Effects of Sustained-Release Bupropion among Persons Interested in Reducing but Not Quitting Smoking Dorothy K. Hatsukami, PhD, Stephen Rennard, MD, Manoj K. Patel, PharmD, Michael Kotlyar, PharmD, Robert Malcolm, MD, Mitchell A. Nides, PhD, Greg Dozier, MPH, Matthew P. Bars, MS, Brenda D. Jamerson, PharmD PURPOSE: To determine whether sustained-release bupro- pion promotes smoking reduction leading to smoking cessation among persons who wish to reduce their amount of smoking, but who are unwilling to quit or who perceive themselves as being unable to quit. METHODS: Current smokers were assigned randomly to re- ceive either sustained-release bupropion (150 mg twice daily) or matching placebo. During an initial 6-month smoking reduc- tion phase, those who were willing to quit entered a 7-week cessation phase, during which study medication was continued. RESULTS: Four-week continuous abstinence rates were 14% (41/295) in the bupropion group and 8% (25/299) in the pla- cebo group (P = 0.02) during treatment. However, this benefit did not continue after treatment was stopped; subsequent con- tinuous abstinence rates were 7% (20/295) in the bupropion group and 5% (16/299) in the placebo group (P = 0.50). Similar proportions of subjects entered the cessation phase in both treatment groups (38% [n = 113] of those in the bupropion group and 34% [n = 101] of those in the placebo group), al- though the time until a cessation attempt was shorter for those taking bupropion (median, 64 days vs. 118 days, P = 0.008). The extent of smoking reduction (measured by urinary cotinine concentrations) among the 327 subjects who did not enter the cessation phase was significantly greater (P 0.05) in those treated with bupropion during the reduction treatment phase, but not during the month 12 follow-up visit (P = 0.25). CONCLUSION: Sustained-release bupropion, when used in smokers initially not willing to make a cessation attempt, can help sustain smoking reduction while subjects are on active medication, reduce the time until the next cessation attempt, and increase short-term abstinence rates. However, these ben- efits were modest and not sustained after bupropion was discontinued. Am J Med. 2004;116:151–157. ©2004 by Excerpta Medica Inc. D espite public health initiatives encouraging smoking cessation, at any given time only 20% of smokers report that they are motivated to stop smoking and about 40% of smokers make quit attempts each year (1,2). It is not known whether smokers who are unwilling to quit, yet are motivated to reduce smoking, would be more likely to quit if they participated in a smoking reduction program. Although quitting is the preferred outcome from interventions for treatment of tobacco use and dependence, smoking reduction may of- fer some health benefits by reducing tobacco exposure or by increasing the motivation to quit, thereby increasing subsequent abstinence rates (3,4). The purpose of this study was to assess the efficacy of sustained-release bupropion in achieving sustained smoking reduction and to determine whether this results in increased abstinence rates. METHODS Subjects Participants were recruited through radio, newspaper, or television advertisements that targeted smokers who were interested in reducing smoking. We recruited adult (18 years of age) smokers who had smoked 20 cigarettes per day and who had not quit for greater than 3 months dur- ing the previous year. Only smokers motivated to reduce their cigarette usage, but who were unwilling or perceived themselves to be unable to quit smoking at the time of screening, were enrolled. Subjects had to have failed at least two previous cessation attempts, one of which in- volved the use of nicotine replacement therapy. All par- ticipants gave written informed consent to enter the study. From the Department of Psychiatry (DKH, MK), and Department of Experimental and Clinical Pharmacology, College of Pharmacy (MK), University of Minnesota at Twin Cities, Minneapolis, Minnesota; Uni- versity of Nebraska Medical Center (SR), Omaha, Nebraska; Glaxo- SmithKline (MKP, MK, GD, BDJ), Research Triangle Park, North Carolina; Institute of Psychiatry (RM), Medical University of South Carolina, Charleston, South Carolina; Los Angeles Clinical Trials (MAN), Los Angeles, California; Smoking Consultation Service (MPB), Fort Lee, New Jersey; and Campbell University Department of Pharma- ceutical Sciences, Clinical Research (BDJ), Durham, North Carolina. This study was supported by GlaxoSmithKline, Research Triangle Park, North Carolina. The sponsor was responsible for finalizing the design of the study and oversight of the research project, had primary responsibility for conducting the data analyses, and reviewed the final paper. Requests for reprints should be addressed to Dorothy K. Hatsukami, PhD, University of Minnesota, Tobacco Use Research Center, 2701 University Avenue, Suite 201, Minneapolis, Minnesota 55414, or hatsu001@umn.edu. Manuscript submitted June 26, 2002, and accepted in revised form July 25, 2003. © 2004 by Excerpta Medica Inc. 0002-9343/04/$–see front matter 151 All rights reserved. doi:10.1016/j.amjmed.2003.07.018