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intelligence tests or nonverbal adaptations of tests are appropriate for younger children with autism and those who have limited verbal skills. For individuals with autism who do not have mental retardation, there is a common pattern of cognitive strengths and weaknesses, in which visual perceptual skills often are significantly better than verbal abilities, and concrete problem solving is better than abstract knowledge. Thus, in high-functioning individuals with autism, there often is a learning disability profile, which necessitates individual approaches to education.

BIBLIOGRAPHY
I . Attwood T: Aspergers Syndrome: A Guide for Parents and Professionals. London, Jessica Kingsley

Publishers, 1998. 2. Bailey A, Phillips W, Rutter M: Autism: Toward an integration of clinical, genetic, neuropsychological,and neurobiological perspectives. J Child Psycho1 Psychiatry 37:89-126, 1996. 3. Bryson S, Smith I: Epidemiology of autism: Prevalence, associated characteristics, and implications for research and service delivery. Ment Retard Dev Disabil Res Rev 4:97-103, 1998. 4. Cohen DJ, Volkmar FR (eds): Handbook of Autism and Pervasive Developmental Disorders, 2nd ed. New York, John Wiley & Sons, 1997. 5. Cook EH: Genetics of autism. Ment Retard Dev Disabil Res Rev 4:113-120, 1998. 6. Courchesne E: Brainstem, cerebellar, and limbic neuroanatomical abnormalities in autism. Curr Opin Neurobiol 7:269-278, 1997. 7. Dawson G (ed): Autism: Nature, Diagnosis, and Treatment. New York, Guilford Press, 1989. 8. Dawson G , Osterling J: Early intervention in autism. In Guralnick MJ (ed): The Effectiveness of Early Intervention. Baltimore, Paul H. Brookes, 1997, pp 307-326. 9. Hagerman RJ, Cronister A (eds): Fragile X Syndrome: Diagnosis, Treatment, and Research. 2nd ed. Baltimore, Johns Hopkins University Press, 1996. 10. Lindberg B: Understanding Retts Syndrome. Toronto, Hogrefe and Huber, 1991. I I . Lord C, Rutter M, LeCouteur A: Autism Diagnostic Interview-Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord 24:659-685, 1994. 12. Lord C, Rutter M, Di Lavore PC: Autism Diagnostic Observation Schedule-Generic. Chicago, University of Chicago Department of Psychiatry, 1998. 13. Schopler E, Reichler RJ, Renner BR: The Childhood Autism Rating Scale (CARS). Los Angeles, Western Psychological Services, 1988.

56. ATTENTION DEFICIT-HYPERACTIVITY DISORDER

William W. D o d s o ~M , .D

1. What is attention deficit-hyperactivity disorder (ADHD)? The first descriptions of ADHD appeared at the turn of the century, and the current medication treatment was first described in 1937. Our understanding of the disorder has developed over time, and the name and diagnostic criteria for ADHD have changed with that understanding. The current diagnosis as it is described in the DSM-IV is: ( I ) a persistent pattern of inattentiodeasy distractibility, (2) behavioral and emotional impulsivity, and sometimes (3) hyperactivity or severe restlessness. These symptoms are significantly more severe than is typical in persons of a similar developmental
level. Inattention, impulsivity, and restlessness must cause significant impairment in at least two areas of function (school, peer relationships, family relationships, and work, mood regulation, and self-esteem) and must have been continuously present for at least 6 months. For example, a child who misbehaves in the classroom and is disruptive, but does not exhibit similar problems o n the playground or at home, does not meet diagnostic criteria.

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DSM-IV Criteria for Attention DeJicit-Hypeructivity Disorder Inattention

Six or more of the following, manifested ofteften: Inattention to details/makes careless mistakes Difficulty sustaining attention Seems not to listen Loses things Fails to finish tasks Difficulty organizing Avoids tasks requiring sustained attention Easily distracted Forgetful

Impulsivity/Hyperactivity Six or more of the following, manifested often: Impulsivity Hyperactivity Blurts out answer before question is finished Fidgets Dificulty awaiting turn Unable to stay seated Inappropriate running/climbing Always on the go Restlessness Difficulty in engaging in leisure activities quietly Talks excessively Interrupts or intrudes on others
The symptoms of inattention or impulsivityhyperactivity: have persisted for 6 months or longer are more frequent and severe than is typical of the individuals level of development have onset prior to age 7 cause some impairment in two or more settings (i.e., cause significant impairment in social. academic, or occupational functioning) are not better accounted for by another mental disorder

2. What are the behavioral signs of ADHD?

The presentation of ADHD varies depending on the age and developmental level of the patient.

Preschool (Ages 3-5)

Always on the go Aggressive (hits or pushes others) Dangerously daring Noisy, interrupts Excessive temper tantrums Insatiable curiosity Low levels of compliance

Elementary School-Age (Ages 6-12) Easily distracted, hard to stay on task

Homework poorly organized, incomplete, and contains careless errors Impatient, blurts out answers, fails to wait turn in games Often out of seat Perceived as immature

Adolescent (Ages 13-18)

Restless, rather than hyperactive School work disorganized and incomplete Procrastination on most tasks Engages in risky behavior (speeding, drug experimentation) Poor peer relationships Poor self-esteem Difficulty with authority figures

Adulthood
Disorganized, fails to plan ahead Forgetful, loses things Multiple jobs, relationships Misjudges time available, frequently late Mood lability and flash anger outbursts Many projects started but few completed

3. Is hyperactivity required for the diagnosis? No. While the hyperactive features are unmistakable when present (and, therefore, were the
main focus of earlier diagnostic frameworks), we now know that fewer than half of persons with

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ADHD are hyperactive. True hyperactivity is much more common in boys, leading them to be identified and treated much more frequently than girls. When hyperactivity is absent, the individuals still are restless, talk incessantly, commonly lose the point of what they are saying, fidget, may be out of their seats walking around, pat their feet or fingers tirelessly, and/or cannot turn off their minds to fall asleep at night.

4. What causes ADHD? The exact cause remains unknown, but there usually is a clear genetic clustering of cases in families. Adoption studies identify that genetics are far more important than environment in the manifestation of the disorder. Twin studies do not show complete concordance, indicating that other factors contribute to the etiology of ADHD. However, to date the only factor clearly demonstrated to be linked to the disorder is maternal smoking during pregnancy. Six studies of twins with ADHD show concordance rates of 60-80%. 5. Does ADHD persist into adulthood? In the time when diagnostic schemes heavily focused on hyperactivity, it was believed that ADHD was a lag in developmental maturation that would go away with age. In the years that followed, however, as the genetic basis was identified and as children with ADHD grew up to be adults with continuing symptoms and impairment, it was recognized that adults can have ADHD. There still are no formal DSM criteria for adults, who must be given the diagnosis of ADHD-In Partial Remission or Not Otherwise Specified. The rate of persistence depends on how persistence is defined. If using the strictest definition of being diagnosed as a child and continuing to meet full criteria as an adult, the persistence rate is about 33%. If persistence is defined as probably having met criteria in childhood and currently meeting 5 out of 9 criteria (instead of 6 out of 9), the persistence rate jumps above 80%. Luckily, adults continue to respond to the same medications and interventions as children do. Often, people diagnosed as adults have additional therapy to do as they mourn all of the time and opportunities lost due to not being treated for their condition. They must also rework a sense of who they are as people with ADHD: they are not lazy, stupid, or crazy.5a

6. How common is ADHD?

ADHD is the most common behavioral condition diagnosed in children. The DSM-IV reports a prevalence in children of 3-5%. When studies were done, however, to determine the impact on prevalence rates of the DSM-IVs emphasis on inattention, researchers were surprised to discover much higher rates both in Tennessee, where every child of school age in an entire county was screened, and in Germany, where the identical study had been performed a year earlier. Both studies demonstrated rates in excess of 10%. Based on new criteria, studies have shown prevalence rates for purely inattentive individuals (4.9-9%) in addition to the impulsivehyperkinetic (3.4-3.9%) and combined subtypes (4.448%). More girls are identified using the DSM-IV criteria than ever before.

