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Primary care clinic in office practice 34 (2007) ppt

Preface
Guest Editors
Primary care clinicians often provide continuity of care, emphasize pre-
vention, and address chronic illness with their patients. All these endeavors
require the active involvement of the patient in treatment planning and
adherence. An active and healthy therapeutic alliance that recogni zes that
patients are the chief consumers of health care is essential in this regard.
This critical role in directing one’s health care can be either facilitated or
complicated by a patient’s emotional, cognitive, and behavioral strengths
or weaknesses (ie, mental health). It is widely recognized that patients
who have mental health concerns often present first to their primary care
physician, and most continue to receive treatment of their mental concerns
(eg, depression, anxiety) in primary care. This reality is compounded
because many health conditions that affect a patient’s level of functioning
(eg, chronic pain, diabetes, headaches) often have mental health comorbid-
ities that influence the course of illness and treatment.
Primary care clinicians are well positioned to identify and assist patients
who have mental health concerns. This centra l or de facto role in mental
health care, however, is compli cated by factors that hinder the delivery of
evidenced-based care that is optimally integrated into the clinical process

as a whole. Among the obstacles to such a rational approach to health care
are an undue focus on acute rather than chronic health issues; lack of spe-
cific training in the recognition, assessment, and management of mental dis-
tress or illness; and financial obstacles (mental health carve-outs and other
obstacles) that prevent the effective collaboration among diverse health pro-
fessionals necessary to implement and manage effective treatment.
Ralph A. Gillies, PhD J. Sloan Manning, MD
0095-4543/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved.
doi:10.1016/j.pop.2007.06.002 primarycare.theclinics.com
Prim Care Clin Office Pract
34 (2007) xi–xii
The articles in this issue present the latest information on mental health
problems commonly seen in primary care. Each article offers practical sug-
gestions on how clinicians can address these problems to improve overall
care. We hope that the information contained here will be embraced by
readers and enrich insight into mental distress and dysfunction as a biopsy-
chosocial phenomenon. It is hoped that someday the fragmentation
currently evidenced in health care delivery that hinders integ rated and
comprehensive ap proaches will give way to systems that honor mental
health as fundamental to health.
Ralph A. Gillies, PhD
HB-3041 1120 15th St.
Department of Family Medicine
Medical College of Georgia
Augusta, GA 30912-3500, USA
E-mail address: rgillies@mcg.edu
J. Sloan Manning, MD
PrimeCare of Hickory Branch
501 Hickory Branch Road
Greensboro, NC 27409, USA
Mood Disorders Clinic
Moses Cone Family Practice Residency
1125 N. Church Street
Greensboro, NC 27401, USA
E-mail address: smanning1@triad.rr.com
xii PREFACE
Attention Deficit/Hyperactivity
Disorder in Adults
Shannon B. Moss, PhD
*
, Rajasree Nair, MD,
Anthony Vallarino, DO, Scott Wang, MD
Baylor Family Medicine Residency at Garland, 601 Clara Barton Boulevard,
Suite 340, Garland, TX 75042, USA
Attention deficit/hyperactivity disorder (ADHD), once considered to be
a disorder only of childhood, has gained recognition as a legitimate disorder
among adults. As professionals’ awareness of this disorder and its concom-
itant media attention have increased, more adults have begun to identify
themselves as having symptoms of adult ADH D, leading them to present
to their primary care providers. Many of these providers, however, may
be ill-equipped to identify, diagnose, and treat the symptoms of adult
ADHD. Reasons for primary care phy sicians’ lack of comfort in managing
ADHD sympt oms in adults may be multifactorial, and include high rates of
self-diagnosis, lack of guidelines for evaluation and management, higher
rates of comorbid psychiatric and substance use disorders, and the need
for treatment with drugs of potential abuse [1,2].
The purpose of this article is to present information on the prevalence,
clinical presentation and associated features, diagnosis, and treatment of
adults who have ADHD, in order to provide primary care physicians with
the necessary tools for managing these patients.
Prevalence
Prevalence estimates of ADHD in children range between 2% and 18%
in community studies. A recent Centers for Disease Control report from the
National Survey of Children’s Health (NSCH-2003) indicated that, in 2003,
approximately 4.4 million children aged 4 to 17 years had a history of
ADHD [3]. Data regarding the persistence of ADHD into adulthood
* Corresponding author.
E-mail address: shannomo@baylorhealth.edu (S.B. Moss).
0095-4543/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved.
doi:10.1016/j.pop.2007.05.005 primarycare.theclinics.com
Prim Care Clin Office Pract
34 (2007) 445–473
(ie, ADHD symptoms among adults previously diagnosed with childhood
ADHD) vary somewhat by study, with reports ranging from 1% to 36%
[4–7]. This variation is likely caused by variation in methodology (eg, pro-
spective reports versus meta-analysis) and diagnostic criteria used; however,
there is some agreement amongst studies that the number of adults who con-
tinue to be functionally impaired because of ADHD symptoms is greater
than the number of adults meeting full ADHD diagnostic criteria. For
example, though one study found 8% of adults who had been diagnosed
with childhood ADHD continued to meet Diagnostic and Statistical Man-
ual of Mental Disorders, Third Editi on, Revised (DSM-III-R) criteria for
ADHD in adulthood, an additional 3% reported continued impairment
due to sub-threshold ADHD symptoms [7]. Similar results were reported
in a later study using Diagnostic and Statistical Manual of Mental Disor-
ders, Fourth Edition (DSM-IV) criteria. In a study of ADHD symptom per-
sistence into adulthood, Faraone and colleagues [8] found a persistence rate
of 15% at age 25 when full DSM-IV criteria were applied; however, persis-
tence was estimated to be between 40% and 60% when including ADHD in
partial remission. Extrapolating from this data and a childhood prevalence
of 8%, the study authors estimate adult ADHD prevalence at age 25 to be
1% for the full criteria and an additional 2% for cases in partial remission
[8]. This finding is somewhat lower than more recent research suggesting
prevalence rates of 4.4% [9]. Further, it appears that those who have
more severe childhood ADHD, defined as having both attentional and
hyperactive symptoms, are at greater risk for persistence than those who
have attentional or hyperactive symptoms alone [6]. As in children, adult
ADHD appears to be more commonly identified in males, with reported
male-to-female ratios ranging from 1.7:1 to 2.2:1 [10,11].
