Manual of Psychiatric Therapeutics: Practical Psychopharmacology and Psychiatry (Little, Browns Paperback Book Series)

Editors: Shader, Richard I.

Title: Manual of Psychiatric Therapeutics, 3rd Edition

Copyright 2003 Lippincott Williams & Wilkins

> Table of Contents > 22 - Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder in Youth and Adults

22

Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder in Youth and Adults

Jessica R. Oesterheld

Richard I. Shader

Paul H. Wender

Attention deficit hyperactivity disorder (ADHD) is the current designation for a group of disorders previously known as minimal brain dysfunction, hyperkinesis, the hyperactive child syndrome, minimal brain damage, and minimal cerebral injury, as well as others. The recognition of ADHD has its roots in pediatric practice, and attribution is usually given to the British pediatrician, George Still, who was made an honorary member of the American Academy of Pediatrics. In 1975, Paul Wender recognized the connection between the dopamine agonist properties of the then available psychostimulants and their efficacy in ADHD. ADHD is among the most common disturbances of behavior seen in the pediatric age group, and it is likely to persist into adulthood. The core symptoms of inattention, hyperactivity, and impulsivity can lead to significant disturbances in family and peer relationships, as well as in school or work.

Treatment of ADHD with psychostimulants was first described in 1937. During subsequent years, countless placebo-controlled trials have established their short-term efficacy. Since 1990, psychostimulant usage has increased fourfold to fivefold in the United States. Critics have written that ADHD is overly diagnosed and have claimed that these symptoms in children are a function of ineffective parents or teachers. Others have asserted that prescribing psychostimulants is unnecessary, addictive, and dangerous. In response, the Drug Enforcement Administration and the National Institutes of Health have undertaken an evaluation of the current scientific data on ADHD. The American Medical Association and the McMaster University Evidence-Based Practice Center in Canada have conducted extensive literature reviews. All sources have affirmed that the diagnosis of ADHD can be made accurately and that treatment with psychostimulants is effective in the short run. Data from the National Institute of Mental Health Multimodal Treatment of Children with ADHD trial have corroborated these findings. Some studies have shown that, although some geographic areas in this country have excess diagnoses of ADHD, it continues to go unrecognized in others.

Recognition of this syndrome in adults and children is important because effective therapy is available and comparatively inexpensive, and the benefit-to-risk ratio is extremely favorable. The American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics have developed practice guidelines. The reader is referred to their publications for further information (see Additional Reading).

I. Attention Deficit Hyperactivity Disorder in Youth

A. General Commentary and Principal Clinical Features

Criteria for the diagnosis of ADHD have evolved over the years. The Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), recognizes the following three subtypes of ADHD: predominantly inattentive, predominantly hyperactive-impulsive, and combined types (Table 22.1).

The DSM-IV requires that the symptoms of ADHD be present before 7 years of age, but this requirement is viewed as arbitrary by numerous clinicians. When the onset is quite early (usually with symptoms of aggression or extreme hyperactivity), the conservative approach is to institute behavioral interventions and to defer the diagnosis of ADHD until the persistence of symptoms is established. Often, waiting until the child has entered school may be reasonable. This avoids making an incorrect diagnosis in a child who may be age-appropriately hyperactive or in one who is undergoing a transient form of disturbance in concentration and activity (e.g., as a direct reaction to parental strife or divorce). If symptoms are severe and unremitting, a full

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Referrals for the evaluation and treatment of ADHD are usually made when schoolwork or home tasks require a greater degree of self-initiated or self-motivated behaviors or more continuous involvement than the child can sustain at school entry; in elementary, junior high, or high school; in college; or even professional school. The following sections highlight certain important clinical and behavioral aspects of ADHD.

• Problems with attention. These include (a) difficulty sustaining attention as shown by an inability to complete tasks once initiated or by a disorganized approach to carrying out tasks; (b) impairment in maintaining focused or selective attention (i.e., a short attention span); (c) frequent forgetting of demands or requests; (d) high levels of distractibility, impaired alertness, or excessive arousal (these children appear fidgety, restless, and often flit from one activity to another); or (e) worsening of

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  attentional processes in unstructured situations or when the tasks at hand require independent functioning and performance. Teachers and parents alike report that the child has difficulty with stick-to-it-iveness both in play patterns and in schoolwork. Some children are even unable to sit through a favorite half-hour television program.

  Children with predominantly inattentive form of ADHD may represent the most common subtype of ADHD in community samples. Although boys with inattentive ADHD still predominate, the incidence of girls in this subgroup may be higher than it is in other subtypes. These children may be less aggressive and less oppositional than children with the combined form, and they usually present as lethargic and socially passive ( couch potatoes ). Consequently, they may be less disliked by their peers than are children with the combined forms of ADHD. These youth may have a later onset of symptoms and a later age of referral than their counterparts with the combined form of ADHD. Whether they have higher rates of learning or anxiety disorders is not clear. Barkley (1990) asserted that the inattention in these children is related to focused or selective attentional processing deficits that are qualitatively different from the deficits in persistence and distractibility in youth with the combined type.

• Impulsivity. Impulsive behavior may be manifested as (a) sloppy school work despite a reasonable effort to perform adequately; (b) frequent speaking out of turn in class or making noises; (c) frequent interruption of, or intrusion into, other children's activities or conversations; (d) difficulty waiting for one's turn in games or in group situations; or (e) frequent fighting with other children, indicating low frustration tolerance rather than calculated intention trouble seems to bump into them. Patterns of impulsive behaviors may change as a function of age. In toddler and preschool years, the condition may manifest as a tendency to aggression; once the child is in elementary school, it may be rushing off to pursue his or her own interests, irrespective of those of the teacher. The child usually has marked difficulty tolerating delays. In preteen and adolescent years, impulsivity may be manifested as talking excessively in class or becoming the class clown.

• Hyperactivity. Hyperactivity per se is neither pathognomonic of ADHD nor is it necessarily present in ADHD. Some children with ADHD are actually hypoactive (see the inattentive form of ADHD above). When hyperactivity is present during preschool and early school years, the child may incessantly, haphazardly, or impulsively run, climb, or crawl. During middle childhood or adolescence, a marked inability to sit still, up and down activity, and fidgeting are characteristic. Hyperactivity often diminishes with age, and it may actually disappear in most children, although an inner sense of restlessness and other signs of ADHD may persist. These activities differ from age norms in both quality and quantity.

• Additional features. Many clinicians believe the following signs and symptoms are seen with increased frequency in children with ADHD.

  • Coordination deficits. About half of ADHD children show some form of incoordination. These may be in the area of fine motor coordination, with children showing difficulty in learning to tie their shoelaces, cutting with scissors, and coloring and later with handwriting. These difficulties may also be in the area of balance; the child may have difficulty learning to roller skate or to ride a two-wheeled bicycle. Finally, difficulties may be present in the area of hand eye coordination; the child may be inept in sports, particularly those requiring throwing, catching, or hitting balls.

  • Emotional behavior. Many ADHD children show age-inappropriate characteristics of younger children, including affective lability (moodiness), a short temper (or short fuse ), and a low frustration tolerance. Their parents often describe them as being too emotional or as having mood swings.

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  • Interpersonal behavior. Children with ADHD typically show abnormalities in interpersonal behavior with their peers or with adults. The child with ADHD may appear outgoing and extroverted. Friendships may be pursued, but they are easily lost due to immaturity, bossiness, or domineering behavior. Because of unpopularity or a need to dominate, the child with ADHD may choose to associate with younger children or peers who are more compliant.

    In relationships with adults, youth with ADHD are frequently refractory to the usual social reinforcers; they seem as if they are insensitive to the consequences of their behavior. Parents and teachers report that discipline or punishment appears to be ineffective in curbing undesirable behaviors. Similarly, positive reinforcers (e.g., praise, extra attention) may not be effective in strengthening desired responses; the child may need more than the typical amount of reinforcement or may perform less well with intermittent levels of reinforcement. A lack of responsiveness to discipline together with impulsivity, which is sometimes interpreted by parents and teachers as willful, is often the basis for referral for psychiatric or pediatric intervention. ADHD should always be considered in the child who is globally described as having behavior problems.

  • Learning problems. An appreciable proportion of ADHD children shows impaired learning in school despite normal intelligence quotients. In fact, academic underachievement with variability of output in school is almost a hallmark of the syndrome. Poor achievement may be a product of decreased attentiveness or stick-to-it-iveness, low frustration tolerance, or specific learning disorders that are frequently seen in association with ADHD. Because routine psychologic examination often does not include the evaluation of educational performance, such an evaluation should always be made in an underachieving child with ADHD.

B. Co-occurring Disorders

Between one-half and two-thirds of youth with ADHD have comorbid conditions, and therefore clinicians must seek out the presence of co-occurring disorders. Common among these are oppositional defiant disorder, conduct disorder, anxiety disorders, and depressive disorders.

Clinical presentation, prognosis, and treatment are affected by comorbidity. For example, both boys and girls with conduct disorder or oppositional defiant disorder and ADHD have a poorer prognosis and a significantly higher risk for psychopathology, drug or alcohol abuse, and school failure. Both groups should be treated with behavioral interventions in addition to medication to optimize the outcome. Children with comorbid anxiety disorder and ADHD may respond equally well to behavioral treatments or psychostimulants. A comprehensive treatment plan that includes comorbidities is essential for effective care.

Discrimination must be made between symptoms of demoralization secondary to academic or social failure and clinical depression. School evaluation and remediation of ADHD symptoms should precede pharmacotherapy for co-occurring depression or anxiety. The finding by Biederman et al. that 11% to 21% of children with ADHD have bipolar affective disorder is not universally accepted. They described children who were angry, active, and difficult to manage, and they did not require the presence of mania with grandiosity or euphoria, depression with vegetative changes, or periods of euthymia. Some clinicians believe that their finding is a consequence of overlapping symptoms in the criteria for ADHD and bipolar disorder rather than representing true comorbidity.

C. Prevalence and Prognosis

ADHD is more common in boys than in girls. Depending on the population studied (e.g., community, school, or clinical samples) and the diagnostic criteria and methods used, the male-to-female ratio varies from 3 to 1 to 9 to 1. These same issues apply to estimates of the overall prevalence

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Follow-up and retrospective studies suggest that motor hyperactivity frequently decreases before adolescence, although other problems may persist. As was noted above, ADHD occurring with a concomitant conduct disorder may be the forerunner of a number of important adult problems, especially adult antisocial personality disorder. From epidemiologic studies, ADHD without comorbidity appears to predispose individuals to early cigarette usage, substance abuse, and alcoholism; the presence of these additional behaviors may obscure the diagnosis of ADHD and may cause it to be undetected in adulthood. Untreated, ADHD is a frequent cause of school dropout, motor vehicle accidents and injuries, and trouble with the law.

D. Gender Differences

Girls with ADHD may be less impulsive than are boys with ADHD, although they may be more impaired socially. Female teens with ADHD have more distress, anxiety, and depression than do their male counterparts.

E. Etiology

Historically, ADHD was usually thought to be secondary to intrauterine or postnatal brain damage; many early cases were recognized in children with postencephalitic behavioral dysfunction after the World War I influenza pandemic. Because the influenza virus affects dopaminergic neurons in adults and after von Economo had observed that brain lesions in children involved dopaminergic neurons, Wender (1971), linking the effectiveness of amphetamines to these findings, proposed the dopamine hypothesis for ADHD. Current evidence indicates that most cases of ADHD are genetically determined. A higher concordance for the disorder is seen among monozygotic twins than among dizygotic twins. A disproportionate number of parents of ADHD children show problems such as alcoholism, antisocial personality disorder, and mood disorders. Twenty percent to 30% of parents of both boys and girls with ADHD had or have ADHD themselves. Evidence that ADHD and major depression share a genetic vulnerability and that ADHD with conduct disorder may be a genetic subtype is beginning to accumulate. By contrast, parents who adopt children with ADHD do not have a higher incidence of these disorders. Whether ADHD is a discrete heritable disorder or is at the high end of a continuum of heritable behavioral traits is moot. Candidate genes within the dopamine system have been investigated. For example, two copies of the 10-repeat allele of the dopamine transporter gene DAT1 on chromosome 5 and the 120-base pair repeat in the 5 untranslated region of the dopamine receptor D4 gene on chromosome 11 appear to be associated with a poor response to methylphenidate. The seven-repeat allele of the dopamine receptor D4 gene on chromosome 11 appears to be linked to a positive response to methylphenidate (within the monoamine oxidase system, the DXS7 locus). Positive associations of these genes and ADHD have been both replicated and refuted in studies, and therefore their association with ADHD awaits clarification. Transgenic mice without DAT1 are calmed by methylphenidate, whereas wild-type mice are activated by this agent.

Food allergies and increased sugar intake have been asserted to cause ADHD; appropriate controlled trials have not supported these claims. Fetal alcohol syndrome, fragile X syndrome, Asperger syndrome, very low birth weight, and lead poisoning are associated with a higher prevalence of ADHD. Socioeconomic factors influence both tolerance for the symptoms of ADHD and the likelihood of their detection, but neither poverty nor poor parenting can cause ADHD.

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F. Diagnosis

• History and current level of functioning. The diagnosis of ADHD is best made based on a detailed psychologic and behavioral history together with a careful description of the child's current level of functioning and an age-appropriate mental status examination. Adequate history-taking requires not only a survey of the kinds of target symptoms already reviewed here and which are presented in DSM-IV but also a thorough developmental history. The creation of a timetable or sequence of the appearance of symptoms in relation to family interactions and behaviors at home, school functioning, and peer interactions may also be useful. Open-ended interviews in this situation can often elicit a history of signs and symptoms of ADHD. If these are uninformative, a structured inquiry covering development and the common areas of psychologic malfunctioning should be completed. Informants should include all those who have observed the child, including parents; parent surrogates; and, after permission is obtained from guardians, teachers. Careful inquiry about family history should also be made, including the presence of alcoholism or drug abuse, tic disorders, or ADHD. ADHD is a syndrome; not all signs and symptoms need to occur in a single patient. Avoiding the use of one's own observation of the child as the sole determinant of an ADHD diagnosis is crucial because, with one to one adult attention, children with ADHD can sometimes function quite well. Use of the standardized instruments described below after discussions with the child's parents and teachers is essential. In addition, careful inquiry must be made about drugs of abuse, over-the-counter products, herbal preparations, and prescribed drugs because symptoms similar to ADHD can be seen with antipsychotics, bronchodilators, chronic marijuana usage, and others.

• Standardized inventories for which normative data are available may be useful for assessing the response to treatment. Among the most frequently used are the Connors Global Index for Parent and Teachers; the Swanson, Nolan, and Pelham questionnaire; the Attention Deficit Disorders Evaluation scales; the Child Behavior Checklist; and the Behavioral Assessment System for Children. Impairment should be evident in two domains, but a lack of concordance is sometimes seen between raters. Obtaining additional information from teachers about a child's school functioning or a classroom observation sometimes clarifies discrepancies. Computerized performance testing does not reliably discriminate children with ADHD from control subjects, but it may be used adjunctively when reliable information from two or more settings is not available. A careful mental status examination of the child, including his or her perceptions of his or her problems and strengths and his or her attitudes about medicine, should be obtained.

• School information and psychologic testing. No psychologic tests are diagnostic. When possible, the school nurse or physician should also be contacted and interviewed. As was noted, many children with ADHD have academic underachievement as a direct result of the behavioral abnormalities or as a consequence of coexistent learning disorders. The underachieving child with suspected ADHD must receive cognitive testing (e.g., Wechsler Intelligence Scale for Children, third edition [WISC-III]) and standardized achievement testing to assess the presence of learning disorders and to obtain a profile of intellectual abilities and vulnerabilities.

• Neurologic examination. Schools frequently request a neurologic examination to determine if the child is neurologically impaired and therefore if he or she is eligible for special placement. The electroencephalogram has no diagnostic utility, and it does not need to be obtained unless a history of seizure disorder is entertained separately. As for any child or adolescent with a psychiatric disorder, every child suspected of having ADHD should have a concurrent pediatric or medical examination.

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• Assessing environmental components. Separating the relative contributions of a presumptive biologic abnormality from a familial or social problem in the etiology of a child's difficulties may be challenging. Because children with ADHD often have parents with ADHD, problems in the home do not rule out ADHD. Familial strife may reflect biologic abnormalities in the parents and may actually strengthen the diagnosis rather than indicate that psychologic forces are producing the ADHD syndrome in the child. Obviously, parental pathology may aggravate the problems of a child with ADHD, even though this does not cause the disorder. Diagnosing the child may be impossible until family pathology is reduced or eliminated. Establishing whether the family is able to monitor medication usage is also crucial because psychostimulants can be misused or abused by the patient or family members.

  Based on history and psychologic test performance measures, the physician may suspect the syndrome. Even with a comprehensive diagnostic workup, uncertainty may remain. In such instances, the physician should discuss this uncertainty with the parent(s) (or guardian[s]) and the child and should schedule a reevaluation for a later date.

G. Management and Treatment

• Education of the family and child. An essential component of the management and treatment of ADHD is explaining the problem to the child's parents and, with proper modifications appropriate to his or her developmental level, to the child. Many parents of youth with ADHD are confused, guilty, and angry, believing that their child's problems reflect their inadequacies as parents. Blame of the other parent and guilt can often be produced or aggravated by contact with a therapist or teacher or family member who attributes the child's psychopathology to parental pathology. Most often, parents do not know how to handle the child, they frequently disagree, and they are highly liable to blame each other. Parents should be helped to distinguish the child's symptoms that may or may not respond to medication from those that are generated or aggravated by their management of the child. Parents should be given a good understanding of which problems will not be ameliorated by improved psychologic management, such as attention deficits, and of those that may be benefitted, such as noncompliance or disobedience. The advantages of parent education in ADHD are demystification, adjustment of expectations, and acquisition of more effective management techniques. As part of the education of the family, aspects of childrearing should be introduced and discussed, including both general techniques, as well as more specific approaches, such as contingency and behavioral management techniques. Some parents will not allow physicians to prescribe psychostimulants or other medications to their children with ADHD. When parents eschew medication, they should be urged to leave the option open if behavioral treatments are insufficient. Organizations such as Children and Adults with Attention Deficit Disorder (CHADD; http://www.chadd.org/) and the National Attention Deficit Disorder Association (http://www.add.org/) can provide helpful information. CHADD support groups can be found in many areas of the country; they provide perspective and support to parents caring for children with ADHD and to adults who struggle with ADHD.

• School placement. When educational problems exist, proper educational placement is essential. As has been noted, many children with ADHD perform badly in school because of their inattentiveness and lack of stick-to-itiveness, which are characteristics of the syndrome, whether or not they also have associated learning disorders. Medications may improve important symptoms of ADHD, but they do not improve specific learning disorders. No technique of parental management or pharmacotherapy can succeed unless the child is given an academic placement consistent with his or her needs. This may require special

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  classes when learning disabilities are present or catch-up classes if the child is of adequate intelligence and has no learning disabilities but has fallen behind in school. Seating the child where the teacher makes the most eye contact allows better supervision and attentional cueing. Working closely with school personnel is essential to optimize the educational environment (e.g., the use of paraprofessionals, resource room, behavioral management strategies that stress positive rewards for appropriate classroom behavior, decreasing distractions). Unfortunately, many desirable educational placements are harder to obtain as economic and political factors shift resources away from the educational system. Clinicians should encourage parents and guardians to be active and effective advocates for the best educational placements for their children.

• Medications. Some important principles govern the use of medication with children in general and in children with ADHD in particular. Boys and girls respond equally well to psychostimulants. Most youth are not able to describe or they do not experience a subjective difference when taking medication. A frank discussion of this fact with the youth should precede treatment.

  The clinician should titrate the medication against specific behaviors, so appropriate monitoring requires reports from parents and teachers. Standardized rating instruments are useful because they can be used to quantify the type and degree of behavioral improvement, and review of these forms or discussion with the teacher before medication adjustment is invaluable. Psychostimulants help approximately 70% to 80% of ADHD children; however, their beneficial effects, although they are at times dramatic, are symptomatic only. Medication may have to be continued for years to control the child's and, later, the adolescent's and adult's signs, symptoms, and behaviors. The fact that medications are not curative, however, should not be interpreted as denigrating their value to the individual with ADHD. By suppressing the symptoms of ADHD, children will be more likely to grow both intellectually and socially.

  As children approach middle school age, they may resist using medication, particularly if they are oppositional at school. This can happen in those who have responded extremely well and even in the child who acknowledges benefits from taking medication. Because this may stem from many factors (e.g., adolescent denial of problems, a reluctance to be stigmatized as ill, a need for increased autonomy), clinicians should anticipate this possibility and should discuss the children's feelings about medication with them during elementary school. This may help to strengthen the clinician's alliance with the child.

  By remaining flexible and inventive, clinicians can encourage appropriate medication usage through positive rewards and planned discontinuations. Trial periods without medication or of placebo substitution (where ethically and legally sanctioned) with a systematic review of changes in rating scale assessments provide objective evidence of whether continued use of medication is warranted and necessary.

  Clinicians need to discuss whether medication will be given only during the school week or on weekends and vacations as well with parents or guardians. In instances in which the child with ADHD has difficulty with peers and parents as well as school problems, medication helps the child by improving his or her ability to work and play with others. To the extent that the child's self-esteem is benefitted by good interaction with others, treatment outside the school setting can be expected to provide further benefit. If the child obtains a good response from medication, trial discontinuations at intervals should be used to determine if medication is still useful. One policy is to offer such medication holidays during psychologically less demanding times (e.g., during the summer vacation) and, when they are successful, to resume medication use when school begins again. Clinical experience suggests that having a child

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  start the school year with medication and later carrying out a trial off the medication is better.

  Assessing the adequacy of psychostimulants to monitor behavior while the medication is affecting the child is particularly important. If psychostimulants are given as they typically are in the morning and at noon and the parent sees the child in the afternoon after the medication has worn off, he or she may inaccurately deem them ineffective. In some schools, local regulations prevent children from receiving medications during the school day. This has made the availability of longer acting alternatives particularly important. Attention to all these aspects of treatment involves considerable clinician time and requires a strong alliance that is fostered by regular and unhurried appointments with the child and family.

  • Psychostimulants. When psychostimulant medications are maximally effective, they frequently reverse many of the psychologic abnormalities that have been described and promote psychologic growth to an extent not seen before the drugs were administered. Many children will demonstrate a longer attention span, an increased tolerance of frustration, greater emotional stability, and increased sensitivity to the requests of peers and parents. The current psychostimulant medications used are the amphetamines (d-amphetamine, Adderall), methylphenidate, and pemoline (Table 22.2).¹

    Methylphenidate and d-methylphenidate (also called Focalin or d-threomethylphenidate) are available in an immediate release (IR) formulation (lasting 2.5 to 4 hours) and in the follow-ing six longer acting preparations: Ritalin-LA, Ritalin-SR, Methylin ER, Metadate-ER, and Metadate-CD, which are 8-hour preparations; and Concerta, a 12-hour osmotically controlled-release formulation.

    Ritalin-SR is available only in a 20 mg dosage. Some clinicians and research groups report that this particular wax matrix preparation, which has a slower onset of action compared with IR preparations, is actually not longer acting than IR formulations, and they believe it is effective for only 4 to 6 hours. Some also suggest that it also may be more vulnerable to tolerance development than are the IR preparations; similar suggestions have been made about Metadate-ER and Methylin-ER. Some suggest that Ritalin-SR tablets can be divided into halves; note that this is contrary to product labeling.

    Limited data exist for all the longer acting forms of methylphenidate. The authors have had clinical experiences that suggest that the Concerta formulation can adequately substitute for the three times a day dosing of the IR preparations and that it lasts at least 8 hours. Concerta is generally well tolerated. When dosages are increased, additional side effects may develop. In some children, a dysphoria develops toward the end of the expected duration of effect; this dysphoria may be lessened by adding 2.5 to 5 mg of an IR formulation about an hour before the dysphoria is expected to occur.

    Manufacturers' product labeling specifically recommends that methylphenidate should not be used for children under the age of 6 years, even though at least six studies support its efficacy and safety in these younger children.

    d-Amphetamine (lasting 4 to 6 hours), Dexedrine spansules (lasting about 6 to 8 hours), Adderall (a mixed salt lasting about 5 hours), and Adderall-XR (lasting 6 to 8 hours) have a longer duration of action than does IR methylphenidate, and they may

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    reduce the total number of daily doses. Dexedrine spansules have a slightly later onset of action than that of d-amphetamine; these two formulations may be given together in the morning to enhance efficacy. Adderall has a similar duration of action to that of d-amphetamine; the XR formulation may be used for once a day dosing.

    TABLE 22.2. CURRENTLY AVAILABLE ORAL PSYCHOSTIMULANTS APPROVED FOR ATTENTION DEFICIT HYPERACTIVITY DISORDERa

    Agent (estimated duration in hours)b Initial Dose Usual Maximum Doseb Immediate-release (IR) methylphenidate (2.5 4)c (many names)    d-threomethylphenidate (2.5 4)d 2.5 5 mg in a.m. or b.i.d. or t.i.d. 60 mg/db Extended-release methylphenidate    Ritalin-LA (8)e 20 mg in a.m. 60 mg/d    Ritalin-SR (4 6, 8 [see text])f 20 mg in a.m. 60 mg/d    Metadate-ER (8)g 10 mg in a.m. 60 mg/d    Metadate-CD (8)h 20 mg in a.m. 60 mg/d    Methylin-ER (8)i 10 mg in a.m. 60 mg/d    Concerta (10 12)j 18 mg in a.m. 72 mg/d Immediate-release    d-amphetamine       Dexedrine (3.5 6)k 2.5 5 mg in a.m. or b.i.d. 40 mg/d    d, dl-amphetamine       Adderall (5)l Sustained-release    d-amphetamine       Dexedrine spansules (5 8)m 5 mg in a.m. 40 mg/d    d, dl-amphetamine       Adderall-XR (6 8)n 10 mg in a.m. 40 mg/d Pemoline 18.75 mg in a.m. 112.5 mg/d    Cylert (5 10)o Abbreviations: b.i.d., twice daily; t.i.d., three times a day. aCurrently, these psychostimulants are classified as class II with the exception of pemoline, which is class IV. bThese estimates of the duration of effect reflect the authors' clinical experience and may differ from the product's labeling. Usual maximums are sometimes exceeded because of factors such as age, weight, or tolerance development. The usual range for methylphenidate in youth is 30 40 mg/d, but a few require up to 70 mg/d. cCurrently available as 5 mg, 10 mg, and 20 mg tablets; this formulation can be opened and the beads can be placed into soft foods such as applesauce. dCurrently available as 2.5 mg, 5 mg, and 10 mg tablets. eCurrently available as 20, 30, and 40 mg capsules. fCurrently available as 20 mg sustained-release (wax matrix) tablets. gCurrently available as 10 mg and 20 mg extended-release tablets. hCurrently available as a 20 mg (biphasic delivery) tablet. iCurrently available in the following two tablet strengths: 10 and 20 mg. jCurrently available in the following four extended-release (osmotic) capsule strengths: 18, 27, 36, and 54 mg. kCurrently available as 5 mg tablets (contain tartrazine). lCurrently available in the following seven tablet strengths (each at 1:1:1:1 ratio of dextroamphetamine saccharate, dextroamphetamine sulphate, amphetamine aspartate, and amphetamine sulphate): 5, 7.5, 10, 12.5, 15, 20, and 30 mg. mCurrently available in three sustained-release capsules as follows: 5, 10, and 15 mg (contain tartrazine). nCurrently available as 10 mg, 20 mg, and 30 mg capsules. oCurrently available as 18.75 mg, 37.5 mg, and 75 mg tablets; also as a 37.5 mg chewable tablet.

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    For d-amphetamine, the product labeling recommendation is for usage in children ages 3 or over. A few clinical trials support this statement.

    Overall, methylphenidate and the amphetamines appear to be about equally effective, and most physicians start with one and switch to the other when the child's response is not optimal. Although the overall percentage response may be the same for both, about one-third of children will do better on one class than they do on the other.

    Longer acting preparations (e.g., Methylin-ER, Metadate-ER, Metadate-CD ², Concerta, Dexedrine spansules, and Adderall-XR) may facilitate once daily dosing, thus avoiding the need to depend on a mid school-day dose administered either by the school nurse, a teacher, or the child (sometimes, an older sibling). Some school-aged children are highly sensitive to being identified as different from their peers, and they may refuse to take the medication during school hours.

    Pemoline has fallen into disfavor because of its linkage to hepatic failure and death. Although it is still marketed in the United States, its product information contains a black-boxed warning indicating these concerns. (Note: Pemoline is no longer marketed in some countries [e.g., Canada, the United Kingdom].) Currently, pemoline is usually considered only if the youth or family has a history of drug abuse or when methylphenidate, amphetamines, and other options have been ineffective. In the past, some physicians prescribed pemoline because it is scheduled in Class IV rather than in Class II; it may be prescribed and renewed for 6 months, rather than having to be prescribed every month. As was noted above, a major concern with pemoline is that a very small percentage of individuals can develop evidence of hepatitis that ranges in severity from asymptomatic increases of serum aminotransferases to acute hepatic failure and even death. Written informed consent outlining these risks and other options for treatment should be obtained before pemoline is prescribed. Obtaining pretreatment liver function tests to establish a baseline is also crucial. That some cases of pemoline-induced hepatic failure developed after many years of apparently safe use and in the presence of previously normal liver function tests should be emphasized. How often on-treatment liver function tests should be obtained is debatable; some clinicians recommend every 2 weeks, and others advocate informing parents or guardians about the signs and symptoms of hepatic dysfunction and obtaining laboratory tests every 6 months. Pemoline also has the potential to cause insomnia, and it may be the psychostimulant with the highest likelihood of causing choreiform movements and tics. Contrary to previous belief, its onset of action is rapid and dose related. Although the usual recommendation is to dose it once daily, many youth require a second dose in the afternoon.

    Atomoxetine is a recently introduced treatment for ADHD. It appears to be a selective inhibitor of the norepinephrine transporter. Because, to date, data do not suggest that it causes euphoria or withdrawal, atomoxetine is not classified as a controlled drug. Atomoxetine is metabolized by cytochrome P-450 (CYP) 2D6. Patients who are poor metabolizers of CYP2D6 and those who are being treated concurrently or those who have recently been treated with potent 2D6 inhibitors (e.g., paroxetine, fluoxetine) will usually have increased plasma concentrations of atomoxetine (increases of up to fivefold). As with other psychostimulants, atomoxetine should not be taken with

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    MAOIs, and it is not recommended for us in patients with narrow angle glaucoma. Atomoxetine can modestly affect weight gain, blood pressure, and heart rate; these parameters should be monitored. Less than 2 percent of patients experience orthostatic hypotension. Common side effects include GI symptoms, fatigue, dizziness, mydriasis, and mood swings. For youth who are at least 6 years of age and less than 70 kg in body weight, this agent should be initiated at 0.5 mg per kg per day and then should be gradually increased to 1.2 mg per kg per day, either as single or twice daily dosing. Total daily dosing should not exceed 100 mg (or 1.4 mg per kg per day). For youth above 70 kg in body weight, 40 mg per day is the initial dose. The dosage can typically be increased to 80 mg per day. The manufacturer suggests that atomoxetine can be discontinued without tapering (note: the authors recommend tapering whenever possible until more clinical experience has confirmed this advice from the manufacturer). This agent is available in 10, 18, 25, 40, and 60 mg capsules.

    A number of other medications have been used in the treatment of ADHD uncomplicated by comorbid conditions when psychostimulants are ineffective or as add-ons to psychostimulants in the presence of comorbid conditions or with incomplete or partial response. These include a variety of antidepressants, such as the less sedating tricyclic antidepressants (TCAs) bupropion and venlafaxine. Of the TCAs, only desipramine has proven efficacy in ADHD, yet many clinicians avoid its use because of the reports of seven deaths of children treated with this agent; some prescribe imipramine or nortriptyline instead. Unlike in depression, the response of ADHD to treatment with TCAs may occur rapidly, but whether their positive effects are sustained beyond a few months is still debated. Those claiming a continued response argue that TCAs must be dosed at maximum dosing of 5 mg per kg per day to be effective in younger children; because many clinicians are reluctant to use such high doses, TCA use is not common. Many clinicians find that these agents treat the inattention symptomology less adequately. Providing parents with a balanced informed consent discussion about the TCAs and doing a careful pretreatment workup are important (Table 22.3).

    Latency children may have a profile of side effects on TCAs that differs from those in adults, including dysphoria, irritability, or aggression; weight loss; increased heart rate; and increased blood pressure (especially diastolic). Although youth appear to be less sensitive than adults to the peripheral anticholinergic side effects, they may be more sensitive to the central anticholinergic symptoms (e.g., confusion, sedation).

    Starting dosing at night is useful for minimizing daytime sedation and treating comorbid insomnia. The dose should be gradually titrated upward as clinical effectiveness is assessed. Latency children should be dosed based on weight. Three to 5 mg per kg per day

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    is a typical target dose range for imipramine, with 5 mg per kg per day as the highest dose. For nortriptyline, 3 mg per kg per day is the highest dose because of its potency. Because of possible cardiac effects from imipramine or other TCAs, a pretreatment electrocardiogram should be obtained, with follow-up electrocardiograms at 3 mg per kg per day and again at the highest dose. Resting blood pressure and pulse should also be obtained (Table 22.4).

    TABLE 22.3. PRETREATMENT WORKUP FOR TRICYCLIC ANTIDEPRESSANTS
    Careful inquiry into patient and family cardiac history, including any history of early or sudden death in first-degree relatives Complete blood count with differential, blood urea nitrogen, creatinine, liver function tests Electrocardiogram Pulse rate Standing and supine blood pressure readings to assess the presence of postural (orthostatic) changes

    TABLE 22.4. CARDIOVASCULAR PARAMETERS AND TRICYCLIC ANTIDEPRESSANTS

    Consultation with a pediatric cardiologist and concomitant reduction of dosage or discontinuation of the TCA is indicated when any one of the following circumstances prevails Age (yr) Resting Heart Rate (beats/min) Resting Blood Pressure in mm Hg (sec) PR Interval (sec) QTc Interval (sec) 10 110 140/90 or 135/85 for more than half the time for 3 weeks 0.18 0.5 >10 100 150/95 or 140/85 for more than half the time for 3 weeks 0.20 0.5 Abbreviation: TCA, tricyclic antidepressant. From Kye C, Ryan N. Pharmacologic treatment of child and adolescent depression. Child and Adolesc Psych Clin North Am 1995;4:261 281, with permission.

    Although the response to treatment has not been shown to correlate with specific blood levels, at least one blood level should be obtained at low dosing to ensure that the child is not a poor metabolizer of CYP 2D6 substrates (see Chapter 29). Because of the potentially serious consequences of overdose, clinicians should emphasize to parents the importance of protecting other children, especially toddler siblings, from accidental ingestion.

    Bupropion has limited research support for efficacy in ADHD, and many clinicians find that it has only mild treatment effects; some clinicians try it because it is scheduled in Class V. Bupropion was voluntarily removed from the United States market in 1986 because of an increased incidence of seizures in bulimic patients, but it was then reentered in 1989. Before treatment is instituted, a history of eating disorders and seizures should be ruled out. Its IR formulation is dosed in a range of 3 to 6 mg per kg per day, divided into three doses, because of bupropion's short half-life. Any single dose should be below 150 mg because higher doses have been associated with an increased risk for seizures (4 in 1,000 in adults). The SR formulation may be dosed twice daily, and it has a lower risk for seizures. The generally accepted maximum daily IR dose for children is 300 mg, and for teens, 450 mg. (Note: The maximum dose for bupropion-SR is 400 mg per day.) Amelioration of symptoms of ADHD may begin as early as the third day. Side effects are generally mild, and they include rash, appetite increases, nausea, stomachache, minimal weight loss, blood pressure fluctuations, agitation, aggravation of tics, and, more seriously, cognitive distortions and delirium. The onset of rash may signify a serious allergic reaction, similar to an autoimmune serum sickness profile, and it thus

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    necessitates discontinuation of the medication. Adding psychostimulants on to bupropion may be necessary to improve its effectiveness. Increased valproic acid levels have been found with coadministration; these are likely related to competition for glucuronide formation.

    The use of ₂-adrenergic agonists has research support; both clonidine and guanfacine are commonly used to treat children with ADHD, particularly those with impulsivity and hyperactivity, comorbid tic disorders, aggressivity, or stimulant sleep problems. Because clonidine affects many receptors (it is sometimes referred to as a dirty drug ), it can cause more sedation, more hypertensive rebound after sudden discontinuation, and more hyperglycemia than does guanfacine. The pretreatment workup for both should include an inquiry about abnormal heart rhythms, and early sudden death of relatives and the exclusion of Raynaud disease and diabetes mellitus. An electrocardiogram should be conducted if it is indicated, and baseline blood pressure and pulse should be recorded as well. Dosing is titrated against behavioral effects. Clonidine dosing is calculated at 5 to 8 g per kg per day in three to four times daily scheduling. A single dose is begun at night. Sedation typically is immediate, but maximum behavioral effectiveness may occur gradually over 2 or 3 months. Although the elimination half-life of clonidine is prolonged, the behavioral half-life may be only 3 to 6 hours. Commonly, sedation, dry mouth, and dizziness may be experienced early in treatment. Later, nighttime awakening, nightmares, and night terrors can occur. Depression may appear in about 5% of children, particularly those with a history of depression. Parents should be aware of the potential for the serious consequences of overdose. Many parents complain of see-saw effectiveness, and a clonidine patch is useful in youth who do not have skin reactions to it because the blood levels of the drug are sustained over the day. Some protection against skin rash is provided by spraying the skin area to which the patch will be applied with a nasal steroid spray (e.g., beclomethazone). Although recommendation is made for weekly patching in the drug insert, many children have better results with 5-day patching with a 2-day overlap of a second patch. TCAs and trazodone inactivate the presser effects of clonidine and possibly its behavioral effects. Some protection against skin rash is provided by spraying the skin area to which the patch will be applied with a nasal steroid spray (e.g., beclomethazone). Although the deaths of four children on methylphenidate and clonidine were reported, further evaluation has not implicated the combination. Guanfacine use is increasing in acceptance; it is dosed in a range from 1.5 to 4 mg per day, often twice daily. When shifting from clonidine to guanfacine, the clinician should cross-taper these drugs to prevent withdrawal reactions.

  • Administration. The general procedure of administration is to begin any of these drugs at a low dose and then to increase the dose until the point of maximum therapeutic benefit is reached or some unpleasant side effect develops. That clinicians use a side-effect scale (e.g., Barkley Side Effect Questionnaire) before and after treatment is recommended to help track psychostimulant side effects. Although psychostimulants may minimally increase pulse and blood pressure, monitoring is not necessary unless the patient has a history of a preexisting arrhythmia or hypertension. These changes are least likely with pemoline. The long-term consequences of these cardiovascular effects are believed to be benign.

    Common side effects of the psychostimulants include appetite loss, irritability, stomachaches, headaches, and insomnia. Some parents

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    express concern about the possible effects of stimulant medication on growth during these critical years. New studies suggest that adult height and weight are unaffected by methylphenidate, except for a small number of individuals with side effects of nausea and vomiting. Weight and height should be monitored at least every 6 months to track growth. Tics, stereotypes, and tremors can appear de novo or they can worsen, but some individuals with preexisting tics will experience little or no change in their severity. Previously, the presence of tics was accepted to be a contraindication to stimulant use, but now most clinicians will use psychostimulants (sometimes covering the tics prophylactically with an anti-tic medication; see Chapter 7) in this population. Amphetamines may be more likely to produce compulsive behaviors, whereas methylphenidate may induce more perseverative behaviors and movement disorders. Rarely, hallucinations (usually of insects crawling) may develop in children with a prior history of hallucinations. Physical dependence to these drugs usually does not occur in childhood, and, in general, tolerance does not occur. Occasionally, tolerance will develop to one of the psychostimulants, and the usual practice then is to switch to a drug of another class. Clinicians should carefully explain all this information to parents or guardians in an informed consent discussion before initiating treatment.

    IR methylphenidate is usually administered in two or three daily doses, in the morning, at noon, and possibly after school. Although some physicians, especially pediatricians, dose methylphenidate by weight (from 0.3 to 0.6 mg per kg per day), little empirical support is seen for this strategy. However, in children weighing less than 25 kg, more than 35 mg per day is associated with increased side effects. The amphetamines are about twice as potent on a per milligram basis as methylphenidate. The spacing of doses for either class of IR drug is purely empirical and is usually every 2.5 to 6 hours. Children with difficulties that are confined to school may require dosing once or twice each day; children with severe difficulties both at home and in school may require three or more doses per day. In children, appropriate bunching of dosing of agents with a short (2 to 3 hours) duration of effect is crucial in maximizing effectiveness, but the need for more frequent dosing may not be evident unless the clinician speaks directly to the teacher. Less experienced clinicians may be reluctant to increase individual doses above 5 to 10 mg, but dosing should be increased in a stepwise fashion to maximum levels until the agent is effective or side effects become evident. If medication is given too late in the day, some youth experience sleep difficulties; others show improved sleep and behavior with an early evening dose. If 60 mg is set as a somewhat arbitrary maximum daily dose, obviously some portion of the day will remain uncovered in children with severe difficulties. Discussion of these dosage issues with guardians and youth is essential in order to individualize regimens that optimize academic and social development. Although oral psychostimulants taken in usual therapeutic doses are not addictive, without a doubt, children or parents can abuse or misuse psychostimulants by taking them in high doses or by snorting or injecting them. Clinicians must evaluate the parents' and school personnel's ability to monitor for misuse of these medications.

• Specific psychologic therapies for the child and the family. Efficacy has been demonstrated in training parents and teachers in contingency management techniques (e.g., time-out, token or point reward systems, response cost). Psychoanalytic psychotherapy and cognitive-behavioral treatments have not been shown to be effective in the treatment of children with ADHD. However, without a doubt, the reduction of family tensions and the structuring of a child's environment are frequently

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  of benefit. Because children with ADHD often have parents with ADHD, a parent's psychiatric pathology sometimes prevents him or her from modifying his or her behavior toward the child. Parental guidance or psychopharmacologic or psychotherapeutic treatment may help to alter the unwanted parental behavior(s). In children with ADHD whose problems have received attention only after they have suffered the accumulative psychologic effects of the syndrome for some years, psychotherapy may potentially be of benefit.

II. Attention Deficit Hyperactivity Disorder in Adults

At present, a growing body of research and other information about ADHD in adults exists. Although a decrement in ADHD symptomology often occurs over time, the evidence for the persistence of ADHD from childhood into adulthood is clear from a number of studies. In the outcome study of Weiss et al. (1985) of the 15-year course of children with ADHD, 30% to 40% of individuals had no significant symptoms, 10% had severe problems (usually drug abuse or antisocial behaviors), and 50% to 60% had moderate symptoms in their work or interpersonal domains. Factors that moderated these adult outcomes included female gender, low aggressivity, no learning disability, no parental pathology, high socioeconomic status, and high intelligence quotient. Increased symptoms of ADHD may emerge as life situations change. For example, a man may function well as an outdoor worker but then may become disorganized and inefficient when he is promoted to management. A housewife whose family tolerated her relaxed style may return to college and become overwhelmed by her own lack of organization. In general, adults with ADHD can be expected to have more job impairments, troubled relationships, parenting difficulties, and automobile accidents when compared with non-ADHD adults. The incidence of women and men diagnosed with ADHD in adulthood is roughly equal; the general assumption is that women were missed in childhood because of their lack of impulsivity or because of cultural bias.

Adults who present for psychiatric evaluation often come with diagnosis in hand after their child has been diagnosed with ADHD or after they have been diagnosed by a spouse or friend. Because the DSM-IV requires that symptoms of ADHD must be present before the age of 7 years, the likelihood of an accurate diagnosis is increased when adults remember a trial of methylphenidate as a child or when they recall efforts by their teachers to keep them quiet.

Adults with ADHD have been shown to describe accurately their childhood symptoms. Consistent with their history of childhood psychopathology, adult women describe more dissatisfaction with their childhood relationships, and they endorse a poorer self-concept than do men with ADHD. Comorbidity may be even more common in adults than in children; estimates of comorbidity are setting dependent (e.g., in a prison setting, the co-occurrence of ADHD with antisocial personality disorder will be extremely high). Clinicians in many instances can also rely on the available parents of adult patients to ascertain childhood ADHD symptoms, to complete retrospective ADHD scales, or to supply any report cards they may have saved. Current adult ADHD symptomology is sometimes reported most accurately by those who live with or work with the adult patient rather than by the adult patient per se.

The studies of Weiss et al. (1985) and Mannuzza et al. (1998) established that certain behaviors of children with ADHD could persist into adulthood. Another group (Wender et al.) subsequently developed two scales to assess these childhood symptoms retrospectively. The Parents Rating Scale is based on the Connors 10-item hyperactivity index, and the Wender Utah Rating Scale is a 61-item questionnaire on which the index adult rates his or her own recalled symptoms from childhood. DSM-IV criteria for ADHD are based on behaviors (signs) in contrast to symptoms. Another diagnostic scale is the Connors Adult Attention Rating Scale; it has good statistical properties and it is recommended by many experts. The Connors Adult Attention Rating Scale comes in two formats observer and self-reports. Both contain 66 items, and, within these, are items reflecting the DSM-IV criteria. Some items seem quite straightforward (e.g., I don't finish things I start, I am restless or overactive ); other items seem more appropriate

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The Wender group developed criteria to delineate a group of adults who were likely to benefit from psychostimulant treatment; these criteria focus both on signs and symptoms. In addition to meeting two behavioral criteria (signs) for combined-type ADHD in childhood (i.e., attentional problems and hyperactivity), these adults must currently have at least two of the following five symptoms, which can be remembered by the following mnemonic TIMID: (a) hot Temper, (b) Impulsivity, (c) Mood lability, (d) Intolerance for stress, and (e) Disorganization. A structured interview, the Targeted Attention Deficit Disorder Scale, elicits data on all seven of these dimensions the two behavioral and the five just listed.

Methylphenidate, d-amphetamine, and pemoline have all shown efficacy in adults selected by these criteria. Some adults with comorbid anxiety who are treated with Adderall may have an increase in anxiety. Clinical observations suggest that, in addition to symptom reduction, improvements in vocational or educational performance and in relationships with spouse or partner, children, or extended family are seen (e.g., rather than getting fired, they get promoted; rather than failing in school, they graduate; rather than divorce, their marriages improve). Specifically, a reduction in the number and intensity of outbursts of temper (rages); an increased ability to cope with stress; increased attention and decreased distractibility; decreased motor restlessness, if present; and improved executive functioning will be seen.

Attentional deficits may present as problems of executive functioning (e.g., trouble organizing tasks, persisting in tasks, or managing affect during tasks). Adults with ADHD show a treatment response to psychostimulants that is similar to that seen in children and adolescents with ADHD (i.e., they do not have the euphoric response to treatment-range doses of psychostimulants that is seen in many non-ADHD adolescents and adults). Similarly, they do not become tolerant to the beneficial effects of psychostimulants.

Dosing of IR methylphenidate to 1 to 2 mg per kg per day or of equivalent amphetamines is typical in adults. The duration of action of IR methylphenidate is about 2 to 3 hours in adults; d-amphetamine's duration of action is about 3.5 to 4.5 hours. A typical dosing regimen for IR methylphenidate could be 10 to 15 mg every 2.5 to 3 hours or about five to six times per day. d-Amphetamine is usually given as 7.5 to 15 mg every 4 hours or three to four times per day. When Dexedrine spansules are given to adults, some clinicians add to these 5 to 7.5 mg of d-amphetamine. More experience is needed with the newer long-acting formulations of methylphenidate to clarify their durations of effect. Because of their characteristic disorganization, some adults with ADHD use multiple-alarm wrist watches to alert them to take their medications as prescribed.