7. Is ADHD over-diagnosed and over-treated? This perception has arisen from a number of factors: Increased awareness of the condition by the public Acceptance of a broader set of diagnostic criteria Greater appreciation of the course of the illness and its ultimate impact on adult life, which justifies lengthier and uninterrupted treatments Diminished concern about growth retardation, predisposition to drug use, and long-term effects of stimulant class medications Increased treatment of adults. In fact, the condition still goes unrecognized and untreated most of the time. Even assuming the lower end of the traditional prevalence estimates (3%), fewer than one in three affected children ever get diagnosed and treated.

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8. How is ADHD diagnosed?

The diagnosis of ADHD is a clinical diagnosis derived from a careful history taken from many individuals and sources. The more data available to the clinician, the better. The process begins by taking a history-either from the childs parents or from the adult patient directly-of persistent, lifelong behavioral patterns that cause significant impairment in every area of the patients life. Various researchers have assembled the common symptoms of ADHD into scales and checklists. Among the best available are:

ADHD Rating Scales

For Clinicians: Brown scales Auchenbach scale

For Teachers: Connors Teachers List Vanderbilt Teachers Rating Scale ADHD ComprehensiveTeacher Rating Scales (ACTeRS)

For Parents: Conners Parents Checklist

School records and report cards are helpful to establish longitudinal patterns of distractibility, behavior problems, and failure to perform up to potential.

9. What is the differential diagnosis of ADHD? A careful history must be taken to rule out conditions that may be mistaken for ADHD. This is complicated by the fact that ADHD may coexist with any of these conditions. Dtffei-entialDiagnosis of ADHD

Coexisting Conditions Conduct disorder Oppositional defiant disorder Learning disabilities Anxiety disorder Mood disorder Speechnanguage disorder

Possible Etiologic Conditions Chronic lead poisoning Post-traumatic or infectious Encephalopathy Fetal alcohol syndrome Fragile X syndrome Phenyl ketonuria

Differential Conditions Age-appropriate high activity Mental retardation Thyroid disorders Absence seizures Sensory deficits Tourettes syndrome Tic disorder Sleep disorders Aspergers or autism Psychosis Substance abuse Environmental Conditions Abuse or neglect Family adversity Situational stress High intelligence with inappropriate school placement

10. Which laboratory tests are helpful? None. Sometimes standard IQ test subtests that involve attention (e.g., Digit span) draw scores that are significantly lower than other subtest scores, or there may be subtest scatter in which the subtest scores vary by more than 4 points. IQ testing scores may be available due to previous academic failure, but should not be obtained as part of an ADHD assessment unless comorbid specific learning disorders also are suspected. Computer-based continuous performance tests (e.g., the TOVA [Test of the Variables of Attention] or Conners test), which measure attention span and impulse control directly, are available. These tests cannot be used to make or deny the diagnosis since they have many false-negative tests and measure inattention/irnpulsivity from any etiology, not just ADHD. Their utility lies in research and in objective determination of the optimal dose of medication. EEG

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rhythm analysis and various scans (e.g., SPECT, PET) currently are being studied, but have not yet demonstrated sufficient validity to justify their high cost. They are not considered a part of the evaluation of ADHD except in the most complicated cases. Once medication therapy has begun, blood levels of stimulant class medications are not useful, since there is no correlation between blood level and effect upon the symptoms of ADHD.
11. Discuss the controversies surrounding the diagnosis of ADHD. The diagnosis often is difficult to make for a number of reasons: No specific diagnostic test is available. The symptoms are nonspecific and can be found in a number of medical and psychiatric conditions. The core symptom of inattention is invisible. (Only the patient is aware that his or her attention has wandered. Learned social behaviors mask the fact that the person is no longer paying attention.) There often is a low rate of agreement between different informants (patient, teachers, parents, and spouses). Many people do not make a clear distinction between having an explanation and having an excuse for misbehavior and failure. It is a cornerstone of American values that any problem can be overcome if you buckle down, work hard enough, and have sufficient self discipline. The reality that some people are born hardwired to be inattentive, impulsive, and fidgety goes against this tenet of faith. The best treatment for ADHD is the stimulant-class medications. These schedule C-I1 drugs make many physicians and parents uncomfortable and are inconvenient to prescribe; hence there is reluctance to diagnose. The diagnosis, treatment planning, and patienuparent education are time consuming and do not fit well into the busy schedules of physicians, parents, and teachers.

12. What is the impact of ADHD on patients lives and the consequences of not treating the condition? Almost without exception, every study of the impact of ADHD on people with the condition has shown compelling evidence that ADHD has a detrimental effect upon the individuals life. Twenty-five percent of affected individuals must repeat at least one grade in spite of adequate academic ability. Despite similar IQ scores and educational attainment, individuals with untreated ADHD have lower occupational attainment and job satisfaction. Adolescents with ADHD who do not take medication have been shown in three studies to be four times more likely to have injury-producing accidents than adolescents with ADHD who do take medication. An old joke that ADD actually stands for Accidental Death and Dismemberment illustrates the strong connection between ADHD and traumatic injury. Adolescents with ADHD have much higher risk for self-inflicted injuries than do adolescents .3% vs. 0.1%). without ADHD (I By the age of 27 the rate of substance use disorders in persons with ADHD who do not take medication is 300% higher than the general population (47% vs. 15%). Patients who continue to take stimulant-class medication for their ADHD have the same risk of developing substance use disorders as does the general population. Stimulant-class medication is protective against the development of these disorders in adolescents and young adults with ADHD. It is becoming more clear as time goes on that the risk lies in not treating ADHD, rather than in using stimulant-class medications.

13. What constitutes optimal treatment for ADHD? The current gold-standard treatment for ADHD is stimulant-class medications. There are now over 170 controlled studies demonstrating that these medications are most effective, as well as safe. Additionally, they continue to be effective without the development of tolerance. It is this latter factor that leads many researchers to look for a mechanism of action other than their stimulant properties. For now, we must say that their mode of action for persons with ADHD is unknown.

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14. Elaborate on the stimulant-class medications.

Stimulants have been used to treat ADHD for a long time. Since Bradleys original article in 1937, we have had more than 60 years of experience with amphetamine and 30 years of experience with methylphenidate, with no negative effects identified from chronic administration. There are three commonly prescribed stimulant-class medications. They come in various immediate and long acting forms:

Generic Name
Methy lphenidate

Trade Name
Ritalin, Methylin Ritalin SR Metadateer Dexedrine, Dextrostat Dexedrine Spansule Adderall

Dosage
5,10,20 mg 20 mg 10,20 mg 5, 10mg 5 , 10, 1.5 mg
5, 10,20, 30 mg

Dextroamphetamine
d, 1 Amphetamine salts

15. Which stimulant is best for ADHD?

Methylphenidate (Ritalin) is by far the most commonly prescribed medication for ADHD, but this pattern is changing as clinicians become familiar with the long-acting preparations of amphetamine (Dexedrine Spansule, Adderall). Five recent double-blind studies comparing methylphenidate directly to Adderall seem to show that the amphetamine product is superior to methylphenidate in treating the core symptoms of ADHD-but more research is needed. The sustained release (SR) fornwlations of methylphenidate are unreliable and come in only one dosage strength (20 mg), which cannot be cut without losing the sustained release effects. Consequently, the Ritalin SR formulation is not recommended or used by most practitioners. Note that medication alone is rarely enough to treat the many impairments of ADHD adequately. Pills dont give skills.Medication levels the neurologic playing field so that individuals with ADHD can have an equal chance at life and begin to do the remedial work necessary to rebuild their lives, work, and relationships.

