A Randomized Double-Blind Trial of Paroxetine and/or Dextroamphetamine and Problem-Focused Therapy for Attention-Deficit/Hyperactivity Disorder in Adults.

Objective: To determine the effect of psychotherapy, dextroamphetamine, and/or paroxetine on attention-deficit/hyperactivity-disorder (ADHD) in adults.

Method: Ninety-eight adults with DSM-IV ADHD were randomly assigned to receive psychotherapy and dextroamphetamine, paroxetine, both, or placebo for 20 weeks. A 2×2 factorial design compared patients who received dextroamphetamine versus no dextroamphetamine with patients who received paroxetine versusno paroxetine. Data were collected from August 2000 until May 2002.

Results: One half of the 98 enrolled subjects were found to have at least 1 lifetime mood or anxiety disorder on the Structured Clinical Interview for DSM-IV. Sixty percent of patients who received medication and 80% of those who received placebo completed the5-month trial. ADHD symptoms were significantly (p = .012) lower in patients in the completer group who received dextroamphetamine. Paroxetine had no effect on ADHD. Hamilton Rating Scales for Anxiety(HAM-A) and Depression (HAM-D) scores were lowto start, and no treatment differences were evident at endpoint. Significantly (p < .001) more patients in the completer group were rated by clinicians as ADHDresponders if they received dextroamphetamine (85.7%) or combined treatment (66.7%) versus paroxetine (20.0%) or placebo (21.1%). Significantly (p = .003) more patients in the completer group were rated byclinicians as mood/anxiety responders if they received paroxetine (100%) or combined treatment (73.3%)
versus those receiving dextroamphetamine (57.15%)or placebo (47.4%). Clinicians rated any patient who received medication and psychological therapy assignificantly more improved overall than those whoreceived placebo and psychological therapy (intentto treat: p = .033; completers: p = .001).

Conclusion: ADHD symptoms improved withdextroamphetamine. Mood and internalizing symptoms were seen as improved with paroxetine by clinicians, despite absence of response on the HAM-A and HAM-D. The presence of a lifetime internalizing disorderattenuated the response to dextroamphetamine. Patients who received both dextroamphetamine and paroxetine had more severe adverse events but did not show greater improvement overall than patients treated with 1 medication. Clinical Trials Registry #GSK707.