Effect of Bupropion on Depression Symptoms in a Smoking Cessation Clinical Trial Caryn Lerman University of Pennsylvania Cancer Center Ray Niaura Brown University School of Medicine Bradley N. Collins, Paul Wileyto, Janet Audrain-McGovern, and Angela Pinto University of Pennsylvania Cancer Center Larry Hawk and Leonard H. Epstein University at Buffalo, State University of New York Bupropion is an antidepressant shown to be efficacious for smoking cessation. This study examined the short- and long-term effects of bupropion (300 mg/day for 10 weeks) versus placebo on depression symptoms among 497 smokers attempting to quit in a randomized trial of bupropion plus behavioral counseling. Depression symptoms were assessed via the Center for Epidemiological Studies Depression Scale (L. Radloff, 1977) at baseline, end of treatment, and at 6-month follow-up. Baseline nicotine dependence level was assessed with the Fagerstro ¨m Test for Nicotine Dependence (T. F. Heatherton, L. T. Kozlowski, R. C. Frecker, & K. O. Fagerstro ¨ m, 1991). A regression model of depression symptoms demonstrated a significant interaction between nicotine dependence and treatment for the treatment phase and during follow-up. Depression symptoms did not mediate the effects of bupropion on abstinence at either time point. Highly nicotine-dependent smokers who receive bupropion are more likely to expe- rience a decrease in depressive symptoms during active treatment but are also more likely to experience a rebound in depressive symptoms when bupropion is discontinued. Bupropion is an antidepressant medication used widely in smok- ing cessation treatment (Holm & Spencer, 2000). The efficacy of bupropion has been documented for standard smoking treatment (Ahluwalia, Harris, Catley, Okuyemi, & Mayo, 2002; Hurt et al., 1997; Lerman, Shields, et al., 2002), as well as in conjunction with nicotine replacement therapy (Jorenby et al., 1999), and for relapse prevention (Hays et al., 2001). Initial reports suggest that bupro- pion is equally efficacious for smokers who tend to be more vulnerable to relapse, such as females (Gonzales et al., 2002), African Americans (Ahluwalia et al., 2002), and individuals with a history of major depression (Hayford et al., 1999). Highly dependent smokers in these trials have a lower likelihood of achieving abstinence and a higher likelihood of relapse; however, there is no evidence for a differential impact of bupropion in smokers with high versus low levels of nicotine dependence (Dale et al., 2001; Hurt et al., 1997). Despite bupropion’s prior approval and long-term use as an antidepressant medication, data on its effects on depression symp- toms in smoking treatment trials remain inconclusive. Two large smoking cessation trials did not find evidence for significant effects of bupropion on depression symptoms (Hurt et al., 1997; Jorenby et al., 1999). However, a recent bupropion trial with African American smokers showed significant reductions in de- pression symptoms during the medication phase, but not during the posttreatment follow-up phase (Ahluwalia et al., 2002). One im- portant difference between these trials was that the later study (Ahluwalia et al., 2002) used a measure of depression symptoms designed for the general population, whereas the previous studies (Hurt et al., 1997; Jorenby et al., 1999) used the Beck Depression Inventory (Beck, Ward, Mendelson, Mock, & Erbaugh, 1961), a clinical measure of depression. Measures that are designed for clinical populations may not be sufficiently sensitive to detect changes in subclinical depression states. Consistent with this premise, two other studies have reported evidence for short-term effects of bupropion on negative mood (Lerman, Roth, et al., 2002; Shiffman et al., 2000). Although the effects of bupropion on depression symptoms may be subtle, such effects may have clin- ical significance for smoking abstinence and relapse prevention. Smokers who experience depression symptoms are more likely than nondepressed smokers to depend on nicotine to alleviate negative affective states (Lerman et al., 1996; Niaura et al., 1999). Caryn Lerman, Bradley N. Collins, Paul Wileyto, Janet Audrain- McGovern, and Angela Pinto, Department of Psychiatry, Abramson Fam- ily Cancer Research Institute, University of Pennsylvania Cancer Center; Ray Niaura, Department of Biomedical Psychiatry & Human Behavior, Brown University School of Medicine; Larry Hawk, Department of Psy- chology, University at Buffalo, State University of New York; Leonard H. Epstein, Department of Pediatrics, University at Buffalo, State University of New York. This research was supported by Grants CA/DAP50 84718 and CA63562 from the National Cancer Institute and National Institute on Drug Abuse to Caryn Lerman. We gratefully acknowledge Susan Kucharski, Jodie Jaroni, and Rocky Palouch for assistance with project coordination and data management, and Maryanne Foster for her technical assistance. Study medication was provided by GlaxoSmithKline. Correspondence concerning this article should be addressed to Caryn Lerman, Tobacco Use Research Center, Department of Psychiatry, Uni- versity of Pennsylvania, 3535 Market Street, Suite 4100, Philadelphia, PA 19104. E-mail: clerman@mail.med.upenn.edu Psychology of Addictive Behaviors Copyright 2004 by the Educational Publishing Foundation 2004, Vol. 18, No. 4, 362–366 0893-164X/04/$12.00 DOI: 10.1037/0893-164X.18.4.362 362 This document is copyrighted by the American Psychological Association or one of its allied publishers. 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