is no
scientific justification for claiming to diagnose ADHD on the basis of other
laboratory studies, computerized tests of attention, electroencephalography
(EEG), or other brain imaging methods.
ADHD
Review Rating Scales and Records
• ADHD rating scales
• Broad-band rating scales
• School and occupational records

Conduct Comprehensive Interview

• ADHD criteria
• Areas of functional impairment
• Comorbid emotional and behavioral
disorders
• Psychosocial context

Confirm or Complete Medical Assessment

• Current medical history
• Cardiac risk factors
• Significant past medical history
• Family history
36

Obtain Educational Testing (if indicated)

• Measure intellectual ability
• Assess academic achievement

Figure 6.  ADHD assessment.

Rating Scales and Record Review

Rating scales provide easily reviewed clinical data that supplement information
obtained during the face-to-face interview. Developmental questionnaires
and behavioral rating scales can be sent to families when the initial assessment
is scheduled. For younger patients, rating scales are usually obtained from par-
ents and teachers. For older individuals, self-reports, as well as ratings from
spouses, partners, employers, family members, and friends, are useful. Ideally,
completed rating scales are available at the intake visit.
Numerous ADHD rating scales are available and used routinely both in ini-
tial assessments and documenting treatment response (Table 6.). It is unnec-
essary for parents, teachers, or patients to complete multiple ADHD-specific
scales, as most are based primarily on DSM symptoms. Most currently avail-
able scales reference DSM-IV, but these remain useful as symptoms remain
 Table 6.  ADHD Rating Scales

Assessment
Rating Scale How Obtained
Children and Adolescents
ADHD Rating Scale-IV Purchase book and copy: DuPaul GJ, Power TJ,
(ADHD-RS) Anastopoulos AD, Reid R. ADHD Rating Scale—IV (for

Chapter 6
Children and Adolescents). Guilford Press.
Brown Attention Purchase: PsychCorp Pearson. www.psychcorp.
Deficit Disorder Scales peasrsonassessments.com
Conners, 3rd Edition Purchase: Multi-Health Systems, Inc. www.mhs.com
Rating Scales
Swanson Nolan and Free download: www.adhd.net
Pelham (SNAP-IV)
Teacher and Parent
Rating Scales
Vanderbilt Teacher and Free download: www.nihcq.org/toolkit
Parent Rating Scales
Adults
Barkley Adult ADHD Purchase and copy: Barkley RA. Barkley’s Adult ADHD
Rating Scale-IV Rating Scale IV (BAARS-IV). Guilford Press.
(BAARS-IV)
Brown Attention Purchase: PsychCorp Pearson. www.psychcorp.
Deficit Disorder Scales peasrsonassessments.com
Conners’ Adult ADHD Purchase: Multi-Health Systems, Inc. www.mhs.com

37
Rating Scales
World Health Download: www.webdoc.nyumc.org/nyumc_d6/files/
Organization Adult psych_adhd_screener.pdf
ADHD Self Report
Scale (ASRS)

unchanged in DSM-5. At times, individuals have their own biases in complet-

ing rating scales and the clinician must carefully balance and assess the impli-
cations of conflicting reports. Other general rating scales, such as the Child
Behavior Checklist (CBCL) or Symptom Checklist-90 Revised (SCL-90R),
are not specific for any diagnosis but are frequently used to obtain broad
measures of psychological functioning and impairment to supplement
ADHD-specific ratings.
In addition to ratings scales, it is important to review any available school
records, standardized test results, employment records, and previous edu-
cational or psychological test reports. Clinicians can quickly review these
records and integrate them with other available data.

Clinical Interview
In younger patients, parents are the primary informants. Interviewing third
parties is less important with older patients and not routine with adults. Except
with very young children, some portion of the initial assessment should be
conducted alone with the patient. Having individual time with children apart
ADHD from parents can help in assessment of ADHD symptoms, social relatedness,
and other psychiatric conditions, as well as provide a foundation for ongoing
treatment. Individual time with older children and adolescents is essential for
building trust and discussing sensitive topics such as sexual activity and illicit
substance use. Adult patients, at times, will ask to include partners or other
adults in their evaluation. It is usually best to allow this only after the initial
private interview is completed.
Approaches to assessment might differ depending on the clinician’s spe-
cialty training or practice setting. Primary care physicians generally have less
time for initial evaluations but better access to past medical history, knowl-
edge of the family, and patient’s community. Specialists, such as psychia-
trists, neurologists, and psychologists, usually have longer initial visits and
are better able to assess psychiatric comorbidities but have less access to
medical records. In all cases, routine use of rating scales completed before
the evaluation and reviewed during the office visit greatly facilitates efficient
clinical management.
In research settings, diagnosis is usually based on structured or semis-
tructured reviews of DSM symptoms using standard interviews such as the
Schedule for Affective Disorders and Schizophrenia for School Age Children
(KSADS). These interviews require specific training and considerable effort.
Minimally, clinicians must methodically determine the presence or absence
of each DSM ADHD symptom and its approximate age of onset. Symptoms
38

must be assessed in their developmental context; that is, they must be of

greater frequency and severity than what is typical for others of the same
sex, age, and cognitive level. Specific impairments should be documented to
verify the diagnosis, establish objective treatment targets, and, if necessary
justify medication use and expected duration of treatment. Most individuals
with ADHD have at least one additional psychiatric disorder (see Chapters
3 and ). Care must be taken to differentiate other disorders that might be
comorbid with ADHD, as well as disorders that share ADHD features and
could be misdiagnosed. The clinical evaluation should review symptoms of
oppositional defiant disorder, disruptive mood dysregulation disorder, con-
duct disorder, anxiety, depression, mania, autism spectrum disorder, specific
learning disorders, intellectual disability, substance abuse, and tic disorders.
Older individuals sometimes adapt to ADHD with lifestyle choices that min-
imize obvious impairments, such as choosing occupations that do not require
sustained attention or denying interest in personal relationships. The clinician
must assess whether these are healthy adaptations to the disorder or denial
of its consequences. Given the potential for adaptation, diagnosis in adults can
be based on a history of multiple impairments over the lifetime, rather than
concurrent impairment in multiple domains at the time of evaluation.
Given that follow-up visits for ADHD management are often limited to
brief appointments, it is crucial during the initial evaluation to consider the
patient’s full psychosocial context. This allows proper consideration of exter-
nal factors that might affect behavior and helps identify the full range of psy-
chosocial problems that might require intervention. In younger patients, it
is necessary to assess whether one or two parents are involved, the nature
of the relationship between parents, style of parenting and discipline, living
arrangements, the degree to which nonparental adults participate in supervi-

Assessment
sion, and nonacademic activities that the child enjoys. In older patients, it is
helpful to understand living arrangements, the nature of personal support
networks, and recreational interests.
Patients might or might not exhibit overactivity in the office setting. If
observed, it helps corroborate ADHD, but its absence does not contra-

Chapter 6
dict the diagnosis. Clinicians should also be mindful that some, particularly
younger, patients can be shy in unfamiliar settings, and that failures to engage
with the examiner might not represent usual behavior.

Developmental Considerations
in the Clinical Interview
Strategies for assessing ADHD were developed primarily from experience
with school-age children. With increased awareness that ADHD occurs in all
age groups, modifications in standard approaches to assessment can better
address developmental differences that occur across the life span.
Preschool-Age Children
Normally high levels of distractibility and overactivity confound differentiating
preschool-age children with and without ADHD. It remains unclear whether

39
teacher-completed rating scales are as well validated and sensitive in differ-
entiating normal and abnormal levels of hyperactivity in very young children
compared to older youth. In DSM field trials, most patients with ADHD had
greater than expected levels of hyperactivity and impulsivity by about age
4. The majority of children brought for ADHD evaluations are in kindergar-
ten or early grade school. However, increasing numbers of preschool-age
children are being diagnosed and subsequently treated with medication.
Difficulties that frequently occur with ADHD in this age group include sleep
irregularities, excessively oppositional and defiant behavior, temper tantrums,
aggression, and increased risk for accidental injuries and conflict both in and
outside of the home. Preschool-age children with more severe ADHD tend
to retain their diagnosis over time, although current presentations seen at ini-
tial diagnosis often change at subsequent assessments. Clinicians should also
assess potential autism spectrum disorders and intellectual disabilities, as well
as problems with hearing, speech and language, elimination disorders, family
approaches to parenting, and overall psychosocial history.
School-Age Children
It is useful in assessing a school-age child to determine what is known or
expected about the clinic visit. A question like “What did your mom tell you
about why you are coming to the doctor today?” can provide a good sense of
the child’s insight into his or her difficulties. Diagnosis in this age group chiefly
relies on parent and teacher reports. Younger children very rarely endorse
ADHD symptoms or related problems. Nonetheless, it is important to
include the child in the assessment, both to aid in evaluation and set the stage
for treatment adherence. Direct observation might reveal obvious problems
ADHD with hyperactive-impulsive behavior, although ADHD symptoms are often
not evident in tightly controlled settings. If feasible, observing the child in a
group setting, such as the lobby waiting area or an actual classroom, pro-
vides more valuable information about potential ADHD behaviors. Common
comorbid disorders include learning disorders, autism spectrum disorders,
oppositional defiant disorder, anxiety, and tic disorders.
It is reassuring when parent and teacher reports report similar patterns of
ADHD symptoms. At times, clinicians will have to make sense of conflicting
information. Parents and teachers might have their own biases that interfere
with accurate reporting. Parental biases might reflect their own psychopa-
thology, including depression or personal histories of ADHD, their ability to
tolerate certain levels of behavioral disruption, and cultural attitudes. One
parent might spend more time with the child and be a more accurate infor-
mant than the other. Parents who have ADHD themselves might be eager to
intervene or might resist seeing anything wrong. Some parents are particularly
motivated to obtain medication and/or academic accommodations, while
others are strongly opposed to medication or are concerned about stigma if
teachers and others find out about the diagnosis.
Teacher reports might also suffer from bias. Some teachers are strong
proponents of ADHD, with expectations that prescription medication will
help both the child and classroom management. Others resist the diagnosis,
sometimes based on negative views of medication or an unwillingness to
40

provide accommodations or special treatment for the student. Some teach-

ers do not have time or are unwilling to complete ratings. Teachers are gen-
erally better observers of hyperactive-impulsive symptoms than inattention
or distractibility.
Impairment in younger patients is generally reflected at home, school, and
with peers. Since diagnosis requires evidence of symptoms and impairment
in multiple settings, it is necessary to consider other sources of information if
parent and teacher reports conflict. Reviewing several years’ school records is
very helpful. While teachers rarely make overtly critical comments on report
cards, difficulties are sometimes subtly evidenced by less-than-glowing behav-
ioral assessments. It is generally advisable to heed teacher complaints of
ADHD-like difficulties when parents fail to see problems, appreciating all the
potential issues of bias in parental reports. In contrast, high levels of parental
complaints in the absence of any school-related difficulty suggests that family
issues may be of greater concern and emphasizes the importance of a thor-
ough psychosocial assessment.

Adolescents
Adolescents evaluated for ADHD are often either highly motivated and
hoping to improve their academic performance in anticipation of college or
having very severe academic, social, or family difficulties with a high risk for
significant life failures. An essential goal of the initial assessment is develop-
ing a degree of trust between the adolescent patient and clinician, which is
essential in subsequently developing an effective treatment strategy. It is gen-
erally advisable to begin the assessment by interviewing the adolescent alone,
prior to meeting with parents, to assess the patient’s motivation and goals,
discuss confidentiality and its limits, and give the patient the first opportunity

Assessment
to describe what is going on. Good initial questions are “What is your under-
standing about what this meeting is for today?” or “How can I help you?”
After providing the adolescent with the initial opportunity to discuss pertinent
information, parents can be invited to join the session and asked to provide
a long-term perspective and other missing information. It is not advisable to

Chapter 6
meet with parents without the teenager present, unless parents convey that
there is highly sensitive information that they would otherwise not discuss.
A teenager’s normal strivings to become independent from parents, particu-
larly regarding peer relationships, sometimes adds to family tension. At times,
parents need assistance differentiating problems related to ADHD from
those of normal adolescent development.
Adolescents are typically the best informants on their own current ADHD
symptoms.2 Parents can usually describe symptom patterns that began early
in childhood, but they generally do not spend enough time with their teenage
children to give accurate descriptions of current behavior. Teacher ratings
are less valuable once students leave elementary school, as students rotate
through different classrooms over the course of the day. Review of past and
current academic records can provide important corroborating evidence for
the diagnosis, which is particularly helpful if the patient is uncooperative.
Adolescents with ADHD often have fewer hyperactive-impulsive symp-
toms than younger children (see Chapter 5). Some symptoms manifest differ-

41
ently. For example, adolescents might complain of inner restlessness instead
of overactivity. Inattention might manifest as problems with motivation, orga-
nization, and completing tasks. Failing to turn in completed assignments is a
common cause of low grades. Neuropsychological testing can be particularly
useful in differentiating mild or predominately inattentive ADHD from other
learning disabilities.
Adolescents with ADHD are at greater risk for early initiation of nicotine
use, illicit drug use, alcohol, and sexual activity, as well traffic violations and
motor vehicle accidents (see Chapter 3). These risks should be assessed dur-
ing the evaluation, and opportunities taken, when indicated, to provide coun-
seling toward reducing them.

Adults
Adults generally come for evaluation from a sense of personal frustration
and lack of accomplishment or due to the insistence of third parties such as
spouses, partners, parents, or employers. It can be helpful to begin the inter-
view by asking, “Why are you coming now for an evaluation of ADHD?” The
questions that best identify adults with ADHD are “Are you easily distracted
by extraneous stimuli?” and “If you are interrupted while doing something, is
it hard to get back to what you were doing before the interruption?” Adults
without clinical disorders will rarely answer yes to these questions. Positive
responses are highly indicative of ADHD or another psychiatric disorder.
Adult patients are generally the primary informants in their own evalua-
tions. Parents, spouses, partners, and others, if available, can provide use-
ful corroborating information, but their involvement is limited due to privacy
needs. DSM criteria require some evidence of symptoms before age 2.
ADHD Adults with superior cognitive abilities or strong levels of academic support
might experience their symptoms and related impairment until they face
demands of higher education, full-time employment, or living independently.
Problems with inattention and executive function often have greater rel-
evance for adults. Common difficulties include problems related to organi-
zation, distractibility, time management, and following through on important
tasks. Psychiatric comorbidity is the rule and not the exception. Common
comorbid conditions include lifetime histories of conduct disorder or antiso-
cial behavior, nicotine dependence, other substance abuse or dependence,
depression, anxiety disorders, and risky behaviors (see Chapters 3 and ).
Some clinicians remain skeptical of the validity of adult ADHD and continue
to view adults seeking evaluations as primarily malingering or drug seeking.
Reliance on adult self-report of ADHD symptoms appears as a major con-
cern, although doubts about symptom self-report do not generally extend to
the diagnosis of other psychiatric disorders. Corroboration of self-reported
history of ADHD symptoms with past records, third-party reports, and an
overall life course consistent with the known developmental outcomes of the
disorder remain the best approach to establishing an ADHD diagnosis.

Medical Assessment
42

Patients diagnosed by nonmedical clinicians require medical assessment prior

to initiation of medication. Physicians, regardless of specialty, should con-
duct a medical assessment as part of their evaluation. This includes review
of current and significant past illnesses, surgeries, current and past chronic
medication history, major accidents and physical injuries, and possible loss of
consciousness. Specialist physicians should confirm that the patient has had
necessary primary care and health maintenance, including appropriate physi-
cal examinations and immunizations. If appropriate for the patient’s devel-
opmental level, the potential onset of risky behaviors, such as nicotine, drug,
and alcohol use, motor vehicle use, and sexual activities, should be discussed.
The clinical interview provides an additional opportunity to counsel patients
on reducing these risks, such as the use of seat belts, not drinking and driving,
and safe sex practices.
Some general medical conditions can mimic or cause ADHD symptoms
and should be considered in the context of other history. Obstructive sleep
apnea or other sleep disorders, seizure disorders, and endocrine disorders,
such as thyroid disease and diabetes, should be considered in the context of
other supportive history.
Physical examination is not typically necessary if the patient has received
appropriate general medical management. Measuring height, weight, and vital
signs is the standard of care. Height and weight should always be documented
in children and adolescents. Blood pressure should be documented for older
patients. If abnormal motor movements or vocalizations, that is, tics, are
present, their nature, frequency, and intensity should be documented. Vision
and hearing tests are not standard but might be considered if indicated by
specific history.
Screening for Cardiac Risk

Assessment
Due to baseline rates of sudden death among individuals under age 35, it is
necessary to screen for cardiac risk prior to initiation of ADHD pharmaco-
therapy. Key questions should be asked of all patients (Box 6.) and answers
recorded. These are the same questions that are assessed in youth sports
physicals. A positive response to any of these suggests the need for further

Chapter 6
cardiac evaluation prior to medication treatment. In the absence of positive
responses, it is generally accepted that additional cardiac workup is unneces-
sary. The American Heart Association supports obtaining electrocardiograms
(EKGs) if one is deemed necessary, but routine EKG screening is not generally
indicated or considered useful (see Chapter 2).
Family History
Given the high heritability of ADHD, it is not uncommon to identify other
family members with or likely to have the disorder. The evaluation should
review the family history for other evidence of learning and academic difficul-
ties, mood and anxiety disorders, and problems with substance abuse and/or
antisocial behavior. While positive family history does not confirm an ADHD
diagnosis, the information is helpful in corroborating the diagnostic picture. It
can also prove useful in treatment planning, particularly if one or both parents
are also affected.

43
Educational Testing
Approximately half of individuals with ADHD have other measurable learn-
ing impairments. Some assessment for learning disability should be part of any

Box 6.  Screening Questions for Identification of Potential

Cardiac Risk Factors for Sudden Death
Is there any history of:
Unexplained shortness of breath with exercise?
History of poor exercise tolerance?
Fainting or seizures with exercise?
Palpitations with exercise?
Family history of sudden or unexplained death in first- or second-degree
relatives?
Long QT syndrome or other hereditary arrhythmias?
Wolff-Parkinson-White syndrome?
Cardiomyopathy, heart transplant, pulmonary hypertension, or an
implantable defibrillator?
Hypertension?
Organic (not functional) heart murmur?
Other cardiac abnormalities?
Answering “yes” to any question should prompt review by an appropriate specialist in
cardiology prior to initiation of medication.
Source: Adapted from Warren et al.4
ADHD
Box 6.2  Tests to Assess Learning Disabilities
Tests of Intellectual Function
Wechsler Preschool and Primary Scale of Intelligence Preschool age
(WPPSI)
Wechsler Intelligence Scale for Children (WISC) School age
Wechsler Adult Intelligence Scale (WAIS) Adults
Tests of Adaptive Functioning or Developmental Level
Denver Developmental Screening Test Preschool age
Vineland Scales of Adaptive Behavior
Tests of Academic Achievement
Woodcock Johnson Tests of Achievement
Wechsler Individual Achievement Test (WIAT)
Wide Range Achievement Test (WRAT)
Nelson-Denny Reading Test

ADHD evaluation. Appropriate tests provide estimates of intellectual ability and

academic achievement, as well as adaptive functioning, if there are questions
of intellectual disability (Box 6.2). Learning disabilities are diagnosed when dis-
44

crepancies exist between measured intellectual level and academic achievement.

Screening tests can be sufficient for an initial assessment with an option to follow
up with more comprehensive testing if specific difficulties are suspected.
Some practical considerations, such as cost and access to testing, impede
routine screening for learning disabilities in ADHD evaluations. Physicians
do not typically perform these examinations, which necessitates referral to
a psychologist or educational specialist. Private medical insurance compa-
nies rarely cover the expense of educational testing, asserting that schools
are obligated to assess learning disabilities. Schools themselves have limited
resources and can resist or delay evaluations. Clinicians can gain a broad sense
of whether testing is necessary by reviewing academic records and standard-
ized tests scores. Any student who consistently underperforms in school or
scores below average on standardized testing should be screened specifically
for learning disabilities. Families can be advised to self-pay for testing if they
have adequate financial resources. Alternatively, parents can be encouraged
to demand assessments from their school districts. This is generally initiated
by submitting a written request to the school’s guidance office.

Non-Evidence-Based Approaches to Assessment

There is great public interest in assessing ADHD with approaches that are less
subjective than clinical interviews and appear to be based on more objective
scientific measures. Many clinicians utilize these methods, possibly to improve
their own perception of diagnostic certainty, create a veneer of science-based
practice, or increase revenue. Although several of these have revealed inter-
esting research findings, their diagnostic specificity in those investigations is
always based on gold-standard clinical interviews. Routine clinical use of these

Assessment
approaches adds considerable expense to health care costs and has not, as
yet, provided added patient benefit.
Neuropsychological Testing
Some clinicians administer larger batteries of neuropsychological tests to

Chapter 6
assess ADHD. Neuropsychological testing has proven useful in identifying
underlying patterns of cognitive difficulties in ADHD, particularly in areas
of attention control and executive functioning. However, these deficits are
identified in only about half of patients with ADHD, and there is no correla-
tion between cognitive findings and DSM symptoms. Neurocognitive findings
provide no information that is predictive of long-term outcome or treatment
response. There is no proven benefit for the routine use of extensive neuro-
psychological testing in evaluating ADHD per se.
Computerized Tests of Attention
Commercially available computerized tests of attention, such as the Test of
Variable Attention (TOVA) or the Conners’ Continuous Performance Test
(CPT), have appeal as objective laboratory measures. These tests can be
administered in the clinician’s office in about 20 minutes. Patients respond to
different stimuli by pushing a button. This records errors of commission (i.e.,
pushing the button in the absence of a proper stimulus) and omission (i.e.,

45
failing to push the button when required), as well as an estimate of reaction
time. Results are compared to known profiles of people with and without
ADHD. Clinicians are able to charge for the tests as diagnostic procedures.
The main limitation of these tests is that results are neither sensitive nor
specific for the diagnosis. Many patients with ADHD excel at computer games
and do not show predicted deficits. Numerous psychiatric and neurologi-
cal conditions are associated with deficits in attention and response inhibi-
tion. Despite their potential appeal, computerized tests of attention have no
added value for assessing ADHD.
Electroencephalography
Some research suggests that patients with ADHD exhibit different patterns
of brain electrical activity as measured by EEG, particularly increased theta
power.3 While these findings provide a basis for future research on ADHD
neurobiology, EEG results have poor predictive power for the diagnosis
itself. Obtaining an EEG is clinically indicated only in the context of history
or physical findings suggestive of seizures or other neurological disorders as
evidenced by functional deterioration or specific neurological symptoms.
Brain Imaging Studies
There is great interest in using brain imaging modalities for ADHD diagnosis.
Considerable research has consistently shown differences in brain structure,
function, and developmental trajectories in groups with and without ADHD
(see Chapter 4). However, it is essential to recognize that these studies assess
group effects, and there is a great deal of variability among individuals within
each group. No data suggest that brain imaging findings for individual patients
have predictive power for the diagnosis. Some practitioners represent that
ADHD they can diagnose ADHD and other psychiatric conditions on the basis of
neuroimaging, particularly using single-photon emission tomography (SPECT)
and positron emission tomography (PET) imaging. There are no scientific data
to support this, and patients and families do not appreciate that the radiation
risk of these procedures is not outweighed by any potential benefit.
Laboratory Studies
There is no role for other laboratory studies, specifically blood and urine
tests, in routine assessment of ADHD. On rare occasions, clinical histories
might suggest an indication for specific tests. Testing for serum lead is reason-
able with a suspicion of lead toxicity because of where the child lives or with
a history of pica. Endocrine studies, such as thyroid tests and fasting blood
glucose, might be indicated if clinical symptoms suggest possible endocrine
disorders. Urine and blood toxicology screens are useful with clinical suspi-
cion of illicit drug use. Although much research has demonstrated genetic
contributions to ADHD risk, none of these findings is specific to the disorder
and there is no justification for genetic testing as an assessment tool.

References
. Lahey BB, Applegate B, McBurnett K, et al. DSM-IV field trials for attention
deficit hyperactivity disorder in children and adolescents. Am J Psychiatry.
46

994;5:673–685.
2. Wilens T, McBurnett K, Bukstein O, et al. Multisite controlled study of OROS
methylphenidate in the treatment of adolescents with attention-deficit/hyper-
activity disorder. Arch Pediatr Adolesc Med. 2006;60:82–90.
3. Loo SK, Makeig S. Clinical utility of EEG in attention-deficit/hyperactivity disor-
der: a research update. Neurotherapuetics. 202;9:569–587.
4. Warren AE, Hamilton RM, Bélanger SA, et al. Cardiac risk assessment before
the use of stimulant medications in children and youth: a joint position state-
ment by the Canadian Paediatric Society, Canadian Cardiovascular Society,
and the Canadian Academy of Child and Adolescent Psychiatry. Can J Cardiol.
2009;25;625–630.

Further Reading
Kooij SJ, Bejerot S, Blackwell A, et al. European consensus statement on diagnosing
and treatment of adult ADHD: The European Network Adult ADHD. BMC
Psychiatry. 200;67.
Nass RD. Evaluation and assessment issues in the diagnosis of attention deficit
hyperactivity disorder. Semin Pediatr Neurol. 2006;2:200–26.
Chapter 7

Treatment Planning
Children and Adolescents

Key Points
• Multimodal approaches to ADHD treatment in youth have proven
successful in maximizing improved global functioning.
• Pharmacotherapy is the only intervention to yield large treatment
effects on core ADHD symptoms.
• Optimal ADHD management usually combines medication treat-
ment with psychosocial interventions that target patient-specific
difficulties.