Pathophysiology
The pathophysiology of adult ADHD is not well- understood, but is con-
sidered to be multifactorial, consisting of genetic, environmental, and neuro-
biologic influences. Medications used to treat ADHD influence the
dopaminergic and noradrenergic systems of the nervous system, which
may give so me insight into abnormalities in neurologic pathways and the
potential for genetic locus identification. With the emerging trends in genetic
evidence, it is increasingly likely that the pathophysiology of ADHD is com-
plex, involving the action of multiple genes and environmental factors.
Family studies
ADHD is considered a heritable disorder, with approximately 70% her-
itability, one of the highest among psychia tric disorders [12,13]. In recent
years, many family, twin, and molecular genetic studies have shown a strong
probability that genetic factors influence the development of ADHD.
446 MOSS et al
Children of parents who have ADHD have up to a sevenfold increase in
their likelihood of developing ADHD when compared with ch ildren of
non-ADHD parents. Although it is important to understand that to date
no single gene has been implicated as the sole cause of ADHD, there is re-
search to support multiple chromosomal sites that may influence the suscep-
tibility of developing ADHD. Specifically, the dopamine receptor gene
(DRD4) and the dopamine transporter gene (DAT) have been associated
with ADHD [13]. A recent adoption study reinforced the genetic link, find-
ing that adoptive relatives of ADHD-affected children had lower rates of
ADHD and other associated conditions than biological relatives of ADHD
patients [14]. In a study of monozygotic twins, behavioral discordance
was evident at age 2, and low birth weight and delayed motor development
were significant markers for development of ADHD [15]. Neuro-imaging of
high-risk concordant twins has yielded significant differences in the affe cted
areas of prefrontal lobes compared with discordant twins, further confirm-
ing a genetic etiology for the development of ADHD [16].
Environmental factors
Although all environmental factors required for emergence of ADHD are
not known, several have been implicated, including physical or toxic as-
saults on the brain and psychological stressors [17]. Prenatal exposure to
nicotine has been identified as a significant risk factor for the development
of ADHD [15,18–20]. Consumption of alcohol and caffeine and maternal
stress during pregnancy have also been implicated in a multitude of studies;
however, a recent meta-analysis failed to identify the significance of these
factors, mainly because of contradictory and inconsi stent findings among
studies [20]. Further, exposure to lead, low birth weight, single parenthood,
and low parental education levels and socioeconomic status have all been
implicated in the etiology of this complex disorder [15,19,21].
Neurobiologic factors
Several structural abnormalities in the brain have been documented in
patients who have ADHD. In 2003, Sowell and colleagues [22] found
a statistically significant correlation between reduced brain volume and
ADHD when compared with non-ADHD peers. Specifically, the prefrontal
lobe, frontal cortex, cerebellum, and subcortical structures were found to be
affected. Further, different areas of the brain were found to be affected in
monozygotic discordant and concordant twins, accounting for genetic and
environmental factors as etiology for these different structural changes
[16]. The concordant high-risk twins showed reduction in brain volume in
orbitofrontal subdivision and posterior corpus callosum, whereas the discor-
dant pairs had volume reduction in the right inferior dorsolateral prefrontal
cortex.
447ATTENTION DEFICIT HYPERACTIVITY DISORDER IN ADULTS
Diagnostic criteria
Diagnostic and Statistical Manual of Mental Disorders criteria
The Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition, Text Revision (DSM-IV-TR) criteria for ADHD diagnosis were
originally developed for the diagnosis of childhood ADHD. These criteria
require either six symptoms of inattention (ie, failure to attend to detail, dif-
ficulty sustaining attention, not listening when spoken to, failure to follow
through on tasks, organizational deficits, difficulty concentrating, losing
items, distractibility, forgetfulness) or hyperactivity/impulsivit y (ie, fidget-
ing, difficulty staying seated, excessive running/climbing, difficulty playing
quietly, acts as though ‘‘driven by a motor,’’ excessive talking, difficulty
awaiting one’s turn, interrupting frequently, prematurely responding to
questions) be present for a diagnosis of ADHD. In addition, the symptoms
must result in significant impairment observable in at least two settings, and
must be present before age 7. Individuals may be diagnosed with one of the
three subtypes: predominantly hyperactive-impulsive type, predominantly
inattentive type, and combined type [23].
The use of the DSM diagnostic criteria has been problematic in adults.
One of the most significant concerns is the lack of adults in the field trials
used to establish the diagnostic criteria for ADHD. In fact, before DSM-
IV, there was no indication in the diagnostic criteria that ADHD could per-
sist into adulthood; as a result, many of the criteria are not age-appropriate
for adults (eg, ‘‘runs or climbs excessively’’) [24]. Though some effort has
been made to adjust the criteria to include behaviors more appropriate
for adults through the addition of words such as ‘‘work’’ and ‘‘workplace,’’
further studies are still needed to determine if the symptoms of ADHD in
childhood are representative of those in adulthood [25,26]. For instance,
one study found that several of the DSM criteria did not adequately discrim-
inate between ADHD and non-ADHD adults; criteria found to discriminate
between the groups included fidgeting, difficulty remaining seated, difficulty
awaiting one’s turn, and engaging in potentially physically harmful behav-
iors [11].
It is also unclear if the minimum of six criteria for children would result
in under-diagnosis when applied to adults, because many ADHD adults
learn to compensate for their deficiencies by modifying their environments,
relying on others, or choosing careers and lifestyles that more easily accom-
modate their symptoms [25,27]. Research regarding the validity of minimum
criteria for diagnosis is inconsistent to date [28]. One of the most recent stud-
ies indica ted significant symptom decline with age, particularly with regard
to hyperactivity and impulsivity [29]. The study authors caution that,
though ADHD adults may not meet full diagnostic criteria, they may con-
tinue to experience significant functional impairment because of their resid-
ual symptoms and thus warrant treatment.
448 MOSS et al
Another concern regarding DSM criteria is the age of onset requirement.
Adults presenting with ADHD symptoms may have difficulty with the ret-
rospective recall required to meet this criterion and rarely present with ele-
mentary school documentation or a family member who can report on their
behaviors before age 7 [25,30,31]. The validity of the age of onset criterion
has been questioned in prior research, which indicated that a large number
of ADHD children did not experience symptoms until after age 7. This was
particularly true for those who have ADHD predominantly inattentive type,
of whom 75% did not have symptoms until after 9 years of age [32]. This
and other research have led some to suggest that the age of onset criterion
be modified or eliminated [25,33].
