Annals of Clinical Psychiatry, Vol. 13, No. 3, September 2001 ( c  2001) Bupropion SR vs. Methylphenidate vs. Placebo for Attention Deficit Hyperactivity Disorder in Adults Samuel Kuperman, MD, 1 Paul J. Perry, PhD, 1,2,4 Gary R. Gaffney, MD, 1 Brian C. Lund, Pharm D, 2 Kristine A. Bever-Stille, Pharm D, 2 Stephan Arndt, PhD, 1,3 Timothy L. Holman, MA, 2 David J. Moser, PhD, 1 and Jane S. Paulsen, PhD 1 Despite the increasing recognition of attention-deficit hyperactivity disorder (ADHD) in adults, there are few controlled trials demonstrating the effectiveness of pharmacological treatments, particularly with nonstimulants. One controlled trial found bupropion SR more effective than placebo in the treatment of ADHD adults. We conducted a controlled study to contrast the effectiveness of bupropion SR and methylphenidate to placebo in ADHD adults. A randomized, double-blind, parallel design was used in this study. Following a 7-day placebo lead-in, 30 ADHD (DSM-IV ) subjects (18–60 years old) were randomized to bupro- pion, methylphenidate, or placebo for 7 weeks. Methylphenidate was titrated over 1 week to a maximum dose of 0.9 mg/kg/d divided into 3 doses while bupropion was titrated over 2 weeks to a maximum dose of 200 mg A.M. and 100 mg P.M. Response rates based on Clinical Global Impression improvement ratings in patients receiving bupropion, methylphenidate, and placebo were 64, 50, and 27%, respectively. The difference in response rates between active treatment and placebo was not statistically significant ( p = 0.14). Neuropsychological testing demonstrated trends favoring drug treatment on measures of immediate recall and ver- bal fluency. While bupropion SR may be a viable clinical alternative for adults with ADHD, further investigation is needed. KEY WORDS: bupropion; methylphenidate; attention deficit disorder with hyperactivity. INTRODUCTION Attention-Deficit Hyperactivity Disorder (ADHD) is one of the most common child psychi- atric disorders, occurring in 3 to 5% of school-age children (1). ADHD persists into adolescence and adulthood yet rarely has received medical or public attention. ADHD is common in adolescents of whom 1 Department of Psychiatry, College of Medicine, University of Iowa, Iowa City, Iowa 52242. 2 Division of Clinical and Administrative Pharmacy, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242. 3 Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa 52242. 4 To whom correspondence should be addressed at S415, Phar- macy Bldg., University of Iowa, Iowa City, Iowa 52242; e-mail: paul-perry@uiowa.edu. only a minority are treated (2). Data suggest that of childhood-onset cases the syndrome persists into adulthood in 30 to 60% of patients (3). Although the psychostimulants are the treat- ments of choice for ADHD in children, there are 6 controlled trials assessing the efficacy of stimulants in adults (4–9). In contrast to the robust response in chil- dren and adolescents, the data suggest a more equiv- ocal response rate that varies from 25% (6) to 78% (9) (mean = 52%). There was no difference in the response rate between methylphenidate (56%) and pemoline (50%). The wide variability in the response rate oftentimes appears to be a function of subther- apeutic doses, high rates of comorbidity, and differ- ing methods of defining ADHD and treatment re- sponse. Spencer et al. (6) had the most robust response (MPH = 78% and placebo = 4%) using DSM-III-R 129 1040-1237/01/0900-0129$19.50/1 C  2001 American Academy of Clinical Psychiatrists