47
47
ADHD medications were first introduced with the caveat that they be used
only when psychosocial and behavioral therapies had proven inadequate. As
the pervasive consequences of ADHD became evident, a view developed
that multimodal approaches to treatment, that is, medication management
combined with a comprehensive range of psychosocial interventions, were
optimal for behavioral improvement and long-term outcomes. This strategy
was tested in the landmark Multimodal Treatment Study of ADHD (MTA),
which randomized children to 4 months of intensive medication manage-
ment, intensive behavioral therapy, combination medication and behavioral
therapy, or community-based treatment. While the study demonstrated
that medication management was most effective for acute control of ADHD
symptoms, combination medication and behavioral interventions yielded the
best improvement in overall functioning. The general approach to treatment
of ADHD in youth since the MTA Study has been an emphasis on pharma-
cotherapy combined with specific psychosocial treatments matched to indi-
vidual patient needs.
Treatment usually requires a team approach that coordinates various
interventions in office, family, and school settings. This includes services by
physicians, psychologists, teachers, and other mental or behavioral health
professionals. Optimal integration of these services can vary based on the
background and strengths of the lead clinician, as well as family needs and
resources. Psychiatrists, pediatricians, other primary care specialists, psychol-
ogists, and other mental health experts likely differ in expertise as well as the
ADHD time they have available for clinic visits. A critical component of successful
treatment planning rests on the ability of the lead clinician to provide nec-
essary care or appropriate referral to collaborating clinicians who can assist
in patient management. This approach is consistent with the medical home
model developed by the American Academy of Pediatrics.

Assessment
More time is typically available for initial assessments than for follow-up visits.
During the initial evaluation, clinicians optimally obtain a comprehensive view
of ADHD symptoms and impairments within the context of the patient’s
family and social functioning (see Chapter 6). It is easier to assist with sub-
sequent difficulties if the full range of patient problems is identified at the
start of treatment. The initial assessment also establishes a level of rapport
between the clinician and family, which can facilitate long-term treatment
adherence and success.
Major areas of concern for children and adolescents with ADHD are dif-
ficulties that impact life at home, school, and with peers. Assessing the degree
to which an individual has problems within these domains is the first step in
developing a comprehensive treatment plan. Standard approaches to ADHD
treatment target single or multiple domains, and they include family, aca-
48

demic, social, and individual interventions (Fig. 7.).

Once a diagnosis is made, clinicians should provide feedback that summa-
rizes the diagnostic impression and places the patient’s difficulties in context
with what is known about ADHD. Patients and families often find reassurance
in learning that their problems are not unique but fall into patterns that are
similar to others with the disorder. It is also useful to describe aspects in which
the individual patient is unique. This provides a solid basis for discussion of
appropriate treatment options.

ADHD Treatment Management

Psychoeducation

Patient Focused
School Focused
Family Focused

Figure 7.  Multimodal approaches to ADHD treatment.

 Treatment Planning
Psychoeducation
Psychoeducation provides information about ADHD that goes beyond
diagnostic feedback and discussion of treatment options.2 Psychoeducation
should begin once the diagnosis is given and should continue throughout clini-
cal care. Psychoeducation is an accepted evidence-based treatment for sev-
eral adult psychiatric disorders, including schizophrenia and bipolar disorder.
Similarly, it is shown to be useful in managing ADHD, a disorder with poten-

Chapter 7
tial lifelong consequences requiring ongoing patient involvement to optimize
treatment adherence.
Psychoeducation ideally presents didactic information about ADHD,
its consequences, and strategies for intervention. There are numerous
approaches to incorporating psychoeducation into an ADHD management
plan. Useful formats include informal discussion, structured lectures, slides and
videos, provision of brochures and information sheets, or referral to books,
websites, and support groups (Box 7.). Skill development through role-play
and problem-solving exercises has proven useful. Psychoeducation is appropri-
ate for parents and children with ADHD. Its emphasis properly shifts to patient
education during adolescence when teenagers are inclined to assume more
responsibility for personal decision making. Psychoeducation is also useful for
teachers and other professionals who interact with ADHD-affected youth.

49
Psychoeducation can be incorporated into regular medication visits, behav-
ioral therapies, family counseling sessions, and professional development
programs. It can be structured into single didactic sessions or comprehen-
sive workshops. Outcome studies indicate that psychoeducational programs
increase parent and teacher awareness, improve maternal well-being and
competence, increase patient and family satisfaction, decrease social stigma
among patients and other family members, decrease family conflict, and
improve compliance with prescribed medication regimens.2

Family-Focused Interventions
It is naïve to assume that pharmacotherapy is sufficient to control all
ADHD-related impairments. Family interventions can play a primary role
with very young children, in patients with milder ADHD, when medications
are ineffective or not tolerated, or when parents are strongly opposed to
medication use.3 Family treatments are particularly useful with comorbid
oppositional defiant disorder or anxiety. Combination approaches result in
greater parent satisfaction than medication alone.
With abuse, significant family chaos, economic hardship, marital diffi-
culties, or other severe stressors, environmental influences are likely to
overwhelm any benefit derived from medication and attempts at effec-
tive parenting. Clinicians must remain cognizant of broader social fac-
tors, which are likely to require interventions that go beyond standard
approaches to ADHD.
ADHD
Box 7.  Resources for Families
Support Groups
Attention Deficit Disorder Association (ADDA)
www.add.org
Children and Adults with Attention Deficit Disorders (CHADD)
www.chadd.org
Edge Foundation
www.edgefoundation.org
Learning Disabilities Association of America (LDA)
www.ldanatl.org
Informative Websites
American Academy of Child and Adolescent Psychiatry (AACAP):
Facts for Families
http://www.aacap.org/AACAP/Families_and_Youth/Facts_for_
Families/Facts_for_Families_Pages/Children_who_Cant_Pay_Attention_
ADHD_06.aspx.
Healthy Children
http://www.healthychildren.org/English/health-issues/conditions/adhd/
Pages/Understanding-ADHD.aspx?
National Institute of Mental Health (NIMH)
50

http://www.nimh.nih.gov/health/publications/adhd/
complete-publication.shtml
US Centers for Disease Control and Prevention
http://www.cdc.gov/ncbddd/adhd/
Books
Barkley RA. Taking Charge of ADHD, Third Edition: The Complete
Authoritative Guide for Parents. Guilford Press; 203.
Monastra VJ. Parenting Children With ADHD: 0 Lessons That Medicine
Cannot Teach. American Psychological Association (APA); 2005.
Pope L, Oswald HM. Colleges That Change Lives: 40 Schools That Will
Change the Way You Think About Colleges. Penguin Books; 202.
Wilens TE. Straight Talk About Psychiatric Medications for Kids, Third Edition.
Guilford Press; 2008.

Behavioral Parent Training

Children and adolescents with ADHD are often difficult to manage and con-
tribute to significant stress within families and between parents. This situation
can be worsened if one or both parents have ADHD. In typical situations,
successful approaches to parenting ADHD-affected children are similar to
those that are useful in parenting most children.
Behavioral parent training methods used in the MTA Study are widely
available, easy to implement, and associated with positive overall improve-
ments in child behaviors.4 Behavioral improvements are not specific to core
ADHD symptoms. Training also contributes to increased parent confidence
and reduced parent stress.
 Social learning theory suggests that antecedents and consequences largely

Treatment Planning
drive behavior, and that parents can modify their children’s behaviors by
changing their own approach to parent–child interactions. Parent training pro-
grams primarily aim to teach parents implementation of behavioral and cogni-
tive techniques proven useful in modifying problematic childhood behaviors.
Programs designed specifically for parents of children with ADHD also com-
monly add a psychoeducational component on the nature and consequences
of the disorder.3
Parent training is suitable for individual or group settings.5 The overarching

Chapter 7
goal is to improve positive interaction patterns between parents and children
and decrease parents’ coercive and negative responses to unwanted behav-
iors. More specific goals include recognizing the importance of structure and
consistency, reducing harsh and critical parenting, and avoiding discipline
approaches that are either lax or overly punitive. Other common topics
include improving child management by setting consistent limits and expecta-
tions, increasing use of positive attention to increase appropriate behaviors,
and developing a set of responses to negative behaviors that includes ignor-
ing, time-out, and natural consequences.
Programs are typically organized into - to 2-hour weekly sessions con-
ducted over 0 to 20 weeks.5 Sessions can be structured so that participants
learn and master one skill before progressing to the next. Participants learn to
identify common parenting errors by watching recorded vignettes, generate

51
solutions and alternatives based on their understanding of behavioral tech-
niques, and practice appropriate parenting skills with role play. Homework
between sessions reinforces key concepts from the lesson. Specific skills often
include design and implementation of daily “report card” and associated
reward systems for home behaviors; focusing on praise, reward, and positive
reinforcement; how to ignore minor annoyances and undesired behaviors;
how to give effective commands; establishing “when-then” contingencies
and the importance of warnings and transitions; and the appropriate use of
“time-out.”
It is useful for clinicians to approach parents of younger children as
co-therapists whose role is to modify behaviors at home through the appli-
cation of appropriate behavioral techniques. As older children and adoles-
cents gain the cognitive capacity to understand the consequences of their
actions, behavioral interventions shift to the larger family and include efforts
to improve communication, problem solving, limit setting, and behavioral
contracting to agree on expected parental responses to positive and negative
child behaviors.
Several programs similar to behavioral parent training are designed spe-
cifically for preschool-age children.6 Parent Child Interaction Training (PCIT)
attempts to improve parent–child interactions using two basic interven-
tions. First, in child-directed interaction, parents engage their child in play to
improve their general relationship. Second, in parent-directed interaction,
parents learn specific behavioral management skills as they play with their
child. Another form of parent training is the Community Parent Education
Program (COPE), which also focuses on improving parent–child relation-
ships and development of more effective parent management skills. Each
ADHD of these, PCIT and COPE, is an evidence-based intervention with strong
empirical support.
Other Family Therapies
Other types of family therapy might be appropriate for specific circumstances.
For example, marital or relationship therapy might improve severe parental
discord; bereavement therapy or grief counseling might be appropriate fol-
lowing a death or other loss; family therapy might be indicated in following
trauma or abuse. Proper management of parental ADHD can be essential to
optimize overall family functioning (see Chapter 8).

School-Focused Interventions
Proper classroom placement and educational planning are essential compo-
nents of ADHD management.7 School interventions for ADHD differ from
those designed to address specific learning disabilities. Families and schools
vary on the level of resources they can provide for school-based ADHD
treatment. Given those limitations, students should be placed in optimal aca-
demic environments with appropriate educational services.
Schools receiving US federal dollars are legally required to meet the edu-
cational needs of all students. Success in fulfilling this mandate is dependent
52

in part on local school standards and budgetary constraints. It is sometimes

helpful for families to obtain educational advocates or other legal aid to assist
in obtaining necessary services. While some private schools emphasize pro-
grams designed for students with ADHD and other behavioral or learning
difficulties, they have no legal obligation to provide special services.
Section 504 Plans
Section 504 plans are required by the Federal Rehabilitation Act of 973 to
ensure that students with disabilities attending elementary and secondary
schools receive appropriate modifications in educational services to support
their academic success and access to learning. Section 504 plans can be imple-
mented in regular classrooms, regular classrooms with supplemental pullouts
for resource assistance, or in specialized, self-contained classrooms. Typical
academic modifications provided under these plans include preferential class-
room seating, extended time on tests, taking examinations in less distract-
ing areas, breaks during examinations, and modified or reduced homework
assignments. These modifications have little financial cost, but successful
implementation depends on cooperation from the classroom teacher.
Students are eligible for 504 plans if they have a physical or mental impair-
ment that limits a major life activity, such as attending school. Schools estab-
lish specific procedures and criteria to determine eligibility under federal
guidelines. A clinician’s note attesting to an ADHD diagnosis is generally
not sufficient to obtain services. Clinicians should direct parents to request
evaluations for 504 plans through the child’s school counseling office. A mul-
tidisciplinary committee determines eligibility based on information derived
from an array of sources, including medical records, psychoeducational tests,
teacher recommendations, social and cultural factors, and physical limita-

Treatment Planning
tions. Schools are obligated to conduct their own evaluations, but they may
consider outside testing reports if available. Parents have the right to appeal
though a due process hearing if they disagree with the committee’s assess-
ment and recommendations.

Individualized Educational Programs

An individualized educational program (IEP) is required by the Federal
Individuals With Disability Education Act (IDEA) to ensure that students

Chapter 7
with disabilities who attend elementary and secondary schools receive spe-
cialized instruction and related services necessary for their educational suc-
cess. Services under IEPs go beyond 504 plans and can include time and
resources for academic tutoring, provision of : classroom aides, placement
in self-contained special education classrooms, additional individual or group
counseling, placement in a publically funded private school, or other services.
Eligibility procedures are similar to 504 plans.

Behavioral Classroom Management

Behavioral classroom management uses approaches that are similar to behavioral
parent training and can be particularly effective when implemented in conjunc-
tion with behavioral approaches used at home.4 Implementation of behavioral
classroom management depends on the classroom teacher and incorporates

53
contingency management procedures that include daily report cards, point sys-
tems and reward programs, and appropriate use of time-out. This approach is
the basis for specialized school programs for ADHD, but some teachers imple-
ment them for individual students in regular classrooms. Behavioral classroom
management results in moderate treatment effects on disruptive behavior,
attention to instruction, rule compliance, and work productivity.

Standardized Testing Accommodations

Schools may allow students to take extra breaks during examinations and also
provide a quiet environment to take tests. Students with ADHD and addi-
tional learning disabilities can sometimes obtain untimed or extended time
on standardized tests and college entrance examinations. These modifications
can be extremely helpful when students are otherwise qualified academi-
cally, but limited in their performance by ADHD. Criteria and procedures
for obtaining extended examination time are typically listed on the testing
organizations’ websites. As with 504 plans and IEPs, eligibility usually requires
some level of psychoeducational testing that goes beyond certification of a
clinical diagnosis.

Patient-Focused Interventions
Health Maintenance
Regardless of who coordinates ADHD treatment, all patients ideally have a
primary care physician to oversee general health maintenance. This includes
periodic physical examinations, charting growth trajectories, and timely
ADHD administration of recommended immunizations. Co-occurring general medi-
cal conditions, such as dermatological, endocrine, or neurological disorders,
should be managed appropriately in conjunction with ADHD therapy.
Health maintenance as a specific focus of ADHD management can be
organized with a developmental focus. With younger children, clinicians
should counsel parents on maintaining safety within and outside the home,
including use of bicycle and skateboard helmets and wearing seat belts while
driving. With older youth, clinicians should address safety issues pertaining to
high-risk activities frequently seen in adolescents with ADHD, including recre-
ational drug and alcohol use, sexual activity, and reckless driving.

Pharmacotherapy
Pharmacotherapy is likely to be recommended for most patients (see Chapter
0). Selection of a particular ADHD medication can depend on prior response
or nonresponse, family preference, ease of administration, required duration
of effect, tolerability, presence of comorbidities, and other factors. An initial
titration period is generally advised before a specific medication and optimal
dose can be prescribed. Clinicians should present medication as part of an inte-
grated treatment strategy and not as the sole solution to a patient’s difficulties.

Social and Peer-Related Activities

Children and adolescents with ADHD demonstrate a range of social compe-
54

tence. Some are popular and talented, despite other difficulties. Others, par-
ticularly those with autism spectrum disorder, have substantial peer-related
problems. As children progress through elementary and middle school, social
interactions are increasingly important in shaping self-perception, interests,
and preferred activities. Promotion of positive peer skills and social relation-
ships is a critical component of ADHD treatment.
Children sometimes develop a negative sense of themselves because
they take medication or attend therapy. The optimal way to improve social
interactions is by supporting a child’s ability to be successful in typical,
age-appropriate activities with friends and peers. To the extent that they are
able, parents should actively facilitate play dates and other peer interactions.
Parents should also encourage participation in activities in which their child
expresses interest and can develop a level of competence and enjoyment.
Examples include team or individual sports, music, art, drama, or other struc-
tured activities typically enjoyed at a given age.

Social Skills Training

Some children are unable to develop appropriate peer interactions with sim-
ple participation in age-appropriate activities. Social skills training programs
help develop and improve individual social skills.4 These programs follow
models similar to those used in behavioral parent and classroom manage-
ment training. Group social skills sessions can be conducted weekly, often in
conjunction with psychoeducation or parent management training for adults.
Specific goals of social skills programs include helping participants to modify
verbal and nonverbal behaviors so they can be more successful in social situa-
tions. As with parent training programs, videos, role play, and homework are
used to reinforce learning specific social skills. Lessons might address learning

Treatment Planning
to wait your turn, calling someone on the telephone, inviting yourself into
a playgroup, recognizing emotions in others, and generating alternatives to
deal with frustration and disappointment. Social skills programs have been
implemented in clinics, schools, summer camp programs, and other ven-
ues. Currently, available research evidence neither supports nor refutes the
potential value of social skills training as a component of ADHD treatment.8
Individual Psychotherapy

Chapter 7
Individual psychotherapy, including cognitive-behavioral therapy, has not
proved useful in pediatric ADHD and is rarely recommended in this age
group. Appropriate forms of individual psychotherapy might be useful and
considered for difficulties often associated with ADHD, such as anxiety,
depression, or low self-esteem.

Promoting Treatment Adherence

Psychosocial and behavioral ADHD treatments are usually time limited.
Medication therapy requires long-term use for ongoing response. Follow-up
studies up to 5 years demonstrate sustained clinical benefit with ongoing
medication use. Nonetheless, despite this and the immediate apparent effects

55
of most ADHD medications, one quarter to one third of patients obtain only
one prescription and one half to two thirds discontinue treatment within
 year. Similar to many chronic medical conditions, promoting long-term
adherence to ADHD treatment remains a challenge.
Numerous factors improve long-term adherence. 9 Most important is
maintenance of an ongoing clinician–patient relationship. Patients are more
likely to remain in treatment after more thorough initial evaluations; if they
understand ADHD as a neurodevelopmental disorder; if they undergo initial
short-term titration with low, medium, and high medication doses; and if they
have frequent monitoring visits with dose adjustments to optimize benefits
and decrease side effects. Current Federal DEA regulations require clinical
assessment prior to medication renewal no less frequently than every 90 days.
Insisting that patients come for clinic visits at least once every 3 months, and
generally refusing to approve refills outside of clinic visits, complies with fed-
eral laws and promotes better treatment compliance. Adherence is improved
further when insurance is available to cover costs, when once-daily medica-
tion formulations are used, and when there is a lack of social stigma among
family and peers regarding medication use.
Younger children typically comply with their prescribed medications when
given to them by parents. For older children and adolescents, acceptance of
medication is more likely when the patient has been involved in treatment
decision making and when there is clear evidence of benefit. Authoritarian
demands on older youth are rarely successful in changing behaviors. Instead,
motivational interview techniques can guide older patients toward recogniz-
ing how medication is useful in helping them accomplish their own goals. For
example, a teenager might be willing to take medication on schooldays if he
ADHD or she wishes to attend a good college but might refuse medication on week-
ends because of side effects. Accepting the patient’s input into the treatment
plan is likely to be more beneficial than rigidly insisting that medication must
be taken without question.

References
. The MTA Cooperative Group. A 4-month randomized clinical trial of treat-
ment strategies for attention-deficit/hyperactivity disorder. Arch Gen Psychiatry.
999;56:073–086.
2. Montoya A, Colom F, Ferrin M. Is psychoeducation for parents and teacher
of children with ADHD efficacious? A systematic literature review. European
Psychiatry. 20;26:66–75.
3. Zwi M, Jones H, Thorgaard C, York A, Dennis JA. Parent training interven-
tions for attention deficit hyperactivity disorder (ADHD) in children aged 5 to
8 years. Cochrane Database Syst Rev. 20;2:CD00308.
4. Pelham WE, Fabiano GA. Evidence-based psychosocial treatments
for attention-deficit/hyperactivity disorder. J Clin Child Adolesc Psychol.
2008;37:84–24.
5. Forehand R, Jones DJ, Parent J. Behavioral parenting interventions for disruptive
behaviors and anxiety: what’s different and what’s the same? Clin Psychol Rev.
203;33:33–45.
6. Charach A, Carson P, Fox S, Ali MU, Beckett J, Lim CG. Interventions for pre-
56

school children at high risk for ADHD: a comparative effectiveness. Pediatrics

203;3:e584–604.
7. Semrud-Clikeman M, Bledsoe J. Updates on attention-deficit/hyperactivity dis-
order and learning disorders. Curr Psychiatry Rep. 20;3:364–373.
8. Storebo OJ, Skoog M, Damm D, Thomsen PH, Simonsen E, Gluud C. Social
skills training for attention deficit hyperactivity disorder (ADHD) in children
aged 5 to 8 years. Cochrane Database Syst Rev. 20;2:CD008223.
9. Charach A, Fernandez R. Enhancing ADHD medication adherence: challenges
and opportunities. Curr Psychiatry Rep. 203;5:37–379.

Further Reading
Fiks AG, Mayne S, Debartolo E, Powers TJ, Guevara JP. Parental preferences and
goals regarding ADHD treatment. Pediatrics. 203;32:692–702.
Subcommittee on Attention-Deficit/Hyperactivity Disorder, Steering Committee
on Quality Improvement and Management. ADHD: clinical practice guidelines
for the diagnosis, evaluation, and treatment of attention- deficit/hyperactivity
disorder in children and adolescents. Pediatrics. 20;28:007–022.
Chapter 8

Treatment Planning
Adults

Key Points
• There is a substantial evidence base supporting pharmacotherapy for
adult ADHD.
• Preliminary evidence supports a potential role for psychosocial inter-
ventions, including psychoeducation, cognitive behavioral and other
therapies, school and workplace accommodations, coaching, and
support groups.
• Optimal treatment generally combines medication management with
problem-specific interventions selected for individual patients.

57
57
For most emotional and behavioral disorders, pediatric treatment strate-
gies are generally derived from those developed initially in adults. ADHD is
one disorder in which management of adults is guided by well-established
approaches to treating children. Pharmacotherapy remains the only adult
treatment with well-established evidence based on large controlled studies.
However, pharmacotherapy is rarely sufficient to address the full range of
adult impairments. Research on adult multimodal interventions is increas-
ing, but development of adult psychosocial and behavioral therapies lags
far behind established approaches for children. The challenge with adults
is to integrate medication use with problem-specific psychosocial inter-
ventions that are most likely to optimize functioning in individual patients.
Comprehensive treatment planning for adults might include psychoeducation,
medication management, individual or group therapies, coaching, school or
work accommodations, advocacy, and support groups (Table 8.). The most
useful interventions tend to be brief, well-structured, skill-oriented, and spe-
cific to ADHD.

Assessment
Treatment planning begins with the initial assessment (see Chapter 6). Given
that more time is generally allotted for evaluation compared with follow-up vis-
its, the initial appointment provides a unique opportunity to establish the diag-
nosis, assess potential comorbidities, identify current symptoms, and quantify
ADHD
Table 8.  Treatment Modalities for Adult ADHD
Multiple Positive Single Randomized or Expert Opinion, Open
Controlled Trials Large Uncontrolled Studies, and Anecdotal
Trials Reports
Stimulant medications Cognitive-behavioral Academic
therapies accommodations
Nonstimulant medications Adaptive technology
Advocacy groups
Coaching
Couples therapy
Educational planning
Occupational
accommodations
Psychoeducation
Support groups
Vocational counseling

specific treatment targets. Optimally, the clinician obtains sufficient informa-

tion about the individual’s life to understand the full psychosocial context of
ADHD-related difficulties. At assessment’s end, the clinician should provide
diagnostic feedback and specifically convey an integrated view of how ADHD
58

has affected the person. Improved long-term treatment adherence is associated

with more comprehensive initial assessments, increased patient self-awareness,
and patient participation in choosing initial management options.2
Unlike children who rarely have insight into the nature and consequences
of the disorder, many adults recognize a link between ADHD symptoms and
lifetime difficulties. Children often have little motivation for treatment, and
implementation of psychosocial interventions is largely dependent on parent
and teacher efforts. In contrast, successful adult treatment depends almost
entirely on the patient’s motivation and commitment. Recognition in the ini-
tial assessment of an individual’s readiness to change provides a framework
for subsequent treatment planning.

Psychoeducation
Psychoeducation should begin in tandem with the initial assessment and con-
tinue throughout treatment.3 Individuals who are well informed about ADHD
and how it affects them are more likely to contribute to treatment planning
decisions and remain adherent over time. Ideally, psychoeducation should
include the patient, spouse or partner, and possibly other family members.
Useful topics address ADHD symptoms and typical impairments, prevalence
rates, the natural course of the disorder, common comorbidities and associ-
ated risks, heritability, neurobiology, and management approaches.
An improved understanding of ADHD and its related effects can assist
patients in recognizing that their problems are not unique but are understand-
able in the context of a well-recognized disorder. Psychoeducation reduces
stigma and can decrease hostility among other family members as they gain

Treatment Planning: Adults
greater understanding of ADHD and its consequences. Integration of psy-
choeducation into the overall management plan enhances the relationship
between patient and clinician and is associated with increased long-term
treatment success.

Health Maintenance
Ideally, patients have primary care physicians who manage general medical
health needs. Unfortunately, many adults with ADHD fail to obtain adequate
medical care. Physicians who prescribe ADHD medications should be mindful
of their patients’ general medical status and refer to appropriate providers as

Chapter 8
needed. Patient weight and vital signs should be monitored routinely. Chronic
medical conditions, such as endocrine disorders or hypertension, should be
appropriately controlled.
Adults with ADHD often make lifestyle choices that are inconsistent with
good health maintenance (see Chapter 3). When indicated, ADHD treat-
ment provides an opportunity for counseling on diet, weight control, smok-
ing, drug and alcohol use, and risky behaviors such as driving and sexual
activity. Physicians managing ADHD should assume a broader medical role
than simply writing prescriptions.

