Online Medical Reference

Attention-Deficit/Hyperactivity Disorder in Adults

George E. Tesar

Raul J. Seballos

Published: August 2010

Definition and etiology

Attention-deficit/hyperactivity disorder (ADHD) is the current diagnosis for what was previously labeled minimal brain damage, minimal brain dysfunction, hyperkinetic impulse disorder, and hyperactive child syndrome.1 Contrary to popular belief, at least 60% of children with ADHD continue to exhibit features of the disorder during adulthood. ADHD in adults is associated with significant psychiatric morbidity and higher than average rates of divorce, unemployment, substance abuse, and motor vehicle accidents.2 Poor adjustment and performance can have an erosive effect on self-esteem, leading to clinically significant anxiety or depression, or both, which are often the presenting features of adult ADHD in the primary care setting.

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Prevalence and risk factors

ADHD is a neurobiologic disorder with strong genetic determinants. Strict application of diagnostic criteria has been associated with a mean prevalence of 5% to 7% across studies of children and adolescents.3 Approximately 60% to 70% of affected children transition into adulthood with some or all of the signs and symptoms of the disorder.3

Family and genetic studies have shown ADHD to be the most heritable of psychiatric disorders.4 Results from the National Comorbidity Survey Replication estimated a 4.4% prevalence of current ADHD in the U.S. adult population.5 There was a high rate of psychiatric comorbidity in ADHD adults: 38% had a mood disorder, 47% had an anxiety disorder, 15% had a substance-use disorder, and nearly 20% had an impulse-control disorder. The odds of having both ADHD and another disorder were highest for drug dependence (odds ratio [OR], 7.9), dysthymia (OR, 7.5), and bipolar disorder (OR, 7.4).5

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Pathophysiology and natural history

A variety of neurochemical and neuroanatomic deficits have been associated with ADHD.1,6,7 Studies employing structural neuroimaging point to an absence, in persons with ADHD, of the frontal lobe asymmetry seen in normal controls1 ; in control subjects (no ADHD), the right frontal lobe tends to be larger than the left. Structural and functional neuroimaging studies have demonstrated decreased function and size of the prefrontal cortex, anterior cingulate, caudate nucleus, and cerebellar vermis in ADHD children, and most (but not all) studies demonstrate this deficit on the right.6-8

Candidate gene selection is based on the hypothesis that deficient dopamine availability contributes to ADHD. Genes studied include those relevant to production of proteins involved in dopamine synthesis (dopa decarboxylase, the enzyme responsible for conversion of l-dopa to dopamine), inactivation (the dopamine and norepinephrine transporters), and degradation (catechol-O-methyltransferase) and in dopamine receptor activity (especially the dopamine D4 receptor).7 No one gene or its protein derivatives has been found to have a consistent relation with ADHD, which suggests that like most psychiatric disorders, ADHD is the consequence of polygenetic influences.

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Signs and symptoms

The manifestations of ADHD in adults are generally less obvious than in children. Adults tend not to exhibit the impulsive, overactive behavior distinctive of many ADHD children and adolescents.1,2 Common dysfunctional behavioral patterns in adults with ADHD include task avoidance, waiting until the last moment to complete a task, completing all but the most important tasks, and taking on new tasks before finishing others (Table 1).2 Impatience, irritability, and explosiveness are common as well. Common comorbidities complicate the array of signs and symptoms that ADHD adults can present with. Abnormal mood, vocational and interpersonal problems, and substance abuse are often the problems that patients present with when the underlying primary diagnosis is ADHD.

Table 1: Common Dysfunctional Behavior Patterns in Adults with ADHD
Behavior Description Short-Term Gain and Long-Term Loss
Anticipatory avoidance Magnifying the difficulty of a pending task and doubts about being able to complete it Defers short-term stress but often creates a self-fulfilling prophecy because the task looms ahead and can seem overwhelming when facing a deadline
Results in rationalizations to justify procrastination
Brinkmanship Waiting until the last moment (e.g., the night before) to complete a task, often when facing an impending deadline Deadline-associated stress can be focusing, but this tactic leaves little room for error and can yield a substantial result
Pseudoefficiency Completing several low-priority, manageable tasks (e.g., checking e-mail) but avoiding high-priority tasks (e.g., a project for work) Creates sense of productivity by reducing items on a to-do list but defers a more difficult project
Juggling Taking on new, exciting projects and feeling busy without completing projects already started It is easier to become motivated to start a novel project than to complete an ongoing one
Pattern usually results in several incomplete projects

ADHD, attention-deficit/hyperactivity disorder.
Adapted with permission from Rostain AL, Ramsay JL: Adults with ADHD? Try medication and psychotherapy. Curr Psychiatry 2006;5:13-27.

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Diagnosis

Diagnostic criteria have been developed for children and adolescents (Box 1)9 but not specifically for adults. Despite having clinically significant ADHD, many adults do not fulfill the threshold of six or more criteria defined for children and adolescents. This points to the fundamental problem of employing a descriptive nosology to define clinical disorders. Future editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM) will struggle with this dilemma until the pathophysiologic mechanisms of specific psychiatric disorders such as ADHD are better understood.

Box 1: Diagnostic Criteria for Attention-Deficit/Hyperactivity Disorder
Diagnostic Criteria
  • Meets symptom criteria
  • Some inattention or hyperactivity-impulse symptoms causing impairment are present before age 7 years
  • Some impairment from symptoms present in two or more settings (e.g., home, school or work, social)
  • Clear evidence of clinically significant impairment in social, academic, or occupational functioning
Symptom Criteria
At least six symptoms of inattention or at least six symptoms of hyperactivity or impulsivity have persisted for at least 6 months and occur often enough to be maladaptive and inconsistent with developmental level.
Inattention
  • Fails to pay close attention to details or makes careless mistakes in schoolwork, work, or other activities
  • Has difficulty sustaining attention in tasks or play activities
  • Does not seem to listen when spoken to directly
  • Does not follow through on instructions and fails to finish schoolwork, chores, or work duties (not due to oppositional behavior or failure to understand)
  • Has difficulty organizing tasks and activities
  • Avoids, dislikes, or is reluctant to engage in tasks requiring mental effort (e.g., schoolwork, homework)
  • Loses things necessary for tasks or activities (e.g., written instructions, school assignments, textbooks, pencils, tools, toys)
  • Is easily distracted by extraneous stimuli
  • Is forgetful in daily activities
Hyperactivity
  • Fidgets with hands or feet and squirms in seat
  • Leaves seat in classroom or other situations where remaining seated is expected
  • Runs about or climbs excessively in situations where these activities are considered inappropriate; in adolescents or adults, this feature may be limited to subjective feelings of restlessness
  • Has difficulty in playing or engaging in leisure activities quietly
  • Is on the go or acts as if driven by a motor
  • Talks excessively
Impulsivity
  • Blurts out answers before questions are completed
  • Has difficulty awaiting turn (impatient)
  • Interrupts or intrudes on others (e.g., butts in on conversations, games)
Exclusion Criteria
  • Symptoms do not occur exclusively during course of a pervasive developmental disorder, schizophrenia, or psychotic disorder.
  • Symptoms are not better accounted for by another mental disorder (e.g., mood disorder, anxiety disorder, dissociative disorder, personality disorder).
Situational Notes
  • Symptoms might not be observable when the patient is in highly structured or novel settings, engages in interesting activity, receives one-on-one attention or supervision, or is in a situation with frequent rewards for appropriate behavior.
  • Symptoms typically worsen in situations that are unstructured, minimally supervised, or boring or that require sustained attention or mental effort.
  • In adolescents (or adults), symptoms include restlessness (rather than hyperactivity, as seen in children), impaired academic performance, low self esteem, poor peer relations, and erratic work record.

Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text rev. Washington, DC: American Psychiatric Association, 2000.