Utah criteria
A second set of criteria often used for adult ADHD diagnosis is the Utah
Criteria [34,35]. The Utah Criteria require that childhood and adult criteria
be met for a diagnosis of ADHD in adults. Childhood criteria include
a childhood diagnosis per the DSM-IV, hyperactivity, attention deficits,
and one of the following: schoo l behavior problems, impulsivity, over-excit-
ability, and temper outbursts. Adult criteria include motor hyperactivity and
attention deficits, and two of the following: labile affect, temper outburst s,
excessive emotional reactivity, disorganization, impulsivity, and associated
features of ADHD. Per the Utah Criteria, adult ADHD may only be diag-
nosed in the absence of other psychiatric disorders.
One of the most frequent criticisms of the Utah Criteria is its exclusion of
inattentive symptoms. This is of particular concern given previous research
indicating slower decline of inattentive symptoms as compared with hyper-
activity and impulsiveness as ADHD patients age [29]. The inclusion of af-
fective symptoms is also of concern given the many mood disorders that
may be characterized by labile moo d [25]. Further, requiring that other psy-
chiatric disorders must be absent for ADHD diagnosi s would likely result in
the under-diagnosis of many symptomatic adults given the high rates of co-
morbidity of ADHD with other psychiatric diagnoses [36,37].
Clinical presentation
With increased public awareness of adult ADHD comes increased self-re-
ferral and self-di agnosis in the general population [2]. Many adults begin to
suspect they suffer from ADHD during the process of having their children
evaluated and treated for ADHD. Whereas children are more likely to be
referred for evaluation because of the negative impact their behavior has
on others, adults are more likely to seek treatment because of the negative
ramifications of their behavior on their own lives, though not all may iden-
tify their symptoms as indicative of ADHD [38]. Faraone and colleagues
identified the primary presenting complaints of adults diagnosed with
449ATTENTION DEFICIT HYPERACTIVITY DISORDER IN ADULTS
ADHD, comparing those who suspected themselves of having ADHD and
those who did not. Interestingly, both groups presented with similar symp-
toms, the most common being difficulty concentrating, disorganization, fail-
ure to complete projects, inattentiveness, and poor school performance.
Affective complaints included anxiety, increased temper, and depression [2].
Other affective complaints, such as hostility and emotional lability, may
also prompt adults who have ADHD to seek treatment [11,39,40]. Cognitive
complaints, including poor concentration and impaired memory, are com-
mon in these patients as well [1,34,37,39,41–43]. Poor academic and work
performance may result in part from poor organizational, prioritization
and time management skills, and lack of attention to details or over-focus
on unimportant details [1,34,37,39–43]. Not surprisingly, these patients also
report making a high rate of careless errors and experiencing impatience,
low frustration tolerance, and impulsivity [37–39,41–43]. Low self-esteem
often accompanies these complaints [40] (Box 1).
Associated features and impact
In trying to understand adult ADHD more fully, it is worthwhile to ex-
amine some of the areas affected by this condition, because functional and
Box 1. Clinical presentations of adult ADHD
Poor concentration
Fidgeting
Difficulty remaining seated
Impulsivity (eg, difficulty awaiting one’s turn)
General disorganization
Failure to complete projects
Inattention
Poor school and work performance
Poor time management
Poor anger management
Cognitive impairment
Anxiety/depression
Hyperfocused
Substance abuse
Hostility
Emotional lability
Low self-esteem
Problems in family and relationships (divorce, separation)
Increased rate of motor vehicle accidents
Adapted from Refs. [1,2,11,37–43].
450
MOSS et al
psychosocial deficits present substantial difficulties in various aspects of the
lives of ADHD adults.
Academic and work performance
The aforementioned deficits may lead ADHD adults to complain of poor
work performance or academic underachievement, which in school may be
accompanied by more grade retention, higher drop-out rates, lower grade
point averages, increase probati on rates, and poor college adjustment
[12,44–47]. Additionally, 20% of ADHD patients may have auditory
processing deficits [12]. At work, symptoms may result in higher rates of
unemployment, frequent job changes, lower occupational status, and more
work absences, which in turn results in lower socioeconomic status
[7,11,34,37,39,42,45,48– 51].
Social interactions
Strained relationships with spouses, other family members, friends, and
coworkers may result from a lack of understanding of the disorder and frus-
tration with the symptoms [11,35,37,39]. In the workplace, inattention, pro-
crastination, and attention to insignificant detail can lead to frequent
frustration and strained relationships. For example, the inability of adults
who have ADHD to manage time appropriately and needing to enlist co-
workers to assist in task completion can cause workplace conflict, as can dif-
ficulty monitoring and inhibiting their own behavior (eg, interrupting,
excessive talking) and engaging in socially inappropriate behavior (eg, ex-
plosive outbursts, making rude comments, engaging in phone conversations
during meetings) [1,2,12,38]. Their interpersonal difficulties may contribute
to conflicts in social acceptance, with ADHD patients exhibiting poorer so-
cial skills and self-esteem than their non-ADHD peers [47,52–54].
Family and romantic relationships can be strained as well, as demon-
strated by higher rates of separation and divorce among ADHD patients
and lower rates of marital, family, and social life satisfaction [11,45,54].
Common complaints include not listening to or interrupting others , inatten-
tiveness to others’ emotional needs, disorganization in managing household
responsibilities (eg, finances), and poor communication and problem-solv-
ing [55]. The presence of an ADHD child can compound the family strain.
The chance of an adult ADHD patient having children who share their di-
agnosis is approximately 50%, which may result in a chaotic household
when symptoms are not well-controlled [2].
Driving
Adults who have ADHD exhibit a significantly higher rate of traffic acci-
dents and greater rates of damage in such accidents as compared with non-
ADHD adults. Barkley and colleagues found that adolescents who had
451ATTENTION DEFICIT HYPERACTIVITY DISORDER IN ADULTS
ADHD were four times more likely to have had a motor vehicle acc ident than
their non-ADHD peers [56]. Their data also found that ADHD adolesc ents
were more likely to have driven an automobile before being of legal driving
age, less likely to employ sound driving habits, more likely to have had their
licenses suspended or revoked, and more likely to have received repeated traf-
fic citations (mostly for speeding). These driving problems are reportedly
apparent to others as well as the patients themselves [11,57].
