Treating Adult ADHD
Pharmacotherapy. Ample data in the pediatric ADHD literature support the efficacy of stimulant medications.64 About 70% of children with ADHD will demonstrate a therapeutic response to stimulant medication.32,65 Early adult ADHD data suggested a less robust treatment response.57,62,66 However, Spencer and colleagues67 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(Drug information on 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 wellknown than methylphenidate and amphetamines, lisdexamfetamine is a pro-drug that converts to dextroamphetamine in the body.) Atomoxetine(Drug information on 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.42,68,69 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.70 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 that is 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.71 Atomoxetine also lacks the midbrain dopamine(Drug information on dopamine) effects that have been linked to addictive potential.72 There is also some evidence that atomoxetine may be particularly effective for adults with comorbid ADHD and depression. 73 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(Drug information on modafinil), and desipramine have also been described as effective for managing ADHD and may be used as second-line agents.32,74,75 Bupropion has demonstrated efficacy in open and controlled studies and may be particularly effective in adults with ADHD who have comorbid mood disorders.74,76-78 Modafinil has also been shown to be efficacious for adult ADHD in 2 double-blind, randomized, placebo-controlled studies. 75,79 Rather than affecting dopamine and norepinephrine(Drug information on norepinephrine) in the striatum, modafinil alters the balance of γ-aminobutyric acid and glutamate. Desipramine has been shown to be efficacious for adult ADHD in a double- blind, placebo-controlled study.80
Findings suggest that adults with ADHD are more likely to require polypharmacy than children with ADHD.23,81-83 In addition, there is some evidence that baseline clinician ratings of ADHD symptoms are stronger predictors of pharmacotherapy treatment outcome than baseline patient reports.84
Cognitive-behavioral therapy. A psychosocial treatment component is generally recommended in addition to pharmacotherapy.85 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.86 Similarly, CBT may be effective for reducing functional impairments in adults with ADHD being treated with stimulants.87
Safren and colleagues87 developed a supplemental CBT program for adults with ADHD who were receiving medication. Initial results from a small-scale study of this manualized therapy have been showing significant benefits beyond those achieved by medication alone.87
Ramsay and Rostain88 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 persons longitudinally across their life spans also presents a unique method of tracking not only interindividual change but also intra-individual 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.89 This sexbased difference, however, appears less marked in adult ADHD.58,90,91 Relative to boys with ADHD, lower rates of externalizing disorders in girls have been found.89,92 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 persons (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 ageat- 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.
Therapeutic Agents in This Article
Atomoxetine (Strattera)
Bupropion (Wellbutrin, Zyban)
D-amphetamine (Dexedrine)
D,L-amphetamine (Adderall)
D,L-amphetamine ER (Adderall XR)
Desipramine (Norpramin, Pertofrane)
Dexmethylphenidate (Focalin)
Dexmethylphenidate ER (Focalin XR)
Lisdexamfetamine (Vyvanse)
Methylphenidate (Ritalin)
Methylphenidate ER (Ritalin LA,
Metadate CD, Concerta, Daytrana)
Modafinil (Provigil)
