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A Randomized, Placebo-Controlled Clinical Trial of Bupropion for the Prevention of Smoking in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder

Michael C. Monuteaux, Sc.D.; Thomas J. Spencer, M.D.; Stephen V. Faraone, Ph.D.; Angela M. Wilson, M.A.; and Joseph Biederman, M.D.

Objective: Since attention-deficit/hyperactivity disorder (ADHD) is a well-documented risk factor for smoking and bupropion has been shown to be effective for smoking cessation, we tested the efficacy of bupropion as a prophylactic agent for the prevention of smoking in children and adolescents with ADHD.

Method: We conducted a longitudinal, randomized, double-blind, placebo-controlled, parallel-group study of bupropion at a large, urban, outpatient medical center. Recruitment began in April 1999, and the last subject was followed until September 2004. Patients were nonsmoking youth, of both sexes, between 9 and 18 years of age, with DSM-IV ADHD. After random assignment to either bupropion or placebo, subjects were assessed weekly for 8 weeks, biweekly for 4 weeks, and monthly thereafter for up to 6.5 years (mean 12 months). Also, patients received treatment with psychostimulants for ADHD symptoms as needed. To assess smoking, we used an assay of cotinine in urine.

Results: Fifty-seven subjects (28 receiving bupropion and 29 receiving placebo) were randomly assigned and included in the analysis. No differences were found between the bupropion and placebo groups on demographic factors. About half of each group was treated with stimulants for ADHD. Statistical separation between bupropion and placebo in the rate of smoking initiation or continued smoking was not demonstrated. However, secondary post hoc analyses revealed that concurrent stimulant treatment was significantly associated with a lower rate of smoking onset (hazard ratio [HR] = 0.2, 95% CI = 0.08 to 0.89; z = -2.2, p = .03) and a lower rate of continued smoking (HR = 0.3, 95% CI = 0.11 to 0.85; z = -2.3, p = .02).

Conclusion: While bupropion was not associated with a lower rate of smoking in youth with ADHD, post hoc analyses suggest that stimulant treatment was. Future controlled studies should investigate the role of stimulants in the prevention of smoking in children and adolescents with ADHD.

(J Clin Psychiatry 2007;68:1094-1101)

Received Dec. 27, 2006; accepted Feb. 21, 2007. From the Pediatric Psychopharmacology Program, Massachusetts General Hospital (Drs. Monuteaux, Spencer, and Biederman and Ms. Wilson), Boston; the Department of Psychiatry, Harvard Medical School, Boston, Mass. (Drs. Monuteaux, Spencer, and Biederman); and the Department of Psychiatry and Behavioral Sciences, the State University of New York Upstate Medical University, Syracuse (Dr. Faraone).

This project was supported in part by grant R01 DA12531-02 from the National Institute of Drug Abuse, Bethesda, Md. (Dr. Biederman). Medications and partial funding were also provided by GlaxoSmithKline, Inc.

Presented in part at the National Cancer Institute Tobacco Control Investigator's Meeting: "Synthesizing Research for the Public's Health," San Diego, Calif., June 2-4, 2004.

Financial disclosure appears at the end of this article.

Corresponding author and reprints: Michael C. Monuteaux, Sc.D., Pediatric Psychopharmacology Program, 55 Fruit Street, Warren 705, Boston, MA 02114 (e-mail: