Diagnosing and Treating ADHD in Adults

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Educational Objectives

After reading this article, you will be familiar with:

• The differences between childhood and adult attention-deficit/hyperactivity disorder (ADHD).
• The extent of functional impairment with ADHD.
• The clinical scales that can be used to diagnose and measure adult ADHD.
• Available options for treating adult ADHD.

Who will benefit from reading this article?
Psychiatrists, primary care physicians, neurologists, nurse practitioners, and other health care professionals. Continuing medical education credit is available for most specialists. To determine whether this article meets the continuing education requirements of your specialty, please contact your state licensing board.

Dr Faraone is professor of psychiatry and behavioral sciences, departments of psychiatry and behavioral sciences and neuroscience and physiology; Drs Antshel and Kunwar are assistant professors in the department of psychiatry and behavioral sciences at the State University of New York Upstate Medical University.

Drs Antshel and Kunwar report that they have no conflicts of interest concerning the subject matter of this article. Dr Faraone reports that he has received research support from Shire Pharmaceutical Development, Pfizer, NIMH, and the National Institute of Drug Abuse; and he is a consultant for Shire Pharmaceutical Development.

In the past 15 years, there has been an increasing awareness of the syndromal persistence of attention-deficit/hyperactivity disorder (ADHD) into adulthood. Once considered only a childhood disorder, ADHD has become increasingly recognized as a valid psychiatric disorder in adults.^1-3 Proponents of ADHD as a valid adult diagnosis do not suggest that ADHD arises de novo in adulthood. Rather, adult ADHD is considered the natural continuation of childhood ADHD, albeit with a different topographical expression of symptoms. The focus of this article is to discuss what is known about ADHD in adults, with a particular emphasis on diagnosis and treatment strategies.

COMPARISONS WITH PEDIATRIC ADHD
Prevalence and symptoms
In children, the prevalence of ADHD is typically cited as between 3% and 5% of the general population while in adults, studies suggest that the prevalence is about 4%.^4,5 This is not surprising given that longitudinal research indicates that the majority (50% to 70%) of children with ADHD continue to show impairing symptoms as they age.⁶ ADHD research in children and adults indicates that inattention and hyperactivity/impulsivity are the defining features of the disorder. For example, in a family study of ADHD, more than two-thirds of nonreferred adult relatives of children with ADHD reported current ADHD symptoms at levels comparable to those in pediatric participants with ADHD.⁷ These data suggest that inattentive and hyperactive/impulsive symptoms are the defining features of ADHD in both clinically referred and nonreferred adults.^8-13 Despite the similar symptoms, several core DSM-IV ADHD symptoms (eg, hyperactivity) lessen or mollify over time.¹⁴ For example, Eaton and colleagues¹⁵ demonstrated that psychomotor activity levels decline after age 9 in the general population. Thus, "running about or climbing on things inappropriately" may have less predictive power as a diagnostic symptom in adulthood.

This has led to some diagnostic confusion and possibly underdiagnosis of adult ADHD.³

In addition, teachers and school personnel are attuned to ADHD and are familiar with the disorder in children, while employers are likely to be less mindful of possible ADHD symptoms in adults. In the absence of a formal screening mechanism, adults with ADHD may also be less likely to be referred for treatment. Although the symptoms appear to be equally defining in children and adults, the topography of these symptoms may be quite different in adults, possibly contributing to ADHD underdiagnosis in adults.¹⁶Comorbidity
Pediatric ADHD commonly co-occurs with multiple psychiatric disorders including mood, anxiety, and disruptive behavioral disorders.^17,18 Likewise, adult ADHD is associated with comorbid mood, anxiety, and substance use disorder diagnoses.^8,13,19-23 Comorbidity rates in adult ADHD do not differ as a function of gender; this is in contrast to the higher prevalence of externalizing disorder comorbidities observed in boys with ADHD.^24,25 ADHD in adults is not always comorbid with other psychiatric conditions, however, and some data suggest that uncomplicated ADHD exists in about 20% to 25% of adults with ADHD.⁸Genetics
ADHD is a highly heritable condition (average heritability index = 0.76).²⁶ Family studies of pediatric ADHD suggest that the parents of children with ADHD are more likely than parents of other children to have ADHD themselves.²⁷ The same holds true in adult ADHD; offspring of parents with ADHD are more likely to have ADHD themselves.^28,29 Biederman and colleagues²⁹ found a 57% prevalence of ADHD in children of adults with the disorder, which is much higher than the 15% prevalence of ADHD among siblings of children with ADHD.

