a LANGE medical book
`
`CURRENT
`
`Diagnosis & Treatment
`Psychiatry
`second edition
`
`BRITIOH LWOW/
`DOCUMENT SUPPPLY CENTRE
`0 9 MAY 2008
`m08/.
`20564
`Peter T. Loosen, MD, rnu
`Professor Emeritus of Psychiatry
`Department of Psychiatry
`Vanderbilt University School of Medicine
`Nashville, Tennesssee
`
`James F. Leckman, MD
`Nelson Harris Professor of Child Psychiatry, Pediatrics,
`and Psychology
`Director of Research
`Yale Child Study Center
`Yale University School of Medicine
`New Haven, Connecticut
`
`Edited by
`
`Michael H. Ebert, MD
`Associate Dean for Veterans Affairs and Professor of
`Psychiatry, Yale University School of Medicine
`Chief of Staff, VA Connecticut Healthcare System
`West Haven, Connecticut
`
`Barry Nurcombe, MD
`Professor of Child and Adolescent Psychiatry,
`Departments of Pediatric Medicine and Psychiatry and
`Neuroscience
`University of Western Australia, Perth, Western Australia
`Professor Emeritus of Psychiatry
`University of Queensland, Herston, Queensland, Australia
`Vanderbilt University School of Medicine
`Nashville, Tennessee
`
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`The McGraw-Hill Com • wiles
`
`Current Diagnosis & Treatment: Psychiatry, Second Edition
`
`Copyright © 2008 by The McGraw-Hill Companies, Inc. All rights reserved. Printed in the United States of America. Except as
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`Page 2
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`

`

`Attention-Deficit Hyperactivity
`Disorder
`
`Thomas Spencer, MD
`
`ESSENTIALS OF DIAGNOSIS
`
`DSM-IV-TR Diagnostic Criteria
`Attention-Deficit/Hyperactivity Disorder
`
`A. Either (1) or (2):
`
`(1) Sx (or more) of the following symptoms
`of inattention have persisted for at least
`6 months to a degree that is maladap-
`tive and inconsistent with developmental
`level:lnattention
`(a) Often fails to give close attention to de-
`tailsor makes careless mistakes in school-
`work, work, or other activities
`(b) Often has difficulty sustaining attention
`in tasks or play activities
`(c) Often does not seem to listen when spo-
`ken to directly
`(d) Often does not follow through on in-
`structions and fails to finish schoolwork,
`chores, or duties in the workplace (not
`due to oppositional behavior or failure
`to understand instructions)
`(e) Often has difficulty organizing tasks and
`activities
`(f) Often avoids, dislikes, or is reluctant to
`engage in tasks that require sustained
`mental effort (such as schoolwork or
`homework)
`(g) Often loses things necessary for tasks or
`activities (e.g., toys, school assignments,
`pencils, books, or tools)
`(h) Is often easily distracted by extraneous
`stimuli
`(i) Is often forgetful in daily activities
`(2) Six (or more) of the following symptoms
`of hyperactivity-impulsivity have persisted
`for at least 6 months to a degree that is mal-
`
`adaptive and inconsistent with developmen-
`tal level: Hyperactivity
`(j) Often fidgets with hands or feet or
`squirms in seat
`(k) Often leaves seat in classroom or in other
`situations in which remaining seated is
`expected
`(I) Often runs about or climbs excessively in
`situations in which it is inappropriate (in
`adolescents or adults, may be limited to
`subjective feelings of restlessness)
`(m) Often has difficulty playing or engaging
`in leisure activities quietly
`(n) Is often "on the go" or often acts as if
`"driven by a motor"
`(o) Often talks excessively
`
`Impulsivity
`
`(g) Often blurts out answers before ques-
`tions have been completed
`(h) Often has difficulty awaiting turn
`(i) Often interrupts or intrudes on others
`(e.g., butts into conversations or games)
`B. Some hyperactive-impulsive or inattentive symp-
`tomsthatcaused impairmentwerepresent before
`age 7 years.
`C. Some impairment from the symptoms is present
`in two or more settings (e.g., at school (or work)
`and at home).
`D. There must be clear evidence of clinically signifi-
`cant impairment in social, academic, or occupa-
`tional functioning.