Figure 1 is an algorithm for diagnosing ADHD in the adult patient. The core criteria for the diagnosis of adult ADHD is the evidence of the disorder during childhood, symptom persistence, and functional impairment.3 Determining whether the patient fulfilled these criteria depends almost exclusively on the patient's knowledge of his or her childhood behavior and school performance. Most adults with ADHD recall some evidence of problems related to either inattention or hyperactivity during childhood. Trouble sitting still, frequent fighting, temper outbursts, tendency to daydream, or suboptimal school performance is typical. Those with clinically significant ADHD who report successful school performance may have compensated with higher-than-average intellectual strengths, had an insufficiently challenging curriculum, or simply do not remember accurately. School performance records or collateral information from parents can be very helpful. Published questionnaires can be used to capture the necessary information and can assist with (but not confirm) the diagnosis (Box 2). Ultimately, however, the clinician must rely on the patient's veracity and accuracy of recall.

Box 2: Rating Scales Used in Diagnosing Attention-Deficit/Hyperactivity Disorder
Adult ADHD Self-Report Scale (AASRS) Symptom Checklist
Barkley ADHD Behavior Checklist for Adults
  • In Barkley RA (ed): Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment, 3rd ed. New York, Guilford Press, 2006.
Conners’ Adult ADHD Rating Scales (CAARS)
Wender-Utah Rating Scale (WURS)

ADHD, attention-deficit/hyperactivity disorder.


There is no diagnostic laboratory test for ADHD. Neuropsychological testing can be used to determine whether or not a learning disability is present (e.g., dyslexia), but it cannot confirm the diagnosis of ADHD (by definition, not a learning disability). Although neuroimaging and genetic testing offer attractive diagnostic potential, they are not sufficiently specific or sensitive for routine clinical use.

The difficulty of diagnosing ADHD in adults results largely from the nonspecificity of this behavior-symptom complex. Compounding the lack of specificity, many adults with long-standing undiagnosed and untreated ADHD develop secondary mood, anxiety, or substance-use disorders, alone or in combination, that become the focus of clinical attention and obscure detection of the more fundamental problem with attention. The National Comorbidity Survey Replication showed that many adults with ADHD are receiving treatment for other comorbid mental or substance-use disorders but not for ADHD.5

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Differential diagnosis

Virtually any type of distress, regardless of the cause, can interfere with normal attention. Therefore, the feature that distinguishes ADHD from other causes of inattention is a lifelong pattern of the behavior-symptom complex. When this criterion is not met, other diagnoses must be considered (Table 2). Adults with ADHD are at greater risk for having or developing mood, anxiety, and substance-use disorders.5 Accurate diagnosis of these disorders and determining whether they are comorbid or secondary to ADHD have important implications for treatment selection and prognosis. Successful treatment of a comorbid disorder reduces symptom burden, but it does not affect the symptoms and behavior of ADHD. On the other hand, successful treatment of ADHD can result in improvement of secondary anxiety, depression, or substance abuse. Certain disorders that are commonly associated with or have features that can mimic ADHD are listed in Table 2.

Table 2: Differential Diagnosis of Attention-Deficit/Hyperactivity Disorder
Diagnosis DSM IV-TR Feature(s) Shared with ADHD
Mood Disorders
Major depression 296.2-3 Trouble concentrating; trouble initiating and completing tasks
Dysthymia 300.4 Trouble concentrating; trouble initiating and completing tasks
Depression NOS 311 Trouble concentrating; trouble initiating and completing tasks
Bipolar disorder 296.4-6 Distractability, hyperactive behavior
Cyclothymia Distractability, hyperactive behavior
Anxiety Disorders
Generalized anxiety disorder 300.02 Inattention, distractability
Social anxiety disorder 300.23 Performance anxiety, task avoidance (especially tasks performed in front of others), unsatisfying social interaction
Obsessive-compulsive disorder 300.3 Repetitious activity
Anxiety disorder NOS 300.00 Inattention, distractability
Substance-Use Disorders
Nicotine dependence 305.10 Poor job performance and socialization
Commonly comorbid with ADHD
Alcohol abuse or dependence 305.0/303.90 Poor job performance and socialization
Commonly comorbid with ADHD
Cannabis abuse or dependence 305.20/304.30 Poor job performance and socialization
Commonly comorbid with ADHD
Impulse-Control Disorders
Intermittent explosive disorder 312.34 Impulsivity, aggression
Impulse control disorder NOS 312.30 Impulsivity, trouble with task completion
Learning Disorders
Learning disorder NOS 315.9 History of poor school and job performance
Early onset dementia 290.10 Poor attention, forgetfulness
Mild MR 317 Trouble with learning, reading, attention
Personality Disorders
Borderline personality disorder 301.83 Impulsivity, aggression
Antisocial personality disorder 301.7 Impulsivity, aggression, history of poor school and job performance

ADHD, attention-deficit/hyperactivity disorder; DSM IV-TR, Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision; MR, mental retardation; NOS, not otherwise specified.

