Clinical Question: Is varenicline (Chantix) more effective than bupropion (Wellbutrin) and placebo for smoking cessation?

Setting: Population-based

Study Design: Randomized controlled trial (double-blinded)

Allocation: Concealed

Synopsis: Varenicline is a nicotinic acetylcholine receptor partial agonist that may reduce the reinforcing effects of nicotine for maintaining smoking behavior. The investigators randomized (concealed allocation) 1,025 generally healthy adult smokers from 18 to 75 years of age to receive varenicline (titrated to 1 mg twice daily), bupropion SR (titrated to 150 mg twice daily), or matching placebo for 12 weeks.

All participants received brief counseling and a self-help booklet for smoking cessation. Those who completed the initial 12-week drug treatment period continued in a nondrug posttreatment follow-up phase for 52 weeks. Smoking cessation was determined by patient self-report and an exhaled carbon monoxide measurement. All individuals assessing outcomes remained blinded to treatment group assignment. Participants withdrawing before study completion were assumed to be continued smokers.

The 52-week study completion rates were 60.5 percent for varenicline, 56 percent for bupropion SR, and 54 percent for placebo. Overall, using intention-to-treat analysis, continuous abstinence rates at 52 weeks were significantly higher for varenicline versus placebo (21.9 versus 8.4 percent; number needed to treat [NNT] = 7; 95% confidence interval [CI], 4 to 15). The difference in quit rates at 52 weeks between varenicline and bupropion (21.9 versus 16.1 percent) was not statistically significant. When reporting 52-week success rates (cumulative abstinence), the authors eliminated patients who failed the previous reporting period; therefore, the success rates at the end of 52 weeks reflected only those who were abstinent at 24 weeks. That is, the authors took the successful patients only and recalculated using this rate as a starting point. Therefore, the overall success rates appear higher than if they had used every participant who began the study.

Adverse events were similar for varenicline and bupropion SR. Nausea was the most common adverse event associated with varenicline. Mean weight gain and dropout rates because of adverse events occurred similarly among all three groups. No differences in effectiveness of varenicline for either sex were reported. The cost for 12 weeks of treatment with varenicline is similar to generic bupropion SR

An identically designed study conducted at another site and published in the same issue(Jorenby DE, et al. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA 2006;296:56–63), found similar results, except that the difference in abstinence rates at 52 weeks between varenicline and bupropion SR was statistically significant (23.0 versus 14.6 percent; NNT= 12; 95% CI, 6 to 43). In a third study reported in the same issue(Tonstad, et al. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. JAMA 2006;296:64–71), smokers who achieved abstinence at the end of 12 weeks of varenicline treatment and were then randomized to an additional 12 weeks of varenicline (instead of placebo) showed a significantly higher continuous abstinence rate at 52 weeks of follow-up (43.6 versus 36.9 percent; NNT= 14; 95% CI, 8 to 73). None of the participants enrolled in any of the trials had a history of previous bupropion therapy, so success rates for varenicline in patients who have failed bupropion therapy are unknown.

Bottom Line: Varenicline therapy for 12 weeks is significantly more effective than placebo at maintaining smoking abstinence at 52 weeks. Varenicline also may be marginally more effective than bupropion SR. Reported success rates are likely to be higher than in real-world settings. (Level of evidence: 1b)