`E. The symptoms do not occur exclusively during
`the course ofa Pervasive Developmental Disorder,
`Schizophrenia, or other Psychotic Disorder and
`are not better accounted for by another mental
`disorder (e.g., Mood Disorder, Anxiety Disorder,
`Dissociative Disorder, or a Personality Disorder).
`Code based on type:
`
`573
`
`Page 3
`
`

`

`574
`
`I CHAPTER 35
`
`Attention-Deficit/Hyperactivity Disorder, Com-
`bined Type: if both Criteria Al and A2 are met for
`the past 6 months
`Attention-Deficit/Hyperactivity Disorder, Predom-
`inantly Inattentive Type: if Criterion Al is met but
`Criterion A2 is not met for the past 6 months
`Attention-Deficit/Hyperactivity Disorder, Predom-
`inantly Hyperactive-Impulsive Type: if Criterion
`A2 is met but Criterion Al is not met for the past
`6 months
`
`General Considerations
`A. EPIDEMIOLOGY
`Attention-deficit hyperactivity disorder (ADHD) is the
`most common emotional, cognitive, and behavioral dis-
`order treated in youth. It is a major clinical and public
`health problem because of its associated morbidity and
`disability in children, adolescents, and adults. Data from
`cross-sectional, retrospective, and follow-up studies in-
`dicate that youth with ADHD are at risk for developing
`other psychiatric difficulties in childhood, adolescence,
`and adulthood including delinquency as well as mood,
`anxiety, and substance-use disorders.
`Early definitions, such as the Hyperkinetic Reaction
`of Childhood in DSM-II, placed the greatest emphasis on
`motoric hyperactivity and overt impulsivity as hallmarks
`of the disorder. The DSM-III represented a paradigm
`shift as it began to emphasize inattention as a signifi-
`cant component of the disorder. DSM-IV now defines
`three subtypes of ADHD: predominantly inattentive,
`predominantly hyperactive—impulsive, and a combined
`subtype. Criteria for each DSM-IV subtype require six
`or greater of nine symptoms in each respective category.
`There are four additional criteria that include age of on-
`set by 7 years, ADHD-specific adaptive impairments,
`pervasiveness, and separation from other existing con-
`ditions. The combined subtype is the most commonly
`represented subgroup accounting for from 50% to 75%
`of all ADHD individuals, followed by the inattentive sub-
`type (20-30%), and the hyperactive—impulsive subtype
`(less than 15%).
`Epidemiologic studies indicate that ADHD is a
`prevalent disorder affecting from 4% to 7% of chil-
`dren worldwide including the United States, New
`Zealand/Australia, Germany, and Brazil. Although previ-
`ously thought to remit largely in adolescence, a growing
`literature supports the persistence of the disorder and/or
`associated impairment into adulthood in a majority of
`cases.
`Prevalence estimates of childhood ADHD in the
`United States are estimated to be 5-8%. Estimates
`
`vary predictably depending on methodology. Defini-
`tions that require both symptom dimensions (hyperactiv-
`ity/impulsivity and inattention) are more restrictive than
`those that require only one of these dimensions. Thus,
`estimates based on pre-DSM III definitions or the ICD
`codes of hyperkinetic disorder produce lower estimates.
`In addition the surveys that estimate based on symptoms
`alone and do not include impairment yield higher esti-
`mates. As recently by Faraone et al. (2003), other factors
`that affect apparent prevalence estimates include perva-
`siveness criteria, informants (teacher, parent, child), use
`of rating scales versus clinical interviews as well as ascer-
`tainment issues. Community samples have higher rates
`than school samples.
`Gender and age of the sample also affect estimates
`prevalence. Girls more commonly have the inatten-
`tive type and also less commonly have accompanying
`ODD/CD, disruptive disorders, factors leading to lower
`rates of diagnosis. The original descriptions were derived
`from a child-focused perspective, and do not reflect what
`are thought to be more salient aspects of adult ADHD:
`the executive function disorders of poor organization,
`poor time management, and memory disturbance asso-
`ciated with academic and occupational failure. The lack
`of appropriate description of adult symptoms may reduce
`the true prevalence of ADHD in adulthood.