Substance abuse
ADHD patients are more likely to develop substance abuse, and at an
earlier age, than those who did not have ADHD [58,59]. The risks of sub-
stance abuse are further increased by the presence of comorbid bipolar or
conduct disorders [7]. Several reasons for the elevated substance abuse rates
have been proposed, including self-medication of ADHD symptoms and
gaining social acceptance [60]. Unfortun ately, ADHD adults have lower re-
mission rates and longer periods of substance abuse than their non-ADHD
peers [26,61].
Health care costs
It is interesting to note that people who have ADH D have higher health
care costs than non-ADHD individuals. A comparison of 9-year median
medical costs between the two groups indicated ADHD medical costs as
$4306 versus non-ADHD medical costs of $1944 [62]. Similar findings
were reported by Secnik and colleagues [49], who found significantly greater
outpatient, inpatient, prescription, and total health care costs among
ADHD individuals as compared with non-ADHD individuals. Higher rates
of substance abuse treatments and increased treatment frequency because of
noncompliance with medical recommendations may contribute to these
health care costs [52]. Further, health care costs of ADHD patients’ family
members are also higher, which may be caused by elevated stress, depres-
sion, and substance abuse found in these families [52,63].
Assessment
Whereas primary care physicians often recognize and treat ADHD in
children, they may experience difficulties in identifying and diagnosing the
disorder in adu lts. As of this writing, there are no tests diagnostic for
ADHD; however, a thorough history accompanied by questionnaire and
checklist data can be beneficial in clarifying the diagnosis. Neuropsycholog-
ical assessment may also help elucidate patients’ deficits and provide target
areas for treatment. It should also be noted that, in addition to the ap-
proaches below, patients should be screened for other psychiatric disorders,
given their high rates of comorbidity with ADHD.
452 MOSS et al
Interviews
The first step in conducting an ADHD assessment is a thorough inter-
view. Patients should be queried about ADHD symptoms, both past and
present. Murphy and Schachar [64] recommend asking specific questions
rather than open-ended questions to improve the accuracy of retrospectively
reported symptoms. Patients should be asked to provide an educational and
occupational history, including conduct a nd disciplinary actions, to deter-
mine if symptoms (eg, losing homework, difficulty staying in one’s seat,
excessive talking, difficulty playing quietly) of ADHD were present in child-
hood, and to discern the functional impact of the symptoms on performance
[1,65]. When possible, collateral information should be obtained; this may
be done by way of reviewing school records or seeking input from patients’
family members [1,65]. Input from each of these sources can provide infor-
mation on the presence of ADHD symptoms during childhood as discussed
above; further, family members may be able to provide infor mation on cur-
rent symptoms and functioning. Questioning patients about their perfor-
mance in a variety of situations during the prior week, the level of effort
required to function, and coping strategies used may also provide valuable
information regarding functional impairment [40,65,66]. Given the heritabil-
ity of ADHD, assessing family history of ADHD may provide insight into
the patient’s presenting symptoms [42]. Although not necessary for obtain-
ing a history of ADHD symptoms, diagnostic interviews are available to
assist with the interview process, including the Brown Attention Deficit
Disorder (ADD) Scale, Conners’ Adult ADHD Diagnostic Interview for
DSM-IV, and the Diagnostic Interview Schedule [40].
Rating scales
Several rating scales are available to assist with adult ADHD diagnosis.
Research indicates significant positive correlations between ratings of adults
who have suspected ADHD and their significant others [11,41,67]; however,
they should not be used alone as diagnostic tools because of unacceptable
rates of false positives [26,68].
Many of the available rating scales use Likert-type scales to assess symp-
toms, have acceptable psycho metric properties, can be administered in
5 minutes or less, and requir e no additional training of the administrator
(eg, Brown ADD Scale for Adults, Conner’s Adult ADHD Rating Scale,
Adult ADHD Self Report Scale, ADHD Rating Scale-IV) [26,69,70]. Scales
such as Connor’s Adult ADHD Rating Scales can be administered to
a spouse or parent, and thus can assist in gathering collaterals’ views of pa-
tients’ symptoms. The Wender Utah Rating Scale, based on the aforemen-
tioned Utah Criteria, takes 10 minutes to administer and is also commonly
used [35]; however, criticism of this scale is similar to that of the Utah cri-
teria on which it is based, with research indicating that it measures affective
and conduct disorders not specific to ADHD and lacks field testing [71,72].
453ATTENTION DEFICIT HYPERACTIVITY DISORDER IN ADULTS
Neuropsychological assessment
Compared with non-ADHD adults, ADHD adults exhibit significant def-
icits in a variety of functional domains and on specific neuropsychological
tests. For example, meta-analyses of neuropsychological performance differ-
ences between ADHD and non-ADHD adults have revealed deficits in
verbal memory, focused and sustained attention, behavioral inhibition, and
abstract problem solving among ADHD adults [73,74]. Reviews of the liter-
ature suggest that specific neuropsychological assessments found to discrim-
inate between the two groups include continuous performan ce tasks, the
Stroop task, Trail Making Tasks, the Controlled Word Association Test,
and Weschler intelligence measures, with most effect sizes being moderate
[75,76]. The Digit Symbol subtest of the Weschler intelligence scale appears
to be the most effective subtest for identifying ADHD adults, particularly
when used in combination with the Arithmetic subtest [75–77]. Both the
Digit Symbol and Arithmetic subtests are measures of working memory,
which suggests that other assessments of working memory may also be sen-
sitive to ADHD in adults.
As with rating scales, there are no neuropsychological assessments to
date that are diagnostic of adult ADHD. Despite this, neuropsychological
assessment can assist patients with legal services, such as seeking accommo-
dations through the Americans with Disabilities Act, and targeting deficient
areas for treatmen t and vocational counseling [66,78].
Laboratory and radiological tests
Routine laboratory and radiological tests are useful for differentiating
ADHD from common medical conditions that can mimic symptoms of
ADHD. Common laboratory tests include complete blood count, metabolic
profile, including liver function tests, and thyroid function studies. Serum
lead level and heavy metal screening should be undertaken if history warrants.
Serum vitamin B12 level should be obtained in patients who have anemia, nu-
tritional deficiencies, and cognitive impairment. Electroencephalogram and
computed tomography of the head should be performed in patients who
have a recent history of trauma to the head or history suggestive of seizure dis-
orders. In patients who have concurrent sleep disorder symptoms, polysom-
nography should be undertaken to rule out obstructive sleep apnea (OSA)
as the etiology for ADHD symptoms [1,79].