Unlike children, adults generally feel subjectively better when the psychostimulants are effective, and they often describe feeling calm and collected and able to think about one thing at a time, being centered, being less impulsive, or getting things done. Adults with ADHD have an increased rate of automobile accidents, and psychostimulants have been shown to improve simulated driving. For these reasons, some appropriately selected adults may benefit from the use of medication while driving, especially during boring long-distance driving. Of theoretical concern is the possibility that ADHD adults and some adolescents could obtain euphoric effects from larger doses of psychostimulants or that they would be more likely than children to divert them to others for illicit use. Many clinicians, therefore, are disinclined to use amphetamines and methylphenidate in older adolescents and adults, to the disadvantage of such patients.

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Although less well studied, many agents that have shown at least some efficacy in children with ADHD can be administered to adults in usual adult doses. Positive results have been found in small to moderate sample size, double-blind, placebo-controlled trials with guanfacine, desipramine, bupropion, and atomoxetine. Monotherapy is the ideal, but combined pharmacotherapy is often necessary. Many adults with ADHD do not find traditional psychotherapies useful. Rather, an approach emphasizing specific organizational skill acquisition and coaching individually or in groups can be helpful. Couples therapy can be useful as the adult with treated ADHD renegotiates couple and parental roles.

III. Online Clinical Practice Guidelines

The American Academy of Pediatrics has an online version of their 2001 ADHD treatment guidelines, Treatment of the School-Aged Child With Attention-Deficit/Hyperactivity Disorder. The online version includes a PDF file called AAP Parent Pages. This file is a useful handout for parent or patient education. It can be found at http://www.aap.org/policy/s0120.html.

ADDITIONAL READING

American Academy of Child and Adolescent Psychiatry. Practice parameters for the assessment and treatment of children, adolescents and adults with attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 1997;36:85S 121S.

Barickman LL, Perry PJ, Allen AJ, et al. Bupropion versus methylphenidate in the treatment of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 1995;34:649 657.

Barkley RA. Attention-deficit hyperactivity disorder: a handbook for diagnosis and treatment. New York: Guilford Press, 1990.

Barkley RA. A clinical workbook: attention-deficit hyperactivity disorder. New York: Guilford Press, 1998.

Barkley RA, Murphy KR. Attention-deficit hyperactivity disorder, 2nd ed. New York: Guilford Press, 1998.

Conners C, Erhardt D, Epstein J, et al. Self-ratings of ADHD symptoms in adults. I. Factor structure and normative data. J Attention Dis 1999;3:141 152.

Conners C, Erhardt D, Sparrow E, et al. The Conners Adult ADHD Rating Scale (CAARS). Toronto: Multi-Health Systems, 1998.

Faraone SV, Biederman J, Mennin D, et al. A prospective four-year follow-up study of children at risk for ADHD: psychiatric, neuropsychological, and psychosocial outcome. J Am Acad Child Adolesc Psychiatry 1996;35:1449 1459.

Findling RL, Short EJ, Manos MJ. Developmental aspects of psychostimulant treatment in children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2001;40:1441 1447.

Goldman LS, Genel M, Bezman RJ, et al. Diagnosis and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Council on Scientific Affairs, American Medical Association. JAMA 1998;279:1100 1107.

Greenhill LL, Osman BB, eds. Ritalin theory and practice, 2nd ed. Larchmont, NY: MA Liebert, 2000.

Hechtman L. Families of children with attention deficit hyperactivity disorder: a review. Can J Psychiatry 1996;41:350 360.

Hechtman L, Weiss G. Controlled prospective fifteen year follow-up of hyperactives as adults: non-medical drug and alcohol use and anti-social behaviour. Can J Psychiatry 1986;31:557 567.

James RS, Sharp WS, Bastain TM, et al. Double-blind, placebo-controlled study of single-dose amphetamine formulations in ADHD. J Am Acad Child Adolesc Psychiatry 2001;40:1268 1276.

Mannuzza S, Klein RG, Bessler A, et al. Adult psychiatric status of hyperactive boys grown up. Am J Psychiatry 1998;155:493 498.

McCann BS, Scheele L, Ward N, et al. Discriminant validity of the Wender Utah rating scale for attention-deficit/hyperactivity disorder in adults. J Neuropsych Clin Neurosci 2000;12:240 245.

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Michelson D, Faries D, Wernicke J, et. al. Atomoxetine in the treatment of children and adolescents with attention deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study. Pediatrics 2001;108:e83.

Murphy K, Barkley RA. Attention deficit hyperactivity disorder adults: comorbidities and adaptive impairments. Compr Psychiatry 1996;37:393 401.

Murphy K, Barkley RA. Updated adult norms for the ADHD behavior checklist for adults. ADHD Rep 1996;4:12 13.

Nadeau K. A comprehensive guide to attention deficit disorder in adults. New York: Brunner-Mazel, 1995.

Schachar R, Taylor E, Wieselberg M, et al. Changes in family function and relationships in children who respond to methylphenidate. J Am Acad Child Adolesc Psychiatry 1987;26:728 732.

Shader RI, Harmatz JS, Oesterheld JR, et al. Population pharmacokinetics of methylphenidate in children with attention-deficit hyperactivity disorder. J Clin Pharmacol 1999;39:775 785.

Spencer T, Biederman J, Wilens T, et al. Effectiveness and tolerance of tomoxetine in adults with attention deficit hyperactivity disorder. Am J Psychiatry 1998;155:693 695.

Spencer T, Wilens T, Biederman J, et al. A double-blind, crossover comparison of methylphenidate and placebo in adults with childhood-onset attention-deficit hyperactivity disorder. Arch Gen Psychiatry 1995;52:434 443.

Swanson J, Lerner M, March J, et al. Assessment and intervention for attention-deficit/hyperactivity disorder in the schools: lessons from the MTA study. Pediatr Clin North Am 1999;46:993 1009.

Taylor FB, Russo J. Comparing guanfacine and dextroamphetamine for the treatment of adult attention-deficit/hyperactivity disorder. J Clin Psychopharmacol 2001;21:223 228.

Weiss G, Hechtman L, Milroy T, et al. Psychiatric status of hyperactives as adults: a controlled prospective 15-year follow-up of 63 hyperactive children. J Am Acad Child Psychiatry 1985;24:211 220.

Weiss M, Hechtman-Trokenberg L, Weiss G. ADHD in adulthood: a guide to current theory, diagnosis, and treatment. Baltimore: Johns Hopkins University Press, 1999.

Wender PH. A possible monoaminergic basis for minimal brain dysfunction. Psychopharmacol Bull 1975;11:36.

Wender PH. Attention-deficit hyperactivity disorder in adults. Psychiatr Clin North Am 1998;21:761 774.

Wender PH. ADHD: attention-deficit hyperactivity disorder in children and adults. New York: Oxford University Press, 2000.

Wilens TE, Biederman J, Spencer TJ, et al. Pharmacotherapy of adult attention deficit/hyperactivity disorder: a review. J Clin Psychopharmacol 1995;15:270 281.

¹Although methamphetamine is still available in a 5 mg oral dosage form, its use is not recommended because of the abuse potential of methamphetamine.

²This formulation consists of immediate and extended release beads. The clinician should keep in mind that these capsules can be opened and placed into soft foods to facilitate ingestion. However, removing some beads and diverting them for other, possibly inappropriate, uses is also possible.