59
Medication Management
Treatment algorithms for medication selection in adults are less established
than those for younger patients (see Chapters 0 and ). The FDA has
approved both stimulant and nonstimulant ADHD medications for adults. As
with children, adult clinical trials consistently show larger treatment effect sizes
for stimulants versus nonstimulants (Fig. 8.).4 Potential benefits of any stimu-
lant are easily assessed with short-term titration. Larger effect sizes, safety, and
ease of titration support the recommendation to use stimulants as first-line
adult treatments, similar to pediatric ADHD. Atomoxetine is also indicated for
adults and provides a second-line alternative if stimulants prove unsatisfactory.
Some clinicians have ongoing concerns about stimulants, drug misuse, and
illicit diversion (see Chapter 2). Studies suggest that the risk of abuse, that
is, using medication to get high or for recreational purposes, is small, par-
ticularly with some extended-release formulations. Clinicians should counsel
older adolescents and adults not to sell or share their medication with oth-
ers. Clinicians are obligated to maintain careful medication records, including
dates, strengths, and quantities prescribed. Any patterns of lost prescriptions
or seeking additional prescriptions should be noted and addressed appropri-
ately with the patient. Nonstimulants might be appropriate first-line treat-
ments in patients with histories of serious substance use difficulties or other
medication misuse.
ADHD medications are largely formulated to meet the needs of chil-
dren who attend school and have after-school homework and activities.
ADHD 1

Effect Size Estimates (Cohens D)

0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
1

ine

lts

ine
nt

at
y

Sa
ud

ud

am

m
ula

nid

ta
ine
St

St

im

et
he

fe
ph
s

am
St

lp

m
nt

nt

hy

am

xa
ula

ula

et
et

de
ph
tro
m

Lis
Am
sti

sti

ex
on

on

d
N

ixe
M
Figure 8. Estimated medication effect sizes for adult ADHD. (Adapted from
Moriyama et al.4)

Many adults have work schedules or other obligations that exceed the 8-
to 2-hour duration of effect that is usually provided by a single dose of
60

an extended-release stimulant. Some adults require medication for most of

their waking hours, while others need benefits only while at work or school.
A review of the patient’s schedule and related needs should inform the
clinician’s recommendations on choice of a specific medication and dosing
regimen. With stimulants, an initial titration should assess response on vari-
ous doses of a single-daily dose extended-release formulation (see Chapter
0). Once the optimal medication and dose are determined, complemen-
tary doses of the same medication in an immediate-release form can extend
the duration of treatment effect. Some nonstimulants, notably atomoxetine,
have associated improvements up to 24 hours after dosing, which is poten-
tially useful when medication is required throughout waking hours. Unlike
stimulants, nonstimulants must be taken daily to maintain effects. Clinicians
should not prescribe nonstimulants to patients who will not agree to take the
medication daily.

Educational Planning and Academic

Accommodations
Older adolescents and young adults should develop educational plans that
promote individual interests, strengths, and long-term objectives. Attending
a traditional 4-year college might or might not be the best choice for some-
one with ADHD. Reasonable plans might include attendance at a junior col-
lege or trade school, joining the military, or beginning to work. For those
attending college, acknowledging one’s ADHD and associated limitations, as
well as utilizing available resources, can aid in accomplishing academic goals.
 Students attending postsecondary schools should contact their institution’s

Treatment Planning: Adults
office of disability services and consider requesting educational accommoda-
tions. Although potential long-term benefits of accommodations have not been
systematically studied, anecdotal evidence suggests they are useful.5 Typical
accommodations include provision of note-taking services and books on tape,
extended test time, taking tests in distraction-free examination areas, alternative
forms of examinations, substitutions for required courses, modified assignments,
academic tutoring, and priority in course registration. In some cases, testing
agencies provide modifications for postgraduate entrance examinations such as
the MCAT or LSAT, as well as for state and national licensing examinations.
Student disability offices and test-specific websites provide recommenda-
tions on current requirements for accommodations. Accommodations are

Chapter 8
granted based on legal requirements to assist individuals with disabilities that
substantially interfere with major life functions. To protect against students
faking symptoms, multiple sources of information, including medical and aca-
demic records, third-party observations, and neuropsychological tests should
be considered during assessment (see Chapter 2).5 Documenting ADHD
alone is insufficient. Eligibility requires clearly demonstrating that ADHD
symptoms contribute to substantial impairments in academic activities.
Assessments must be recent and reflect current functioning.
There is ongoing controversy as to whether impairment should be estab-
lished relative to an individual’s measured aptitude, others with whom the

61
student competes academically, or the general population.5 In the United
States, courts have ruled in favor of both the educational-peer and general
population standard for modifications on high-stakes standardized tests.
Nonetheless, there is a growing trend to use the general population standard.
This can make it extremely difficult to obtain accommodations for graduate
or professional school entrance or licensing examinations.

Vocational Counseling and Work

Accommodations
Assisting adults in finding suitable occupations is a critical component of treat-
ment planning. Adults with ADHD often have occupational difficulties due to
poor matching between job requirements and their own strengths and limita-
tions. Some adults with ADHD are very successful when self-employed or
with jobs that provide flexible work schedules, physical activity, or high levels
of stimulation. Vocational testing and counseling can be useful for those with
uncertain occupational interests and objectives.
Under the Americans With Disabilities Act, employees are entitled to
reasonable accommodations at work for disabilities that “substantially limit
a major life activity.” Companies with 5 or more employees are obligated
to provide accommodations under the Act. As with academic accom-
modations, eligibility requires clear documentation of the diagnosis and
related impairments. Employees wishing to obtain accommodations must
disclose their diagnosis and apply in writing to their supervisor or com-
pany’s human resources department. The employee must be otherwise
ADHD qualified for the position and requested accommodations cannot create
an undue employer burden. Typical accommodations include working in
distraction-free areas, flexible scheduling to allow work during periods of
higher productivity, working at home, assigning work that better utilizes an
employee’s strengths and minimizes the need for weaker skills, and provid-
ing assistance devices or software that supports efforts at organization and
effective time management.

Individual Therapies
Medications are at best estimated to reduce ADHD symptoms by 50%, leav-
ing patients with significant residual difficulties. For some, individual therapy
potentially provides further improvement. Several ADHD-specific forms
of individual therapy have preliminary evidence of treatment effectiveness.
These are increasingly available in community settings and should be consid-
ered for appropriate patients.
Cognitive-Behavioral Therapy
Cognitive-behavioral therapy (CBT) appears to be ineffective for pediatric
ADHD. Unlike children and adolescents, adults seeking treatment generally
have greater awareness of their deficits and are motivated to improve. Early
62

studies, including some controlled trials, suggest that CBT is effective for
adults, particularly in conjunction with adequate medication management.6
The theoretical basis for CBT rests on the assumption that core ADHD symp-
toms arise from underlying deficits in sustained attention, inhibitory control,
working memory, and motivation. These lead to lifetime underachievement,
contributing to false and negative beliefs that reinforce ongoing dysfunction
and limit development of adequate coping skills.
Successful CBT programs are time limited, requiring an average of 0 ses-
sions, and are highly structured. Programs typically teach ADHD-specific
compensatory skills and include opportunities to practice between sessions,
usually in conjunction with a workbook. Programs address both emotional
and cognitive strategies. Emotional strategies seek improvements in emotional
regulation, impulse control, motivation, and self-esteem. Cognitive strate-
gies emphasize learning to recognize mental distortions, setting priorities,
improved organization and planning, problem solving, anger and stress man-
agement, relationship issues, mindfulness, and psychoeducation. Interventions
address maladaptive thought patterns that limit acquisition of adaptive life
skills. Behavioral skills are overpracticed until they are automatic, contributing
to overall functional improvement. Therapist manuals and patient workbooks
organized into individual training modules and based on effective CBT pro-
grams have been published and are commercially available (Box 8.).
ADHD Coaching
ADHD coaching is increasingly popular, although research supporting its effec-
tiveness is limited.7 Coaching has potential value for individuals having particu-
lar difficulties with motivation, time management, and organization. Coaching
attempts to change life skills directly, often using motivation and reward.
 Treatment Planning: Adults
Box 8.  Resources for Adult ADHD Cognitive-Behavioral
Therapy Programs
For Patients and Families
Safren SA, Sprich S, Perlman CA, Otto MW. Mastering Your Adult
ADHD: A Cognitive-Behavioral Treatment Program Client Workbook (Treatments
That Work). Oxford University Press; 2005.
For Clinicians
Safren SA, Perlman CA, Sprich S, Otto MW. Mastering Your Adult
ADHD: A Cognitive-Behavioral Treatment Program Therapist Guide (Treatments
That Work). Oxford University Press; 2005.
Solanto MV. Cognitive-Behavioral Therapy for Adult ADHD: Targeting Executive

Chapter 8
Dysfunction. Guilford Press; 20.

Coaching is similar to CBT in that its emphasis is behavioral and not insight
oriented. Unlike CBT, which focuses on general approaches and skills likely to
be useful in a variety of contexts, coaching is primarily directed toward specific
goals and objectives. While CBT is usually conducted in time-limited, formally
structured sessions, coaches are generally available as needed and sessions tend
to be flexible, brief, and frequent. Coaches work in individual or group settings

63
and might utilize phone, text, and e-mail messages to prompt adaptive behavior.
Standards and core competencies for coaching have been established, although
coaches are generally unlicensed and have a variety of educational backgrounds.
Other Individual Psychotherapies
Other forms of psychotherapy are appropriately recommended depending
on individual needs. Problems related to anxiety or depression, substance
abuse, relationship difficulties, or self-esteem are all potential indications for
psychotherapy. These therapies are generally not specific for ADHD but
address problems that commonly co-occur with the disorder.

Marital and Couples Therapy

Adults with significant marital or relationship difficulties might benefit from
couples therapy. Couples therapy promotes a realistic joint understanding of
ADHD, its effects on the relationship, and potential changes in the relationship
for mutual benefit. It is also critical to avoid blaming the ADHD-affected indi-
vidual or the disorder for all of the couple’s difficulties. Similarly, it is important
to avoid using an ADHD diagnosis as an excuse for inconsiderate or irrespon-
sible behavior.

Group Therapies
Group interventions are a time and cost-effective means of provid-
ing helpful care. There has been considerable interest in developing
group treatments for adult ADHD, and some have shown preliminary
ADHD effectiveness in small controlled trials. Group therapies typically empha-
size methods to improve attention and acquisition of compensatory skills
for disorder-related deficits. Group treatments also provide support for
individual participants.
Dialectical Behavioral Therapy Groups
Dialectical behavioral therapy (DBT) groups were originally developed for
treatment of borderline personality disorder. Although borderline person-
ality disorder and ADHD are distinct, they share common difficulties with
emotional regulation, impulse control, low self-esteem, and interpersonal
relationships. There is some initial success using DBT groups for ADHD.8
Treatment is organized into time-limited weekly sessions. Specific modules
address psychoeducation, mindfulness training, dysfunctional behavior analy-
sis, emotion regulation, impulse control, depression, organization strategies,
relationships, stress management, and substance abuse. In preliminary trials,
treatment effects on ADHD symptoms were small but significant, with larger
improvements seen with general health and mood. DBT might play an adjunc-
tive role with ADHD medication, particularly in adults with overreactivity and
other mood symptoms.
Metacognitive Therapy
Group metacognitive therapy is a manualized treatment developed for
64

ADHD that provides CBT with a particular focus on time management,

organization, and planning.8 The program is highly structured and organized
into weekly sessions that emphasize making new skills automatic through
repeated practice. One initial open pilot study demonstrated significant
improvements in medicated individuals on measures of attention and execu-
tive function.
Cognitive-Behaviorally Oriented Group Rehabilitation
Cognitive-behaviorally oriented group rehabilitation also uses a CBT approach
to address ADHD symptoms and related difficulties.8 Treatment occurs in 0
to 2 weekly sessions that are organized around review of previous home-
work, introduction of a new topic, new homework, and a self-reflective
assessment of the day’s program. Topics typically address ADHD neurobiol-
ogy and pharmacotherapy, motivation and activity initiation, communication,
impulse control, managing comorbidity, and self-esteem. An initial open pilot
demonstrated improvements in ADHD and related mood symptoms.

Use of Technology and Devices

Although their use has not been assessed scientifically, many clinicians
encourage patients to make full use of new technologies to aid in ADHD
management. Apps and other programs for smart phones, tablets, and other
devices are increasingly available to help manage time and organize contacts,
schedules, and assignments. Mobile devices can be programmed to provide
alarms and reminders for certain tasks. Automatic payment plans are easily
established and ensure that individuals pay bills promptly.
 Advocacy and Support Groups

Treatment Planning: Adults
Some adults wish to participate in support or advocacy groups. Among
others, patients and families can be referred to two national organizations,
Children and Adults With Attention Deficit Disorders (CHADD) (www.
chadd.org) and the Attention Deficit Disorder Association (ADDA) (www.
add.org). Each sponsors annual national meetings as well as many local
chapters and regional events. Group websites are excellent sources of cur-
rent information.

References

Chapter 8
. Murphy K. Psychosocial treatments for ADHD in teens and adults:  a
practice-friendly review. J Clin Psychol. 2005;6:607–69.
2. Charach A, Fernandez R. Enhancing ADHD medication adherence: challenges
and opportunities. Curr Psychiatry Rep. 203;5:37–379.
3. Kooij SJ, Bejerot S. Blackwell A, et al. European consensus statement on diagno-
sis and treatment of adult ADHD: The European Network Adult ADHD. BMC
Psychiatry. 200;0:67.
4. Moriyama TS, Polanczyk GV, Terzi FS, Faria KM, Rohde LA. Psychopharmacology
and psychotherapy for the treatment of adults with ADHD—a systematic
review of available meta-analyses. CNS Spectrums. 203;6:–2.

65
5. Weyandt LL, DuPaul GJ. ADHD in college students: developmental findings.
Dev Dis Res Rev. 2008;4:3–39.
6. Mongia M, Hechtman L. Cognitive behavioral therapy for adults with
attention-deficit/hyperactivity disorder: a review or recent randomized con-
trolled trials. Curr Psychiatry Rep. 202;4:562–567.
7. Kubik JA. Efficacy of ADHD coaching for adults with ADHD. J Atten Disord.
200;3:442–453.
8. Knouse LE, Cooper-Vince C, Sprich S, Saffren SA. Recent develop-
ments in the psychosocial treatment of adult ADHD. Expert Rev Neurother.
2008;8:537–548.

Further Reading
Harrison AG, Rosenblum Y. ADHD documentation for students receiving accom-
modations at the postsecondary level. Can Fam Physician. 200;56:76–765.
Manos MJ. Psychosocial therapy for adults with attention-deficit/hyperactivity dis-
order. Postgrad Med. 203;25:5–64.
Murphy K, Ratey N, Maynard S, Sussman S, Wright SD. Coaching for ADHD. J
Atten Disord. 200;3:546–552.
Rostain AL, Ramsay JR. A combined treatment approach for adults with ADHD—
results of an open study. J Atten Disord. 2006;0;50–59.
Chapter 9

Basic Pharmacology
Key Points
• Approved ADHD medications include stimulants and nonstimulants.
• ADHD medications influence catecholamine activity in the prefrontal
cortex (PFC) and to varying degrees enhance ratios of preferred “sig-
nal” to nonpreferred “noise” pathways, leading to improved attention
and motor control.
• The PFC functions optimally within a narrow range of catecholamine
activity, but dose effects of ADHD medications vary widely.
• Extended-release stimulant formulations are designed to maximize
the duration of ascending pharmacokinetic profiles and avoid potential
tolerance to steady-state or decreasing plasma drug concentrations.

67
67
Since Bradley’s discovery in the 930s that amphetamine (AMPH) improved
concentration and behavior in hyperactive children, medication has been
the mainstay of ADHD treatment (see Chapter 2). Virtually all psychotropic
drugs have been considered as potential ADHD pharmacotherapies. Those
proven effective generally enhance central noradrenergic and dopaminergic
signaling, or increase noradrenergic activity alone.

The Universe of ADHD Medications

The ADHD medication armamentarium includes agents with Food and Drug
Administration (FDA) or other regulatory agency approval, as well as drugs
used off-label (Table 9.). Stimulants are regarded as most effective with
the most robust treatment effect sizes. FDA-approved nonstimulants are
atomoxetine, a noradrenergic reuptake inhibitor, and the alpha-2 agonists,
guanfacine extended-release (ER) and clonidine ER. Commercially available
medications prescribed off-label include immediate-release (IR) alpha-2 ago-
nists, certain wake-promoting agents, tricyclic and some other antidepres-
sants, antipsychotic agents, and monoamine oxidase inhibitors.

Stimulants
Stimulants have been proven safe and efficacious in over 300 controlled clini-
cal studies.2 It is commonly stated that 70% of patients respond favorably
ADHD Table 9.  The Universe of ADHD Medications
FDA-Approved Medications Off-Label Medications
Stimulants Nonstimulants
Immediate-release alpha-2
agonists
Methylphenidates Atomoxetine Buproprion
D-Methylphenidates Extended-release alpha-2 Modafinil
agonists
D-Amphetamines Tricyclic antidepressants
Mixed amphetamine Antipsychotics
salts
Lisdexamfetamine Monoamine oxidase
inhibitors

to stimulants. In fact, approximately 70% respond favorably to the first

stimulant prescribed, whether a methylphenidate (MPH) or amphetamine
(AMPH).3 Of those who fail, an additional 70% respond favorably to the
alternative class. As such, more than 90% of patients have satisfactory
clinical improvement with stimulants, at least during acute treatment. Some
patients respond preferentially to one or another stimulant class, but there
is no method other than clinical trial and error to predict whether MPH or
68

AMPH is the optimal choice.

Stimulants are typically effective within an hour of dosing, but symptoms
return once medication wears off. Ongoing use is necessary to maintain
improvement. All have similar potential side effects. The most common is
appetite loss, which is highly dose dependent. Other common side effects
include weight loss, sleep disturbance, nausea, abdominal pain, headache, diz-
ziness, dry mouth, and dysphoria (see Chapter 0). Some of these are seen
frequently in patients taking placebo and might be associated with ADHD
itself and not medication.4 Increased irritability or “rebound hyperactivity”
can occur when drug effects wear off in late afternoon (see Chapter 0).
There is clear evidence that ADHD medications, particularly stimulants, can
decelerate growth, particularly during the first 8 months of therapy (see
Chapter 2). All MPH and AMPH formulations are Schedule II drugs, suggest-
ing a high risk for abuse, and require use of controlled prescriptions in many
jurisdictions. A black box warning informs on potential abuse. There are class
warnings on cardiovascular risks.
Methylphenidates
A summary of MPH formulations appears in Table 9.2. Immediate-release
MPH (MPH-IR, Ritalin®, Methylin™), more specifically d,l-MPH, contains a
50/50 racemic mixture of d-threo and l-threo isomers. MPH has been used
since the 960s, when it was viewed as milder and less prone to abuse
than AMPH. Prior to introduction of effective ER stimulant formulations,
MPH-IR accounted for more than 90% of ADHD prescriptions. A single
isomer IR formulation, d-threo-MPH (d-MPH-IR, Focalin®), was introduced
in 200. Both MPH-IR and d-MPH-IR typically have effect onsets within 30
Table 9.2  FDA-Approved Methylphenidate (MPH)

Basic Pharmacology
Formulations for ADHD
Brand Name Doses Available Usual Dosing*
Immediate Release (MPH-IR)
Ritalin® 2.5, 5, 0, 20 mg 5 mg–20 mg/bid–tid;
Max 60 mg/day:
Methylin™ 2.5, 5, 0 mg chew Children: 2.5–0 mg/bid–tid
0 mg/5 ml Adults: 5–5 mg/bid–tid
solution

Chapter 9
Focalin® 2.5, 5, 0 mg 2.5–0 mg/bid; max 20 mg/
day
Sustained Release (MPH-SR)
Ritalin SR® 20 mg 20–60 mg/qd–bid
Max 60 mg/day
Metadate ER® 20 mg 20 mg–60 mg/qd–bid
Max 60 mg/day
Extended Release (MPH-ER)
Concerta® 8, 27, 36, 54 mg Children: 8–54 mg/day
Adults: 8–72 mg/day
Ritalin LA® 0, 20, 30, 40 mg Children: 20–40 mg/day
Adults: 20–60 mg/day

69
Metadate CD® 0, 20, 30, 40, 50, 20–60 mg/day
60 mg
Daytrana® 0, 5, 20, 30 mg 0–30 mg/day; 9 hours wear
patch
Quillivant XR™ 25 mg/5 ml 20–60 mg/day
solution
Focalin XR® 5, 0, 5, 20, 25, Children: 0–30 mg/day
30, 35, 40 mg Adults: 0–40 mg/day
*May exceed FDA dosing.
bid, twice daily; qd, once daily; tid, three times daily.

to 45 minutes after administration, are effective for approximately 4 to 6

hours, and require 2 or 3 times daily dosing to maintain improvements into
early evening.5 Regular tablets cannot be crushed, but chewable tablets
(Methylin™) and liquid (Methylin™ solution) are options if swallowing pills
is difficult.
Sustained-release preparations (MPH-SR, Ritalin-SR®, Metadate-ER®) were
introduced to avoid lunchtime dosing while maintaining symptom control over
an 8-hour school day.5 These formulations embed MPH in a waxy matrix that
dissolves after ingestion and gradually releases medication over time. Although
popular among some, little evidence suggests that MPH-SR has longer effect
durations than MPH-IR. SR formulations are increasingly dispensed as generic
equivalents of brand name MPH-ER, but they fail to provide equal benefits.
Beginning in the late 990s, several technologies allowed creation of
MPH-ER formulations that are effective 8 to 2 hours after dosing.5,6 The
ADHD OROS (Osmotic [Controlled] Release Oral [Delivery] System) formulation
(OROS-MPH, Concerta®) is a multicompartment capsule comprising MPH,
osmotic control agents, and a rate-controlling membrane. Once ingested, a
capsule overcoat immediately releases MPH similar to MPH-IR. As the cap-
sule proceeds through the gut, fluids enter the OROS chamber and force
medication out through a laser-drilled hole, leading to an ascending plasma
profile similar to MPH-IR administered three times daily at 4-hour intervals.
The capsule must be swallowed intact, and it cannot be crushed, divided,
chewed, or dissolved in liquid. OROS-MPH has been shown in classroom
laboratory studies to be effective for 0–2 hours, although shorter dura-
tions are sometimes reported in clinical settings.
Several MPH-ER formulations (Ritalin LA®, Metadate CD®, Focalin XR®)
use pulsed-release beaded technologies and combine mixtures of immediate
and delayed-release MPH or d-MPH.5,6 IR beads enter circulation rapidly and
initiate medication effects. Delayed-release beads are initially protected with
a coating that dissolves after exposure to intestinal fluids to release a second
bolus of MPH or d-MPH approximately 4 hours after ingestion. Improvement
can persist 8 to 2 hours. For patients unable to swallow pills, these formula-
tions can be opened and sprinkled on food.
Two additional MPH-ER compounds are particularly useful when swal-
lowing is difficult. The MPH transdermal system (MTS, Daytrana®) is a
drug-containing patch that is applied each morning and worn 9 hours under
70

clothing. One unique feature is enhanced control of treatment onset and off-
set. Since the patch creates an MPH reservoir in the skin, benefits persist for
up to 3 hours after patch removal. Although MTS is appealing for younger
children who resist swallowing, one major impediment is frequent develop-
ment of skin irritation under the application site. A liquid MPH-ER (Quillivant
XR™) is also available, and classroom laboratory studies suggest up to 2
hours of improvement compared with placebo.
Amphetamines
Racemic dl-AMPH was synthesized in the late 880s and eventually marketed
in aerosol form as a bronchodilator. Various AMPH formulations have been
used for ADHD, beginning with Bradley’s initial use of dl-AMPH (Benzedrine)
in 937 (see Chapter 2). Concerns in the 960s and 970s over AMPH abuse
risks led to a preference for MPH in ADHD treatment, although few data
exist to confirm differences between the two. A summary of AMPH formula-
tions appears in Table 9.3.
Immediate-release d-AMPH (d-AMPH-IR, Dexedrine®, Dextrostat®)
is generally effective within an hour of administration.5 D-AMPH-IR typi-
cally remains effective 4 to 6 hours after ingestion and requires dosing 2
or 3 times daily to maintain daylong benefit. A second IR-AMPH formula-
tion, mixed amphetamine salts (MAS-IR, Adderall®), contains equal parts
dl-AMPH aspartate monohydrate, d-AMPH saccharate, d-AMPH sulfate, and
dl-AMPH sulfate, providing a 3: ration of d- to l-AMPH. MAS-IR was origi-
nally marketed as the weight loss medication Obitrol®. However, amphet-
amines are no longer indicated for weigh loss due to risks of abuse. Similar to
d-AMPH-IR, MAS-IR generally reduces ADHD symptoms for 4–6 hours and
requires multiple daily dosing to maintain improvements.
Table 9.3  FDA-Approved Amphetamine (AMPH) Formulations

Basic Pharmacology
for ADHD
Brand Name Doses Available Usual Dosing*
Immediate Release (AMPH-IR)
Dexedrine® 5, 7.5, 0, 5, 20, 2.5–40 mg/qd–tid
Dextrostat® 30 mg Max 40 mg/day
Adderall® 5, 7.5, 0, 2.5, 5, 20, 5–40 mg/qd–tid
30 mg Max 40 mg/day
Vyvanse ® 20, 30, 40, 50, 60, 30–70 mg/day

Chapter 9
70 mg
Sustained Release (AMPH-SR)
Dexedrine® 5, 0, 5 mg 5–40 mg/qd–bid
spansules® Max 60 mg/day
Extended Release (AMPH-ER)
Adderall XR® 5, 0, 5, 20, 30 mg Children: 5–30 mg/day
Adults: 5–60 mg/day
*May exceed FDA dosing.
bid, twice daily; qd, once daily; tid, three times daily.