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Treatment

Figure 2 is a management algorithm. Optimal treatment of adult ADHD invariably requires pharmacotherapy. Adding life-skills coaching or cognitive-behavioral therapy, or both, in either individual or group settings can further improve outcome, but by themselves they are generally insufficient. Partners and family members can benefit from better understanding of the impact of ADHD on the patient's behavior and interpersonal style.2

Baseline measures of weight, heart rate, and blood pressure should be obtained before starting stimulant or nonstimulant medication. The patient with a history of cardiovascular abnormalities, in particular structural heart disease (e.g., idiopathic hypertrophic subaortic stenosis) should avoid stimulant medication in favor of a nonstimulant agent such as atomoxetine, bupropion, or modafanil. Treatment of such patients should involve close collaboration with an internist or cardiologist.

Medications

The standard of care for adults has evolved largely from studies in children, and the medications used in adults are the same as those used in children and adolescents with ADHD (Table 3).

Table 3: Medications for Attention-Deficit/Hyperactivity Disorder
Drug Trade Name Dosage Form (mg) Dose* (mg) Duration (h) Frequency Comments
CNS Stimulants
Dexmethylphenidate Focalin 2.5, 5, 10 5-20 3-6 tid-qid Dextroisomer of methylphenidate
Start at 50% of current daily dose to convert from methylphenidate
Focalin XR 2.5, 5, 10 10-20 8-10 qd-bid Dextroisomer of methylphenidate
Start at 50% of current daily dose to convert from methylphenidate
Dextroamphetamine Dexedrine 5 10-30 3-6 bid-tid
Dexedrine spansule 5, 10, 15 10-30 6-8 qd-bid Dexedrine spansule
Methylphenidate Concerta 18, 27, 36, 54 18-54 10-12 qd The FDA-approved max dosage in children and adolescents is 54 mg qd, but doses of 108 mg qd have been used successfully in children and adults
Metadate ER 10, 20 20-60 6-8 qd-bid
Metadate CD 10, 20, 30, 40, 50, 60 8-10 qd-bid
Methylin 5, 10, 20 15-45 3-6 tid-qid
5/5 mL, 10/5 mL solution
Methylin ER 6-8 qd-bid
Ritalin 5, 10, 20 10-40 3-6 tid-qid
Ritalin SR 20 6-8 qd-bid
Ritalin LA 20, 30, 40 6-8 qd-bid Lasts longer than SR
Mixed-amphetamine salts Adderall 5, 7.5, 10, 12.5, 15, 20, 30 6-8 qd-bid
Adderall XR 5, 10, 15, 20, 25, 30 20-60 8-10 qd-bid
Vyvanse 30, 50, 70 30-100 12 qd-bid Pro-drug
Selective Norepinephrine Reuptake Inhibitor
Atomoxetine Strattera 10, 18, 25, 40, 60 40-100 24 qd-bid Better than placebo, but not as effective as CNS stimulants in controlled trials for ADHD
Alternative Medications
Bupropion Wellbutrin 75, 100 150-450 24 tid
Wellbutrin SR 100, 150, 200 150-450 24 bid
Wellbutrin XL 150, 300 150-450 24 qd
Desipramine Norpramin 10, 25, 50, 75, 100, 150 100-200 24 qd
Modafinil Provigil 100, 200 100-400 qd

ADHD, attention-deficit/hyperactivity disorder; CNS, central nervous system; FDA, U.S. Food and Drug Administration.
* The last dose is the FDA-approved maximum daily dosage in children.
† There is no obvious difference between these two products in terms of dosage, duration, and efficacy.
‡ These agents may be effective in some instances of ADHD but have not been shown in controlled trials to be more effective than placebo. They are not approved by the FDA for treating ADHD.