Genetic factors appear to play a stronger role in those who continue to demonstrate clinically significant ADHD into adulthood than in those whose symptoms are in remission.^30,31 For example, a prospective ADHD study with a 4-year follow-up examined 140 boys with ADHD and 120 boys without ADHD at baseline. By midadolescence, 85% of the boys with ADHD continued to have the disorder. The prevalence of ADHD was significantly higher among the relatives of children with persistent ADHD than among relatives of children with ADHD whose symptoms were in remission.³²

Parents of persistent ADHD probands were 20 times more likely to have ADHD than parents of controls, whereas parents of nonpersistent ADHD probands showed only a 5-fold increased risk. Similarly, siblings of persistent ADHD probands were 17 times more likely to have ADHD than siblings of controls, while siblings of nonpersistent ADHD probands showed only a 4-fold increased risk.³³ When ADHD persists into adulthood, it is decidedly familial.

FUNCTIONAL IMPAIRMENTS
Significant functional impairment in educational, marital, interpersonal, and occupational realms and in motor vehicle operation is common in adult ADHD.^13,34-40 In fact, recently published longitudinal research findings indicate that ADHD in adults is a far more impairing disorder than many other disorders (eg, anxiety and mood disorders) across multiple domains of major life activities, especially educational and occupational functioning, money management, and management of daily responsibilities.²³ Adults with ADHD are also more likely to receive speeding violations and have their driver's license suspended.^13,41 These motor vehiclerelated infractions are not related to deficits in driving skills or knowledge.¹³ Computer-simulated driving tests also demonstrate that adults with ADHD have more accidents and near-accidents.¹³ Similar functional impairment findings have been seen in other studies that compared adults with ADHD and psychiatric control samples.^8,13,24 Morrison²⁰ compared adults with ADHD to age- and sex-matched psychiatric controls on educational and occupational achievement variables. Relative to psychiatric controls, adults with ADHD had fewer years of education and lower rates of professional employment. There is evidence that the lower rates of professional employment are not accounted for by comorbid psychopathology.⁴²

It is not surprising that adults with ADHD have lower rates of professional employment, given that academic underachievement and learning disabilities are common in children with ADHD.^37,38 A community study showed that the profile of impairments of adults with ADHD diagnosed in the community was similar to that seen in samples in whom ADHD was diagnosed in academic centers.³⁹ Likewise, data from adults with previously undiagnosed ADHD indicated more psychiatric comorbidity and functional impairments than did non-ADHD controls; even when unrecognized, ADHD in adults is functionally impairing.⁴⁰

Elevated prevalence of substance abuse/dependence has consistently been reported in adults with ADHD.^41,43,44 An estimated 17% to 45% of adults with ADHD have histories of alcohol abuse or dependence and 9% to 30% have histories of drug abuse or dependence.^44,45 A study of treatment-naive adults with ADHD found that the risk of substance abuse/dependence developing over the life span is 2-fold compared with adults who do not have ADHD (52% vs 27%, respectively). Although a history of conduct or bipolar disorders increases that risk, ADHD is an independent risk factor for later substance abuse/dependence.^35,45-47 Studies have shown that compared with adults who do not have ADHD, adults with comorbid ADHD and substance abuse/dependence have an earlier onset and a greater severity of substance abuse.^36,48,49

Likewise, findings indicate that ADHD is elevated in substance users.^47,50,51 Studies of substance-dependent populations report the prevalence of ADHD ranges from 15% to 25%.⁴² The presence of ADHD appears to potentiate the substance abuse/dependence, resulting in a more severe disorder and poorer outcomes.^42,52 The increased prevalence of substance abuse/dependence in ADHD has been reported in longitudinal studies that followed children with well-characterized ADHD into adulthood, as well as individuals with ADHD that is diagnosed in adulthood.^10,22,46,53 Finally, among those with substance abuse disorder, adults with ADHD have higher rates of separation and divorce and lower occupational achievement than their peers.⁴²DIAGNOSING ADULT ADHD
DSM-IV criteria for ADHD symptoms are based on earlier DSM editions, expert clinical opinion, and a field trial of the psychometric properties and utility of the item pool.²⁴ The proposed DSM-IV ADHD items were field-tested using a sample of 380 clinically referred children aged 4 to 17 years. The 18 items that appear in DSM-IV correlate highly with parent and teacher ratings of impairment and best differentiate ADHD from non-ADHD disorders.²⁴

Adults were not included in the ADHD field trials for DSM-IV. Thus, there was no attempt to assess the developmental appropriateness of the ADHD symptoms for diagnosing the disorder in adults. For example, DSM-IV symptoms such as "runs and climbs excessively" are clearly inappropriate for adults. Similarly, the cutoff score of 6 of 9 symptoms was based on pediatric data, which may be too restrictive for adults.^24,54 Unlike diagnosing ADHD in children, diagnosing ADHD in adults relies highly on self-report. Asking a 42-year-old man to recall behaviors before age 7 most likely introduces recall biases.⁵⁵ For this and other reasons, the age of onset should be redefined as early adolescence.^56,57

To study the validity of the age of onset criterion, Faraone and colleagues⁵⁷ studied 127 subjects with full ADHD who met all DSM-IV criteria for childhood-onset ADHD, 79 subjects with late-onset ADHD who met all criteria except the age-at-onset criterion, 41 subjects with subthreshold ADHD who did not meet full symptom criteria for ADHD, and 123 subjects without ADHD. Those with late-onset and full ADHD had similar patterns of psychiatric comorbidity, functional impairment, and familial transmission. Subthreshold ADHD was milder and showed a pattern of familial transmission different from that of the other forms of ADHD. These data demonstrate that criteria requiring strict adherence to an age at onset of 7 years may not be especially sensitive for diagnosing ADHD in adults.

In addition to DSM-based checklists, the Wender Utah Rating Scale (WURS) is also used in the diagnosis of adult ADHD.⁵⁸ A self-report instrument, the WURS was designed to aid in the retrospective assessment of ADHD but was not intended for diagnosis of childhood ADHD in the absence of other clinical information. The WURS is often applied to diagnosing ADHD by the Utah criteria, which include 7 symptom clusters that characterize adult ADHD⁵⁹:

• Inattentiveness.
• Hyperactivity.
• Mood lability.
• Irritability and hot temper.
• Impaired stress tolerance.
• Disorganization.
• Impulsivity.

To meet diagnostic criteria for ADHD in adults, the Utah criteria require a retrospective childhood diagnosis, ongoing difficulties with inattentiveness and hyperactivity, and at least 2 of the remaining 5 symptoms. Some have argued that the Utah criteria are not specific enough for ADHD and may capture psychiatric comorbidities such as depression.⁶⁰

The 40-item Brown Attention-Deficit Disorder Scale for Adults,⁶¹ which is used to assess symptoms beyond the DSM-IV 9-item inattention symptom list, may be the best tool for clinical diagnosis of adult ADHD.^61,62 This scale measures 5 clusters (hyperactivity and impulsivity are not assessed on this scale):

• Organizing and activating to work.
• Sustaining attention and concentration.
• Sustaining energy and effort.
• Managing affective interference.
• Using working memory and accessing recall.

The Conners Adult Attention-Deficit/Hyperactivity Disorder Rating Scale: Screening Version⁶³ is a self- and other-report measure of ADHD symptom severity during the past week. The instrument has 30 items that contribute to 3 subscales: inattention (9 items); hyperactivity/impulsivity (9 items); and ADHD index (12 items).

