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Efficacy of Varenicline, an 42 Nicotinic Acetylcholine Receptor Partial Agonist, vs Placebo or Sustained-Release Bupropion for Smoking Cessation

A Randomized Controlled Trial

Douglas E. Jorenby, PhD; J. Taylor Hays, MD; Nancy A. Rigotti, MD; Salomon Azoulay, MD; Eric J. Watsky, MD; Kathryn E. Williams, PhD; Clare B. Billing, MS; Jason Gong, MD; Karen R. Reeves, MD; for the Varenicline Phase 3 Study Group

JAMA. 2006;296:56-63.

Context  Varenicline, a partial agonist at the 42 nicotinic acetylcholine receptor, has the potential to aid smoking cessation by relieving nicotine withdrawal symptoms and reducing the rewarding properties of nicotine.

Objective  To determine the efficacy and safety of varenicline for smoking cessation compared with placebo or sustained-release bupropion (bupropion SR).

Design, Setting, and Participants  A randomized, double-blind, placebo-controlled trial conducted between June 2003 and March 2005 at 14 research centers with a 12-week treatment period and follow-up of smoking status to week 52. Of 1413 adult smokers who volunteered for the study, 1027 were enrolled; 65% of randomized participants completed the study.

Intervention  Varenicline titrated to 1 mg twice daily (n = 344) or bupropion SR titrated to 150 mg twice daily (n = 342) or placebo (n = 341) for 12 weeks, plus weekly brief smoking cessation counseling.

Main Outcome Measures  Continuous abstinence from smoking during the last 4 weeks of treatment (weeks 9-12; primary end point) and through the follow-up period (weeks 9-24 and 9-52).

Results  During the last 4 weeks of treatment (weeks 9-12), 43.9% of participants in the varenicline group were continuously abstinent from smoking compared with 17.6% in the placebo group (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.69-5.50; P<.001) and 29.8% in the bupropion SR group (OR, 1.90; 95% CI, 1.38-2.62; P<.001). For weeks 9 through 24, 29.7% of participants in the varenicline group were continuously abstinent compared with 13.2% in the placebo group (OR, 2.83; 95% CI, 1.91-4.19; P<.001) and 20.2% in the bupropion group (OR, 1.69; 95% CI, 1.19-2.42; P = .003). For weeks 9 through 52, 23% of participants in the varenicline group were continuously abstinent compared with 10.3% in the placebo group (OR, 2.66; 95% CI, 1.72-4.11; P<.001) and 14.6% in the bupropion SR group (OR, 1.77; 95% CI, 1.19-2.63; P = .004). Treatment was discontinued due to adverse events by 10.5% of participants in the varenicline group, 12.6% in the bupropion SR group, and 7.3% in the placebo group. The most common adverse event with varenicline was nausea, which occurred in 101 participants (29.4%).

Conclusions  Varenicline is an efficacious, safe, and well-tolerated smoking cessation pharmacotherapy. Varenicline's short-term and long-term efficacy exceeded that of both placebo and bupropion SR.

Trial Registration  clinicaltrials.gov Identifier: NCT00143364

Author Affiliations: University of Wisconsin School of Medicine and Public Health, Center for Tobacco Research and Intervention, Madison, Wis (Dr Jorenby); Division of General Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minn (Dr Hays); Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Mass (Dr Rigotti); and Pfizer Global Research and Development, Groton, Conn (Drs Azoulay, Watsky, Williams, Gong, and Reeves and Mr Billing).

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