Central nervous system (CNS) stimulants such as dextroamphetamine, methyphenidate, and dexmethylphenidate are the drugs of choice for ADHD in both children and adults. Their therapeutic effect is associated with enhancement of central dopaminergic and noradrenergic activity.1 CNS stimulant compounds augment synaptic catecholamine concentrations by triggering presynaptic release of dopamine (and to a lesser extent norepinephrine) and also by blocking their reuptake.7 Drugs that influence both dopaminergic and noradrenergic function (e.g., dextroamphetamine, methylphenidate, dexmethylphenidate) are stimulants, and those that have less or no impact on dopamine and more on norepinephrine are nonstimulants, such as atomoxetine (Strattera). Other nonstimulant agents whose mechanism of action in ADHD is not fully understood include bupropion and imipramine.

Dose

The dosage of medication must be individualized by increasing gradually to maximal benefit while avoiding side effects. These principles hold for both stimulant and nonstimulant drugs. Clinical experience suggests a fine line between too little and too much medication.

Onset of Effect

Stimulant drugs have a rapid onset of effect. Clinical effects are felt within 15 to 30 minutes of oral administration, and peak blood levels are achieved within approximately 2 hours. It can take a week or more, however, to achieve full therapeutic effect. Assessing the patient's response to medication must account for exposure to circumstances that affect attention (e.g., comorbid disorders, environmental stress) and how effectively the patient monitors his or her response to medication. The nonstimulants work more gradually and can take days to weeks to achieve a full therapeutic effect.

The stimulants come in immediate-release and sustained-release forms (see Table 3). Immediate-release forms last anywhere from 2 to 6 hours, necessitating 2 to 4 doses daily. Sustained-release forms last 8 to 12 hours, permitting once- or twice-daily dosing.

Side Effects

Stimulant side effects are typically dose related and include nausea, headache, jitteriness, tics, high blood pressure, and high heart rate. They also have potential for abuse. Patients with baseline tachyarrhythmia, hypertension, or structural heart disease are at high risk for stimulant-induced aggravation of these abnormalities. The nonstimulant atomoxetine can cause increases in heart rate and blood pressure, but it is far less likely to do so than stimulants are. Its most common side effects include dry mouth, nausea, and sexual difficulties. Nonstimulants have no abuse potential.

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Prevention and screening

It is reasonable to expect that timely and effective treatment should reduce the risk of psychosocial morbidity associated with ADHD. A small but growing body of evidence suggests that patients with ADHD who are treated for it have less substance abuse, better work and academic performance, and better outcomes in general than those who are not treated.10

If the extensive psychosocial morbidity of ADHD can be prevented, then it stands to reason that it should be identified and treated as early as possible. In fact, many adults go through life without recognizing they have ADHD. This, as well as the complex comorbidities (e.g., depression, anxiety, substance abuse) that often trigger a request for help, make it difficult to detect ADHD.

Three validated patient self-report instruments are available to screen for ADHD in adults; alternatively, they can be used to substantiate a physician's clinical impression. The World Health Organization (WHO) Adult Self-Report Screener (ASRS) for Adult Attention Deficit Disorder (ADD) includes six questions rated on a scale from 0 to 4 (0 = never, 1 = rarely, 2 = sometimes, 3 = often, 4 = very often). The maximum score is 24; the higher the score, the more likely that ADHD is present. The Wender Utah Rating Scale (WURS) was originally used as a research instrument and validated as a screener subsequently. A score of 46 or more obtained from adding the ratings on items 3-7, 9-12, 15-17, 20, 21, 24-29, 40, 41, 51, 56, and 59 is highly predictive of a diagnosis of ADHD. The Conner Adult ADHD Rating Scales (CAARS) elicit self reports and observer ratings. Further information about these scales and their acquisition is available in Box 2.