The World Health Organization Adult ADHD Self-Report Scale⁶⁴ is another screening tool. The scale includes 18 items generated from symptoms of ADHD typically expressed by adults with ADHD. The 18 items are then mapped onto each of the 18 DSM-IV Criterion A symptoms. Six of these items-4 inattention and 2 hyperactivity/ impulsivity-were found to be the most predictive of adult ADHD.⁶⁴ A response of "often" or "very often" on these 6 items is a strong indication of ADHD:

• How often do you have trouble wrapping up the fine details of a project once the challenging parts have been done?
• How often do you have difficulty with getting things in order when you have to do a task that requires organization?
• When you have a task that requires a lot of thought, how often do you avoid or delay getting started?
• How often do you have problems remembering appointments or obligations?
• How often do you fidget or squirm with your hands or your feet when you have to sit down for a long time?
• How often do you feel overly active and compelled to do things, as if you were driven by a motor?

TREATING ADULT ADHD
Pharmacotherapy
There are ample data in the pediatric ADHD literature to support the efficacy of stimulant medications.⁶⁵ Approximately 70% of children with ADHD will demonstrate a therapeutic response to stimulant medication.^32,66 Early adult ADHD data suggested a less robust treatment response.^58,63,67 However, Spencer and colleagues⁶⁸ hypothesized that this may have been because of insufficient dosing. To test this hypothesis, the investigators completed a double-blind, placebo-controlled study of methylphenidate for adult ADHD that achieved an average daily dose of 1.0 mg/kg. The response rate of the stimulant-treated patients (74%) was similar to that seen in children with ADHD and was significantly greater than the 4% rate seen for placebo. The efficacy of these higher doses was confirmed by meta-analysis.³⁰

Methylphenidate, amphetamines, and lisdexamfetamine are stimulants that are FDA-approved. (Less well-known than methylphenidate and amphetamines, lisdexamfetamine is a pro-drug that converts to dextroamphetamine in the body.) Atomoxetine is a nonstimulant that is FDA-approved for managing adult ADHD. Both the stimulants and atomoxetine improve core symptoms of hyperactivity, inattention, and impulsivity.^42,69,70 Thus, the same pharmacological agents that are effective in the pediatric ADHD population have also been demonstrated to be effective in adults with ADHD. See the Table for a summary of pharmacological approaches to managing ADHD in adults.

Stimulant medications are generally started at a low dosage and titrated as needed to optimize the symptom improvement without causing significant adverse effects. Common adverse effects are dry mouth, insomnia, decreased appetite, and headache. The optimal dosage is best determined by each patient's response. Traditionally, a trial with an immediate-release stimulant was undertaken before switching to a long-acting form; however, more recently, the American Academy of Child and Adolescent Psychiatry amended its practice parameters to recommend that long-acting agents be initiated first and titrated accordingly.⁷¹ A stimulant is effective as long as it remains in the system and does not have long-lasting cumulative effects. Because immediate-release stimulants have to be taken multiple times, compliance can be an issue, especially in a population known to be forgetful and disorganized.¹⁶

Atomoxetine is taken orally once or twice daily. Even with once-daily dosing, it provides full coverage in the evening with less rebound than may be observed with stimulants.⁷² Atomoxetine also lacks the midbrain dopamine effects that have been linked to addictive potential.⁷³ There is also some evidence that atomoxetine may be particularly effective for adults with comorbid ADHD and depression.⁷⁴ Common adverse effects associated with atomoxetine are dry mouth, insomnia, nausea, decreased appetite, constipation, and sexual dysfunction. There is a black box warning for increased suicidal ideation in children but not in adults.

While the stimulants and atomoxetine are more commonly prescribed for adult ADHD, bupropion, modafinil, and desipramine have also been described as effective for managing ADHD and may be used as second-line agents.^32,75,76 Bupropion has demonstrated efficacy in open and controlled studies and may be particularly effective in adults with ADHD who have comorbid mood disorders.^75,77-79 Modafinil has also been shown to be efficacious for adult ADHD in 2 double-blind, randomized, placebo-controlled studies.^76,80 Rather than affecting dopamine and norepinephrine in the striatum, modafinil alters the balance of g-aminobutyric acid and glutamate. Desipramine has been shown to be efficacious for adult ADHD in a double-blind, placebo-controlled study.⁸¹

Findings suggest that adults with ADHD are more likely to require polypharmacy than children with ADHD.^23,82-84 In addition, there is some evidence that baseline clinician ratings of ADHD symptoms are stronger predictors of pharmacotherapy treatment outcome than baseline patient reports.85