16. How is the optimal dose of medication determined?

For many years practitioners used weight-based nomograms to determine the dose of stimulant. This was largely a misunderstanding. The nomograms had been taken from the original blinded studies that demonstrated the effectiveness of this class of medications. The nomograms were intended to protect the double-blind conditions and were not recommended as the best way to determine the right dose of medication. We now know that the dose at which a unique individual gets optimal benefit varies widely from as low as 1 mg per dose to as high as 40 mg per dose. There is no known way to predict the optimal dose. It usually is found through a trial-and-error titration. Take home message: Optimal doses vary widely and must be fine-tuned to each patient. Most patients detect a difference in their function even at a dosage change of 2 mg. More is not better. The dose that achieves optimal focus of attention, impulse control, mood stability, and no side effects is different for each patient!

17. Describe a trial-and-error titration. A typical titration protocol starts with just 2.5 mg of medication every 4 hours for methylphenidate or immediate release dextroamphetamine, and every 5 to 7 hours for long-acting amphetamine products. The dose is then increased by 2.5 mg of medication every 1-3 days. With each increase in dose the patient should notice a clear improvement in performance, impulse control, and mood stability, without side effects other than mild appetite suppression. At some point, the dose is increased by 2.5 mg but the patient doesnt notice any improvement over the previous dose. At that point, the optimal dose for that individual is the lower of the two doses. This dose does not change for many years; tolerance does not develop.

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Clinical Pearl: All of the stimulant-class medications are moderately strong bases (pH 12-1 3). If these medications are present in the lumen of the gut with organic acids such as citric acid or ascorbic acid (vitamin C), the stimulant medication is ionized and cannot be absorbed from the gut into the blood stream. The following foods should be avoided for 1 hour before and after taking a dose of stimulant class medication: Kool Aid, lemonade, Gatorade Citrus fruit Poptarts, granola bars, breakfast bars Citrus juices Oral suspension medications Fruit juices with citric acid as a preservative Vitamins and food supplements containing Sodashrbonated beverages vitamin C 18. What are the adverse effects of stimulant-classmedications? At the dose that is optimal for a given individual, there should be no side effects other than a transient loss of appetite. The adverse effects that do occur generally are mild, short lived, and responsive to small decreases in dose or adjustments in the timing of doses. The more common adverse effects reflect overdosage and include insomnia, jitteriness, irritability, headache (especially as a dose wears off), mild hand tremor, and palpitations. Stimulants may unmask a tic disorder, but do not cause tics. In very rare instances, stimulants can precipitate a psychosis. When psychosis occurs, a coexisting diagnosis of either bipolar mood disorder or schizophrenia must be considered. There was once a concern that stimulants caused growth retardation in children. When this has been found, compensatory growth always has occurred, and each subject has ultimately reached their full predicted stature.

19. Does treatment of ADHD with stimulant-classmedication lead to future drug abuse?
Several prospective studies demonstrate that treatment of ADHD with first-line stimulant class medications seems to protect against the development of substance use disorders. The risk comes from not treating ADHD.

20. Are there other stimulant medications used to treat ADHD? Pemoline (Cylert) is a derivative of methylphenidate that is effective for about 70% of persons with ADHD. In multiple clinical trials, pemoline has been shown to be effective in doses of 75-100 mg given once a day in the morning. Unlike the other stimulants which are completely effective as soon as they are absorbed, pemoline often requires 3 weeks to accumulate effectiveness. The major side effect is difficulty falling asleep. Rarely, children develop hepatotoxicity, which has been fatal in more than 20 cases worldwide. Although liver function studies are recommended every 2 4 weeks for at least the first year of treatment, several cases of hepatotoxicity have been so quickly progressive that LFTs would not have caught the hepatitis in time. Due to the potential for fatal hepatotoxicity, the FDA no longer recommends pemoline as a first-line medication. Nonetheless, it is a good alternative for the patient at risk of substance abuse or who is so disorganized and forgetful that once-a-day dosing is all they can manage.

