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ABSTRACT
Background: Tobacco is the leading cause of preventable death in the world. Current cessation medications include nicotine replacement therapy (NRT), varenicline, and bupropion, while combination therapy primarily entails NRT with either varenicline or bupropion. However, recent studies have examined varenicline and bupropion in combination. Objectives: A systematic review assessing the efficacy and safety of combination varenicline and bupropion was conducted. Methods: PubMed and Clinicaltrials.gov were searched using terms: “varenicline combination”, “bupropion combination”, “bupropion AND varenicline”, and “bupropion AND varenicline combination smoking cessation”, yielding four studies including 1193 total patients. Results: Combination therapy yielded greater efficacy than varenicline monotherapy in two randomized controlled trials and one retrospective outcomes study. One single-arm Phase II trial provided additional efficacy and safety data. Of the prospective trials, one displayed a greater 4-week smoking abstinence for weeks 8–11 with combination (39.8%) versus monotherapy (25.9%) (OR = 1.89; 95% CI = 1.07–3.35). The other demonstrated greater prolonged abstinence (continuous abstinence from week 2) at 12 weeks (OR = 1.49; 95% CI = 1.05–2.12) and 26 weeks (OR = 1.52; 95% CI = 1.04–2.22), though results were not significant at 52 weeks in this study. The retrospective study displayed higher success rates (continuous abstinence rates at 52 weeks) with combination varenicline and bupropion (55.0%; compared to varenicline monotherapy (32.1%), p < 0.001). Subgroup analyses suggest that this combination may be more beneficial in males and patients with higher baseline nicotine dependence. Conclusion: To the authors’ knowledge, this is the first review conducted to compile current literature on this novel pharmacotherapy combination for smoking cessation. Combination bupropion SR and varenicline displayed greater efficacy in smoking cessation than varenicline monotherapy, though further safety analysis is warranted to rule out additive psychiatric adverse effects.
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.
