Over the past decade, bupropion has become a major pharmacotherapy for smoking cessation in the Western world. Unlike other smoking cessation pharmacotherapies, bupropion is a non-nicotine treatment. Compared with a placebo control, bupropion approximately doubles smoking quit rates. Most smoking cessation pharmacotherapies are thought to work, in part, by reducing nicotine withdrawal and craving. This article reviews preclinical, human laboratory and clinical trial studies of the effect of bupropion on nicotine withdrawal and craving. Preclinical studies demonstrate that in rats undergoing nicotine withdrawal, bupropion can dose-dependently lower changes in brain-reward threshold and somatic signs of nicotine withdrawal. Human laboratory studies have demonstrated that bupropion can alleviate some nicotine withdrawal symptoms, including depressed mood, irritability, difficulty concentrating and increased appetite. Moreover, bupropion has shown some efficacy in alleviating craving to smoke. Clinical trials of bupropion have offered mixed support of its ability to reduce nicotine withdrawal, weight gain during treatment and craving. Strong mediational evidence of bupropion's action through relief of withdrawal and craving in smoking cessation is growing. Greater understanding of the psychological mechanisms of bupropion action will likely be obtained through advances in the conceptualization and measurement of withdrawal and craving. Improvements in the efficacy of bupropion may be achieved through pharmacogenetic studies, with particular emphasis on its metabolites. Ultimately, the efficacy of bupropion may be augmented by combination with other agents that target withdrawal and craving through complementary neurobiological processes.
Bibliographical noteFunding Information:
ME Mooney has conducted research with nicotine replacement products and bupropion provided courtesy of GlaxoSmithK-line. M Sofuoglu has no relevant conflicts to disclose. This research paper was supported by NIDA grants P50-DA13333, K01-DA019446, P50-DA018197 and R01-DA014537. The authors wish to thank Tim Baker, Megan Piper and Danielle McCarthy for sharing their developing studies of mediation in bupropion clinical trials. Paul Pentel and Andy Harris provided helpful comments on the preclinical section of this paper. The authors also thank the anonymous reviewers for their detailed comments on this manuscript.
- Negative affect
- Nicotine withdrawal
- Positive effect
- Smoking cessation