`
`B. ETIOLOGY
`Biological adversity—Several biologic factors have
`been proposed as contributors to ADHD, including food
`additives/diet, lead contamination, cigarette and alcohol
`exposure, maternal smoking during pregnancy, and low-
`birth weight. Although the Feingold diet for ADHD was
`popularized by the media and accepted by many parents,
`systematic studies showed that this diet was ineffective
`and that food additives do not cause this disorder. Sev-
`eral investigators have shown that lead contamination
`can cause symptoms ofADHD. However, lead does not
`account for the majority ofADHD cases, and many chil-
`dren with high-lead exposure do not develop ADHD.
`An emerging literature documents that maternal smok-
`ing and alcohol exposure during pregnancy, low-birth
`weight, and psychosocial adversity are additional inde-
`pendent risk factors for ADHD.
`Pregnancy and delivery complications (i.e., toxemia,
`eclampsia, poor maternal health, maternal age, fetal
`postmaturity, duration of labor, fetal distress, low-birth
`weight, antepartum hemorrhage) appear to have a pre-
`disposition for ADHD. Several studies documented that
`maternal smoking during pregnancy is an independent
`risk factor for ADHD.
`Psychosocial adversity—Findings of recent studies
`stress the importance of adverse family—environment
`variables as risk factors for ADHD. In particular, chronic
`
`Page 4
`
`

`

`ATTENTION-DEFICIT HYPERACTIVITY DISORDER
`
`/ 575
`
`family conflict, decreased family cohesion, and exposure
`to parental psychopathology (particularly maternal) are
`more common in ADHD families compared with con-
`trol families. It is important to note that, although many
`studies provide powerful evidence for the importance of
`psychosocial adversity in ADHD, such factors tend to
`emerge as universal predictors of children's adaptive func-
`tioning and emotional health, rather than specific predic-
`tors of ADHD. As such, they can be conceptualized as
`nonspecific triggers of an underlying predisposition or as
`modifiers of the course of illness.
`C. GENETICS
`Because ADHD is believed to be highly genetic, stud-
`ies of twins have been used to establish its heritabil-
`ity or the degree to which this disorder is influenced
`by genetic factors. Based on numerous studies of twins,
`which varied considerably in methodology and defini-
`tions of ADHD, the mean heritability for ADHD was
`shown to be 77%. Seven candidate genes show statisti-
`cally significant evidence of association with ADHD on
`the basis of the pooled odds ratio (1.18-1.46) across stud-
`ies: DRD4, DRD5, DAT, DBH, 5-HTT, HTR1B, and
`SNAP-25.
`
`Clinical Findings
`A. SIGNS & SYMPTOMS
`The diagnosis of ADHD is made by careful clinical his-
`tory. A child with ADHD is characterized by a consider-
`able degree of inattentiveness, distractibility, impulsivity,
`and often hyperactivity that is inappropriate for the devel-
`opmental stage of the child. Other common symptoms
`include low-frustration tolerance, shifting activities fre-
`quently, difficulty organizing, and daydreaming. These
`symptoms are usually pervasive; however, they may not
`all occur in all settings. Adults must have childhood-
`onset, persistent, and current symptoms of ADHD to
`be diagnosed with the disorder. Adults with ADHD
`often present with marked inattention, distractibility,
`organization difficulties and poor efficiency, which cul-
`minate in life histories of academic and occupational
`failure.
`B. RATING SCALES
`Rating scales are extremely helpful in documenting the
`individual profile of ADHD symptoms as well as assess-
`ing the response to treatments. It is important to empha-
`size that they should not be used for diagnosis without
`careful clinical confirmation and elicitation of the other
`criteria necessary for diagnosis. Although neuropsycho-
`logical testing is not relied upon to diagnose ADHD
`it may serve to identify particular weaknesses within
`ADHD or specific learning disabilities co-occurring with
`ADHD.