Sustained-release d-AMPH (d-AMPH-SR, Dexedrine® Spansule®,

71
Dexedrine® SR) contains two forms of beads with half released immedi-
ately and the remainder released gradually over several hours. However,
no differences were found in studies comparing duration effects of
d-AMPH-IR and d-AMPH-SR. AMPH-SR formulations remain available but
are rarely used.
An ER preparation of mixed AMPH salts (MAS-ER, Adderall XR®) uses
a two-phased pulsed-released formulation to deliver 50% of MAS beads
immediately, followed by a second pulse approximately 4 hours later.5,6
In laboratory studies, MAS-ER provided significant benefits compared to
placebo up to 2 hours after dosing. Clinically, most patients improve for
8–2 hours. Capsules can be opened and sprinkled on food if swallowing
is difficult.
Lisdexamfetamine (LDX, Vyvanse®) is an AMPH prodrug formed by
covalent bonding of d-AMPH with the amino acid lysine. LDX is a pro-
drug and not psychoactive as the parent compound. Once ingested and
absorbed, LDX is cleaved through enzymatic processes located on red
blood cells into separate lysine and d-AMPH molecules. Since enzymatic
hydrolysis of AMPH occurs slowly, the delayed release reduces the abuse
risks seen with other stimulants that can be inhaled or injected to provide
rapid euphoria and cocaine-like effects. LDX is available in 20, 30, 40 50,
60, and 70 mg capsules, which can be opened and mixed with water if a
patient has difficulty swallowing without affecting the slow-release proper-
ties. Total AMPH released in 30, 50, and 70 mg LDX is roughly equivalent to
0, 20, and 30 mg of MAS-XR, respectively. Classroom laboratory studies
have shown positive differences on ADHD symptoms between LDX and
placebo for up to 4 hours after dosing, although shorter effect durations
can be seen in clinical settings.
ADHD
Nonstimulants
Several FDA-approved nonstimulants are summarized in Table 9.4. Given
lower response rates and smaller treatment effect sizes, nonstimulants are
regarded as second-line medications.2,5 They are particularly useful when
stimulants are ineffective or not tolerated, concerned about high risk for
stimulant misuse, addressing certain comorbid conditions, and in combination
with stimulants to improve tolerability or enhance treatment response.
Atomoxetine
Atomoxetine (Strattera®) is a noradrenergic reuptake inhibitor. The medi-
cation is available in capsule form and cannot be opened or sprinkled.
Atomoxetine is primarily metabolized by CYP2D6 hepatic enzymes, which
creates the potential for interactions with many other drugs and increased
toxicity in slow metabolizers. Dosing is weight based. The recommended
dose range is .2–.4 mg/kg per day up to 00 mg. The maximum dose of .8
mg/kg per day was established as a safety threshold for patients who might
be CYP2D6 slow metabolizers. Concomitant administration with fluoxetine
or other medications that inhibit CYP2D6 will cause the patient to become
a slow atomoxetine metabolizer with increased risk for elevated plasma con-
centrations and concomitant adverse events.
72

Atomoxetine is useful when stimulants are not tolerated, particularly when

irritability is a stimulant side effect, or when comorbid tic or anxiety disorders
are present. Atomoxetine has a mild beneficial effect on tic expression and has
proven efficacy as a single agent for both ADHD and comorbid anxiety symp-
toms. When effective, atomoxetine lacks the daily on/off effects seen with
stimulants and has been shown to decrease ADHD symptoms at least 24 hours
after dosing. Also unlike stimulants, benefits appear to increase with sustained
use, with maximal treatment effects 3–4 weeks after initiating the full dose.
However, if no response is in evidence after  week of the maximum dose, it

Table 9.4  FDA-Approved Nonstimulant Medications for ADHD

Brand Name Doses Available Usual Dosing
Noradrenergic Reuptake Inhibitors
Strattera® 0, 8, 25, 40, 60, Begin 0.5 mg/kg per day
(atomoxetine) 80, 00 mg Increase to .2–.4 mg/
kg per day
Max 00 mg/day
Give qd or divided bid
Alpha-2 Agonists
Intuniv® , 2, 3, 4 mg –4 mg/qd*
(guanfacine-ER)
Kapvay® 0., 0.2 mg 0.–0.4 mg/day, qd or
(clonidine-ER) divided bid*
*Pediatric dosing only. Not approved for adult use.
bid, twice daily; ER, extended release; qd, once daily.
is unlikely that subsequent benefits will be seen. Atomoxetine can be adminis-

Basic Pharmacology
tered as a single daily dose or divided twice daily in morning and evening. Twice
daily dosing decreases side effect risk and enhances 24-hour responses. Since
symptom reductions are dependent on sustained use, patients who frequently
miss prescribed doses are likely to lose treatment benefit.
The side effect profile differs from stimulants. Common side effects include
headache, nausea, and drowsiness. These often subside after initial titration.
Atomoxetine is usually initiated at approximately 0.5 mg/kg per day to reduce
side effect risk. Doses are best increased at no less than weekly intervals until

Chapter 9
the optimal target dose is reached.
Alpha-2 Agonists
Alpha-2 agonists were originally approved as antihypertensive agents, but they
are effective for ADHD.2,5 Two ER formulations, guanfacine-ER (Intuniv®)
and clonidine-ER (Kapvay®), have FDA approval for ADHD in pediatric age
groups, both as monotherapies and in combination with stimulants. Patients
require blood pressure monitoring, particularly when treatment is initiated.
For either agent, clinicians should begin with the lowest dose and increase by
the smallest available increment, as tolerated, but no more frequently than
once weekly. Somnolence is often the limiting factor during dose titration,
but it generally improves over time. Other common side effects include head-
ache, abdominal pain, disrupted sleep, fatigue, and dizziness. Guanfacine-ER

73
is given once daily, either in morning or at night. Clonidine-ER can be admin-
istered once or twice daily.
Interestingly, although alpha-2 agonists are sedating, their primary benefit
in ADHD appears to be on inattentive symptoms.7 Some evidence suggests
that combination alpha-2 agonist and stimulant treatment enhances cogni-
tion and leads to greater ADHD improvement than with either monotherapy.
Alpha-2 agonists suppress tics and are particularly useful, alone or in stimulant
combination, in treating ADHD with comorbid tic disorders.
Off-Label Medications
IR guanfacine (Tenex®) and clonidine (Catapres®) are commonly used in
off-label ADHD treatment, either as monotherapy or in combination with a
stimulant.2,5 Guanfacine is available in  and 2 mg tablets and usually admin-
istered in 0.5 to .5 mg doses given twice daily. Clonidine is available in 0.,
0.2, and 0.3 mg tablets and usually administered in.05 to. mg doses given
one to three times daily. Other off-label therapies are typically employed only
when FDA-approved medications are proven unsatisfactory. These include
the wake-promoting agent modafinil; tricyclic antidepressants; buproprion;
venlafaxine; the antipsychotics haloperidol, risperidone, and aripiprazole; and
monoamine oxidase inhibitors. Most of these have limited evidence of ben-
efit and/or associated safety concerns that necessitate special monitoring.

Drug Targets and Mechanisms of Action

Most ADHD medications act directly in the central nervous system
to increase synaptic levels of the catecholamines dopamine and/or
ADHD norepinephrine (Fig. 9.).8 Increased norepinephrine activity appears essen-
tial for symptom reduction, but optimal ADHD treatment seems to require
perturbation of both noradrenergic and dopaminergic systems. AMPH has a
broader range of drug targets than MPH. Both AMPH and MPH inhibit cat-
echolamine reuptake into presynaptic neurons by blocking norepinephrine
and dopamine transporters. AMPH further directly displaces norepinephrine
and dopamine from presynaptic storage vesicles, and it inhibits monoamine
oxidase and subsequent neurotransmitter breakdown. The direct action of
atomoxetine is similar to MPH, but it is selective for blockade of noradrener-
gic and not dopaminergic transporters.
Recent research suggests that ADHD treatment response is not a direct
effect of increased catecholamine release, but that increased levels of nor-
epinephrine and dopamine have indirect modulating effects on glutaminergic
signaling in the prefrontal cortex (PFC) (Fig. 9.2).9 PFC circuits are intrinsi-
cally involved in ADHD and regulate processes related to attention, executive
function, motor inhibition, emotion regulation, and reward. One subset of
PFC networks mediates active attention to “preferred” inputs or “signals,”
while another subset mediates attention to “nonpreferred” inputs or noise.
Ion channels in neuronal membrane in preferred PFC networks are kept open
by cyclic adenosine monophosphate (cAMP). Activation of alpha-2 adrener-
gic receptors on these neurons, directly by alpha-2 agonists or indirectly by
increased norepinephrine, inhibits cAMP with subsequent ion channel closure
74

and enhanced neuronal signaling in preferred directions. Conversely, activa-

tion of the dopamine- receptor by increased dopamine on nonpreferred
networks increases cAMP with subsequent ion channel opening, decreased
circuit connectivity, and reduced attention to noise.

Presynaptic Neuron AMPH diffuses into

vesicle, causing DA or NE
Autoreceptor AMPH blocks DA or NE release
intake into vesicle

Storage Vesicle
Cytoplasmic DA
or NE DA or NE
Transporter
MPH and
AMPH inhibit
Synapse reuptake

Receptors Postsynaptic Neuron

Figure 9.  Stimulant drug targets. AMPH, amphetamine; DA, dopamine; MPH,

methylphenidate; NE, norepinephrine.
 Basic Pharmacology
NE NET DAT
DA
Glutamate
NE GFC Signaling
CLN DA
α2A D1
SIGNALS K+ NOISE
K
+
Pyramidal

Chapter 9
DA action at D1 receptor
NE action at α2A receptor Cell
K+ opens ion channels
closes ion channels Dendrite
decreasing attention
increasing attention to
to “noise.”
“signal.”

Figure 9.2  Prefrontal cortex network connections. α2A, alpha-2a receptor; D,

dopamine  receptor; DA, dopamine; DAT, dopamine transporter; NE, norepineph-
rine; NET, norepinephrine transporter. (Adapted from Arnsten and Rubia.9)

Stimulant Pharmacodynamics and Acute

Tolerance

75
ADHD treatment can be viewed as a rebalancing of “signal” to “noise” ratios,
either through indirect effects of increased catecholamines or direct effects
of alpha-2 agonists on glutaminergic signaling in the PFC.0 Ideally, individuals
should appropriately focus on important tasks (signal), while retaining some
awareness of background activity (noise) and the ability to shift attention flex-
ibly when required. Optimal balancing of signal to noise ratios in the PFC is
dependent on a narrow range of catecholaminergic activity. If catecholamine
levels are excessively elevated, perhaps from too high medication doses or
stress, PFC networks collapse with concomitant deteriorations in cogni-
tion and motor control. Dopamine increases that might be useful for tasks
requiring highly focused attention could also cause problems with overfocus,
cognitive rigidity, and a loss of personality and spontaneity. This view is con-
sistent with older work that posited separate “inverted U-shaped” stimulant
dose–response curves for cognition and behavior, in which improvements
increase with increasing doses up to an optimal point, followed by response
deterioration. Related work suggested that optimal doses for improved
attention are lower than those necessary to improve behavior, suggesting that
medication doses required to control overactivity might, in fact, impede cog-
nitive functioning. No absolute stimulant plasma concentration predicts clini-
cal improvement. Individuals with and without ADHD generally have similar
cognitive and behavioral responses to stimulants, but optimal doses vary from
person to person. Individual dose–response relationships likely depend on
multiple factors including age, sex, and genetic polymorphisms.
Little evidence suggests that patients become tolerant to medication effects
with sustained treatment (see Chapter 2). However, there has been much
ADHD debate over the possibility of acute tolerance, or tachyphylaxis, with ADHD
stimulants.2 Compelling evidence, particularly with MPH, suggests that stimu-
lant effects diminish rapidly when plasma drug concentrations are stable, and
that it is important to maintain an ascending plasma drug profile to sustain
symptom response.3 This is consistent with earlier observations that stron-
gest stimulant responses occur during the absorption phase of the plasma drug
profile with maximum effects seen at the time of maximum drug concentration
(Tmax). Evidence supporting the possibility of stimulant tachyphylaxis is stron-
gest for MPH, although some research suggests it occurs with some forms of
AMPH. Theories of acute tolerance explain the lack of expected efficacy in SR
stimulant formulations designed to achieve steady-state plasma concentrations.
Ideas about acute tolerance and the need to maintain ascending plasma concen-
trations are particularly relevant when choosing multiple daily stimulant doses.

Stimulant Pharmacokinetics
D-MPH-IR is readily absorbed when taken orally and reaches peak plasma
levels in –2 hours. Its half-life (T/2) is approximately 3–4 hours. The
l-isomer has much poorer absorption, with plasma levels approximating %
of d-MPH. MPH is primarily de-esterified to ritalinic acid via carboxylesterase
 (CES). A CES polymorphism is associated with elevated plasma MPH lev-
76

els. Maximum plasma concentration (Cmax) and time to maximum concen-

tration (Tmax) are increased when MPH is taken with food or alcohol.
D-AMPH-IR is also rapidly absorbed with a Cmax of 3–4 hours, although
its T/2 is approximately  hours. As with MPH, the duration response
is not related to drug half-life and the largest effects occur prior to Cmax.
Significant, but decreasing, effects compared against placebo continue for sev-
eral hours thereafter. About half of ingested AMPH is metabolized by the
liver with the remainder excreted unchanged in the urine. The major hepatic
pathway is through CYPD3A4 enzymes. A genetic variant for this enzyme,
more common in African Americans, leads to decreased metabolism and
possible increases in Cmax. A secondary pathway is mediated by CYP2D6.
CYPD2D6 polymorphisms can result in slower metabolism with possibly
increased Cmax and risk of side effects. Highly acidic foods, such as grape-
fruit, enhance urinary excretion, leading to decreases in plasma concentration
and drug half-life.
While ideas about stimulants and acute tolerance are not universally
accepted, they were a guiding force for the development of virtually all cur-
rently available once-daily ER stimulants.6 These are largely formulated to
sustain the ascending plasma drug concentration and extend Tmax. AMPH
formulations exhibit longer benefits beyond Tmax than MPH. Interestingly,
theories of acute tolerance do not appear to apply to LDX, which reportedly
demonstrates up to 4 hours of benefit with a mean Cmax of 4–5 hours.4
LDX also exhibits less pharmacokinetic variability than equivalent doses of
MAS-XR, suggesting more reliable release of active AMPH over the desired
period of treatment benefit and less residual AMPH 24 hours after dosing.4
 Pharmacokinetic profiles and potential for acute tolerance are relevant

Basic Pharmacology
in consideration of generic stimulants. For approval of generic substitutes,
the FDA requires 80% to 20% bioequivalence for Cmax and area under the
plasma concentration-time curve (AUC) values compared with an approved
brand-name medication. While sensible for medications with clear therapeu-
tic windows, using this approach with ADHD stimulants does not address the
critical importance of ascending plasma drug profiles on treatment response.
Generic substitutes might well be less effective than branded drugs for ADHD
if they lack comparable ascending drug concentration profiles.

Chapter 9
References
  . Wigal SB. Efficacy and safety limitations of attention-deficit hyperactivity dis-
order pharmacotherapy in children and adults. CNS Drugs. 2009;23:2–3.
  2. Biederman J, Spencer TJ. Psychopharmacological interventions. Child Adolesc
Psychiatr Clin N Am. 2008;7:439–458.
  3. Elia J, Borcherding BG, Rapoport JL, Keysor CS. Methylphenidate and dex-
troamphetamine treatment of hyperactivity: are there true nonresponders?
Psychiatry Res. 99;36:4–55.
  4. Barkley RA, McMurray MB, Edelbrock CS, Robbins K. Side effects of methyl-
phenidate in children with attention deficit hyperactivity disorder: a systemic,
placebo-controlled evaluation. Pediatrics. 990;86:84–92.

77
  5. Daughton JM, Kratochvil CJ. Review of ADHD pharmacotherapies: advan-
tages, disadvantages, and clinical pearls. J Am Acad Child Adolesc Psychiatry.
2009;48:240–248.
  6. Connor DF, Steingard RJ. New formulations of stimulants for attention-deficit
hyperactivity disorder. CNS Drugs. 2004;8:0–030.
  7. Sallee F, Connor DF, Newcorn JH. A review of the rationale and clinical uti-
lization of α2-adrenoceptor agonists for the treatment of attention-deficit/
hyperactivity disorder. J Child Adolesc Psychopharmacol. 203;23:308–39.
  8. Arnsten SF, Pliszka SR. Catecholamine influences on prefrontal cortex func-
tion: relevance to treatment of attention deficit hyperactivity disorder and
related disorders. Pharmacol Biochem Behav. 20;99:2–26.
  9. Arnsten AF, Rubia K. Neurobiological circuits regulating attention, cognitive
control, motivation, and emotion: disruptions in neurodevelopmental disor-
ders. J Am Acad Child Adolesc Psychiatry. 202;5:356–367.
0. Gamo NJ, Wang M, Arnsten AF. Methylphenidate and atomoxetine enhance
prefrontal function through α2-adrenergic and dopamine D receptors. J Am
Acad Child Adolesc Psychiatry. 200;49:0–023.
. Swanson J, Baler D, Volkow ND. Understanding the effects of stimulant medi-
cation on cognition in individuals with attention-deficit/hyperactivity disor-
der: a decade of progress. Neuropsychopharm Rev. 20;36:207–226.
2. Swanson J, Gupta S, Guinta D, et al. Acute tolerance to methylphenidate in the
treatment of attention deficit hyperactivity disorder in children. Clin Pharmacol
Ther. 999;56:073–086.
3. Swanson J, Gupta S, Lam A. et al. Development of a new once-day formula-
tion of methylphenidate for the treatment of attention-deficit/hyperactivity
disorder. Arch Gen Psychiatry. 2003;60;204–2.
ADHD 4. Biederman J, Boellner SW, Childress A, Lopez FA, Krishna S, Zhang Y.
Lisexamfetamine dimesyltate and mixed amphetamine salts extended-release
in children with ADHD: a double-blind, placebo-controlled, crossover analog
classroom study. Biol Psychiatry. 2007;62:970–976.

Further Reading
Arnsten AF. Catecholamine influences on dorsolateral prefrontal cortical net-
works. Biol Psychiatry. 20;69:e89–e99.
Bidwell LC, Dew RE, Kollins SH. Alpha-2 adrenergic receptors and attention-deficit/
hyperactivity disorder. Curr Psychiatry Rep. 200;2:366–373.
78
Chapter 0

Clinical Medication
Management
Key Points
• FDA-approved stimulants for ADHD are first-line pharmacotherapies
followed by FDA-approved nonstimulants.
• Optimal medication titration promotes rapid symptom management
and efficient use of clinical resources by assessing responses with the
range of usual therapeutic doses over 2–3 weeks.
• Long-term adherence is enhanced by psychoeducation, patient and
family participation in treatment decisions, and scheduling follow-up
visits at regular intervals.
• Most side effects are easily managed by changes in medication, dose,

79
79
or dosing schedule, or with combination pharmacotherapy.

In most cases, a diagnosis of ADHD leads to recommendations for pharma-

cotherapy (see Chapters 7 and 8). Although comprehensive treatment plan-
ning includes targeted academic, behavioral, and social interventions, only
medication robustly addresses core ADHD symptoms. Pharmacotherapy is
apt to be employed except in borderline or mild cases, with very young chil-
dren, or if families are strongly opposed.

Initial Medication Selection

Medication selection follows an evidence-based approach. FDA-approved
medications should be considered before those without ADHD indications.
Stimulant medications have the largest treatment effects, largest number of
placebo-controlled trials, longest history of use, and most accumulated safety
data. Stimulants are easily titrated and with optimal doses effects are imme-
diately evident. As such, practice algorithms for ADHD place stimulants as
first-line therapies.-3
Prior to use in a specific patient, all stimulants have the same potential
benefits and risks (see Chapter 9). Initial stimulant choice should be tai-
lored to individual patient needs and consider daily schedules and necessary
effect duration, tolerability, compliance and ease of use, and patient/family
preference. While research data suggest that methylphenidate (MPH) and
ADHD
Step 0 Assessment/Psychoeducation/
Treatment Planning

Non-med Treatments

Step 1 MPH or AMPH

1a. AMPH not used in Step 1

Step 2 Stimulant not used in Step 1

2a. AMPH not used in Step 2

Figure 0.  ADHD medication treatment algorithm, steps 0–2. AMPH, amphet-

amine; MPH, methylphenidate. (Adapted from Pliszka et al.)

amphetamine (AMPH) compounds have similar side effects, MPH is shown

to be milder in meta-analysis.4 As such, some prefer MPH initially in younger
patients. Conversely, AMPH formulations might more reliably provide
80

extended durations of effect required by older individuals. Whether or not

a patient can swallow pills or capsules can bear on selection. Various medi-
cations might or might not be available on individual insurance formularies.
Adequate consideration must be given to patient resources and ability to pay
long-term prescription costs.
Initial steps for ADHD pharmacotherapy appear in Figure 0.. Once
an initial formulation of MPH or AMPH is chosen, the patient should be
titrated on escalating doses within the standard therapeutic range over a 2-
to 3-week period. If the medication is effective but has too long a duration
of effect, for example, sleep is disturbed, a shorter acting form of the same
stimulant might prove beneficial. If the initial choice does not provide suf-
ficient improvement, or if there are problems with side effects or tolerability,
a second trial with the alternative stimulant class (MPH or AMPH) should
be initiated. There is little point in successive trials of different formulations
of the same medication if one trial suggests it is ineffective or not tolerated.
One exception is allowance for a second AMPH trial with the alternative
AMPH, for example, mixed amphetamine salts (MAS) or lisdexamfetamine
(LDX), not initially used, since some differences might emerge between
mixed salts and prodrug AMPH.
The introduction of effective extended-release (ER) stimulants estab-
lished once-daily dosing as the clinical standard.5 Most clinicians begin titra-
tion with a once-daily ER stimulant, although some prefer an initial trial of an
immediate-release (IR) form to confirm the patient can tolerate the drug. IR
stimulants are commonly used to supplement once-daily ER forms to achieve
a longer duration of clinical benefit (see Chapter 9). Some patients, particu-
larly adults, prefer IR forms that allow them to restrict medication use to
 Clinical Medication Management
Step 3 Atomoxetine or Alpha-2 Agonist

3a. Add stimulant to Step 3

Step 4 Agent not tried in Step 3

Step 5 Buproprion or TCA

Step 6 Second-generation antipsychotic

Consultation

Chapter 0
Figure 0.2  ADHD medication treatment algorithm, steps 3–6. TCA, tricyclic anti-
depressant. (Adapted from Pliszka et al.)

more limited periods of time. Others choose IR medication secondary to

cost or insurance constraints.
FDA-approved nonstimulant medications are employed once a patient has

81
failed stimulants (Fig. 0.2). More research data are available supporting use
of atomoxetine than the ER alpha-2 agonists guanfacine and clonidine. This
suggests that atomoxetine should be considered prior to the other nonstimu-
lants. Atomoxetine may be considered first-line monotherapy for patients
with comorbid tic or anxiety disorders. Nonstimulants may also be consid-
ered first-line treatments when there is high concern over potential stimulant
misuse (see Chapters  and 2).
When monotherapy is partially effective or limited by side effects, combi-
nation stimulant and nonstimulant regimens can prove beneficial. Examples
are combinations of MPH or AMPH with atomoxetine or alpha-2 agonists.6,7
FDA approval has been granted for combination stimulant and ER alpha-2
agonist therapy, although combination therapy with stimulants and atomox-
etine does not have FDA approval. Numerous agents without FDA approval
are sometimes effective and typically used when approved medications fail,
as adjunctive agents to augment treatment response, to address comorbidity,
and when there is strong potential for stimulant misuse. Use of IR guanfacine
and clonidine is substantially supported by research literature as well as FDA
approval of the ER formulations. Other medications commonly prescribed
off-label include modafinil, tricyclic antidepressants, buproprion, and certain
antipsychotic agents. While some research evidence supports their use, effi-
cacy data are limited and heightened attention to safety monitoring is advised.

Medication Titration
Following assessment and recommendations for pharmacotherapy, the ini-
tial medication trial should not be seen as provision of optimized treatment,
ADHD but rather an opportunity to assess clinical response at various doses of the
chosen drug in an individual patient. The goal of initial titration is to deter-
mine as quickly and efficiently as possible the optimal dose of an effective
and well-tolerated medication. Generally, 5–7 days on a fixed stimulant dose
is sufficient to assess treatment response and develop some tolerance to side
effects. Shorter trials do not provide a sufficient sampling of response to attri-
bute changes to medication effects. Longer trials, such as providing an initial
prescription of a low-dose stimulant for 30 days or more, fail to assess poten-
tial benefits with higher doses and unnecessarily delay the time to achieving
symptom improvement.
Medication titration can be constrained by local norms, clinician and patient
time demands, and third-party payers. Insurance companies increasingly
demand 30-day prescriptions for chronically administered medications and
create obstacles for determination of optimal doses with an initial titration.
Clinicians must devise titration methods that suit local circumstances, keeping
in mind the need to assess a range of doses within a reasonable time frame.
One approach to stimulant titration is summarized in Table 0.. Patients
are provided with a prescription for a low dose of the chosen stimulant and
instructed to take as directed. A written information sheet given to patients
can direct them to take one tablet or capsule daily for the first 5 days, two for
the second 5 days, and three for the third 5 days. In a slight variation for LDX
titration, two prescriptions, one for 20 mg and one for 30 mg, are required.
82

Medication should be taken all at once following breakfast. The information

sheet should further direct patients to note their responses at various doses,
summarize potential side effects, and request that they contact the physician’s
office if serious problems emerge. Absent significant difficulties, patients
return for an office visit after 2–3 weeks to review responses and help the
clinician determine which dose appears most effective and well tolerated.
Clinicians may then provide a 30-day supply of the apparent best dose and
schedule a -month follow-up visit to verify optimized response. If after the
-month trial both patient and clinician are satisfied with treatment response,
follow-up visits for ongoing stimulant management can be scheduled every
3 months. If a satisfactory medication and dose are not identified during initial
titration, the process is repeated with a different agent.
Titration of nonstimulant medications follows a slightly different approach.
Atomoxetine dosing is weight based with a target of .2–.4 mg/kg per day
and maximum of 00 mg per day. Problems with tolerability most frequently
emerge when initial dose is too high or if doses are increased too quickly.
Clinicians should initiate atomoxetine at 0.5 mg/kg or less per day for the
initial week of therapy. If the dose is tolerated after  week, the dose may be
doubled. This does not necessarily require an office assessment unless there
are significant concerns about tolerability. Clinicians should assess response
–2 weeks after the dose is doubled, and then increase to the full target dose
if well tolerated. Atomoxetine can be taken once or twice daily in divided
doses. Some benefit should be evident after a week at full dose, but improve-
ments can continue to increase over several weeks. If there is insufficient
improvement after a month at full dose, atomoxetine is unlikely to be benefi-
cial and should be discontinued.
 Clinical Medication Management
Table 0.  Sample Stimulant Titration Regimens—Patient Is
Given a Prescription Along With Written Instructions for How
to Take
Medication/Dose Number Patient Instructions
(#) Dispensed/
Script*
OROS-MPH 8 mg #30 First 5 days:  tab
–2 qam as directed Second 5 days: 2 tabs
Third 5 days: 3 tabs
D-MPH-ER 5 mg #30 First 5 days:  tab
Patient <25 kg –2 qam as directed Second 5 days: 2 tabs
Third 5 days: 3 tabs
D-MPH-ER 5 mg #50 First 5 days: 2 tabs

Chapter 0
Patient ≥25 kg 2–3 qam as directed Second 5 days: 3 tabs
Third 5 days: 4 tabs
MAS-ER 0 mg #30 First 5 days:  tab
–2 qam as directed Second 5 days: 2 tabs
Third 5 days: 3 tabs
LDX 30 mg #30 First 5 days:
Plus  qam as directed  X 30 mg

83
LDX 20 mg #30 Second 5 days:
(two prescriptions given) –2 qam as directed  X 30 mg plus  X 20 mg
Third 5 days:
 X 30 mg plus 2 X 20 mg
*Written scripts can be modified to meet local pharmacy/insurance requirements.
D-MPH, dexmethylphenidate; ER, extended release; LDX, isdexamfetamine; MAS, mixed
amphetamine salts; MPH, methylphenidate; qam, each morning.

