Combination Varenicline and Bupropion SR for Tobacco-Dependence Treatment in Cigarette Smokers: A Randomized Trial

Study Questions:

Does the combination of varenicline and bupropion improve smoking abstinence compared to varenicline alone?


This was a randomized, blinded, placebo-controlled, multicenter clinical trial with a 12-week treatment period and follow-up through 52 weeks, conducted between October 2009 and April 2013, at three mid-western clinical research sites. A total of 506 adult (≥18 years) cigarette smokers were randomly assigned, and 315 (62%) completed the study. The intervention consisted of 12 weeks of varenicline and bupropion sustained relief (SR) or varenicline and placebo. The primary outcome of interest was abstinence rates at week 12, defined as prolonged (no smoking from 2 weeks after the target quit date) abstinence and 7-day point-prevalence (no smoking past 7 days) abstinence. Secondary outcomes were prolonged prevalence and point-prevalence smoking abstinence rates at weeks 26 and 52. All outcomes were biochemically confirmed.


A total of 635 adults were potentially eligible; of these, 506 (80%) were randomly assigned to varenicline and bupropion SR (n = 249) or varenicline and placebo (n = 257). Study completion rates were 63% (158 participants) in the varenicline and bupropion SR group (combination therapy) and 61% (157 participants) in the varenicline and placebo group (varenicline monotherapy). At 12 weeks, 53.0% of the combination therapy group achieved prolonged smoking abstinence, and 56.2% achieved 7-day point-prevalence smoking abstinence compared with 43.2% and 48.6% in varenicline monotherapy (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.05-2.12; p = 0.03 and OR, 1.36; 95% CI, 0.95-1.93; p = 0.09, respectively). At 26 weeks, 36.6% of the combination therapy group achieved prolonged and 38.2% achieved 7-day point-prevalence smoking abstinence compared with 27.6% and 31.9% in varenicline monotherapy (OR, 1.52; 95% CI, 1.04-2.22; p = 0.03 and OR, 1.32; 95% CI, 0.91-1.91; p = 0.14, respectively). At 52 weeks, 30.9% of the combination therapy group achieved prolonged and 36.6% achieved 7-day point-prevalence smoking abstinence compared with 24.5% and 29.2% in varenicline monotherapy (OR, 1.39; 95% CI, 0.93-2.07; p = 0.11 and OR, 1.40; 95% CI, 0.96-2.05; p = 0.08, respectively). Participants receiving combination therapy reported more anxiety (7.2% vs. 3.1%; p = 0.04) and depressive symptoms (3.6% vs. 0.8%; p = 0.03).


The investigators concluded that among cigarette smokers, combined use of varenicline and bupropion, compared with varenicline alone, increased prolonged abstinence, but not 7-day point prevalence at 12 and 26 weeks. Neither outcome was significantly different at 52 weeks.


This well-done study suggests that combination therapy may assist some smokers in quitting; however, further research is warranted to understand what types of smokers will benefit and which ones may not.

Clinical Topics: Prevention, Smoking

Keywords: Depression, Histidine-tRNA Ligase, Cardiovascular Diseases, Psychotherapy, Group, Confidence Intervals, Quinoxalines, Tobacco Use Disorder, Combined Modality Therapy, Benzazepines, Smoking, Bupropion

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