Comorbidity
Psychiatric comorbidity is significantly higher in ADHD adults as com-
pared with non-ADHD controls, and may often be the primary concern
with which patients present to their primary care providers [36,37]. Bieder-
man and colleagues [53] found that 44% of a sample of ADHD adults had
454 MOSS et al
at least one comorbid psychiatric diagnosis. Mood disorders are among the
most commonly reported comorbidities in the literature, and occur at signif-
icantly higher rates in ADHD adults as compared with controls [11,49,80,81].
Rates of major depressive disorder among adult ADHD samples range from
11.5% to 53.5%, and dysthym ia rates range from 11.5% to 25% [9,41,82–
84]. Rates of bipolar disorder and cyclothymia are reported to be 19.4% and
25%, respectively [9,82]. The high rate of mood disorders in this population
may be caused in part by the difficulties of living with the symptoms of
ADHD; however, it is not possible to attribute causality, because the cause
for each disorder is likely multifactorial [39]. It is important that comorbid
psychopathology be identified, given that failure to identify bipolar illness
or misattributing mood symptoms solely to ADHD may lead to iatrogenic
worsening of a bipolar disorder treated with antidepressants or
psychostimulants.
Anxiety disorders are also commonly reported at a greater rate among
ADHD adults than controls [49,53,80,81]. For example, rates of generalized
anxiety disorder range from 8% to 53% among ADHD adults [9,82,83].
Similarly, agoraphobia, panic disorder, post-traumatic stress disorder, so-
cial phobia, and specific phobia have been noted to occur at higher rates
among ADHD adults than non-ADHD peers [9,54].
Antisocial disorder, conduct disorder, and oppositional defiant disorder
among ADHD adults have also been frequently investigated. The majority
of research to date indicates a higher rate of each of these disorders among
ADHD adults [7,11,41,49,53,81]. One study suggests that the prevalence of
comorbid antisocial personality disorder in ADHD adults is tenfold com-
pared with non-ADHD peers [7]. Both condu ct disorder and antisocial per-
sonality disorder have been found to be more common in adult ADHD
males than females [54].
Rates of substance use have also been found to occur at significantly
higher rates among ADHD adults versus non-ADHD adults, with one study
reporting a five times greater risk [7,9,11,41,49,53,81]. Identified substances
of abuse have included alcohol, cannabis, and amphetamines [84]. Some
gender differences have been identified, with males exhibiting significantly
greater rates of alcohol abuse than females [54]. One potential explanation
for the elevated rates of substance use is self-medication of unt reated
ADHD symptoms [43]. It is also possible that impulsivity characteristic of
ADHD contributes to higher rates of abuse in this population.
Other disorders identified more frequently among ADHD adults include
enuresis, stuttering, speech and language disorders, and tics [53,54].
Differential diagnosis
ADHD should be considered in the differential of any condition present-
ing with complaints of inattention, fatigue, and hyperactivity, as well as in
455ATTENTION DEFICIT HYPERACTIVITY DISORDER IN ADULTS
patients presenting with depression, anxiety, substance abuse or bipolar
disorder [2,53] (Table 1).
Medical diagnoses
A complete history and physical examination should be conducted in pa-
tients presenting with symptoms of ADHD. A medical diagnosis should be
suspected particularly in patients with recent onset of symptoms. The most
common disorders that may present with symptoms similar to those of
ADHD include thyroid disorders (hypo- and hyperthyroidism), seizure dis-
orders (petit mal or partial complex), drug interactions, hepatic diseases,
lead toxicity, post-head injury and hearing deficits [1]. Sleep-disordered
breathing, OSA, has been found to present with sleep disturbances, inatten-
tion, and cognitive impairment, which resolve with treatment for OSA.
Hence, OSA should be considered in the differential of patients who have
ADHD and who have symptoms of snoring, excessive daytime somnolence,
inattention, and memory difficulties [79].
Psychiatric diagnoses
Given the frequency of comorbid psychiatric diagnoses with ADHD and
its symptoms overlapping with other psychiatric diagnoses (eg, poor concen-
tration, restlessness, talkativeness), conducting a thorough history and
symptom evaluation is paramount. Mood disorders share many symptoms
with ADHD. For example, both major depressive disorder and ADHD
share symptoms of decreased concentration, attention, and memory; how-
ever, unlike ADHD, major depressive disorder is marked by neuro-vegeta-
tive symptoms (eg, anhedonia and appetite disturbance) [1,48]. Questioning
the patient about the course of symptoms to determine if cognitive symp-
toms occur in the absence of mood symptoms can also clarify the diagnosis
[66]. Bipolar disorder and ADHD also share common symptoms, including
Table 1
Differential diagnosis of adult ADHD
Medical Psychiatric
Thyroid disorders (hypo/hyperthyroidism) Major depression
Head trauma Bipolar disorders
Obstructive sleep apnea Generalized anxiety disorder
Seizure disorders
(petit mal or partial complex)
Substance abuse and dependence
Vitamin B12 deficiency Personality disorders (antisocial and borderline)
Drug interactions
Heavy metal poisoning
Hearing deficits
Liver disease
Lead toxicity
Adapted from Refs. [2,79,85].
456
MOSS et al
hyperactivity, decreased attention, and mood lability [1] . Excessive spend-
ing, delusions or other ps ychotic symptoms, grandiosity, racing thoughts,
and decreased need for sleep help differentiate ADHD from mania or hypo-
mania. Anxiety disorders (eg, generalized anxiety disorder) share attention
and concentration deficits with ADHD, but excessive worry and somatic
symptoms seen in these disorders are not characteristic of ADHD [1,66].
Personality disorders must also be differentiated from ADHD. Borderline
personality disorde r, like ADHD, is characterized by impulsivity, mood
lability, and hostility [48]; however, these symptoms in ADHD patients
are typically intermittent, shorter in duration, an d less severe. Further,
ADHD is not characterized by the dichotomous thinking, abandonment
fears, or self-injurious behavior seen in borderline personality disorder [48].
Antisocial personality disorder shares impulsivity and affective lability with
ADHD; however, an arrest history and lack of insi ght into and remorse
regarding the behaviors seen in antisocial personality disorder can assist in
differentiating the two disorders [1,85] (Table 2).