Limiting factors in titrating alpha-2 agonists are sedation and hypotension.

Optimal titration requires weekly assessment of tolerability and symptom
response until sufficient improvement is attained. Medication should be initi-
ated at the lowest available dose and increased weekly by the same increment
as tolerated. ER guanfacine is administered once daily, ER clonidine once or
twice daily, IR guanfacine twice daily, and IR clonidine three times daily.

Combination Pharmacotherapy
It is preferable to keep medication regimens as simple as possible. However,
combination pharmacotherapies are appropriately utilized to address residual
symptoms, problems with tolerability and side effects, and comorbid disor-
ders.8 One commonly used combination is administering an IR stimulant in
the afternoon to extend the duration of clinical benefit derived from an ER
stimulant taken in the morning. In this instance, it is usually best to use the
same medication in ER and IR forms, and to dose the IR at a level apt to
maintain the same ascending plasma profile achieved with the morning ER
ADHD
Table 0.2  Stimulant Release Profiles: Matching
Extended-Release and Immediate-Release Doses
Drug Dose Equivalent Afternoon IR
Supplement
OROS-MPH 8 mg MPH-IR 5 mg tid MPH-IR 5 mg
(Concerta®) 36 mg MPH-IR 0 mg tid MPH-IR 0 mg
54 mg MPH-IR 5 mg tid MPH-IR 5 mg
MPH-ER 0 mg MPH-IR 5 mg bid MPH-IR 5 mg
(Ritalin LA®) 20 mg MPH-IR 0 mg bid MPH-IR 0 mg
40 mg MPH-IR 20 mg bid MPH-IR 20 mg
MPH-ER 0 mg MPH-IR 3 mg am/7 mg noon MPH-IR 0 mg
(Metadate CD®) 40 mg MPH-IR 2 mg am/ 28mg noon MPH-IR 30 mg
D-MPH-ER 5 mg D-MPH-IR 2.5 mg bid D-MPH-IR 2.5 mg
(Focalin XR®) 0 mg D-MPH-IR 5 mg bid D-MPH-IR 5 mg
20 mg D-MPH-IR 0 mg bid D-MPH-IR 0 mg
MAS-ER 0 mg MAS-IR 5 mg bid MAS-IR 5 mg
(Adderall XR®) 20 mg MAS-IR 0 mg bid MAS-IR 0 mg
30 mg MAS-IR 5 mg bid MAS-IR 5 mg
Lisdexamfetamine 30 mg MAS-XR 0 mg MAS-IR 5 mg
(Vyvanse ®) 50 mg MAS-XR 20 mg MAS-IR 0 mg
84

70 mg MAS-XR 30 mg MAS-IR5 mg
bid, twice daily morning and noon; D-MPH, dexmethylphenidate; ER, extended release; IR,
immediate release; MAS, mixed amphetamine salts; MPH, methylphenidate; tid, three times daily.

dose (Table 0.2) (see Chapter 9). Stimulant and nonstimulant combinations
are often useful when stimulant doses require reduction due to weight loss or
when addressing tic exacerbations, rebound hyperactivity, late afternoon irri-
tability, and sleep difficulties. With the exception of stimulants and ER alpha-2
agonists in treating treatment refractory ADHD symptoms, these combina-
tions are considered off-label uses.

Long-Term Maintenance
Once an apparently optimal medication and dose have been identified, it is
advisable to provide a -month prescription and then reassess to confirm
that symptoms are adequately controlled. After the clinician and patient
agree that clinical needs are well addressed, subsequent follow-up visits
can be scheduled every 3 months. Assessment of height, weight, pulse, and
blood pressure can be limited to every 6 months.9 Some clinicians are con-
tent to provide long-term refills without requiring patient appointments
and only reassess patients as needed. This is not an acceptable standard
of care.
As with all chronic conditions, patient adherence with prescribed treat-
ment is improved by regular clinical contact and active inclusion of patients
and families in their medical decision making. 0 Clinical improvement is
best maintained with regular monitoring and dose adjustments, likely to be

Clinical Medication Management

required as the patient grows. Clinicians are not able to assist with ongoing
management if not regularly apprised of patient needs. Regular assessment
facilitates initiation of family, academic, and social interventions as needed.
Treatment compliance is further improved with more extensive evaluation
and provision of appropriate education about the disorder.0
Finally, the US Drug Enforcement Agency (DEA) only allows up to a 90-day
prescription of Schedule II drugs and requires clinical reassessment before
additional refills can be provided. Depending on the patient’s insurance plan,
clinicians can write for a single 90-day supply or provide three separate pre-
scriptions for 30-day supplies, with notations that prescriptions not be filled
until  and 2 months later for the second and third prescriptions, respec-
tively. Nonstimulant medications are not limited to 90-day supplies and can
be renewed without clinical reassessment. However, patients still benefit

Chapter 0
from consistent and regularly scheduled follow-up visits for the other reasons
described. Careful documentation of all prescribed medications is essential.

Managing Common Side Effects

Most side effects to ADHD medication are mild to moderate in sever-
ity. General management strategies include changes in dose or dose forms,

85
switching to alternative medications, or combination drug treatments.
Medications that cause unacceptable side effects or are not tolerated must
be discontinued.

Appetite Loss and Growth Delay

It is advisable to anticipate appetite loss and recommend calorie supple-
mentation when stimulant therapy is initiated, not after weight loss occurs.
Medication is best taken after eating breakfast and other meals, and late eve-
ning meals and high-caloric snacks should be encouraged. Appetite, height,
weight, and body mass index should be assessed at least every 6 months. 9
It is important to differentiate baseline “picky” eating from stimulant-related
appetite suppression and parental concerns about decreased appetite from
documented weight losses. Loss of 5% or more body weight from baseline or
failure to gain height or weight over a year should be addressed with stimulant
dose reductions, switch to shorter acting stimulant or alternative drug class,
or medication holidays on weekends and vacations. Children who exhibit
deceleration of growth rate usually make up their growth losses once medi-
cation is discontinued (see Chapter 2). Medication holidays over two, but
not one, summer vacations promote successful recovery from lost growth.
Children at or below the 3rd percentile for height at a given age should be
referred for evaluation by a pediatric endocrinologist.

Headache, Stomachache, Nausea

It can be difficult to determine whether headache, stomachache, nausea, and
other somatic complaints are caused by medication or underlying ADHD. In
many studies, these effects occur equally in children taking active stimulants
ADHD or placebo.2 Management approaches include on-off-on medications trials,
dose reductions, taking medication with food, and switching to alternative
medication. These side effects are particularly common with atomoxetine
and alpha-2 agonists, and they can respond to dose reductions. Palliative
treatment, such as acetaminophen or ibuprofen for headache, can be consid-
ered and used if effective in relieving symptoms. A change in medication class
or abandonment of pharmacotherapy might be necessary if these symptoms
persist at intolerable levels.
Mood Lability and Irritability
It is important to differentiate mood changes that span the entire day from
briefer “rebound” episodes that occur in the late afternoon when stimulant
effects are wearing off. With pervasive mood changes, the possibility of
comorbid mood or anxiety disorders should be reconsidered. Atomoxetine
can be preferentially beneficial in individuals exhibiting stimulant-related
mood changes. Serotonin reuptake inhibitors (SRIs) might be indicated
as adjunctive stimulant treatment with evidence of depression, anxiety, or
chronic irritability.
Psychosis
True psychotic symptoms are rare with ADHD medications. The most typical
psychotic symptom attributable to stimulants is formication, the sense that
86

insects are crawling under the skin. The first step when psychotic symptoms
emerge is to confirm that the patient is not exceeding therapeutic drug doses.
Lowering the medication dose or stopping medication altogether allows
determination of whether symptoms cease or persist. If psychotic symptoms
resolve, a medication rechallenge at the previous dose can establish whether
the psychosis is related to drug effects. Persistent psychotic symptoms neces-
sitate additional diagnostic clarification.
Rebound Hyperactivity
Many individuals on stimulant therapy have persistent adverse reactions
in mid- to late afternoon when medication effects are waning. These can
include increased mood lability, irritability, hyperactivity and restlessness,
and fatigue. Several strategies to assess this difficulty can be tried on a
case-by-case basis. These include switching to a longer acting or alternative
stimulant, addition of a nonstimulant, or switching to nonstimulant mono-
therapy. Ensuring that the child has a balanced snack after school can also
prove helpful, particularly when lunch is skipped due to appetite loss or
other reasons.
Sleep Difficulties
Many individuals with ADHD have sleep difficulties, on or off medication.9
A typical picture is that ADHD patients have severe problems settling to
bed in the evening, but once asleep they are very difficult to arouse. It is
essential to document baseline sleep patterns prior to initiation of medica-
tion. Sleep laboratory assessment might be indicated if there are suspicions
of sleep apnea, episodic nocturnal phenomena, excessive limb movements,
or unexplained daytime drowsiness. Proper sleep hygiene, including the
implementation of a standard bedtime routine and minimal use of electron-

Clinical Medication Management

ics after dinner, must be emphasized prior to any changes in pharmaco-
therapy. Once sleep difficulties are clearly attributed to ADHD medication,
options might include addition of a low-dose short-acting stimulant in the
evening to counteract rebound hyperactivity, switching to a shorter acting
stimulant formulation for morning administration, or adjunctive treatment
with an IR alpha-2 agonists given after dinner or twice daily. Melatonin is
useful for some patients, but care must be taken to ensure that only pharma-
ceutical grade drug is administered.
Suicidality
Suicidal thoughts and behaviors are extremely rare during ADHD pharma-
cotherapy. Their emergence suggests the existence of comorbid psychiatric
disorders or severe psychosocial stress.9 As with psychosis, it might be useful
to assess symptoms after lowering doses or discontinuing medication, but

Chapter 0
absent any clear relationship with suicidal symptoms, there is no contraindica-
tion to continuing ADHD treatment.

Discontinuing Medication
While it is undeniable that ADHD medications provide short-term benefits,

87
evidence supporting positive effects on long-term functioning beyond symp-
tom control remains limited.3 Many patients and families discontinue medi-
cation on their own, providing immediate evidence about whether ongoing
treatment is warranted. Alternatively, scheduled breaks from medication
are also helpful in determining whether pharmacotherapy remains justified.
Decisions over starting, continuing, or discontinuing medication must be indi-
vidualized. Clinicians remain obligated on at least an annual basis to reassess
relative benefits and risks of sustained pharmacotherapy.

References
. Pliszka SR, Crismon ML, Hughes CW, et al. The Texas Children’s Medication
Algorithm Project:  revision of the algorithm for pharmacotherapy of
attention-deficit//hyperactivity disorder. J Am Acad Child Adolesc Psychiatry.
2006;45:642–667.
2. Subcommittee on Attention-Deficit/Hyperactivity Disorder, Steering
Committee on Quality Improvement and Management. ADHD:  clini-
cal practice guidelines for the diagnosis, evaluation, and treatment of
attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics.
20;28;007–022.
3. Kooij SJ, Bejerot S, Blackwell A, et al. European consensus statement on diag-
nosing and treatment of adult ADHD: The European Network Adult ADHD.
BMC Psychiatry. 200;67.
4. Faraone SV, Buitelaar J. Comparing the efficacy of stimulants for ADHD
in children and adolescents using met-analysis. Eur Child Adolesc Psychiatry.
200;9:353–364.
5. Biederman J, Spencer T. Psychopharmacological interventions. Child Adolesc
Psychiatry Clin N Am. 2008;7:439–458.
ADHD   6. Wilens TE, Bukstein O, Brams M, et al. A controlled trial of extended-release
guanfacine and psychostimulants for attention-deficit/hyperactivity disorder. J
Am Acad Child Adolesc Psychiatry. 202;5:74–85.
  7. Treuer T, Gau SS, Médez L, et al. A systematic review of combination therapy
with stimulants and atomoxetine for attention-deficit/hyperactivity disorder,
including patient characteristics, treatment strategies, effectiveness, and toler-
ability. J Child Adolesc Psychopharmacol. 203;23:79–93.
  8. Wilens TE. Combined pharmacotherapy in pediatric psychopharmacol-
ogy: friend or foe? J Child Adolesc Psychopharmacol. 2009;9:484–484.
  9. Cortese S, Holtmann M, Banaschewski T, et al. Practitioner review: current
best practice in the management of adverse events during treatment with
ADHD medications in children and adolescents. J Child Psychol Psychiatry.
203:54:227–246.
0. Charach A, Fernandez R. Enhancing ADHD medication adherence: challenges
and opportunities. Curr Psychiatry Rep. 203;5:37.
. Martins S, Tramontina S, Polanczyk G, et al. Weekend holidays during meth-
ylphenidate use in ADHD children: a randomized clinical trial. J Child Adolesc
Psychopharmacol. 2004;4:95–205.
2. Barkley RA, McMurray MB, Edelbrock CS, Robbins K. Side effects of methyl-
phenidate in children with attention deficit hyperactivity disorder: a systemic,
placebo-controlled evaluation. Pediatrics. 990;86:84–92.
3. Van de Loo-Neus GH, Rommelse N, Buitelaar JK. To stop or not to stop: how
long should medication treatment of attention-deficit hyperactivity disorder
88

be extended? Eur Neuropsychopharmacol. 20;2:584–599.

Further Reading
McBurnett K, Swetye M, Muhr H, Hendren RL. Pharmacotherapy of inattention
and ADHD in adolescents. Adolesc Med State Art Rev. 203;24:39–405.
Riddle MA, dosReis S, Reeves GM, Wissow LS, Preitt DB, Foy JM. Pediatric psy-
chopharmacology in primary care: a conceptual framework. Adolesc Med State
Art Rev. 203;24:37–390.
Wilens TE, Morrison NR, Prince J. An update on the pharmacotherapy
of attention-deficit/hyperactivity in adults. Expert Rev Neurother. 20;
:443–465.
Chapter 

Comorbidity
Key Points
• Comorbidity is common with ADHD.
• ADHD treatment frequently requires concurrent management of
other disorders.

Potential comorbidity should be considered during initial ADHD evalu-

ations and whenever treatment response is unsatisfactory (see Chapter
6). Given limited resources, clinicians must carefully integrate the range of
treatments necessary to relieve both ADHD and co-occurring disorders.
This includes pharmacotherapy as well as numerous behavioral and psycho-
social interventions with evidence supporting their utility for specific condi-

89
89
tions (Box .).

Disruptive Behavior Disorders

Oppositional defiant disorder (ODD) and conduct disorder (CD) are the
most common co-occurring conditions in pediatric ADHD, approaching 50%
lifetime prevalence. ODD is typified by frequent and persistent patterns of
angry or irritable mood, argumentative and defiant behavior, and vindictive-
ness. CD is characterized by persistent behaviors that violate either basic
rights of others or major age-appropriate social norms.
Virtually all children with ODD or CD have ADHD. Between 30% and 50%
of ODD is evident by age 5.2 Recent research suggests that ODD comprises
two distinct dimensions, with irritable mood symptoms predicting subsequent
depression and anxiety, and argumentative/defiant behaviors predicting sub-
sequent conduct disorder.3 As with ADHD, the severity and frequency of
ODD symptoms must exceed what is developmentally expected. For exam-
ple, occasional temper outbursts and defiance are common in preschoolers
and would not indicate the diagnosis. Symptoms cannot be limited to strug-
gles over schoolwork related to ADHD or other learning impairments. In
older youth, particularly in families with strict cultural expectations, parental
concerns about oppositional behaviors and defiance must be balanced against
general societal norms as well as the individual’s maturity level and emerging
independence. In most cases, ODD remits by mid to late adolescence.
Distinctions between childhood- and adolescent-onset CD are long noted.
Childhood-onset CD requires emergence of at least one symptom by age 0.
ADHD
Box .  Evidenced-Based Behavioral and Psychosocial
Treatments
General
Psychoeducation
Disruptive Behavior Disorders
Behavioral contracting
Contingency management
Multisystemic therapy (MST)
Parent management training
Learning Disorders
Academic accommodations
Substance Use Disorders
Cognitive-behavioral therapy (CBT)
Multidimensional family therapy (MDFT)
Anxiety Disorders
CBT
Exposure therapy
Exposure/response prevention
90

Depression
CBT
Interpersonal psychotherapy (IPT)
Bipolar Disorders
Family-focused treatment (FFT)
Tic Disorders
Habit reversal therapy (HRT)

Childhood-onset CD is almost always preceded by ADHD and ODD, although

the majority of children do not subsequently develop CD. Childhood onset
predicts significantly more lifetime pathology, including higher rates of school
and occupational failure, substance use difficulties, aggression, and antisocial
behaviors. The worst outcomes associated with ADHD are largely mediated by
CD. Children with ADHD and childhood-onset CD typically have lower socio-
economic status and higher rates of antisocial and aggressive behaviors among
first-degree family members. Conversely, only a third of individuals with
adolescent-onset CD exhibit co-occurring ADHD. Adolescent onset is more
usually time limited, associated with acute psychosocial stress, and less likely to
include significant aggression or inadequate development of peer relationships.
Stimulants are effective in treating ODD and CD, apart from independent
improvements in ADHD. ODD symptoms also respond to atomoxetine and
alpha-2 agonists. Stimulants improve compliance with parental demands and
reduce overt and covert aggression, lying, stealing, and vandalism. Limited evi-
dence suggests that lithium and divalproex sodium are better than placebo in
controlling aggressive outbursts, but they are ineffective for ADHD. Several

Comorbidity
studies suggest some role for second-generation antipsychotic medications,
particularly risperidone, in controlling irritability and aggression.2 However,
these carry significant risks for weight gain, metabolic syndrome, and other
adverse outcomes. None of these are currently FDA-approved uses.
Psychosocial interventions are often important in managing ODD and CD,

Chapter 
whether or not pharmacotherapy is employed. The same psychosocial and
behavioral treatments recommended for ADHD, particularly parent man-
agement training, are useful with ODD (see Chapter 7). For older children,
parent management approaches can give way to negotiation of behavioral
contracts that establish clear behavioral expectations and consequences.
Some older children also benefit from cognitive interventions that teach
improved problem solving, communication, social skills, and impulse control.
New evidence suggests that multifamily psychoeducational psychotherapy
(MF-PEP), developed for treatment of mood disorders, might have similarly
positive effects for ODD, but not CD.4
CD interventions are difficult and expensive. Treatment, including phar-
macotherapy if indicated, should be initiated for any identifiable comorbid
disorder, such as ADHD, depression, anxiety, or substance use. CD is often
associated with high levels of family chaos. This suggests it is best to empha-
size behaviorally focused, time-limited interventions that teach clear guide-
lines for parental responses toward their children’s behaviors. Multisystemic

91
therapy (MST) is a type of parent management training that provides a com-
prehensive approach to family, marital, academic, and peer-related issues.
MST has proven useful in controlled trials, but it is expensive, time intensive,
and not widely available. Less specialized patient-based cognitive approaches
and parent management strategies are also used, but they are not supported
by a substantial evidence base.
Group therapies, which increase exposure to other youth with severe
behavioral difficulties, as well as individual psychodynamic or psychoanalytic
therapies, or open-ended family treatments, are generally regarded as inef-
fective interventions for disruptive behavior disorders.

Learning Disorders
Between 0% and 50% of individuals with ADHD have specific learning dis-
orders.2 Learning disorders are defined by persistent difficulties acquiring
critical academic skills combined with academic achievement levels that are
substantially below expectations for the student’s age or developmental level.
Specific learning disorders in reading, spelling, and mathematics appear to
have some genetic basis, but they are also influenced by family and environ-
mental factors. Assessment requires administration of standardized tests that
allow comparisons of intellectual ability with academic performance.
ADHD medications can enhance success on academic tests, although
there are no FDA-approved medication treatments for learning disability.
Remedial tutoring can improve academic skills, particularly when individual-
ized approaches to learning are incorporated. Academic accommodations,
ADHD including preferential classroom seating, modified work assignments,
note-taking services, and additional time on standardized tests can be imple-
mented under individualized education plans (IEPs) (see Chapters 7 and 8).

Substance Use Disorders

Compared with unaffected youth, individuals with ADHD are more likely
to experiment with psychoactive substances at younger ages and develop
problems related to substance use.5 Lifetime prevalence estimates of sub-
stance use disorders in ADHD range from 20% to 25% for adolescents and
45% to 55% for adults. Suggestions that substance use represents attempts
at self-medicating ADHD have not been borne out by research. The most
commonly used psychoactive substances are nicotine, alcohol, and canna-
bis, which reflect societal patterns. Numerous studies confirm that ADHD
treatment does not increase subsequent risk for substance use difficulties,
nor does ADHD pharmacotherapy during childhood and adolescence reduce
future substance use risk.5 More severe substance use disorders are generally
associated with a history of conduct disorder.
It is critically important to document the nature and extent of psychoactive
substance in patients with ADHD. Core features of substance use disorders
include impaired control of use, social impairment, risky behaviors, or fea-
92

tures of tolerance or withdrawal. Substance use is not equal to substance

use disorder. For example, it could be argued that occasional recreational use
of alcohol or marijuana is normative in some age groups and not associated
with any of these core features described. Individuals reporting intermittent
recreational alcohol or marijuana use are likely to be very different than those
with daily cocaine or opiate use. Recognition of these differences is critical for
effective treatment planning.
Clinicians should differentiate substance use and use disorders from misuse
and diversion. Misuse is use of a substance for a purpose other than which it
was intended. One-time recreational use of a prescription drug is not misuse
unless criteria for a substance use disorder are also met. Diversion is the
transfer of prescription medication from one person to another, regardless
of subsequent use. Patients with comorbid conduct or substance use disor-
ders have increased risks for misuse and diversion of prescription ADHD
medications.
There is no clear consensus on clinical management of patients with
ADHD and comorbid substance use disorders (see Chapter 2). In addition
to quantifying substance use, it is essential for clinicians to very carefully docu-
ment specific target symptoms, treatment responses, and doses and quanti-
ties of medication provided with each prescription. Some physicians refuse to
prescribe medication for adult ADHD due to concerns about potential abuse
and misuse. This is an extreme position. In contrast, although stimulants are
contraindicated for concomitant use with other psychoactive drugs, many
physicians are comfortable prescribing them despite occasional recreational
use of alcohol or cannabis. Nonstimulant ADHD medications are acceptable
alternatives if the provider determines there is too much risk with a stimulant
prescription. As substance use disorders increase in severity, clinical empha-

Comorbidity
sis generally shifts from ADHD to substance use. There is no evidence that
ADHD medications worsen co-occurring substance use or increase success
of substance use treatment.