21. Discuss the use of second-line medications.

The second-line medications are second for two reasons: (1) they are only about half as effective as the first-line stimulants, and (2) their effectiveness commonly decreases over time and may suddenly stop altogether. Since their mechanism of action is unknown, it is not known why this tachyphylaxis occurs. The tricyclic antidepressant (TCA) medications imipramine and desipramine have been used longest. Some research recommends doses of 2-4 mg/kg, while other literature recommends low doses of no more than 60 mg/day even for adults. Either way, TCAs slow cardiac conduction, and an EKG is recommended before initiation of therapy. TCAs may be the best choice for the patient with mild to moderate ADHD and comorbid depression or panic. Buproprion (Wellbutrin) is an antidepressant that has metabolytes similar in clinical structure to amphetamine. Three studies report that buproprion improved the core symptoms at doses up to

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400 mg/day in adults and 150-250 mg/day in children. Buproprion usually is well tolerated, with mild headache, nausea, and insomnia the most commonly reported side effects. One study reports a significant benefit for adults with ADHD from venlafaxine (Effexor) at 75 mg bid.

22. What is the role of alpha-2 agonists?

The two alpha-2 adrenergic agonists currently on the market4lonidine (Catapres) and guanfacine (Tenex)-have been extensively studied. The hyperactive symptoms respond best to the alpha agonists, but they have no effect on other core symptoms of inattention and impulsivity. Consequently, the alpha agonists almost always are used in conjunction with stimulant-class medications, especially in the treatment of children with significant hyperactivity. The alpha agonists have extra utility for patients with coexisting tics and/or Tourettes syndrome. Their side effects of sedation also may be useful to help patients with ADHD shut off their brains and bodies to fall asleep at night. Treatment is started at low doses (one-half of a 0.1 mg-tablet of clonidine twice a day) and increased gradually to allow development of tolerance to the sedative side effects and because the decrease in hyperactivity may take 2 weeks or more to develop. Once the optimal dose is determined (0.2-0.4 mg/day of clonidine), it can be administered by a transdermal patch. Alpha agonist treatment should not be discontinued abruptly due to the potential for hypertensive rebound. The combination of stimulants and clonidine was studied extensively following reports of five deaths of children prescribed this combination. The medications seemed to have no causal linkage to the deaths, and the combination is now considered to be both safe and effective.

23. What modalities are not effective for the treatment of ADHD? More than 20 studies have refuted the claims of dietary manipulations, such as the Feingold diet or elimination diets. Other interventions that have been shown to be largely ineffective in treating core symptoms are: Individual psychotherapy Chiropractic manipulation Cognitive therapy Megavitamins Play therapy Eye movement therapy EEG biofeedback Trying harder Allergy treatments
BIBLIOGRAPHY
I. American Academy of Child and Adolescent Psychiatry: Practice parameters for the assessment and treatment of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 36(Suppl 10):85S-121S, 1991. 2. Biederman J, Wilens TE, Mick E, et al: Pharmacotherapy of attention deficithyperactivity disorder reduces risk of substance use disorder. Pediatrics 104(2),Internet edition, p e20, 1999. 3. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC, American Psychiatric Association, 1994. 4. Elia J , Ambrosini PJ, Rapoport JL: Treatment of attention-deficit-hyperactivity disorder. N Engl J Med 340:78&788, 1999. 5. Goldman LS, Gene1 M, Bezman RJ, et al: Diagnosis and treatment of attention-deficithyperactivity disorder in children and adolescents. JAMA 279: 110G1107, 1998. 5a. Kelly K, Ramundo P: You Mean Im Not Lazy, Stupid, or Crazy? New York, Scribner, 1995. 6. Pliszka SR: Comorbidity of attention-deficithyperactivitydisorder: An overview. J Clin Psychiatry 59(Suppl 7):50-58, 1998. 7. Wolraich ML, Hannah JN, Pinnock TY, et al: Comparison of diagnostic criteria for attention-deficit hyperactivity disorder in a county-wide sample. J Am Acad Child Adolesc Psychiatry 35:319-324, 1996. 8. Zametkin AJ, Ernst M: Problems in the management of attention-deficit-hyperactivity disorder. N Engl J Med 340:40116, 1999. 9. Zametkin AJ, Liotta W: The neurobiology of attention-deficit/hyperactivity disorder. J Clin Psychiatry 59(suppl 7): 17-23, 1998.