Treatment
The mainstay of adult ADHD treatment includes pharmacological inter-
ventions, behavioral interventions, or a combination of both, with the goals
of symptom remission and return to full social functioning. Studies in chil-
dren indicate that combined treatment results in greater symptom improve-
ment and is superior to pharmacotherapy alone, especially in improving
non-ADHD symptoms and functional impairment [86]. Multiple other stud-
ies comparing cognitive-behavioral therapy to pharmacological manage-
ment indicate that cognitive-be havioral therapy alone may be insufficient,
and that combined treatment is more effective than either treatment alone
in control of symptoms and improving functional status [80,83,87].
Table 2
Differentiating ADHD from other psychiatric diagnoses
Psychiatric diagnosis Distinguishing characteristics
Major depressive disorder Neuro-vegetative symptoms
(eg, anhedonia, appetite disturbance)
Bipolar disorder Excessive spending
Delusions
Insomnia
Anxiety disorders Excessive worry
Somatic complaints
Borderline personality disorder Dichotomous thinking
Abandonment fears
Self-injurious behavior
Antisocial personality disorder Arrest history
Lack of insight into and remorse for behaviors
Adapted from Refs. [1,48,66,85].
457
ATTENTION DEFICIT HYPERACTIVITY DISORDER IN ADULTS
Pharmacological
As in childhood ADHD, medications, especially central nervous system
stimulants, have shown to significantly improve adult ADHD symptoms
[88–91]. Much of the evidence for adult ADHD treatment is based on treat-
ment efficacy in children and adolescents; long-term data are lacking in the
treatment of adult ADHD. The presence of psychiatric and medical comor-
bidities and substance abuse in adults who have ADHD makes drug choices
difficult. Patients should be counseled that medications provide only symp-
tomatic relief, and that concurrent psychotherapy and counseling are
recommended to acquire necessary organizational and social skills for
independent adult functioning.
Although stimulants are effective in ADHD treatment, physicians’ con-
cerns about the use of controlled substances with abuse potential play a sig-
nificant role in the choice of medications. In a recent survey, 38% of
physicians responded that they prefer prescribing a nonstimulant medica-
tion, and 58% preferred prescribing a noncontrolled medication without ev-
idence of abuse potential [92]. In 2003, atomoxetine, a nonstimulant, was the
first drug to receive United States Food and Drug Administration (USFDA)
approval for the treatment of adult ADHD.
Stimulants
Stimulants are typically the first-line agents used in the treatment of adult
ADHD [89–91]. Patients who have moderate to severe impai rment in two
different settings (occupational, social, academic, and family) should be con-
sidered for treatment with stimulants [89]. Methylphenidate (MPH), dextro-
amphetamines (DEX), mixed amphetamine salts (levoamphetamine and
dextroamphetamine) (AMP) and pe moline are the stimulants commonly
used in the treatment of adult ADHD [89]. They act by blocking the
reuptake of dopamine and norepinephrine, resulting in their accumulation
in the presynaptic cleft. Amphetamines also increase these neurotrans-
mitter levels in the presynaptic cleft by direct release of dopamine and
norepinephrine.
MPH and amphetamines are the most commonly used agents in the treat-
ment of adult ADHD, with no significant differences in efficacy, side-effect
profiles, and response rates [87,89]. Pemoline, a weak stimulant, has been
withdrawn from the market amid concerns of increased risk of hepatotoxic-
ity [93]. Earlier studies in adults showed a lesser stimulant response rate in
adults compared with children, with r ates ranging f rom 25% to 78% [88,94,95].
This difference in clinical response could be caused by the diagnostic criteria
used, insufficient doses of medication, and the presence of comorbid psychi-
atric disorders. Recent studies with higher doses of stimulants (1.1 mg/kg/
day of MPH) have shown more than 75% therapeutic response in ADHD
symptoms [96–98]. Similar results were described by Weisler and colleagues
[98] using mixed amphetamine salts.
458 MOSS et al
Stimulants have an immediate onset of action, and extended-release formu-
lations should be used whenever possible to increase compliance, provide lon-
ger duration of symptom relief, and decrease the potential for abuse. Some of
these are Concerta (McNeil Pediatrics, Fort Washington, Pennsylvania),
Adderrall XR (Shire, Wayne, Pennsylvania), and Ritalin LA (Novartis, East
Hanover, New Jersey). Patients should be initiated on the lowest dose avail-
able and titrated up until symptom relief is obtained with least side effects.
Patients who fail to have a response to one group should be tried on the other
before initiating second line treatments [89]. Most patients on stimulant
therapy take ‘‘drug holidays’’ on weekends and on vacation, mainly from con-
cerns of adverse effects; however, there are no significant data on the efficacy of
this practice, and it should not be advocated to patients [2,89].
In addition to relief of ADHD symptoms, stimulants have been shown to
improve self-esteem, cognition, and social and family functioning [89]. They
also have shown improvement on comorbid anxiety, condu ct, and tic disor-
ders [89]. Further, stimulants have a protective effect against substance
abuse and improve driving skills [99,100]. A recent meta-analysis of six stud-
ies (two with follow-up in adolescence and four in young adulthood) showed
a 1.9-fold reduction in risk for substance use disorders and later drug and
alcohol use disorders in youths who were treated with stimulants compared
with youths who did not receive pharmacotherapy for ADHD [99].
Nonstimulants
Nonstimulants are typically used to treat patients who do not tolerate
stimulants, or who have comorbid psychiatric or medical conditions in
which stimulants are contraindicated [89]. These agents can be used in com-
bination with stimulants to treat comorbid psychiatric disorders and may
help in decreasing the stimulant dose required. Commonly used medic ations
include atomoxetine, tricyclic antidepressants (TCAs), and buproprion.
Atomoxetine, a norepinephrine reuptake inhibitor, is the first drug to re-
ceive USFDA approval for the treatment of adult ADHD. Earlier studies of
atomoxetine in children have shown similar efficacy and tolerability com-
pared with stimulants [87,90] . Two large, multicenter, randomized control
trials of 10 weeks duration using atomoxetine indicated reduction of inatten-
tive and hyperactive and impulsive symptoms, with less than 10% discontin-
uation rate caused by adverse effects [101]. It has been increasingly used in
patients who have comorbid an xiety disorders, substance use disorders, and
tics. A use study for treatment initiation with atomoxetine indicated that
patients were more likely to receive atomoxetine than a stimulant if they
had a psychiatric diagnosis or alcohol dependence [102]. Atomoxetine has
the added benefit of not being a controlled substance and having no abuse
potential.