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Special populations

Geriatric Patients

There is no age limit for the diagnosis of ADHD. Geriatric-age patients with a diagnosis of ADHD can benefit considerably from appropriate treatment. Older patients are more likely, however, to have coexisting cardiovascular abnormalities that warrant careful monitoring during treatment with stimulant medication.

Potential Substance Abusers

The challenge for the prescribing physician is to keep stimulant medications out of the hands of persons prone to drug or alcohol addiction. The risk of stimulant-induced substance abuse in uncomplicated adult ADHD is minimal. This risk liability is further reduced by the use of long-acting agents (see Table 3). Effective treatment of ADHD should reduce the risk of substance abuse, especially when substance abuse is secondary to ADHD. For persons with ADHD and comorbid substance abuse or dependence, the treatment of choice includes a nonstimulant agent such as atomoxetine, buproprion, or imipramine. A blanket policy of refusal to prescribe CNS stimulants to patients with a history of drug abuse, however, is ill advised. In all cases, substance abuse must be stabilized first, and ADHD treatment can be initiated as soon as the substance abuse is stabilized.

Patients with Cardiovascular Disease

CNS stimulant medications are relatively contraindicated in patients with hypertension, cardiac arrhythmia, tachycardia, coronary artery disease, and structural heart disease (e.g., idiopathic hypertrophic subaortic stenosis). Nonpharmacologic therapies or nonstimulant medications should be tried first in such patients. If these are ineffective, however, and the fully informed patient desires a trial of stimulant medication, it should be prescribed with careful monitoring in conjunction with the supervision of a cardiologist or internist to minimize the risk of adverse outcome.

Epileptic Patients

CNS stimulants do not cause a clinically significant reduction in seizure threshold and therefore can be used safely in patients with epilepsy.

Pregnant Women

All CNS stimulant drugs are listed as class C and should therefore be avoided if possible during pregnancy.

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Summary

  • Adult attention-deficit/hyperactivity disorder (ADHD) is a familial disorder with first manifestations before age 7 years.
  • At least 60% of children with ADHD continue to exhibit clinically significant features of the disorder as adults.
  • ADHD is among the most heritable of psychiatric disorders.
  • Undiagnosed or untreated ADHD is associated with significant morbidity, including higher-than-expected rates of maladaptive behavior, family problems including divorce, problematic employment, substance abuse, motor vehicle accidents, and secondary mood and anxiety disorders.
  • The primary treatment for adult ADHD is a methylphenidate- or amphetamine-based compound supplemented when necessary with structured, skills-based cognitive-behavioral therapy.

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References

  1. Barkley RA. Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment. 2nd ed. New York: Guilford Press, 1998, pp 3-55.
  2. Rostain AL, Ramsay JL. Adults with ADHD? Try medication and psychotherapy. Curr Psychiatry. 2006, 5: 13-27.
  3. McGough JJ, Barkley RA. Diagnostic controversies in adult attention deficit hyperactivity disorder. Am J Psychiatry. 2004, 161: 1948-1956.
  4. Hudziak JJ, Derks EM, Althoff RR, et al: The genetic and environmental contributions to attention deficit hyperactivity disorder as measured by the Conners' Rating Scales—Revised. Am J Psychiatry. 2005, 162: 1614-1620.
  5. Kessler RC, Adler L, Barkley R, et al: The prevalence and correlates of adult ADHD in the United States: Results from the national comorbidity survey replication. Am J Psychiatry. 2006, 163: 716-723.
  6. Vaidya CJ, Bunge SA, Dudukovic NM, et al: Altered neural substrates of cognitive control in childhood ADHD: Evidence from functional magnetic resonance imaging. Am J Psychiatry. 2005, 162: 1605-1613.
  7. Pliszka SR. Neuroscience for the Mental Health Clinician. New York: Guilford Press, 2003, pp 147-150.
  8. Biederman J, Safren SA, Seidman LJ, et al: ADHD: Applying practice guidelines to improve patient outcome and executive function. J Clin Psychiatry. 2006, 67: 2014-2025.
  9. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association, 2000.
  10. Lamberg L. ADHD often undiagnosed in adults. Appropriate treatment may benefit work family social life. JAMA. 2003, 290: 1565-1597.

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