Anxiety Disorders

Chapter 
Approximately one third of children and up to half of adults with ADHD
have clinically significant anxiety.  Many meet full diagnostic criteria for
social phobia, generalized anxiety disorder, and, in youth, separation anxiety
disorder. Others suffer substantial anxiety-related impairments but do not
strictly meet specific categorical criteria. Anxious children with ADHD have
more school- and peer-related difficulties than those with ADHD alone.
Families of these children exhibit higher rates of marital difficulties, separa-
tions, and divorce.
Several early stimulant studies described decreased symptom responses
and increased adverse event rates in anxious children with ADHD, suggesting
that anxiety is a contraindication for stimulant therapy. Other reports fail to
support this view. Numerous and more recent controlled studies demonstrate
that children with and without anxiety have similar rates of stimulant-related
ADHD response. In the Multimodal Treatment Study of ADHD (MTA), 34%

93
of participants had clinically significant anxiety. Anxiety was not associated
with worse outcomes, and many participants had meaningful reductions in
anxiety with stimulant monotherapy. Anxious children were more likely to
benefit from combination medication and psychosocial interventions than
those with ADHD alone.6 It has been proposed that anxious children and
their families might be more treatment adherent when provided additional
support through parent management and other psychosocial interventions,
but this has not been tested scientifically. In a pilot study based on MTA find-
ings, participants with ADHD and comorbid anxiety disorders were initially
titrated on a stimulant to reduce ADHD symptoms and then randomized to
fluvoxamine or placebo.7 About 0% had clinically significant reductions in
anxiety with stimulant alone. Those subsequently randomized to fluvoxamine
showed a trend for improved anxiety, although this did not meet statistical sig-
nificance in the small sample. In a randomized controlled study atomoxetine
was effective for both ADHD and anxiety; however, atomoxetine is not FDA
approved as an anxiety medication.
Based on these and other studies, one approach to medication manage-
ment is to initiate stimulant treatment (Fig. .). Given that stimulants can
be titrated quickly, this often allows for rapid improvement in ADHD, and
some individuals might also have significant reductions in anxiety. In those
with ongoing anxiety-related impairment, combination therapy with a selec-
tive serotonin reuptake inhibitor can be initiated. An alternative approach is
to initiate treatment with a nonstimulant, either atomoxetine or an alpha-2
agonist, that might be effective for both ADHD and anxiety symptoms (Fig.
.2). Again, however, neither of these medications has an FDA indication for
anxiety treatment.
ADHD
Step 0 Assessment/Psychoeducation/
Treatment Planning

Non-med Treatments

Step 1 Stimulant

ADHD & Anxiety

Both Improve
Continue
ADHD Improves;
But Not Anxiety
No Response ADHD or Anxiety
Step 2 Atomoxetine Add an SSRI

Figure .  Treatment algorithm for ADHD and comorbid anxiety disorders; choice
to begin with stimulant. SSRI, selective serotonin reuptake inhibitor. (Adapted from
Pliszka et al.3)

Step 0 Assessment/Psychoeducation/
Treatment Planning
94

Non-med Treatments

Step 1 Atomoxetine

ADHD & Anxiety

Both Improve
Continue
No Response
ADHD or Anxiety

Step 2 Stimulant Algorithm

Figure .2  Treatment algorithm for ADHD and comorbid anxiety disorders; choice
to begin with nonstimulant. (Adapted from Pliszka et al.3)

Parents of anxious children are often anxious themselves and might be

more reluctant than others to accept recommendations for pharmacotherapy.
Patients with anxiety are often more prone to experience medication-related
side effects. In general, a conservative approach that uses lower initial medi-
cation doses and more gradual dose titrations, particularly with an SSRI,
promotes greater acceptance of treatment with gradual exposure. Other
psychosocial approaches to anxiety disorders, particularly psychoeducational
and cognitive-behavioral therapies, are often useful with this group.
Depression
Over their lifetimes, 20% of individuals with ADHD have at least one epi-
sode of major depression.2 Depression is two to three times greater in
 Comorbidity
Step 0 Assessment/Psychoeducation/
Treatment Planning

Non-med Treatments

Chapter 
Step 1 Begin ADHD Algorithm
Both ADHD &
Depression Improve
Continue Depression Worsens;
No ADHD Response
ADHD Improves;
No Depression Response
Step 2 Add MDD Treatment Stop ADHD Treatment;
Begin MDD Treatment

Figure .3  Treatment algorithm for ADHD and comorbid depression; ADHD

more impairing. MDD, major depressive disorder. (Adapted from Pliszka et al.3)

ADHD-affected youth. Precise rates of juvenile depression can be difficult to

determine because parents and children often differ in reported symptoms.
Many depressive symptoms are not disorder specific. Concentration deficits

95
are seen in mood and anxiety disorders as well as ADHD. Irritability is a core
feature of juvenile depression, oppositional defiant disorder, and disruptive
mood dysregulation disorder. Some youth appear depressed and anhedonic
when frustrated about school or punished for some aspect of their behavior,
but they are readily engaged and motivated to participate in nonacademic or
social activities. Some view this picture as evidence of demoralization and not
depression. In other cases, particularly with persistent low mood, sleep or
appetite disturbances, decreased energy distinct from usual functioning, or
excessive guilt and low self-esteem, depression is more likely.
A general approach to treatment of ADHD and comorbid depression is
to determine initially which condition is more impairing. With demoraliza-
tion or milder depression, initial stimulant treatment can rapidly improve
ADHD symptoms and related feelings of failure and other mood symptoms
(Fig. .3). Subsequent antidepressant therapy is appropriate in those with
lingering mood-related difficulties. In cases dominated by low mood, particu-
larly with any degree of suicidality, it is typically better to initiate appropriate
treatment for depression, possibly including both therapy and antidepressant
medication (Fig. .4). Adjunctive stimulant medication can be initiated if
ADHD persists subsequent to resolution of mood symptoms. An alternative
to this sequential approach is to utilize a medication that might improve both
ADHD and depression. Buproprion has been proved effective in both juve-
nile and adult ADHD and is useful in adult depression, although it is not FDA
approved for ADHD. A study of atomoxetine in pediatric patients showed
ADHD improvement but no antidepressant response. Atomoxetine and sub-
sequent combination therapy with fluoxetine appears effective for ADHD
and depression.8
ADHD
Step 0 Assessment/Psychoeducation/
Treatment Planning

Non-med Treatments

Step 1 Begin MDD Treatment

ADHD & Depression

Both Improve
Continue
Depression Improves;
No ADHD Response
Step 2 Begin ADHD Algorithm;
Add to MDD Treatment

Figure .4  Treatment algorithm for ADHD and comorbid depression; depression

more impairing. MDD, major depressive disorder. (Adapted from Pliszka et al.3)

The potential role of psychotherapy for depression treatment should not

be ignored. There is a strong evidence base for cognitive-behavioral therapy
96

and interpersonal psychotherapy, among others, for both juvenile and adult
depression. Medication is appropriately used with persistent or more severe
depressive episodes, when daily mood symptoms occurring more often than
not, or with associated problems with sleep, appetite, or suicidality. Several
selective serotonin reuptake inhibitors (SSRIs) are indicated for pediatric
depression, although treatment effect sizes are not as large as with adults.
Combination strategies that integrate appropriate therapy and medication
are usually most effective in children and adolescents. SSRIs are not useful
for ADHD symptoms. There is a small potential for interactions between
some SSRIs and stimulants due to genetic variability in metabolic pathways,
but these are rarely significant clinically.

Bipolar Disorders
There is long-standing controversy on the purported co-occurrence of
ADHD and bipolar disorder. Some studies concluded that 20% of children
with ADHD also met criteria for mania.9 Unlike adults who typically exhibit
discrete episodes of euphoria and grandiosity, these children and adolescents
were more likely to exhibit chronic difficulties with irritability and hyper-
arousal. Subsequent research determined, among other differences, that
children with chronic irritability were more likely as young adults to be diag-
nosed with ADHD and depression, while those with episodic irritability had
higher lifetime risks for psychosis, subsequent manic episodes, and a parent
with classic bipolar disorder.0 DSM-5 criteria for bipolar disorder clarify that
manic symptoms must occur within distinct episodes that depart from usual
behavior. This clarification eliminated the bipolar diagnosis in individuals with

Comorbidity
a defining feature of chronic irritability.
Given past inconsistencies in the application of DSM bipolar criteria in
youth with ADHD, reliable estimates of comorbidity are unknown. Based
on DSM-5, clinicians must carefully distinguish ADHD symptoms, which are
expected to have childhood onset, persistent duration, and may or may not

Chapter 
be associated with chronic irritability, from acute-onset manic symptoms
that occur during discrete episodes with associated changes in mood, sleep,
overactivity, distractibility, or risk taking that clearly differs from usual func-
tioning. While comorbidity rates of bipolar disorder and ADHD may not be
as high as previously thought, clinicians should remain alert to their possible
co-occurrence.
When present, manic symptoms must be controlled using a standard
mood stabilizer or second-generation antipsychotic. Lithium, aripiprazole,
and risperidone are approved treatments for mania in children aged 0 years
and older. Off-label therapies, including use of these medications in younger
patients as well as divalproex sodium, are also employed, although evidence
supporting their use is scant. Once euthymia is attained, a stimulant can be
added to mood-stabilizing therapy to address residual ADHD. Several studies
have shown that adding stimulants to either lithium or divalproex is safe and
leads to improvement in ADHD compared with placebo. Careful monitoring
for potential exacerbations of mania or psychosis is essential. Alternatively,

97
an initial stimulant trial under close supervision is acceptable with an uncertain
history of mania, as severe ADHD symptoms are sometimes confused for
bipolar disorder. Long-term stimulant use does not appear to increase risk for
mania provided that treatment antimanic therapy is sustained.

Disruptive Mood Dysregulation Disorder

Early definitions of ADHD included affective instability and irritability as core
features, although these were removed from DSM-III and subsequent criteria.
Some aspects of chronic irritability and related difficulties were incorporated
into criteria for oppositional defiant disorder. Research on chronic irritability
initiated in response to questions about juvenile bipolar disorder proposed a
category called severe mood dysregulation (SMD), defined by frequent and
severe temper outbursts, persistent irritable or angry mood, and symptoms
of hyperarousal such as insomnia, distractibility, or intrusiveness. Individuals
with SMD have distinct biological and cognitive profiles, and increased risk
for ADHD, mood, and anxiety disorders. This research led to inclusion in
DSM-5 of disruptive mood dysregulation disorder (DMDD), a new diagnostic
category defined similarly to SMD without the requirement for hyperarousal.
Research on rates of co-occurring DMDD and ADHD, as well as optimal
approaches to treatment, remains limited. The ultimate utility of DMDD as a
diagnostic category has not been determined.
Despite uncertainties in nomenclature, a clear subset of individuals with
ADHD manifests chronic irritability and associated temper outbursts or
aggressive episodes. Treatment with second-generation antipsychotic agents,
ADHD such as risperidone or ziprasidone, decreases irritability and aggression but is
associated with serious side effects. None of these medication treatments has
an FDA indication for this use. Some research on SMD suggests that stimulant
treatment with adjunctive SSRI therapy might be a better tolerated and more
optimal approach to DMDD, but this requires additional study. Family-based
behavioral therapies are potentially important, particularly those that incor-
porate cognitive-behavioral approaches to affective regulation. Substantial
research is required before definitive recommendations regarding comorbid
DMDD can be made.

Tic Disorders
Motor tics, that is, rapid, recurrent, involuntary movements, are common and
often unnoticed. Tic disorders, including both motor and vocal tics, require
symptom persistence for at least  year and are associated with varying lev-
els of distress and impairment. Tics typically have onset before puberty and
most commonly decrease in frequency and severity during adolescence.
Approximately 0% of children with ADHD have tic disorders—much higher
than seen in the general population. Some have proposed genetic relation-
ships between the two disorders.
Tics naturally wax and wane and shift affected muscle groups and vocaliza-
98

tions over time. Episodic exacerbations often alternate with periods of relief.
Tic disorders were once considered absolute contraindication for stimulant
treatment. Current meta-analyses reveal that long-term stimulant treatment
has little overall impact on tic expression.2
Current recommendations suggest that stimulants remain first-line ADHD
therapies, even in the presence of tics. If a clear exacerbation of tics occurs
following treatment initiation, an alternative class of stimulants can be tried. If
the second stimulant is also associated with increased tics, a switch to a non-
stimulant ADHD medication is warranted. Nonstimulants are also accept-
able as initial therapies, although the ADHD response is generally less robust
than seen with stimulants. Atomoxetine has no impact on tics but is effective
for ADHD. Alpha-2 agonists are shown to reduce tics and improve ADHD,
although these are off-label treatments. Combination therapies, in particu-
lar, adding an alpha-2 agonist to a stimulant, can be especially effective and
can provide additional ADHD benefit as well as tic control. If tics remain
severe and refractory, first-generation antipsychotics such as haloperidol or
pimozide, which have FDA approval as tic therapies, or second-generation
agents such as risperidone or ziprasidone, which do not have an FDA indi-
cation, may be justified. Adjunctive treatment with habit reversal therapy, a
cognitive-behavioral treatment shown to be effective in reducing tics, can be
a useful component of overall management.

References
. Pliszka S. Psychiatric comorbidities in children with attention deficit hyperac-
tivity disorder. Pediatr Drugs. 2003;5:742–750.
 2. Spencer TJ. Issues in the management of patients with complex

Comorbidity
attention-deficit/hyperactivity symptoms. CNS Drugs. 2009;23:9–20.
  3. Burke JD, Hipwell AE, Loeber R. Dimensions of oppositional defiant disorder
as predictors of depression and conduct disorder in preadolescent girls. J Am
Acad Child Adolesc Psychiatry. 200;9:49:484–492.
  4. Boylan K, Macpherson HA, Fristad MA. Examination of disruptive behavior

Chapter 
outcomes and moderation in a randomized psychotherapy trial for mood dis-
orders. J Am Acad Child Adolesc Psychiatry. 203;52:699–708.
  5. Wilens TE, Martelon M, Joshi G, et al. Does ADHD predict substance-use
disorders? A 0-year follow-up study of young adults with ADHD. J Am Acad
Child Adolesc Psychiatry. 20;50:543–553.
  6. March JS, Swanson JM, Arnold LE, et al. Anxiety as a predictor and outcome
variable in the multimodal treatment study of children with ADHD (MTA). J
Abnorm Child Psychol. 2000;28:527–54.
  7. Abikoff H, McGough J, Vitiello B, et al. Sequential pharmacotherapy for chil-
dren with comorbid attention-deficit/hyperactivity and anxiety disorders. J
Am Acad Child Adolesc Psychiatry. 2005;44:48–427.
  8. Kratochvil CJ, Newcorn JH, Arnold LE, et al. Atomoxetine alone or combined
with fluoxetine for treating ADHD with comorbid depressive or anxiety symp-
toms. J Am Acad Child Adolesc Psychiatry. 2005;44:95–924.
  9. Wozniak J, Biederman J, Kiely K, et al. Mania-like symptoms suggestive of
childhood-onset bipolar disorder in clinically referred children. J Am Acad Child
Adolesc Psychiatry. 995;34:867–876.

99
0. Brotman MA, Schmajuk M, Rich BA, et al. Prevalence, clinical correlates, and
longitudinal course of severe mood dysregulation in children. Biol Psychiatry.
2006;60:99–997.
. Leibenluft E. Severe mood dysregulation, irritability, and the diagnostic bound-
aries of bipolar disorder in youths. Am J Psychiatry. 20;68:29–42.
2. Bloch MH, Panza KE, Landeros-Weisenberger A, Lechman JF.
Meta-analysis:  treatment of attention-deficit/hyperactivity disorder in
children with comorbid tic disorders. J Am Acad Child Adolesc Psychiatry.
2009;48:884–893.
3. Pliszka SR, Crismon ML, Hughes CW, et al. The Texas Children’s Medication
Algorithm Project:  revision of the algorithm for pharmacotherapy of
attention-deficit/hyperactivity disorder. J Am Acad Chlld Adolesc Psychiatry.
2006;45:642–657.

Further Reading
Bond DJ, Hadjipavlou G, Lam RW, et al. The Canadian Network for Mood and
Anxiety Treatments (CANMAT) task force recommendations for the manage-
ment of patients with mood disorders and comorbid attention-deficit/hyper-
activity disorder. Ann Clin Psychiatry. 202;24:23–37.
Upadhyaya HP. Managing attention-deficit/hyperactivity disorder in the presence
of substance use disorder. J Clin Psychiatry. 2007; 68:23–30.
Chapter 2

Medication Controversies
Key Points
• Medications for ADHD have been used for over 70 years and are
widely regarded as safe and effective.
• ADHD medications have some side effect risks that must be balanced
against potential treatment benefits.
• Some serious concerns about the safety of ADHD medications have
no factual basis.

ADHD medications have been widely used for over 70 years (see Chapter
2). Despite hundreds of clinical trials demonstrating efficacy and safety, as

101
101
well as epidemiological evidence resulting from millions of prescriptions
written annually, recurrent concerns about these medications persist among
medical professionals and the lay public. This chapter summarizes informa-
tion on common controversies surrounding ADHD pharmacotherapy.

Do ADHD Medications Stunt Growth?

Ongoing debate continues as to whether ADHD medications cause
delayed growth and decreased height. These concerns arise from the
well-recognized appetite suppressive and weight loss effects of stimulants,
as well as known inhibitory effects of increased synaptic dopamine on
growth hormone. Although only some patients lose significant weight dur-
ing stimulant treatment, virtually all clinical trials have shown that children
fail to make expected gains in weight and height, particularly during the ear-
liest period of treatment. Growth delays appear greatest in younger versus
older youth and in children who are taller and heavier than age-matched
peers. Growth rates in early adolescence appear to be unaffected.
Numerous investigations have compared growth trajectories in medi-
cated and never-medicated children, as well as typically developing youth
without ADHD. Stimulants are clearly associated with decreased growth
velocity, with gains in height and weight less than expected for a given age.
At the point of greatest deficit, these children are on average 2 cm shorter
than nonmedicated peers. Stimulant-treated patients continue to grow, but
more slowly than anticipated. Growth decelerations are most significant
during the first 8 months but attenuate with ongoing treatment. The MTA
ADHD Study found greatest deficits in growth velocity during year , decreased
deficits in year 2, and normalization by year 3.2 Similarly, other investiga-
tions suggest that height deficits are greatest during the first 6 months of
treatment but decrease over time. Growth deficits are smaller in indi-
viduals with previous stimulant trials, providing further evidence that these
effects diminish with ongoing therapy. Importantly, children appear to reach
expected sizes within 2 years of treatment cessation, and several studies
indicate that ultimate adult height is not affected. Similar patterns are seen
in clinical trials of atomoxetine.3
Other research is less consistent. Some reports suggest greater growth
delays with amphetamine, while others describe equivalent deficits with
amphetamine and methylphenidate formulations. Deficits occur across the
dose range but are positively correlated with increasing medication doses.
One study suggested that a medication holiday over one summer did not
improve growth velocity, but holidays over two summers led to improved
growth rates.3 Weekend medication holidays do not appear to effect growth
rates, but discontinuing medication over extended school breaks may have
some benefit.
The main clinical issue is whether the potential for short-term decreases in
expected growth outweigh the potential benefits of treating a child’s ADHD.
Given the known risks associated with the disorder, this assessment generally
favors providing medication.
102

Can ADHD Medications Cause

Sudden Death?
Intermittent reports of sudden death in patients taking ADHD medications
contribute to ongoing concerns about potential cardiac risks. In response to
reports of sudden death in patients taking mixed amphetamine salts, officials
in Canada removed the drug from their market, although this was subse-
quently reversed. Stimulants are associated with increases of 2–5 mm Hg sys-
tolic and –3 mm Hg diastolic blood pressures, as well as small but significant
increases in average pulse rate. These increases might be expected to cre-
ate increased risk for cardiovascular problems. However, after considerable
study, there is general consensus that the frequency of sudden cardiac death
in young patients treated with ADHD medications is within the expected rate
for the general population.4
Clinical medication trials are too small and short in duration to assess
long-term cardiac risks. However, several large epidemiological studies provide
reassurance. In one study of over 70,000 youth, there were no differences in
rates of cardiovascular events such as myocardial infarctions, cerebrovascular
accidents, or sudden cardiac death in individuals prescribed ADHD medica-
tion lacking known cardiac risk factors.5 There were no differences between
those prescribed or not prescribed stimulants or in those taking methylpheni-
date versus amphetamine. A second study of more than 440,000 young and
middle-aged adults also failed to demonstrate any differences in cardiac risks
associated with current, remote, or no stimulant use.6
 Frequent reports of sudden cardiac death in athletes and other young and

Medication Controversies
apparently healthy individuals are also attributable to general population risk.
Cardiac risk screening is a major reason for physical examinations prior to
participation in competitive sports (see Chapter 6). Viewed in these terms,
cardiac risks associated with ADHD medications are comparable to those
engendered by youth recreational sports and other common physical activities.
The US Food and Drug Administration warns that “sudden death has
been reported in association with CNS stimulant treatment at usual doses in
children and adolescents with structural cardiac abnormalities or other seri-
ous heart problems.” Current practice standards require assessment prior
to initiation of ADHD medications of any personal history of syncope, diz-
ziness, palpitations, or chest pain, any family history early sudden cardiac

Chapter 2
death, and completion of a careful cardiac examination (see Chapter 6).
The FDA also recommends intermittent clinical pulse and blood pressure
monitoring in patients prescribed ADHD medications (see Chapter 0).

Should an Electrocardiogram Be Obtained

Before Starting Medication?
Some clinicians routinely obtain electrocardiograms (EKGs) prior to initiating
medication, and American Heart Association guidelines support this when

103
clinically indicated. However, no compelling data suggest that routine EKGs
effectively screen for early sudden cardiac death, and the American Academy
of Pediatrics does not endorse routine screening prior to initiation of ADHD
medication.7 Rather than obtaining an EKG, it is preferable to screen patients
based on history and cardiac examination findings and refer individuals
deemed at risk for more comprehensive assessment by an appropriate spe-
cialist (see Chapter 6).

Can ADHD Medications Cause Birth Defects?

With increasing ADHD pharmacotherapy in older adolescents and adults,
concerns have emerged about potential medication risks to a developing fetus
or young infant. Women are generally advised to avoid or minimize medica-
tion use while pregnant or breastfeeding. At times, however, the mother’s clin-
ical needs warrant ongoing treatment. Concerns also exist about women who
are attempting to become pregnant or are unaware of an early pregnancy.
Most clinical trials exclude pregnant participants, and no studies have
examined potential teratogenic effects of ADHD medications. Animal studies
suggest that stimulants cross the placenta and enter fetal circulation, although
direct human data are unavailable. No teratogenic effects were seen in rats,
but an increased incidence of spina bifida occurred in rabbits with methylphe-
nidate exposure 40 times the usual therapeutic doses.
One report identified 80 women who had taken methylphenidate dur-
ing their first trimester of pregnancy.8 Of these, four children with major
birth defects were observed, a rate within the expected population range.
ADHD Although limited, these data provide reassurance regarding stimulant-related
birth defect risks.
The solubility and low molecular weight of methylphenidate suggests that
it enters breast milk, but drug amounts available for infant ingestion vary with
maternal dose, absorption, and metabolism. Estimates of relative infant dose,
defined as the ratio of the amount ingested by baby and mother, are within a
range generally accepted as safe.
Available evidence suggests that there is no to very little risk of fetal drug
exposure in the earliest weeks of gestation, so there is no apparent need to
stop medication in anticipation of pregnancy.8 A decision to continue or not
during pregnancy or breastfeeding must balance individual clinical necessity
and potential risk.

Can ADHD Medications Cause Cancer?

One small study in 2 children found an association with methylphenidate and
chromosomal abnormalities in peripheral lymphocytes.9 This raised concern
over possible increased cancer risk with methylphenidate treatment. Children
served as their own controls, with assessments of chromosome damage per-
formed before and after medication use. Several follow-up studies using simi-
lar methods failed to detect chromosomal change.
104

Another investigation of over 20,000 individuals with ADHD evaluated

drug use profiles and emergent cancer rates.0 Medications examined included
methylphenidate, amphetamine, other ADHD medications, antidepressants,
antipsychotics, and combination therapies. No increased risk for cancer was
detected for methylphenidate, any other drug, or any drug class.
Larger studies and longer periods of observation would be useful in evalu-
ating potential links between ADHD medications and cancer risk, but current
evidence does not support any association.

Do ADHD Medications Lead to Drug Abuse

and Addiction?
News media frequently report widespread abuse of ADHD medications. While
these stories raise legitimate concerns, they conflate problems related to stimu-
lants prescribed for ADHD and other stimulants, such as Ecstasy, cocaine, and
“street” methamphetamine, and fail to distinguish patterns of use, including
abuse, misuse, and diversion. Drug “use” includes taking medication as pre-
scribed to reduce ADHD symptoms, for recreational mind-altering effects such
as intoxication or euphoria, for other purposes such as weight loss, or for per-
formance enhancement. Strictly defined, “abuse” refers to a pattern of use con-
sistent with the DSM-5 definition of substance use disorder, which requires use in
situations that create risk for harm, failure to meet personal obligations, or symp-
toms of tolerance, withdrawal, or dependence. “Diversion” is the transfer of
medication to someone for whom it is not prescribed. “Misuse” is the taking of
medication by someone for whom it is not prescribed or in ways not prescribed.
 Rates of misuse and diversion are estimated at 4.5% of middle and high

Medication Controversies
school students. Numerous studies suggest that between 2% and 6% of
college student misuse ADHD medications. Of students with ADHD, 25%
to 30% describe being asked to sell their medication and % has done so.
The majority of misuse among college-age youth is for purposes of academic
performance enhancement. About 30% is for recreational purposes, that is,
to get high. Medications are most commonly obtained from peers or family
members, and their highest use is during exam periods or other times of high
academic stress. In one study, a third of students misusing ADHD medication
stole it, 20% faked ADHD symptoms to obtain it from a physician, and 5%
bought it from an Internet pharmacy.
Misuse is more common at colleges in the Northeast and those with

Chapter 2
highly competitive admissions. Misuse occurs more frequently among
students who are White, male, in fraternities, and have lower grades.
Students involved in misuse and diversion of ADHD medications have
higher rates of alcohol, tobacco, and recreational drug use, and other dif-
ficulties with substance use disorders and conduct-disordered behavior.
Even when misused, most medications are taken orally. Medications are
also commonly crushed and either injected or taken intranasally by those
seeking intoxication.
Physicians prescribing ADHD medications should be mindful of patient
groups at highest risk for diversion and misuse. Physicians should counsel

105
high-risk patients about the need to safeguard prescriptions and obtain com-
mitments that medication will not be diverted or shared. Extended-release
and pro-drug formulations have less risk for abuse than immediate-release
stimulants and are preferred options when the potential for misuse is a clinical
concern. Physicians can also choose nonstimulant ADHD treatments when
the risks for abuse and misuse exceed what can be managed with confidence.
Related issues are whether patients become addicted to their ADHD
medications and if stimulant treatment creates future risk for other substance
use. Longitudinal studies clearly show there is no risk of stimulant addiction
or increased risk for substance use disorders in young adult previously treated
for ADHD.2 Other evidence suggests that stimulant treatment in childhood
and adolescence protects against the increased risk of substance use that
occurs in untreated ADHD (see Chapters 3 and ), although these results
are less clear.3 No data support withholding ADHD medications for fear of
causing substance use difficulties.

Do People Fake ADHD to Get Drugs?

Many clinicians, particularly those who do not assess and treat childhood
ADHD, remain suspicious that adults requesting evaluations are feigning
symptoms to obtain medication or other special services. Consistent with
this, one study suggests that half of university students presenting for ADHD
assessments exaggerate symptoms. Consequently, many university health
services refuse to evaluate students for ADHD and many practitioners refuse
to prescribe ADHD medication for adults.
ADHD Several approaches are proposed to differentiate adults with true ADHD
from those who are feigning symptoms to pursue various benefits. Solicitation
of clinical information from multiple sources, including parents, employers,
spouses, partners, and friends, as well as review past school and medical
records, is a critical step in confirming a diagnosis. Consistent use of self and
other-informant rating scales, neuropsychological assessments, computerized
tests of attention such as the Conners’ Continuous Performance Test (CPT),
and quantitative electroencephalography (EEG) have been proposed, but
none of these has been effective in improving diagnostic accuracy. Additional
research and development of validated biological markers are sorely needed.
Presently, the clinician must rely on individual judgment to assess the potential
benefits and risks of prescribing treatment in any given patient.