Most of the evidence on TCA efficacy for ADHD is based on child and
adolescent studies. For example, in one study, desipramine at a target dos e
of 200 mg yielded a 68% response rate over placebo in a 6-week period
459ATTENTION DEFICIT HYPERACTIVITY DISORDER IN ADULTS
[103]. Most common adverse effects include cardiac side effects, increased
seizure risk, dry mouth, and constipation.
Buproprion is an antidepressant with dopamine and noradrenergic ago-
nist effects. It has been shown to be efficaci ous as a second-line agent in
the treatment of ADHD, especially in patients who have comorbid bipolar
disorder, depression, or substance abuse [104]. In a 6-week trial comparing
patients receiving sustained-release bupropion (up to 200 mg twice a day) to
patients receiving placebo, bupropion treatment was associated with a 42%
improvement in ADHD symptoms, compared with 24% reduction in pla-
cebo [105].
Other rarely used nonstimulant medications include mono amino oxidase
inhibitors, clonidine, and cholinergic agents with structural similarities to
nicotine (ABT-418) [106]. Clondine may also be used as an adjunct to stim-
ulants in the treatment of comorbid aggression and insomnia [89].
Adverse effects
Most common side effects of stimula nts are mild and include distur-
bances of sleep, appetite and mood, weight loss, nervousness, irritability, ag-
itation, and confusion [87,89,96]. Most of these side effects can be effectively
managed by giving medications with meals, lowering the dose, changing the
timing of administration to earlier in the day, or using long-acting prepara-
tions [89]. Stimulants are contraindicated mainly in patients who have pre-
vious hist ory of sensitivity, glaucoma, hyperthyroidism, hypertension, and
acute psychosis. Further, they should be used with caution in patients
who have a prior history of abuse of stimulants [89]. MPH and bupropion
may cause seizures in adults who have seizure disorders; hence, these pa-
tients should be stabilized with anti-seizure medications before using higher
doses of medications [89].
Stimulant and nonstimulant medications may also be associated with in-
creased rates of cardiovascular side effects, such as palpitation, tachycardia,
and hypertension, because of their pressor and chronotropic effects; hence,
close monitoring of vitals should be done before the initiation of treatment
and at periodic intervals [96,107–109]. In 2006, the USFDA issued a warning
on all stimulants, prompted by sudden unexpected deaths in children and
adolescents using stimulants between 1999 and 2003 [110]. They recommend
against the use of stimulants in children or adolescents who have known
serious structural cardiac abnormalities, cardiom yopathy, heart rhythm
abnormalities, or other serious cardiac disorders. Further, the American
Heart Association suggests careful evaluation for cardiac disease before ini-
tiation of stimulant therapy in adults. They recommend careful evaluation
of patients’ family histories for sudden death at less than 40 years of age,
long QT Syndrome, cardiac arrhythmias, hypertrophic cardiomyopathy
and personal history of heart disease, symptoms of palpitation, dizziness,
or syncope [111]. A basal electrocardiogram before the initiation of medica-
tions (especially TCAs) may be useful in monitoring of these patients.
460 MOSS et al
In 2006, the USFDA also issued a warning on all stimulants and atom-
oxetine because of the potential for psychotic or manic symptom develop-
ment, especially in children and adolescents. Atomoxetine may also
increase suicidal thoughts and thus carries an additional USFDA warning
[112]. Hence, patients should be closely monitored for behavior change, psy-
chosis, and suicidal ideation while on treatment with these medications.
Nonpharmacological
Numerous strategies for assisting ADHD adults in managing their symp-
toms have been suggested anecdotally; however, there is a paucity of re-
search investigating the benefits of nonpharmacologic interventions [113].
The most frequently researched interventions are cognitive-behavioral, of-
fered both in individual and group formats, and with and without pharma-
cological treatment. Cognitive-behavioral therapy includes identification
and modification of patients’ maladaptive thought patterns and instruction
in behavioral modifications to minimize functional impairment [114]. Data
indicate that cognitive-behavior al therapy results in statistically significant
improvements in ADHD symptoms, functional impairment, depress ion,
anxiety, hopelessness, health status, and self-esteem [80,83,115,116].
Skills typically taught during cognitive-behavioral therapy include
psychoeducation about ADHD symptoms and medications, strategies for
improving motivation, concentra tion (eg, minimizing distractions, self-mon-
itoring), listening, impulsivity, organization and time management (eg, using
a calendar, making lists; working during personally optimal times of day),
emotional regulation, self-esteem, problem-solving skills, and mindfulness
[1,37,80,115,116]. Additional specific recommendations are listed in Box 2.
Other strategies recommended to assist ADHD adults include couples/fam-
ily therapy and support groups, such as the Attention Deficit Disorder
Association (www.add.org) and Children and Adults with Attention Deficit
Disorder (www.chadd.org) [34,117,118].
Special considerations
Primary care/psychiatry
Adult ADHD is often under-diagnosed. In one study, only 25% of adults
who had ADHD were diagnosed in childhood, even though retrospective as-
sessments supported the presence of childhood ADHD. One potential expla-
nation for under-diagnosis of adult ADHD is primary care physicians’ lack
of knowledge of ADHD presentation in adults. Rates of adult ADHD iden-
tification are significantly higher among psychiatric settings as compared
with primary care settings (52% versus 27%), and ADHD is recognized
at younger ages in prim ary care settings [2]. Education and training may
be necessary to overcome this discrepancy [2].
461ATTENTION DEFICIT HYPERACTIVITY DISORDER IN ADULTS
Substance abuse
ADHD symptoms, such as poor impulse control, may present unique
challenges to treatment, especially in patients with concurrent substance
abuse [60,120,121]. Early treatment of ADHD, with concomit ant manage-
ment of substance abuse, may result in increased rates of compliance and
abstinence [60,120,121]. Stimulants should be used with caution in patients
who have history of stimulant abuse or dependence [89]. Recent studies of
long-acting stimulants in patients who had ADHD and history of substance
abuse yield positive effects, with no significant increase in substance abuse
[120,121]. In patients who have concurrent substance abuse, atomexitine,
desipramine, and bupropion may be preferable to methylphenidate because
they are associated with a decreased risk of abuse [26]. W hen treating
Box 2. Strategies for management of ADHD symptoms
Behavioral strategies
 Minimize distractions (eg, no clutter on desk, no working near
windows)
 Develop a daily routine
 Use a calendar to schedule activities
 Make ‘‘to do’’ lists, and keep them in sight
 Keep note pads available to write down things to remember
 Use a filing system
 Take time each evening to prepare for the next day
 Work at personally optimal times of day
 Break large tasks down into smaller tasks and create respective
deadlines
 Prioritize tasks
 Consider and determine pros and cons of multiple options
before acting
 Delegate tasks when necessary
 Ask friends or family to remind of dates and deadlines
 Take a ‘‘time out’’ when becoming upset or frustrated
 Make multiple sets of keys
Other beneficial strategies
 Educate patient about ADHD symptoms and medications
 Anger management
 Mindfulness training (eg, meditation)
 Encourage patient to reward self for positive changes and
symptom management
Adapted from Refs. [2,37,38,80,114,115,117–119].
