EVIDENCE-BASED ANSWER
Central nervous system stimulants improve symptoms of attention deficit–hyperactivity disorder (ADHD) in adults (strength of recommendation: B, based on an older, inconclusive systematic review, a lesser-quality systematic review, and several newer small randomized controlled trials).
Although not the focus of this question, nonstimulant medications (including buproprion, modafinil, and guanfacine) have also been studied in the treatment of ADHD in adults. Recently, atomoxetine became the only nonstimulant medication to receive approval by the US Food and Drug Administration for the treatment of ADHD.
Evidence summary
A well-done systematic review of 12 trials assessing the efficacy of stimulant therapy in the treatment of adult ADHD did not find sufficient evidence that stimulants were effective.1 Significant heterogeneity and poor reporting of methodology was seen among the studies.
The 1 study rated as high-quality was a 7-week randomized controlled trial using a crossover comparison of methylphenidate and placebo.2 There was a favorable response in 78% (18/23) of subjects while takin methylphenidate, in contrast to 4% (1/23) while taking placebo (number needed to treat [NNT]=1.4; P<.0001). A favorable response was assessed by the Clinical Global Impression Scale, a measure of illness severity and improvement, and a >30% reduction in symptoms as measured by the ADHD Rating Scale. A more recent, but less rigorous, systematic review identified 15 studies of stimulant efficacy in adults.3 Researchers concluded that under controlled conditions, stimulants are efficacious in the treatment of ADHD in adults. The rate of response among the studies ranged from 25% to 78%.
One of the better studies in this review was a randomized, double-blind, 3-phase crossover study of dextroamphetamine, modafinil (a drug used to treat narcolepsy), and placebo.4 Each phase was 2 weeks long, with a 4-day washout in between. A favorable response was defined as a reduction of ADHD symptoms by at least 30% on the DSM-IV ADHD Behavior Checklist for Adults. Dextroamphetamine and modafinil showed the same response rate in 10 of 21 patients. Both treatments had a significant improvement over placebo (P<.001). It was unclear from the study what percentage of subjects responded to placebo.
A similar study compared dextroamphetamine, guanfacine (an antihypertensive agent), and placebo in 17 patients.5 On the DSM-IV ADHD Behavior Checklist for Adults, subjects taking dextroamphetamine or guanfacine reported similar decreases in mean ADHD scores compared with placebo (24 vs 22 vs 30; P<.05). They did not report the number of subjects who had a 30% reduction in symptoms. Of note: at the end of the study but prior to unblinding, subjects were asked which medication they preferred. Twelve subjects chose dextroamphetamine, 4 chose guanfacine, and 1 chose placebo. Subjects’ stated reason for choosing dextroamphetamine was the positive effect it had on their motivation.
Another study included in this review was a randomized controlled trial of mixed amphetamine salts. Of the 27 adults who completed the study, 19 (70%) responded favorably to mixed amphetamine salts compared with 2 (7.4%) receiving placebo (NNT=1.6; P<.001).6 Favorable response was defined as more than a 30% reduction of symptoms on the ADHD Rating Scale. Not included in either review was a 7-week randomized controlled trial comparing methylphenidate with sustained-release buproprion.7 Thirty out of 37 subjects completed at least 1 week of the study. The primary indicator of a favorable response was the Clinical Global Impression Scale. The rate of response was 50% for methylphenidate, 64% for sustained-release buproprion, and 27% for placebo (P<.14).
Recommendations from others
The American Academy of Child and Adolescent Psychiatry8 concluded that stimulant medication can be used to treat adults who have been carefully evaluated. They recommend starting methylphenidate, dextroamphetamine, or mixed amphetamine salts according to patient and clinician preference (Table). They do not recommend the use of pemoline due to the potential for hepatic failure.
TABLE
Stimulants used to treat ADHD in adults
| Drug | Starting dose | Maximum daily dose |
|---|---|---|
| Methylphenidate | ||
| Ritalin, Methylin | 5 mg twice daily | 65 mg* |
| Ritalin-SR, Methylin ER, Metadate ER, Metadate CR | 20 mg every morning | 65 mg* |
| Concerta | 18 mg every morning | 54 mg |
| Dextroamphetamine sulfate | ||
| Dexedrine | 2.5 mg twice daily | 45 mg* |
| Dexedrine spansules | 5 mg every morning | 45 mg* |
| Mixed amphetamine salts | ||
| Adderall | 5 mg | 40 mg |
| Adderall XR | 10 mg every morning | 30 mg |
| *American Academy of Child and Adolescent Psychiatry Practice Parameter | ||
CLINICAL COMMENTARY
Medication can help even well-adapted adults with ADHD
Daniel Triezenberg, MD
Family Practice Residency, Saint Joseph Regional Medical Center, South Bend, Ind
Stimulant therapy benefits many adult patients with ADHD. While some adults need scheduled dosing, others do well with as-needed dosing.
Adults with ADHD often have made behavioral adaptations that allow success without medication. Drugs help these patients when focused attention is critical for specific tasks. A salesman doing a month-end report may find the improvement in attention helpful, but not needed for most daily tasks. A college student may need medication only for a specific class or project. Physicians can help patients with ADHD through anticipatory guidance in choosing a program of study or career goal and then collaborating in choosing appropriate behavioral and medication therapies.