Should ADHD Medications Be Prescribed

If Someone Is Using Recreational
Drugs or Alcohol?
Recreational drug use is common among individuals with ADHD. Clinicians
must decide whether to provide prescription medication to patients who are
currently abusing other psychoactive substances. In addition to heightened
106

concerns about misuse and illicit diversion, there is a potential for negative
drug interactions and worsening of underlying problems with concomitant
prescription and illicit substance use. Conversely, in some appropriate treat-
ment could potentially improve substance use.
There are no clear consensus guidelines for prescribing ADHD medications
with concurrent psychoactive substance use or use disorders.4 Most ADHD
clinical trials exclude participants with significant active use, so empirical evi-
dence to direct treatment is lacking. A decision to treat or not depends on sev-
eral factors, including the degree of diagnostic uncertainty, potential overlap of
ADHD and substance use symptoms, risk of substance use exacerbation, and
the clinician’s ability to monitor prescription compliance and response. The
type of drugs used, patterns, frequency and consequences of use, and degree
of dependence are all factors to be considered on a case-by-case basis.
Available research is both reassuring and disappointing. Treatment of
ADHD during concurrent recreational drug use does not appear to worsen
any substance use disorder.5 Both stimulants and atomoxetine are proven
effective in multiple studies for reducing ADHD symptoms even during
active recreational drug use. However, ADHD treatment does not appear to
improve substance use itself.5
Delaying ADHD treatment until after substance use issues are resolved
facilitates more accurate ADHD diagnosis and assessment of treatment out-
comes without confounding effects of other psychoactive drugs. However,
given that some degree of recreational substance use is normative, strict insis-
tence on a sobriety prior to diagnosis and initiation of treatment is likely to
be counterproductive. Conversely, very frequent and heavy recreational use
of psychoactive substances is apt to obscure any potential ADHD treatment
benefit. If the clinician determines that treatment is appropriate, proper

Medication Controversies
documentation of target symptoms, prescription information, and treatment
outcomes in the medical record is essential to good practice.

Is It Useful to Get Stimulant Blood Levels?

Some clinicians obtain laboratory measurement of stimulant plasma levels as
part of clinical management. Although these tests are readily available from
commercial laboratories, no standard therapeutic window for medication
response has been established and no relationship between plasma concen-
tration and behavioral or cardiovascular response has been demonstrated.

Chapter 2
Laboratory assessment can document medication compliance on a given
day, but it does not provide any additional value in routine clinical care.

Do Medications Stop Working?

Separate from questions about acute tolerance to stimulants over the course
of daily treatment is the larger issue of potential loss of medication bene-
fit with long-term use. Parents and patients often inquire about the risk of
dependency or addiction to ADHD medications. Despite US FDA warnings

107
that long-term use of stimulants can lead to dependence, longitudinal stud-
ies convincingly demonstrate that patients prescribed ADHD medications
do not become addicted to them.2 Whether or not some patients develop
long-term medication tolerance is a more nuanced question for which avail-
able evidence fails to provide a clear answer.
In numerous open-label stimulant studies of –2 years duration, most par-
ticipants do not require medication adjustments once optimal doses are estab-
lished. Similarly, many patients are treated clinically for many years without
any need for dose or medication changes, suggesting that long-term medica-
tion tolerance does not occur. This contrasts with evidence from the MTA
Study in which participants in the optimal medication management arm typi-
cally required ongoing dose adjustments to maximize benefits.6 It was unclear
whether this reflected the need for increasing doses as patients grew or the
possibility of long-term tolerance effects. While not common, some patients
treated clinically do complain that previously effective medications stop work-
ing. It is also possible that some patients discontinue therapy due to lack of sus-
tained effects. Finally, the phenomenon of “rebound hyperactivity” in which
patients exhibit symptoms at or worse than baseline during late afternoon
when medications are losing effect is well described, and it further suggests
that stimulants cause acute brain changes that might negatively affect behavior.
Although development of long-term tolerance does not seem to be a
major clinical concern, it might be in some cases. One small study provided
a potential physiological explanation for tolerance effects. Investigators using
positron emission tomography (PET) and a dopamine transporter ligand
assessed the effects of 2 months of methylphenidate treatment on striatal
dopamine transporter densities.7 Dopamine transporter densities increased
ADHD in participants on stimulant therapy, suggesting that brain adaptations occur
with treatment. Authors hypothesized that upregulation of the dopamine
transporter system could lead to increased symptoms and decreased medi-
cation effects. The study did not assess dopamine signaling in the prefrontal
cortex, nor did it address noradrenergic mechanisms. Furthermore, clinical
implications of these changes have not been elucidated. The potential for
long-term tolerance and brain changes resulting from stimulant use requires
further investigation. Absent a clear understanding of this phenomenon,
standard clinical approaches to medication adjustment remain the best
course when treatments cease to provide positive effects.

References
  . Faraone SV, Biederman J, Morley CP, Spencer TJ. Effect of stimulants on height
and weight: a review of the literature. J Am Acad Child Adolesc Psychiatry.
2008;47:994–009.
  2. Swanson JM, Elliott GR, Greenhill LL, et al. The effects of long-term stimulant
medication on growth rates across 3 years in the MTA follow-up. J Am Acad
Child Adolesc Psychiatry. 2007;46:05–027.
  3. Kratochvil CJ, Wilens TR, Greenhill LL, et al. Effects of long-term atomoxetine
treatment for young children with attention-deficit/hyperactivity disorder. J
Am Acad Child Adolesc Psychiatry. 2006;45:99–927.
108

  4. Hammerness P, Perrin JM, Shelley-Abrahamson R, Wilens TR. Cardiovascular

risk of stimulant treatment in pediatric attention-deficit/hyperactivity disor-
der: update and clinical recommendations. J Am Acad Child Adolesc Psychiatry.
20;50:978–990.
  5. Olfson M, Huang C, Gerhard T, et al. Stimulants and cardiovascular events in
youth with attention-deficit/hyperactivity disorder. J Amer Acad Child Adolesc
Psychiatry. 202;5:47–56.
  6. Habel LA, Cooper WO, Sox CM, et  al. ADHD medications and risk of
serious cardiovascular events in young and middle-aged adults. JAMA.
20;306:2673–2683.
  7. Perrin JM, Friedman RA, Knilans TK, Black Box Working Group, Section on
Cardiology and Cardiac Surgery. Cardiovascular monitoring and stimulant drugs
for attention-deficit/hyperactivity disorder. Pediatrics. 2008;22:45–453.
  8. Dideriksen D, Pottegard A, Hallas J, Aagaard L, Damkier P. First trimester in
utero exposure to methylphenidate. Basic Clin Pharmacol Tox. 202;2:73–76.
  9. El-Zein RA, Abdel-Rahman SZ, Hay MJ, et al. Cytogenic effects in children
treated with methylphenidate. Cancer Lett. 2005;230:284–29.
0. Steinhausen HC, Helenius D. The association between medication for atten-
tion deficit hyperactivity disorder and cancer. J Child Adolesc Psychopharmacol.
203;23:208–23.
. Rabiner DL. Stimulant prescription cautions: addressing misuse, diversion and
malingering. Curr Psychiatry Rep. 203;5:375.
2. Barkley RA, Fischer M, Smallish L, Fletcher K. Does the treatment of
attention-deficit/hyperactivity disorder with stimulants contribute to drug
use/abuse?: a 3-year prospective study. Pediatrics. 2003;:97–09.
3. Wilens TE, Adamson J, Monuteaux MC, et al. Effect of prior stimulant treat-
ment for attention-deficit/hyperactivity disorder on subsequent risk for
 cigarette smoking and alcohol and drug use disorders in adolescents. Arch

Medication Controversies
Pediatr Adolesc Med. 2008;62:96–92.
4. Upadhyaya HP. Managing attention-deficit/hyperactivity disorder in the pres-
ence of substance use disorder. J Clin Psychiatry. 2007;68:23–30.
5. Mariani JJ, Levin FR. Treatment strategies for co-occurring ADHD and sub-
stance use disorders. Am J Addict. 2007;6:45–54.
6. MTA Cooperative Group. National Institute of Mental Health Multimodal
Treatment Study of ADHD follow-up:  24-month outcomes of treat-
ment strategies for attention-deficit/hyperactivity disorder. Pediatrics.
2004;3:754–76.
7. Wang GJ, Volkow ND, Wigal T, et al. Long-term stimulant treatment affects
brain dopamine transporter levels in patients with attention deficit hyperactiv-

Chapter 2
ity disorder. PloS One. 203;8:e63023.

Further Reading
Bolea-Alamanac BM, Green A, Verma G, Maxwell P, Davies SJ. Methylphenidate
use in pregnancy and lactation:  a systematic review of evidence. Br J Clin
Pharmacol. 204;77:96–0.
Cooper WO, Habel LA, Sox CM, et al. ADHD drugs and serious cardiovascular
events in children and young adults. N Eng J Med. 20;365:896–904.
Faraone SV, Wilens TE. Effect of stimulant medications for attention-deficit/

109
hyperactivity disorder on later substance use and the potential for stimulant
misuse, abuse, and diversion. J Clin Psychiatry. 2006;68:5–22.
Chapter 3

Complementary and
Alternative Medicine Therapies
Key Points
• There is tremendous lay interest in complementary and alternative
medicine approaches to ADHD.
• The only complementary or alternative ADHD treatment with suf-
ficient evidence to support its use is omega-3 fatty acid supplemen-
tation, which given a small positive effect size is recommended as a
potentially useful adjunctive therapy with standard pharmacotherapy.
• Patients and families who refuse established treatments in lieu of
complementary and alternative approaches risk increased negative
consequences of untreated ADHD.

111
111
There is tremendous interest in complementary and alternative medicine
(CAM) treatments for ADHD. Parents and patients are often concerned
about medication safety and prefer therapies that avoid pharmacotherapy or
are viewed as “natural.” Some patients respond poorly to medication. Even
when beneficial, medications have side effects, rarely normalize behavior,
and have little evidence of long-term benefit. By definition, complementary
treatments are used in conjunction with standard therapies, while alterna-
tive treatments are used in place of them. CAM treatments might be reason-
able options when patients fail or have inadequate responses to conventional
therapies. It is estimated that over 60% of children and large numbers of
adults have used CAM treatments for ADHD.
Despite their popularity, almost all CAM therapies have failed to meet cri-
teria as evidence-based treatments or demonstrated sufficient benefit to sup-
port recommendations for use (Box 3.).,2 While there are many published
studies of CAM treatments for ADHD, most are methodologically flawed.
Sample sizes are small, randomization is suspect, control groups are absent
or poorly designed, patients are inadequately diagnosed, and articles are writ-
ten by investigators with financial incentives to promote treatments. Positive
meta-analyses are commonly based on ratings by individuals with strong pre-
existing beliefs in treatment efficacy or significant time investments in provid-
ing the intervention. These raters, usually parents or therapists, tend to inflate
treatment effect sizes. Results are also commonly confounded by medication
use. For almost all CAM treatments, positive effects vanish when based on
blinded assessments in unmedicated participants.2
ADHD
Box 3.  Evidence for Complementary and Alternative ADHD
Treatments Based on Blinded Ratings
Sufficient Evidence Supporting Recommendation for Use
Omega-3 fatty acid supplementation
Mean effect size = .6, suggesting possible role as adjunctive therapy
Lack Sufficient Evidence Supporting Recommendation for
Use
Acupuncture Massage therapy
Amino acid supplements Mindfulness-based meditation, yoga
Caffeine Nutraceutical supplements
Chiropractic therapy Repetitive transcranial magnetic
stimulation
Cognitive training Restriction/elimination diets
Electroencephalographic Sensory integration therapy
neurofeedback
Exercise Vision therapy
Homeopathy Vitamin and mineral supplements
Interactive metronome therapy
Source: Data taken from Sonuga-Barke et al.2
112

The primary risk of most CAM treatments is the failure to administer stan-
dard therapies with proven efficacy and safety. Families can devote substantial
effort and resources pursuing nonmedication interventions that lack any evi-
dence of positive benefit. Some CAM treatments themselves have risks for tox-
icity or other adverse outcomes. Clinicians should maintain awareness about
CAM research so that they can properly advise patients on treatment choices.

Restriction/Elimination Diets
There is widespread belief that ADHD is caused by or can be treated with
diet. Most research on dietary interventions has serious methodological flaws,
including inadequate comparison groups, investigator and publication bias,
unblinded or biased parent raters, and a lack of confirmation by blinded symp-
tom reports. Of all restricted diets, only artificial food coloring elimination has
shown significant benefit on blinded ratings. However, long-term adherence to
restricted diets is extremely difficult, can lead to nutritional deficiencies, and
appears justified only in small subsets of patients with particular sensitivities.3
Feingold Diet
Beginning in the 970s, some proposed that childhood hyperactivity was
caused by increased sensitivity to certain foods. Dr. Ben Feingold, a pedia-
trician and allergist, wrote several books espousing dietary treatment for
childhood behavioral problems that eliminated synthetic food colors, flavors,
and preservatives, and foods containing salicylates, such as certain nuts and
fruits. Although Feingold originally reported behavioral improvements in over
50% of treated children, subsequent research revealed that many foods in his
diet actually contained salicylates. Numerous blinded controlled trials failed

Medicine Therapies
to show any benefits, with the exception of a small group of preschool-age
youth who reacted negatively when additives and preservatives were added
blindly to their diets. Although proponents continue to debate these largely
negative conclusions, there is no current evidence suggesting the Feingold
Diet is effective for ADHD.
Oligoantigenic Elimination Diet
Other diet strategies propose that hyperactivity is an abnormal reaction to

Chapter 3
an array of certain foods, including cow’s milk, cheese, eggs, nuts, wheat
products, and citrus. One highly publicized approach touts an “oligoanti-
genic” diet comprised of a very limited number of supposedly hypoallergenic
foods such as lamb, chicken, certain vegetables, salt, pepper, and particular
food supplements. Although meta-analysis suggests that 30% of children
would benefit from oligoantigenic elimination, studies themselves have major
limitations.4 Treatments required extensive involvement from unblinded par-
ents. Control conditions were poorly designed. Concomitant medications
were not controlled. Positive effects disappeared when restricted to blinded
ratings. Practically, this diet is too restrictive for long-term maintenance and
carries substantial risk for nutritional deficiencies.
Sugar-Restricted Diets
There are persistent beliefs that eating refined sugar causes hyperactivity.

113
However, numerous blinded studies failed to detect any behavioral effects
from dietary sugar. In blinded comparisons of sugar versus placebo, mothers
report increased motor activity when they believed their children ate sugar
regardless of what was actually eaten.5 Diets high in refined sugar are clearly
related to obesity and other health risks. As a matter of good health mainte-
nance, clinicians should advise parents and patients to maintain diets contain-
ing wide varieties of lightly processed foods. However, nothing suggests that
occasional consumption of refined sugar or other treats is associated with
meaningful health risks. No evidence suggests that restriction of dietary sugar
improves ADHD.
Artificial Food Coloring
Artificial food coloring elimination is the one restricted diet with some level of
scientifically meaningful support. Positive effects are demonstrated on blinded
and unblinded ratings, although these lose significance in meta-analyses
restricted to studies with low or no medication use.2 Benefits might be stron-
gest in groups selected for food sensitivities, which some suggest is related
to individual genetic risk. Regulatory authorities in the United Kingdom
required restrictive labeling for artificial food colorings following reports of
diet-related behavioral improvements in preschool children. The US Food
and Drug Administration (FDA) found insufficient scientific data to warrant
this approach.
One meta-analysis concluded that up to 8% of ADHD symptoms in the
general population might be attributed to artificial food coloring.4 Food col-
oring restrictions yield small treatment effects, much smaller than ADHD
medications. Even these small effects might be overestimates given the strong
ADHD likelihood of publication bias against negative reports. There is no consensus
on which additives putatively cause risk, although yellow dye 5 containing tar-
trazine has garnered much attention. Artificial food colorings have no nutri-
tional value. While any benefit from their restriction is likely to be small, there
are no apparent harms if parents choose to avoid them.

Dietary Supplements
Essential Fatty Acids
Essential fatty acid (EFA) supplementation is another one of a few CAM thera-
pies with proven benefit.6 Over a dozen trials have been conducted, with wide
variations in design, comparison controls, and dose. Some of the largest only
assessed ADHD symptoms and had no systematic approach for assigning an
actual ADHD diagnosis. Study dropout rates are high, and there are concerns
about the fishy taste of supplements, which can lead to treatment unblinding.
Meta-analysis suggests mean effect sizes in the range of.6, which are small
but remain significant for both unblinded and blinded ratings and when studies
allowing concomitant stimulants were eliminated.2 A trial of EFA supplementa-
tion might be justified if a parent strongly opposes stimulants. However, given
that treatment effect sizes are small, evidence suggests that EFA supplements,
if used, be given adjunctively with conventional ADHD medication.
114

Main dietary sources of EFA include cold-water fish, walnuts, almonds, dark
green leafy vegetables, whole grain foods, eggs, and olive oil. Two main types
are omega-3 fatty acids, which include docosahexanoic acid (DHA) and eicos-
apentaenoic acid (EPA), and omega-6 fatty acids, which include arachidonic
acid and γ-linolenic acid (GLA). Supplements vary widely in their rations of
omega-3 and omega-6 compounds. Optimal formulations appear to contain
more omega-3 EFAs, particulalry EPA. Optimal doses are in the range of ,000
mg of omega-3 daily. Primary benfits appear to be on improved attention and
behavior, and require 3 to 4 months of consistent therapy. EFA supplementa-
tion has other presumed benefits, particulalry on cardiovascular health, and is
presumed to be safe when avoiding preparations that contain mercury.3
Vitamin and Mineral Supplements
While a general recommendation for multivitamin use is supported for all
children with dietary deficiencies, there is no evidence to suggest that vita-
min therapy is useful for ADHD.3 Children who took a daily multivitamin at
standard doses meeting minimal daily requirements had improved nonverbal
intelligence, concentration, and motor control. However, these benefits were
seen primarily in children with poor diets and were not specific to ADHD.
Some children with ADHD typically have poor dietary habits that could ben-
efit with multivitamin supplementation.
Claims for ADHD benefits are also made for various individual vitamins
and minerals, both with standard- and mega-dose therapy. None of these
claims has been studied systematically. Positive results from open trials from
zinc were not confirmed in blinded studies. Iron supplementation has been
useful only in children with iron deficiencies. Iron-related improvements in
children without anemia were noted only on parent, but not teacher ratings.

Medicine Therapies
Given the toxicities that are associated with high doses of iron, magnesium,
and other minerals, as well as high-dosed vitamin therapy, supplementation
should be limited to those with documented insufficiencies.7
Amino Acids
Several short-term studies of various amino acids as potential ADHD treat-
ments have been conducted. The most commonly studied agent is ace-
tyl L-carnitine (ALC), an amino acid derivative. Other amino acids tested

Chapter 3
include gamma-aminobutyric acid (GABA), glycine, L-tyrosine, taurine,
L-tyrosine, 5-hydroxytryptophan (5-HTP), dimethylaminoethanol (DMAE),
and s-adenosyl-L-methionine (SAMe). None have demonstrated improved
ADHD and none are recommended as ADHD therapy.
Other Supplements
Nutraceuticals are products derived from food, including herbs, iso-
lated nutrients, dietary supplements, and other sources, which are taken
in medicinal forms not associated with food and are presumed to have
physiological or health benefits. In addition to supplements previously
described, numerous others are marketed for improving attention, over-
activity, or ADHD. These products are very popular among parents and
patients who wish to avoid prescription drugs and use treatments they

115
believe are “natural.”
Various nutraceuticals are marketed individually or as components of
proprietary blends. Few have any proven benefit and some are associ-
ated with potential risks. Herbal supplements are derived from flowers
or other plant products. Extracts of Gingko biloba are mild monoamine
oxidase and catecholamine reuptake inhibitors. There are some benefits
of Gingko for dementia, but ADHD effects are uncertain. St. John’s Wort,
another popular nutraceutical, is used for a variety of reasons, but it has
no demonstrated ADHD benefit. Pycnogenol, derived from pine tree bark,
reportedly increases blood circulation, but it is ineffective for ADHD.
Glyconutrients are plant-based carbohydrates, which reportedly support
brain cell function and connectivity, but ADHD studies have significant
methodological difficulties and unclear results. Valerian and kava-kava
exhibit gabaminergic activity with associated calming effects, but it has no
demonstrated utility for ADHD. Kava use has been implicated with risk for
liver toxicity. Melatonin has some value as a sleep aid, but it has no proven
ADHD benefit. Several proprietary blends, including FOCUSFactor®,
AttentiveChildTM, On TaskTM, and Kids Calm Multi, are marketed as treat-
ments for behavioral problems and hyperactivity but have no scientific evi-
dence supporting this use.
The FDA does not regulate nutraceuticals and other supplements in the
same way as prescription medications. There is no requirement for mak-
ers of these products to demonstrate efficacy and safety data in support of
their health-promoting claims. There are no guarantees about product qual-
ity control and some products contain components that are not described
in their labels.
ADHD Caffeine
Many believe that caffeine is beneficial for ADHD. The stimulating effects of
caffeine rely on very different mechanisms of action than ADHD medica-
tions. Caffeine can lead to wakefulness and brief increases in attention, but it
does not have any more than negligible effects on ADHD symptoms.8
Homeopathy
Homeopathic approaches to disease have been employed for over 50 years.
In homeopathy, very small quantities of substances that cause particular symp-
toms in healthy individuals are given to patients with the expectation that those
symptoms will be reduced. Systematic reviews of homeopathic research,
including several trials in ADHD, have failed to demonstrate any benefits.9

Neuropsychological Treatments
Cognitive Training
Cognitive training approaches to ADHD attempt to strengthen neuropsy-
chological processes seen as deficient in the disorder, such as attention or
working memory. Several commercially available, computer-based, propri-
etary programs are designed to improve cognitive functioning and, by exten-
sion, ADHD. One of the most popular is CogMed, which provides training
116

in either verbal or spatial working memory. Other programs purport to pro-

vide attention training, cognitive remediation, executive function training, and
enhanced cognitive control.
A course of CogMed requires 25 sessions of 30–45 minutes each, usu-
ally over 5 weeks. Numerous studies report benefits from CogMed as well
as other cognitive training therapies. Positive outcomes are reported for
unblinded parent and teacher reports, but these effects disappear with
blinded ratings.2 In several reports, CogMed has been associated with
improved working memory performance on computerized tests, but these
results do not correlate with improved ADHD symptoms. The current evi-
dence base does not support use of CogMed or other cognitive training pro-
grams as ADHD treatments.

Electroencephalographic Neurofeedback/Biofeedback
For over 20 years, EEG neurofeedback has been one of the most popular
CAM treatments for ADHD. Neurofeedback training is based on observa-
tions that some individuals with ADHD exhibit increased theta and decreased
beta spectral power during electroencephalography (EEG). Increased theta
activity is associated with inattention, impulsivity, and hyperactivity, while
decreased beta activity is associated with poor concentration and under-
arousal. Methylphenidate increases beta activity in medication responders, but
not in nonresponders. During neurofeedback training, patients undergo EEG
monitoring, usually via scalp electrodes, and receive real-time visual feedback,
typically on a computer screen, about patterns of brain activity. By respond-
ing to this feedback, patients self-regulate to decrease theta and increase beta
wave activity. Treatments occur in 30- to 60-minute sessions conducted two

Medicine Therapies
to three times weekly over a course of approximately 3 weeks.
There are over a dozen double-blind controlled studies of EEG neuro-
feedback for ADHD. One meta-analysis reported moderate treatment
effects comparable to results found typically with nonstimulant ADHD
medications.0 However, studies included in the analysis suffered numer-
ous limitations. Treatments were not standardized. Many lacked true
“triple-blinding” of children, parents, and therapists to treatment assignment,
leading to inadequate blinding of “sham” control treatments. Concomitant

Chapter 3
medication received inconsistent consideration. While ratings from parents,
who were generally unblinded and highly invested in treatment success,
demonstrated statistically significant improvements, these findings were not
replicated by blinded teacher reports.2 One well-designed, well-controlled,
triple-blinded sham-comparison study funded by the National Institute of
Mental Health failed to show any difference between active treatment and
control groups. EEG neurofeedback is an expensive, time-intensive therapy
that remains unproven for ADHD. Despite its widespread popularity, nei-
ther the American Academy of Pediatrics nor the American Academy of
Child and Adolescent Psychiatry endorses its use.

Mind-Body Therapies

117
Acupuncture
Acupuncture is reasonably safe and increasingly used outside of Asian cul-
tures for a range of indications. Use of acupuncture for ADHD is based on
Chinese beliefs that the disorder arises from physical imbalances that are cor-
rected by treatment. Scientific studies of acupuncture treatment do not sup-
port its use in ADHD.2
Chiropractic Adjustment
There is inherent appeal for chiropractic adjustment as an ADHD treatment,
particularly for those who oppose or are reluctant to use pharmacotherapy.
Publications about chiropractic interventions for ADHD are limited in num-
ber and are mostly case reports that suffer significant design flaws, including
small sample sizes, inadequate diagnostic assessment, and inadequate control
groups. The purported mechanism of action, that is, restoration of dysfunc-
tional brain systems through correcting subluxations of the spinal column,
is not consistent with known ADHD pathophysiology. There is no scientific
evidence supporting chiropractic interventions for ADHD.

Exercise
It is reasonable to assume that exercise and increased physical activity would
benefit individuals who suffer from motoric overactivity and restlessness.
Numerous studies suggest that regular exercise has positive effects on behav-
ior, cognition, and mood. Only a small subset, however, have examined a
specific role for exercise in ADHD, and these suffer from small sample sizes
ADHD and inadequate control comparisons. While broad recommendations for
increased physical activity might facilitate general overall health, there are
insufficient data to support exercise as a general ADHD treatment.