462
MOSS et al
patients who have concurrent substance abuse, increased vigilance is advised
to include compliance evaluation, random drug screens, and coordination
with addiction counselors [122].
Pregnancy and lactati on
There is little known about the effect of ADHD treatment on pregnancy
and lactation. Patients who have ADHD have 38% more unplanned preg-
nancies, and more and more young adults who have ADHD present to pri-
mary care physicians for preconception counseling [12]. All stimulants and
nonstimulants except bupropion are pregnancy category C (ie, inability to
rule out risk); however, there is no indication for therapeutic termination
of pregnancy for patients who become pregnant on ADHD medication.
Further, abrupt withdrawal of psychotropic medications upon diagnosis
of pregnancy may result in unfavorable physiological effects and possible re-
emergence of symptoms [123]. Therefore, each patient should be properly
counseled regarding risks and benefits of treatment, and patients wishing
to discontinue or change medications should be closely monitored.
A recent evaluation by the National Toxicology Program Center for the
Evaluation of Risks to Human Reproduction concluded that there are insuf-
ficient data associati ng methylphenidate therapy in pregnant women and
pregnancy loss and reproductive effects in humans [124]; however, a similar
study of amphetamines and methamphetamine [125] revealed potential neu-
robehavioral alterations, low birth weight, and shortened gestation. A con-
founding effect of other potential drug use could not be ruled out in these
patients. The effects of stimulant and nonstimulant medications on lactation
are still unknown, and amphetamines and methylphenidate are contraindi-
cated by American Academy of Pediatrics during lactation [126] (Table 3).
Pearls
Adult patients who present with cognitive complaints (including inatten-
tion), mood complaints, and functional impairment in school, work,
and interpersonal relationships may be exhibiting ADHD symptoms.
Assessment of adult ADHD should include educational and occupational
history, collateral information (both from significant others and school
records when available), and assessment of prior and current func-
tional impairment. Diagnostic interviews and rating scales may facili-
tate this process.
Neuropsychological testing may be helpful for treatment planning, voca-
tional counseling, and assisting patients with legal services.
Assessment for adult ADHD should include assessment of mood, anxi-
ety, and personality disorders, and substance abuse caused by high
rates of comorbidity and symptom overlap.
463ATTENTION DEFICIT HYPERACTIVITY DISORDER IN ADULTS
Table 3
Treatment of adult ADHD
Medication
Duration
of action Dose Side effects Comments
Methylphenidate (MPH)
Short-acting: (Ritalin, Methylin)
Intermediate-acting: (Ritalin
SR, Methylin ER, Metadate ER)
Long-acting: (Metadate CD,
Ritalin LA)
Concerta
Daytrana (patch)
3–5 h
3–8 h
8–12 h
10–12 h
10–12 h
10–80 mg/day
20–80 mg/day
10–80 mg/day
18–72 mg/day
10–60 mg/day patch
Insomnia
Loss of appetite
Weight loss
Headache
Nervousness
Increase in
pulse rate and
blood pressure
Titrate dose weekly by 5–10 mg.
Monitor pulse rate and Blood pressure.
Pregnancy risk: category C
a
Contraindicated in lactation.
Patch on for 9 hours and off for 15 h.
Dextroamphetamine (DEX)
Short-acting (Dexedrine)
Long-acting (Dexedrine spansules)
4–6 h
6–8 h
5–45 mg/day
5–45 mg/day
Insomnia
Loss of
appetite
Weight loss
Headache
Nervousness
Increase in
pulse rate and
blood pressure
Titrate by 5 mg per week.
Pregnancy category C
Monitor blood pressure and
pulse.
464 MOSS et al
Mixed amphetamine salts (AMP)
Adderall
Adderall XR
4–6 h
8–10 h
5–40 mg/day
5–60 mg/day
Insomnia
Loss of
appetite
Weight loss
Headache
Nervousness
Palpitation,
tachycardia,
elevation of
blood
pressure
Pregnancy category C
Monitor blood pressure and
pulse.
Dosing in the morning to
reduce sleep disturbances.
Titrate by 2.5–5 mg per week.
Bupropion
(Wellbutrin)
12 h 37.5–450 mg/day Insomnia
Increased risk
of seizures
Headache
Pregnancy category B
Effect on lactation unknown.
Contraindicated in patients
with seizures and bulimia.
Response after 4–5 weeks
Atomoxetine
(Strattera)
24 h 40–80 mg/day Sleep
disturbance
Nausea
Vomiting
Dyspepsia
Abdominal
pain
Headache
Changes in
blood
pressure and
pulse rate
Jaundice and
hepatotoxicity
Pregnancy category C
Effect on lactation unknown.
Should be discontinued in
patients who develop jaundice
or have elevated liver function tests.
(continued on next page)
465ATTENTION DEFICIT HYPERACTIVITY DISORDER IN ADULTS
Table 3 (continued )
Medication
Duration
of action Dose Side effects Comments
Tricyclic antidepressants (TCA)
Desipramine or imipramine
Nortriptyline (Pamelor)
24 h 10–150 mg/day
10–150 mg/day
Dry mouth
Constipation
Changes in
pulse rate,
blood pressure
Conduction
abnormalities
Monitor therapeutic levels.
Response after 4 weeks
Monitor ECG before and after
stabilization on treatment.
Pemoline
(Cyclert)
37.5–75 mg/day Insomnia
Weight loss
Decreased
appetite
Headaches
Nervousness
Hepatotoxicity
Pregnancy Category B
Effect on lactation unknown.
Withdrawn from the market because of
hepatotoxicity.
Monitor liver function tests.
a
FDA use in pregnancy ratings: category A, no risk indicated in controlled studies; B, no evidence of risk in humans; C, inability to rule out risk;
D, positive evidence of risk; X, contraindicated in pregnancy.
Data from Refs. [2,88,89].
466 MOSS et al

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