`
`Rating scales are available for all age groups and can be
`useful in assessing and monitoring home, academic and
`occupational performance. Increasingly, there has been a
`congruence of opinion in this area with a number of the
`most widely used scales consisting of Likert ratings of the
`existing DSM-IV criteria. There are two types of scales
`in wide use, the so-called "narrow" scales that are specific
`for ADHD and "broad" scales that measure additional
`dimensions including comorbidity. The broad scales are
`useful for separating straightforward and complex cases,
`and the narrow scales are most useful for honing in on
`exclusively ADHD dimensions both diagnosis and to
`monitor specific responses to treatment. In looking to
`the future, there are proposals to expand the set of diag-
`nostic symptoms to include executive functions (such as
`time management and multitasking) especially in older
`individuals.
`
`C. PSYCHOLOGICAL TESTING
`Psychological testing is not necessary for the routine diag-
`nosis ofADHD and does not readily distinguish children
`with and without ADHD. Nonetheless, psychometric
`testing can be valuable in narrowing the differential
`diagnosis and identifying comorbid learning difficul-
`ties. Many children with ADHD have difficulties with
`abstract reasoning, mental flexibility, planning, and
`working memory, a collection of skills broadly catego-
`rized as executive functioning skills. They can also present
`with verbal and nonverbal performance skills and/or
`visual—spatial processing deficits. In such circumstances,
`neuropsychological assessments can be valuable and may
`help to clarify the diagnosis. Children with learning, lan-
`guage, visual—motor, or auditory processing problems
`usually perform poorly only in their particular problem
`area, whereas children with ADHD may perform poorly
`in several areas of evaluation.
`
`Laboratory Findings
`Nonroutine laboratory studies are not indicated un-
`less the history or physical examination is suggestive
`of seizures, neurodcvelopmental regression, or localiz-
`ing neurologic signs, or if an acute or chronic medical
`disorder is suspected.
`
`NEUROIMAGING
`The neurobiology of ADHD is not completely under-
`stood, although imbalances in dopaminergic and nora-
`drenergic systems have been implicated in the core symp-
`toms that characterize this disorder. Many brain regions
`are candidates for impaired functioning in ADHD. Pre-
`frontal hypotheses in ADHD have primarily involved
`the dorsolateral prefrontal cortex, associated with orga-
`nizational, planning, working memory, and attentional
`
`Page 5
`
`

`

`576
`
`/ CHAPTER 35
`
`dysfunctions and Orbital lesions associated with social
`disinhibition and impulse control disorders.
`Structural imaging studies, using computerized to-
`mography or magnetic resonance imaging found evi-
`dence of structural brain abnormalities among ADHD
`patients, with the most common findings being smaller
`volumes in frontal cortex, cerebellum, and subcortical
`structures. Castellanos and colleagues found smaller to-
`tal cerebral brain volumes from childhood through ado-
`lescence. This work suggested that genetic or early envi-
`ronmental influences on brain development in ADHD
`are fixed, nonprogressive, and unrelated to stimulant
`treatment. Numerous fMRI studies have reported Dor-
`sal Anterior Cingulate Cortex (dACC) hypofunction in
`ADHD on tasks of inhibitory control
`Brain imaging studies fit well with the concept that
`dysfunction in fronto-subcortical pathways occurs in
`ADHD. Three subcortical structures implicated by the
`imaging studies (i.e., caudate, putamen, and globus pal-
`lidus) are part of the neural circuitry underlying mo-
`tor control, executive functions, inhibition of behavior,
`and the modulation of reward pathways. These frontal—
`striatal—pallidal—thalamic circuits provide feedback to the
`cortex for the regulation of behavior.
`The fronto-subcortical systems pathways associated
`with ADHD are rich in catecholamines, which are in-
`volved in the mechanism of action of stimulant med-
`ications used to treat this disorder. A plausible model
`for the effects of medications in ADHD suggests that,
`through dopaminergic and/or noradrenergic pathways,
`these agents increase the inhibitory influences of frontal
`cortical activity on subcortical structures.
`Imaging studies also implicate the cerebellum and cor-
`pus callosum in the pathophysiology of ADHD. The
`cerebellum contributes significantly to cognitive func-
`tioning, presumably through cerebellar—cortical path-
`ways involving the pons and thalamus. The corpus cal-
`losum connects homotypic regions of the two cerebral
`hemispheres. Size variations in the callosum and volume
`differences in number of cortical neurons may degrade
`communication between the hemispheres, which may ac-
`count for some of the cognitive and behavioral symptoms
`of ADHD.