Interactive Metronome Training

Interactive metronome training was introduced by occupational therapists as
an ADHD treatment in the early 990s. The intervention requires patients to
match the rhythmic beat of computer-generated tones by tapping their feet
or clapping their hands and is purported to improve attention, concentration,
and physical coordination. Published research findings are scant and limited
by small sample sizes, inadequate control groups, and investigator bias. The
evidence base is inadequate to support its use as an ADHD therapy.

Meditation, Mindfulness, Yoga, and Massage

Although there is widespread interest, very few studies have examined medi-
tation, mindfulness training, yoga, or massage therapy for ADHD. Published
reports utilize small adult samples and lack adequate controls. There are gen-
erally two types of meditation studies, mantra meditation and yoga. No dif-
ferences have been found between groups assigned to meditation or usual
medication treatment, although sample sizes in these studies lack sufficient
power to detect differences that might be really present.3 These studies should
not be misconstrued to imply that meditation and medication effects are equal.
118

One adult study of mindfulness training had loose entry criteria and claimed
to show positive change on cognitive testing, but it was uncontrolled. Authors
of these studies convey strong convictions that the interventions are effective.
However, there is insufficient evidence from objective reviews to claim positive
effects for ADHD or to support recommendations as ADHD treatments.

Repetitive Transcranial Magnetic Stimulation

Repetitive transcranial magnetic stimulation (rTMS) utilizes an electromagnet
to generate a low-grade electrical current across the scalp, which is believed
to stimulate small areas of the brain leading to increased brain signaling. Some
positive results with rTMS are evidenced in treatment-refractory depression
and patients recovering from stroke. Studies in ADHD are limited to small
adult samples and fail to provide sufficient evidence to support rTMS as an
ADHD treatment.

Sensory Integration Training

“Sensory processing disorder” is a term used by occupational therapists
for individuals who are overly sensitive to a range of environmental stimuli,
including some with ADHD. The term is not a recognized medical disorder.
Sensory integration training comprises physical exercises that are intended
to improve the body’s sense of its relationship to external space. As with
studies of interactive metronome treatment, published reports suffer from
significant methodological flaws, particularly overly broad inclusion criteria,
small sample sizes, inadequate controls, and investigator bias. There is no
objective evidence base supporting sensory integration training for ADHD.
Vision Therapy

Medicine Therapies
Some behavioral optometrists offer vision therapy for a range of disorders
that includes autism spectrum disorder, learning disorders, and ADHD.
Exercises are practiced in the office and at home with the goal of train-
ing the eyes to remain focused on various visual stimuli. There is debate
among optometrists as to whether vision therapy is effective for ADHD
itself or undetected vision problems that frequently lead to misdiagnosis
of ADHD. One double-blind sham-controlled study found support for
treating convergence insufficiency, but no studies support its use in psy-

Chapter 3
chiatric disorders.4 Neither the American Academy of Pediatrics or the
Academy of Child and Adolescent Psychiatry recommends vision therapy
in its ADHD practice guidelines.

References
  . Bader A, Adesman A. Complementary and alternative therapies for children
and adolescents with ADHD. Curr Op Pediatrics. 202;24:760–769.
  2. Sonuga-Barke EJ, Brandeis D, Daley D, et  al. Nonpharmacological inter-
ventions for ADHD:  systematic review and meta-analysis of randomized
controlled trials of dietary and psychological treatments. Am J Psychiatry.
203;70:275–289.
  3. Hurt EA, Arnold LE, Lofthouse N. Dietary and nutritional treatment for

119
attention-deficit/hyperactivity disorder; current research support and recom-
mendations for practitioners. Curr Psychiatry Rep. 20;3:323–332.
  4. Nigg JT, Lewis K, Edinger T, Falk M. Meta-analysis of attention-deficit/hyper-
activity disorder or attention-deficit/hyperactivity disorder symptoms, restric-
tion diet, and synthetic food color additives. J Am Acad Child Adolesc Psychiatry.
202;5:86–97.
  5. Hoover DW, Milich R. Effects of sugar ingestion expectancies on mother-child
interactions. J Abnorm Child Psychol. 994;22:50–55.
  6. Bloch MH, Qawasmi A. Omega-3 fatty acid supplementation for the treat-
ment of children with attention-deficit/hyperactivity disorder symptomatol-
ogy: systematic review and meta-analysis. J Am Acad Child Adolesc Psychiatry.
20;50:969–97.
  7. Millichap JG, Yee MM. The diet factor in attention-deficit/hyperactivity disor-
der. Pediatrics. 202;29:330–337.
  8. Leon MR. Effects of caffeine on cognitive, psychomotor, and affective perfor-
mance of children with attention-deficit/hyperactivity disorder. J Atten Disord.
2000;4:27–47.
  9. Ernst E. Homeopathy: what does the “best” evidence tell us? Med J Aust.
200;92:458–460.
0. Lofthouse N, Arnold LE, Hersch S, Hurt E, DeBeus. A review of neurofeed-
back treatment for pediatric ADHD. J Atten Disord. 202;6:35–372.
. Arnold LE, Lofthouse N, Hersch S, et  al. EEG neurofeedback for
ADHD:  double-blind sham-controlled pilot feasibility trial. J Atten Disord.
203;7:40–49.
2. Li S, Yu B, Zhou D, et al. Acupuncture for attention deficit hyperactivity disor-
der (ADHD) in children and adolescents (review). Cochrane Database Syst Rev.
20;4;CD007839.
ADHD 3. Krisanaprakornkit T, Ngamjarus C, Witoonch C, Piyavhatkul N. Meditation
therapies for attention deficit hyperactivity disorder (ADHD) (Review).
Cochrane Database Syst Rev. 200;6:CD006507.
4. Barnhardt C, Cotter SA, Mitchell GL, Scheiman M, Kulp MT, CITT Study
Group. Symptoms in children with convergence insufficiency: before and after
treatment. Optom Vis Sci. 202;89:52–520.

Further Reading
Skokauskas N, McNicholas F, Masaud T, Frodl T. Complementary medicine for
children and young people who have attention deficit hyperactivity disorder.
Curr Opin Psychiatry. 20;24:29–300.
120
Index

Page numbers followed by f or t indicate figures and tables.

absenteeism, 14 alpha-2 agonists, 72t, 73, attention, computerized tests

academic accommodations, 93, 98 of, 45
53, 60–61, 91–92 alternative treatments. See Attention Deficit Disorder
academic underperformance, 13 complementary and Association (ADDA), 65
acetyl L-carnitine (ALC), 115 alternative medicine attention-deficit/hyperactivity
acupuncture, 117 (CAM) treatments disorder (ADHD)
acute tolerance, 75–76 American Academy of in adolescents, 10
ADDA (Attention Deficit Child and Adolescent in adults, 10, 11–12
Disorder Association), 65 Psychiatry, 117, 119 age of onset, 31–32
Adderall, 70, 71t American Academy of biological basis of, 17–18, 18f
Adderall XR, 71, 71t, 84t Pediatrics, 103, 117, 119 in children, 10
addiction, 104–5 American Heart Association, comorbid, 12, 12t. See also
ADHD. See attention-deficit/ 103 comorbid disorders
hyperactivity disorder Americans with Disabilities costs associated with,
(ADHD) Act, 61 14–15
adjunctive stimulant amino acids, 115 critics of, 1–2
medication, 95, 98 AMPH-ER, 71t definition of, 1–2, 6–8
adolescent ADHD amphetamine (AMPH), 6, description of, 3–5

121
academic accommodations, 70–71, 79–80, 102, 104 diet and, 19
60–61 AMPH-IR, 71t dual-pathway model of, 24
assessment of, 35, 40–41 AMPH-SR, 71t history of, 3–8
conduct disorder and, 90 antidepressant therapy, 95 hyperactive-impulsive
prevalence of, 10 anxiety disorders, 93–96, 94f symptoms of, 29t
social and peer-related appetite loss, 85–87 inattentive symptoms
activities, 54 apps, 64 of, 29t
standardized testing aripiprazole, 97 male/female ratios, 9
accommodations, 53 artificial food coloring prevalence of, 1, 9–10
symptoms of, 41 elimination, 113–14 subtypes of, 32–33
teacher ratings, 41 assessment of ADHD symptoms of, 3, 4t, 5. See
adult ADHD in academic activities, 61 also diagnostic criteria
academic adolescent, 40–41 terms to describe, 4t
underperformance in, adult, 41–42, 57–58 timeline, 4f
13–14 cardiac risk screening, 43 See also adolescent
assessment of, 41–42, clinical interview, 37–39 ADHD; adult ADHD;
57–58 developmental childhood ADHD
cognitive-behavioral considerations in, 39–42 autism spectrum disorder, 119
therapy, 62–63 direct observation, 39–40
health maintenance, 59 face-to-face interview, 35 behavioral classroom
medication management, family history, 43 management, 53
59–60 for learning disabilities, behavioral parent training, 50–52
occupational achievement 43–44 Benzedrine, 6
and, 13–14 medical, 42–43 bereavement therapy, 52
prevalence of, 10 non-evidence-based biofeedback, 116–17
psychoeducation, 58–59 approach to, 44–46 biological basis of ADHD,
rating scales, 37t parental biases, 40 17–18
risky behaviors in, 12, 13f preschool-age children, 39 bipolar disorders, 90, 96–97
treatment modalities rating scales, 36–37, 36f birth defects, 103–4
for, 58t school-age children, 39–40 blood toxicology, 46
work accommodations, symptoms, 38 Bradley, Charles, 6
61–62 teacher reports, 40 brain abnormalities, 22
work productivity, 14–15 treatment planning and, brain imaging, 8, 22, 45–46
advocacy groups, 65 48–49 See also structural imaging
age of onset, 31–32, 41–42 atomoxetine, 59, 72–73, 72t, studies
alcohol consumption, 19, 92 82, 86, 90–95, 98 buproprion, 95
INDEX caffeine, 116 Community Parent Education demoralization, 95
CAM (complementary and Program (COPE), 51–52 depression, 90, 94–96
alternative medicine) comorbid disorders Der Philosophische Arzt
treatments in adults, 11–12, 11f (Weikard), 3
definition of, 111 anxiety disorders, 93–96, 94f Desoxyn, 6
dietary supplements, assessment for, 38 devices and technology, 64
114–16 bipolar disorders, 96–97 Dexedrine, 6, 70, 71t
elimination diets and, in children, 10–11, 11f dextroamphetamine, 6
112–14 depression, 94–96 Dextrostat, 70, 71t
evidence for, 111–12 disruptive behavior, 89–91 Diagnostic and Statistical
mind-body therapies, disruptive mood Manual of Mental
117–19 dysregulation disorder Disorders
neuropsychological (DMDD), 95, 97–98 ADHD symptoms defined
treatments, 116–17 oppositional defiant in, 28–30
risk factors, 112 disorder, 89–91 editions of, 4t, 6–8
cardiac risk, 43, 102–3 of other psychiatric historical perspectives of,
Catapres, 73 disorders, 11f 27–28
categorical disorder, 30 psychiatric, 10–12 diagnostic criteria
CBT (cognitive-behavioral severe mood dysregulation age of onset, 31–32
therapy), 55, 62 (SMD), 97 categorical disorder, 30
CD (conduct disorder), substance use disorders, differential diagnosis, 32
89–91 92–93 dimensional disorder, 30
CHADD (Children and tic disorders, 90, 98 DSM symptom definitions,
Adults With Attention types of, 40 28–30
Deficit Disorders), 65 complementary and exaggerated symptoms for
Child Behavior Checklist alternative medicine access to, 105–6
(CBCL), 37 (CAM) treatments historical perspectives of,
child-directed interaction, 51 definition of, 111 27–28
childhood ADHD dietary supplements, hyperactive-impulsive
assessment of, 35, 39–40 114–16 symptoms, 29t
122

clinical interview, 37–39 elimination diets and, impairment domains, 32

comorbid disorders, 11f, 112–14 inattentive symptoms, 29t
89–90 evidence for, 111–12 mimicking ADHD
conduct disorder and, mind-body therapies, symptoms, 42
89–90 117–19 self-reporting, 42
criminal behaviors in, 13 neuropsychological specifiers, 32–33
economic burden, 14 treatments, 116–17 symptom thresholds,
growth delay and, 101–2 risk factors, 112 30–31
oppositional defiant computerized tests of unspecified ADHD, 33
disorder and, 89 attention, 45 dialectical behavioral therapy
rating scales, 37t computerized tomography (DBT), 64
social and peer-related (CT) imaging, 22 diet, 19, 112–14
activities, 54 Concerta, 69–70, 69t, 70, 84t dietary supplements, 114–16
standardized testing concomitant medication, dimensional disorder, 30
accommodations, 53 116–17 direct observation, 39–40
Children and Adults With conduct disorder (CD), 89–91 disruptive behavior
Attention Deficit Conners’ Continuous disorders, 89–91
Disorders (CHADD), 65 Performance Test (CPT), disruptive mood
chiropractic adjustment, 117 45, 106 dysregulation disorder
chronic irritability, 96–97 COPE (Community Parent (DMDD), 95, 97–98
chronic medical conditions, Education Program), divalproex sodium, 90–91
59 51–52 diversion, 104–5
clinical interview, 37–42 copy number variants D-MPH-ER, 83t, 84t
clonidine, 73 (CNVs), 21 dopamine transporter
clonidine-ER, 72t, 73 costs associated with ADHD, system, 107–8
CNVs (copy number 14–15 drug abuse, 104–5
variants), 21 couples therapy, 52, 63 See also substance use
coaching, 62–63 Crichton, Alexander, 3–5 disorders
CogMed, 116 criminal behaviors, 13, 15 DSM-II, 4t, 6–7, 27
cognitive-behavioral therapy CT (computerized DSM-III, 4t, 7, 27–28, 31
(CBT), 55, 62 tomography) imaging, 22 DSM-III-R, 4t, 28
cognitive interventions, 91 DSM-IV, 4t, 7–8, 28, 29–30,
cognitive strategies, 62 Daytrana, 69t 31, 32–33
cognitive training, 116 DBT (dialectical behavioral DSM-5, 4t, 8, 28, 30, 33,
combination therapy), 64 96–97, 104
pharmacotherapy, 83–84, DEA (US Drug Enforcement dual-pathway model of
98 Agency), 85 ADHD, 24
economic burden of ADHD, heritability of ADHD, 19–20, mania, 97

INDEX
14–15 20f marijuana, 92
educational history of ADHD, 3–8 marital therapy, 52, 63
accommodations, 53, Hoffman, Heinrich, 5 MAS-ER, 83t, 84t
60–61, 91–92 homeopathy, 116 massage therapy, 118
electrocardiograms (EKGs), hyperactive-impulsive MBD (minimal brain
103 symptoms of ADHD, 29t dysfunction), 6
electroencephalography hyperactivity, 86 medical assessment, 42–43
(EEG), 45, 116–17 hyperarousal, 96 medical costs, 14
elimination diets, 112–14 hyperkinetic reaction, 4t, 7 medication management,
emotional strategies, 62 hyperkinetic syndrome, 4t, 6 62, 93
endocrine studies, 46 medications
essential fatty acid (EFA) IDEA (Individuals With acute tolerance, 75–76
supplementation, 114 Disability Education amphetamines, 6, 70–71,
evidence-based treatments, Act), 53 71t, 79–80, 102, 104
111 imaging studies, 8, 22 atomoxetine, 59
executive functions (EFs), See also brain imaging birth defects and, 103–4
23–24 immediate-release cancer and, 104
exercise, 117–18 medications, 68, 70, cardiac risk with, 102–3
extended release 80–81, 105 discontinuing, 87
medications, 69–70, 69t, inattentive symptoms of drug abuse and, 104–5
71, 71t, 80, 105 ADHD, 29t effect sizes, 59–60, 60f
individualized educational exaggerated symptoms for
family-focused interventions, program (IEP), 53, 92 access to, 105–6
49–52 individual psychotherapy, 55 extended release, 69t, 71,
See also parents Individuals With Disability 71t, 80
fathers. See parents Education Act (IDEA), 53 FDA-approved, 68t
FDA (US Food and Drug intellectual disability, 43–44 growth delay and, 85,
Administration), 113, 115 interactive metronome 101–2
Federal Rehabilitation Act training, 118 immediate release, 69t,

123
of1973, 52 interventions 80–81
Feingold, Ben, 112–13 cognitive, 91 for learning disorders, 91–92
Feingold diet, 112–13 cognitive-behavioral long-term use of, 84–85,
female/male ratios of therapy, 62 107–8
ADHD, 9 family, 49–52 mechanisms of action,
fetal drug exposure, 104 group, 63–64 73–74
“Fidgety Phil,”5 patient-focused, 53–55 methylphenidates (MPH),
fluoxetine, 95 psychosocial, 91, 93 68–70, 79–80
fluvoxamine, 93 school-focused, 52–53 nonstimulants, 59, 68t,
Focalin, 68, 69t Intuniv, 72t 72–73, 72t, 81
Focalin XR, 69t, 70, 84t IR guanfacine, 73 off-label, 68t, 73
food coloring restrictions, iron supplementation, selection of, 79–81
113–14 114–15 side effects, managing,
functional imaging studies, 8 irritability, 95, 96–97 85–87
functional impairments, 13–14 stimulant pharmacodynamics,
Kapvay, 72t, 73 75–76
gene-environment kava-kava, 115 stimulant
interactions, 21–22 KSADS (Schedule for pharmacokinetics, 76
genetic linkage studies, 20–21 Affective Disorders and stimulant plasma levels
genetics, 19–22 Schizophrenia for School and, 107
genome-wide association Age Children), 38 stimulants, 59, 67–71, 68t,
studies (GWAS), 21 79–80
Gingko biloba, 115 lead toxicity, 19, 46 sustained release, 69t,
glyconutrients, 115 learning disorders, 43–44, 90, 71, 71t
grief counseling, 52 91–92, 119 universe of, 68t
group social skills training, linkage studies, 20–21 See also medication
54–55 lisdexamfetamine (LDX), therapy
group therapies, 63–64, 91 71, 84t medication therapy
growth delay, 85, 101–2 lithium, 90–91, 97 adult ADHD, 59–60
guanfacine-ER, 72t, 73 long-term use of childhood ADHD, 55–56
GWAS (genome-wide medications, 84–85, combination
association studies), 21 107–8 pharmacotherapy,
83–84
habit reversal therapy, 98 magnetic resonance imaging initial, 80
headache, 85–86 (MRI), 22 long-term, 84–85, 107–8
health maintenance, 53–54, 59 male/female ratios of treatment planning and, 54
herbal supplements, 115 ADHD, 9 See also medications
INDEX medication titration, 81–83 combination primary care physicians, 38,
medication treatment pharmacotherapy, 84 53–54
algorithm, 80f, 81f for substance use psychiatric comorbidities,
meditation, 118 disorders, 92–93 10–12, 42
melatonin, 87, 115 for tic disorders, 90 psychoactive substances, 92
Metadate CD, 69t, 70, 84t titration of, 82 psychoeducation, 49, 58–59
Metadate ER, 69t types of, 72–73, 72t psychosis, 86
methamphetamine, 6 noradrenergic reuptake psychosocial interventions,
Methylin, 68, 69t inhibitors, 72, 72t 91, 93
methylphenidates (MPH) nutraceuticals, 115 psychosocial risk factors, 17–18
birth defects and, 103–4 nutrition, 19 psychotherapy, individual,
FDA-approved 55, 63
formulations for, 69t Obitrol, 70 pycnogenol, 115
mechanisms of action, occupational achievement,
74, 76 13–14 Quillivant XR, 69t
pharmacotherapy of, oligoantigenic elimination
68–70 diet, 113 Racemic dl-AMPH, 70–71
side effects of, 79–80 oppositional defiant disorder radioligand binding studies,
mind-body therapies, 117–19 (ODD), 89–91, 95 22
mindfulness training, 118 OROS-MPH, 69–70, 83t, 84t rating scales, 36–37, 37t, 38
mineral supplements, 114–15 Osmotic Controlled Release rebound hyperactivity, 86
minimal brain disorder, 5–6 Oral System (OROS), recreational drug use, 106–7
minimal brain dysfunction 69–70 relationship therapy, 52
(MBD), 4t, 6 repetitive transcranial
misuse of substances, 92, palliative treatment, 86 magnetic stimulation
104–5 parental biases, 40 (rTMS), 118
mobile devices, 64 Parent Child Interaction restriction diets, 112–14
monotherapy, 81 Training (PCIT), 51 risk factors
“moral control,”5 parent-directed interaction, alcohol consumption, 19
mothers. See parents 51 environmental, 19
124

motivational interview parent management, 91, 93 gene-environment

techniques, 55–56 parents interactions, 21–22
MPH (methylphenidates) behavioral training for, genetics, 19–22
birth defects and, 103–4 50–52 nicotine exposure, 19
FDA-approved as co-therapists, 51 perinatal, 18
formulations for, 69t family-focused postnatal, 18
mechanisms of action, interventions, 49–52 prenatal, 18
74, 76 fathers, 18 psychosocial, 17–18
pharmacotherapy of, ineffective, 18 serum lead, 19
68–70 mothers, 18, 19 risperidone, 97
side effects of, 79–80 patient-focused Ritalin, 6, 68, 69t
MPH-ER, 84t interventions, 53–55 Ritalin LA, 69t, 70, 84t
MRI (magnetic resonance pediatric ADHD, 55, 59, Ritalin SR, 69t
imaging), 22 62, 89 rTMS (repetitive transcranial
Multimodal Treatment Study peer-related activities, 54 magnetic stimulation), 118
of ADHD (MTA), 47, 93, perinatal risk factors, 18
101–2, 107 PET (positron emission Schedule for Affective
multisystemic therapy tomography), 22, 45–46, Disorders and
(MST), 91 107 Schizophrenia for School
multivitamin use, 114 PFC networks, 74, 75 Age Children (KSADS), 38
pharmacodynamics, 75–76 school-focused interventions,
National Comorbidity Survey pharmacokinetics, 76–77 52–53
Replication, 10 pharmacology. See Section 504 plans, 52–53
National Institute of Mental medications sensory integration training,
Health, 117 pharmacotherapy, 54, 80, 118
nausea, 85–86 83–84, 91 sensory processing disorder,
neurofeedback training, See also medication 118
116–17 therapy serotonin reuptake inhibitors
neuropsychological tests, physical activity, 117–18 (SRIs), 86
23–24, 41, 45 physical examination, 42 serum lead, 19, 46
neuropsychological positron emission severe mood dysregulation
treatments, 116–17 tomography (PET), 22, (SMD), 97
nicotine exposure, 19 45–46, 107 sexually transmitted disease, 12
nonamphetamine postnatal risk factors, 18 side effects
methylphenidate, 6 pregnancy, 18, 103–4 of alpha-2 agonists, 73
nonstimulant medications prescriptions. See alternative treatments
for anxiety disorders, 94f medications and, 111
 of atomoxetine, 73 targets of, 74f comorbid disorders and, 91

INDEX
decreasing, 55, 72–73 for tic disorders, 90 couples therapy, 52
managing, 85–87 stimulant pharmacodynamics, educational planning,
medication selection and, 75–76 60–61
79–80 stimulant pharmacokinetics, family-focused
monotherapy and, 81 76–77 interventions, 49–52
of stimulant stimulant plasma levels, 107 group therapies, 63–64
pharmacokinetics, 76 stimulant therapy, 93 health maintenance,
of stimulants, 68, 72 stimulant titration, 82, 83t 53–54, 59
tolerance to, 82 St. John’s Wort, 115 long-term adherence to,
signal to noise ratios, 75 stomachache, 85–86 55–56
single-nucleotide Strattera, 72–73, 72t for mania, 97
polymorphisms (SNPs), structural imaging studies, medication management,
21 8, 22 59–60
single-photon emission See also brain imaging medication therapy, 55–56
computerized Struwelpeter(Hoffman), 5 multimodal approach to,
tomography (SPECT), substance use disorders, 90, 47–48, 48f
22, 45–46 92–93, 104–5 patient-focused
sleep difficulties, 86–87 sugar-restricted diets, 113 interventions, 53–55
social and peer-related suicidal thoughts, 87 psychoeducation, 49,
activities, 54 support groups, 65 58–59
social learning theory, 51 sustained release school-focused
social skills training, 54–55 medications, 69, 71 interventions, 52–53
Spansules, 71t Symptom Checklist-90 Section 504 plans, 52–53
specifiers, 32–33 Revised, 37 support groups, 65
SPECT (single-photon symptoms of ADHD. See team approach to, 47–48
emission computerized diagnostic criteria technology and devices, 64
tomography), 22, 45–46 See also complementary
sports, 43, 54, 103 tachyphylaxis, 75–76 and alternative
SRIs (serotonin reuptake teachers, 40, 41 medicine (CAM)

125
inhibitors), 86 technology and devices, 64 treatments
standardized testing Tenex, 73
accommodations, 53 Test of Variable Attention urine screens, 46
Still, George Frederick, 5 (TOVA), 45 US Drug Enforcement
stimulant medications tic disorders, 90, 98 Agency (DEA), 85
amphetamines, 70–71 tics, 42 US Food and Drug
for anxiety disorders, 94f titration, medication, 81–83 Administration (FDA),
combinations, 84 treatment planning 113, 115
for conduct disorders, academic accommodations,
90–91 60–61 valerian root, 115
definition of, 67–68 acute tolerance to vision therapy, 119
effects of, 6 medications, 75–76 vitamin supplements, 114–15
growth delay and, 101 advocacy groups, 65 vocational counseling, 61–62
management of, 59 assessment, 48–49, Vyvanse, 71, 71t, 84t
methylphenidates (MPH), 57–58
68–70 behavioral parent training, Weikard, Melchior Adam, 3
selection of, 79–80 50–52 work accommodations,
side effects of, 68 coaching, 62–63 61–62
for substance use cognitive-behavioral
disorders, 92–93, 105 therapy, 62 yoga, 118