Combination therapy of varenicline and bupropion in smoking cessation: A meta-analysis of the randomized controlled trials

Background: The effects of the combination therapy of varenicline and bupropion in smoking cessation are still controversial. Methods: Databases including PubMed, EMBASE, Cochrane Library and Web of Science were scanned without time and language limitation. Subgroup analysis was performed to assess the effect of combination therapy in smokers with different level of nicotine dependence and cigarette consumption. Results: Four randomized controlled trials involving a total of 1230 smokers were included. Compared with varenicline monotherapy, combination treatment with varenicline and bupropion could significantly improve the abstinence rate at the end of treatment (RR 1.153, 95% CI 1.019 to 1.305, P = 0.024). The benefit existed at 6 months follow-up (RR 1.231, 95% CI 1.017 to 1.490, P = 0.033), disappeared at 12 months follow-up (RR 1.130, 95% CI 0.894 to 1.428, P = 0.305), and mainly concentrated in highly dependent smokers (RR 1.631, 95% CI 1.290 to 2.061, P < 0.001) and heavy smokers (RR 1.515, 95% CI 1.226 to 1.873, P < 0.001) rather than individuals with low nicotine dependence (RR 0.989, 95% CI 0.815 to 1.199, P = 0.907) or low cigarette consumption (RR 0.985, 95% CI 0.800 to 1.212, P = 0.252). For safety outcomes, the combination treatment was associated with more anxiety (RR 1.717, 95% CI 1.176 to 2.505, P= 0.005) and insomnia (RR 1.268, 95% CI 1.076 to 1.494, P= 0.005) symptoms compared with varenicline monotherapy. Conclusion: Compared with varenicline monotherapy, combination treatment with varenicline and bupropion can significantly improve the abstinence rate at the end of treatment and 6 months follow-up, mainly in highly dependent smokers and heavy smokers. (C) 2019 The Author(s). Published by Elsevier Inc.