`
`Course of Illness
`Samples ascertained before the publication of DSM-III
`relied on earlier definitions that highlighted hyperactiv-
`ity as a hallmark of ADHD. Since it is hyperactivity that
`wanes earliest, it may be that older samples were en-
`riched with subjects more likely to remit from ADHD
`than individuals identified today. There is evidence for
`this hypothesis in the data. In a recent analysis, the per-
`sistence rate was lowest in studies ascertained accord-
`ing to DSM-II ADD and highest in those studies ascer-
`tained according to DSM-III-R ADHD. The available
`
`data also suggests a continuation of childhood behavior
`problems and emerging antisocial behavior among many
`in this group of children. For example, researchers have
`noted the rate of conduct disorders among children with
`ADHD to range between 25% and 50% at follow-up
`during adolescence. Reports also suggest that a majority
`of children with ADHD continue to exhibit deficits in
`attention and/or activity level in adulthood, with only
`about 30% of children evidencing a remission of symp-
`toms by adolescence and early adulthood. Recent work
`also suggests that ADHD youth disproportionately be-
`come involved with cigarettes, alcohol, and then drugs.
`Individuals with ADHD, independent of comorbidity,
`tend to maintain their addiction longer compared to their
`non-ADHD peers.
`
`Differential Diagnosis
`(Including Comorbid Conditions)
`A. OPPOSITIONAL DEFIANT DISORDER AND
`CONDUCT DISORDER
`There are important nosologic distinctions between at-
`tention and hyperactivity per se and that of associated
`symptoms common to the disruptive behavioral disor-
`der category. Oppositional defiant disorder (ODD) is
`characterized by a pattern of negativistic, hostile and de-
`fiant behavior. ADHD and ODD/CD have been found
`to co-occur in 30-50% of cases in both epidemiologic
`and clinical samples. In contrast, conduct disorder (CD)
`is a more severe, and less common, disorder of habitual
`rule breaking defined by a pattern of aggression, destruc-
`tion, lying, stealing, or truancy. While CD is a strong
`predictor of substance abuse, ODD without CD is not.
`
`B. MOOD DISORDERS
`Unipolar depression in a child may be apparent from a sad
`or irritable mood, a persistent loss of interest, or pleasure
`in the child's favorite activities. Other signs and symp-
`toms include physiologic disturbances such as in changes
`in appetite and weight, abnormal sleep patterns, psy-
`chomotor abnormalities, fatigue, and diminished ability
`to think, as well as feelings of worthlessness or guilt and
`suicidal preoccupation.
`Classical mania in adults is characterized by euphoria,
`elation, grandiosity, and increased energy. However, in
`many adults and most children, mania is more commonly
`manifested by extreme irritability or explosive mood with
`associated poor psychosocial functioning that is often
`devastating to the patient and family. In milder condi-
`tions, additional symptoms include unmodulated high
`energy such as a decreased sleep, over talkativeness, rac-
`ing thoughts, or increased goal-directed activity (social,
`work, school, sexual) or an associated manifestation of
`markedly poor judgment such as thrill-seeking or reck-
`less activities.
`
`Page 6
`
`

`

`ATTENTION-DEFICIT HYPERACTIVITY DISORDER
`
`/ 577
`
`In epidemiologic studies and several controlled,
`prospective studies, higher rates of depression were found
`in ADHD. A baseline diagnosis of major depression
`predicted lower psychosocial functioning, a higher rate
`of hospitalization as well as impairments in interper-
`sonal and family functioning. Similarly, higher rates
`of mania were detected in follow-up studies. ADHD
`children with comorbid mania at either baseline or
`follow-up assessment had other correlates expected in
`mania including additional psychopathology, psychiatric
`hospitalization, severely impaired psychosocial func-
`tioning as well as a greater family history of mood
`disorders.
`
`C. CHILDHOOD ANXIETY DISORDERS
`Childhood anxiety disorders are often not suspected in
`an overactive child, just as ADHD is often not assessed
`in inhibited children. When present, both contribute to
`social, behavioral, and academic dysfunction. In addition
`anxiety may be associated with intense intrapsychic suf-
`fering. Thus, having both AD HD and anxiety disorders
`may substantially worsen the outcome of children with
`both disorders. In the MGH follow-up study, ADHD
`children with comorbid anxiety disorder had increased
`psychiatric treatment, more impaired psychosocial func-
`tioning as well as a greater fin-I-lily history of anxiety
`disorders.
`
`D. COGNITIVE PERFORMANCE AND LEARNING
`DISABILITIES
`Children with ADHD perform more poorly than con-
`trols on standard measures of intelligence and achieve-
`ment. In addition, children with ADHD perform more
`poorly in school than do controls, as evidenced by
`more grade repetitions, poorer grades in academic sub-
`jects, more placements in special classes, and more
`tutoring. The reported degree of overlap varies by
`definition, the more restrictive definition has a rate of
`20-25%.
`
`E. ADHD PLUS Tics
`Children with ADHD have higher rates of Tic disorders
`that may contribute additional dysfunction due to dis-
`tractions and social impairments directly attributable to
`the movements or vocalizations themselves. A number of
`studies have noted that anti-ADHD treatment is highly
`effective for ADHD behaviors, aggression, and social skill
`deficits in children with TS or chronic tics.
`
`F. SUBSTANCE-USE DISORDERS
`Combined data from retrospective accounts ofadults and
`prospective observations of youth indicates that juveniles
`with ADHD are at increased risk for cigarette smoking
`•
`and substance abuse during adolescence.
`
`Treatment
`The ADHD adolescent and young adult is at risk for
`school failure, emotional difficulties, poor peer rela-
`tionships, and trouble with the law. Factors identifi-
`able in younger youth that predict the persistence of
`ADHD into adulthood include familiality with ADHD
`and psychiatric comorbidity—particularly aggression or
`delinquency problems. Although the literature provides
`compelling evidence that the diagnosis of ADHD in
`childhood predicts persistent ADHD and poor outcome
`in adolescence, these findings also suggest that such a
`comprised outcome is not shared by all ADHD chil-
`dren. The discussion thus far has not addressed a related
`clinical question: Can the functioning of ADHD chil-
`dren normalize in the context of persistent ADHD? We
`analyzed data from a 4-year longitudinal study of referred
`children and adolescents with ADHD, to assess normal-
`ization of functioning and its predictors among boys with
`persistent ADHD.
`Using indices of emotional, educational, and social
`adjustment, we found that 20% of children with persis-
`tent ADHD functioned poorly at follow-up in all three
`domains, 20% did well in all three domains, and 60% had
`intermediate outcomes. These findings suggested that the
`syndromatic persistence ofADHD is not associated with
`a uniform functional outcome but leads instead to a wide
`range of emotional, educational, and social adjustment
`outcomes that can be partially predicted by exposure to
`maternal psychopathology, larger family size, psychiatric
`comorbidity, and impulsive symptoms.
`
`A. PSYCHOPHARMACOLOGIC INTERVENTIONS
`Medications remain a mainstay of treatment for chil-
`dren, adolescents, and adults with ADHD. In fact, recent
`multisite studies support that medication management
`of ADHD is the most important variable in outcome
`in context to multimodal treatment. For example, in
`a large prospective and randomized long-term trial of
`ADHD youth, those receiving stimulants alone were
`observed to have similar improvement in core ADHD
`symptoms at 14 months follow-up compared to those
`randomized to receive stimulants plus psychotherapy. Of
`interest, both medicated groups had a better overall out-
`come than those receiving extensive psychotherapy with-
`out stimulants. The stimulants, specific norepinephrine
`reuptake inhibitors (SNRIs), certain antidepressants, and
`certain antihypertensives comprise the available agents
`for ADHD. Stimulants, SNRIs, and antidepressants
`have been demonstrated to have similar pharmacologi-
`cal responsivity across the lifespan including school-aged
`children, adolescents, and adult groups with ADHD.
`
`B. STIMULANTS
`The stimulants are the most commonly prescribed
`agents for pediatric and adult groups with ADHD.