Cognitive-behavioral therapy
A psychosocial treatment component is generally recommended in addition to pharmacotherapy.⁸⁶ Although cognitive-behavioral therapy (CBT) has not been shown to be effective in children with ADHD, there are reasons to be optimistic that CBT may be effective in adults with ADHD. For example, CBT is generally more effective in adolescents than in preadolescents.⁸⁷ Similarly, CBT may be effective for reducing functional impairments in adults with ADHD being treated with stimulants.⁸⁸

Safren and colleagues⁸⁸ developed a supplemental CBT program for adults with ADHD who were recieving medication. Initial results from a small-scale study of this manualized therapy have been showing significant benefits beyond those achieved by medication alone.⁸⁸

Ramsay and Rostain⁸⁹ have also created a CBT program for adults with ADHD. In their open study, 43 adults with ADHD were treated for 6 months with a combination of pharmacotherapy and CBT. Findings from this study suggest that the combined treatment approach was effective across both symptom and functional parameters.

Future directions
Despite our increased understanding of adults with ADHD, there is much that we still do not know. For example, most of the adult ADHD research has used samples of college students or adults under the age of 40. Thus, we know far less about ADHD in middle age and beyond. Following children longitudinally across the life span also presents a unique method of tracking not only interindividual change but also intraindividual change. The use of cross-sectional research designs limits our ability to assess these parameters. As Barkley, Biederman, and others' longitudinal samples continue to age, we will know more about the continuation of ADHD in middle and late adulthood.

Pediatric ADHD is more common in boys than in girls.⁹⁰ This sex-based difference, however, appears less marked in adult ADHD.^58,91,92 Relative to boys with ADHD, lower rates of externalizing disorders in girls have been found.^90,93 The presence of an externalizing comorbid condition increases the likelihood that a child will be clinically referred for ADHD. Referral biases are possibly less salient for adults who, unlike children, can refer themselves for treatment. While this hypothesis has intuitive appeal, future studies should consider possible sex-based differences in ADHD across the life span.

Further research is needed to clarify whether the DSM-IV approach to ADHD should be modified for adults. DSM-IV recognizes developmental changes in the expression of ADHD in several ways. It cautions diagnosticians that with maturation, symptoms become less conspicuous. Older children may be restless and fidgety but not overly hyperactive. With age, inattention may predominate as tasks at school require increasing levels of attention. DSM specifies that symptoms are considered present only if they are maladaptive and inconsistent with developmental level.

DSM-IV includes the category of ADHD in partial remission for individuals (especially adolescents and adults) who currently have symptoms but no longer meet full criteria. The net effect of developmental changes is to make it more difficult for children with ADHD to meet criteria for the disorder as they get older. Although this reflects the true remission of the disorder to some extent, it may also be because of the use of insensitive diagnostic criteria.

For example, Barkley and colleagues²³ examined the utility of DSM criteria for ADHD when used with adults, and they showed that only 6 to 8 symptoms were required to diagnose ADHD in adults. (DSM-IV stipulates that 12 symptoms must be present to diagnose ADHD.) The single symptom of "often being distractible" was sufficient to differentiate ADHD from typically developing adults while 5 to 7 more symptoms were needed to discriminate those with ADHD from clinic-referred adults. Inattention and verbal impulsivity symptoms were the best discriminators between patients with ADHD and clinical controls.²³ Barkley's work as well as the work of others on the developmental sensitivity of ADHD symptoms has clear implications for the development of DSM-V.

Also relevant to DSM-V, the age-of-onset criterion (onset before 7 years) has virtually no empirical support.⁵⁶ Other investigators have argued that the onset criterion should be broadened to include midadolescence or more generically phrased as "onset in childhood."²³

Finally, as a function of educational and occupational impairments, clinicians may be asked to make recommendations concerning the need for and types of accommodations for those settings. In addition to a need for the clinician to be familiar with the standards of the Americans with Disabilities Act, which is required for obtaining such accommodations, it will also be important for future research to consider which accommodations are effective. For as often as they are used, there is remarkably little evidence that "extra time on tests" and/or "testing in a quiet, nondistracting environment" are effective for adults with ADHD.

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