`
`Page 7
`
`

`

`578
`
`/ CHAPTER 35
`
`The most commonly used compounds in this class in-
`clude methylphenidate (Ritalin, Concerta, Metadate, Fo-
`calin, and others) and amphetamine (Dexedrine, Adder-
`all). Stimulants are sympathomimetic drugs, which in-
`crease intrasynaptic catecholamines (mainly dopamine)
`by inhibiting the presynaptic reuptake mechanism
`and releasing presynaptic catecholamines. Whereas
`methylphenidate specifically blocks the dopamine trans-
`porter protein, amphetamines also release dopamine
`stores and cytoplasmic dopamine directly into the synap-
`tic cleft. Recent data suggests that acute tolerance to stim-
`ulants may develop rapidly necessitating an ascending-
`or pulsing-pharmacokinetic profiles for ADHD efficacy.
`Methylphenidate and d-amphetamine are both short-
`acting compounds, with an onset of action within 30-
`60 minutes and a peak clinical effect usually seen be-
`tween 1 and 2 hours after administration lasting 2-5
`hours. The amphetamine compounds (Adderall) and
`sustained release preparations of methylphenidate and
`dextroamphetamine are intermediate-acting compounds
`with an onset ofaction within 60 minutes and duration of
`6-8 hours.
`Given the need to additionally treat ADHD outside
`of academic settings (i.e., social, homework) and to re-
`duce the need for in school dosing and likelihood for
`diversion, there has been great interest in extended re-
`lease preparations of the stimulants. Extended release
`preparations greatly reduce untoward peak adverse ef-
`fects of stimulants such as headaches and moodiness,
`as well as essentially eliminating afternoon wear off and
`rebound.
`A new generation of highly sophisticated, well-
`developed, safe and effective long-acting preparations
`of stimulant drugs has reached the market and rev-
`olutionized the treatment of ADHD. These com-
`pounds employ novel delivery systems to overcome
`acute tolerance termed "tachyphylaxis." There are sev-
`eral long-acting methylphenidate formulations and a
`long-acting methylphenidate formulation. While Con-
`certa is a 12-hour formulation, Metadate-CD and
`Ritalin LA are 8-hour methylphenidate formulations. In
`addition Adderall XR is a 12-hour amphetamine for-
`mulations. Methylphenidate as a secondary amine gives
`rise to four optical isomers: d-threo, 1-threo, d-erythro,
`and 1-erythro. Recently the active stereoisomer, d-threo-
`methylphenidate compound has been available in an
`immediate release and long-acting form as Focalin and
`Focalin XR.
`Stimulants appear to work in all age groups of in-
`dividuals with ADHD. Studies in preschoolers report
`improvement in ADHD symptoms, structured tasks as
`well as mother—child interactions; however, there may
`be a higher side effect burden compared to other age
`groups. Similarly, in adolescents response has been re-
`ported as moderate to robust, with no abuse or tolerance
`
`noted. In addition, stimulant treatment has been found
`to be effective in adults with ADHD.
`Predictable short-term adverse effects include reduced
`appetite, insomnia, edginess, and GI upset. In adults,
`elevated vital signs may emerge necessitating baseline
`and on-drug monitoring. There are a number of con-
`troversial issues related to chronic stimulant use. Al-
`though stimulants may produce anorexia and weight
`loss, their effect on ultimate height remains less certain.
`While initial reports suggested that there was a persis-
`tent stimulant-associated decrease in growth in height in
`children, other reports have failed to substantiate this
`finding, and still others question the possibility that
`growth deficits may represent maturational delays re-
`lated to ADHD itself rather than to stimulant treat-
`ment. Stimulants may precipitate or exacerbate tic symp-
`toms in ADHD children. Recent work suggests that the
`majority of ADHD youth with tics can tolerate stimu-
`lant medications; however, up to one third of children
`with tics may have worsening of their tics with stim-
`ulant exposure. Current consensus suggests that stimu-
`lants can be used in youth with comorbid ADHD plus
`tics with careful monitoring for stimulant-induced tic
`exacerbation.
`Despite case reports of stimulant misuse, there is
`a paucity of scientific data supporting that stimulant-
`treated ADHD individuals abuse their medication; how-
`ever, data suggests that diversion of stimulants to non-
`ADHD youth continues to be a concern. Families should
`closely monitor stimulant medication and college stu-
`dents receiving stimulants should be advised to carefully
`store their medication. Despite the findings on efficacy
`of the stimulants,