Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation

Background: The selective nicotinic acetylcholine receptor partial agonist, varenicline tartrate, represents a novel type of therapy for smoking cessation. This study evaluated the efficacy, safety, and tolerability of 4 varenicline dose regimens, 2 with progressive dosing over the first week ( eg, titrated) and 2 with a fixed dosing schedule ( eg, nontitrated), for promoting smoking cessation. Methods: This multicenter, double-blind, placebo-controlled study randomized healthy smokers ( aged 18-65 years) to varenicline tartrate, 0.5 mg twice daily nontitrated ( n=129), 0.5 mg twice daily titrated ( n=130), 1.0 mg twice daily nontitrated ( n= 129), 1.0 mg twice daily titrated ( n= 130), or placebo ( n= 129) for 12 weeks to aid in smoking cessation. A 40-week follow-up period assessed long-term efficacy. The primary efficacy measures were the carbon monoxide-confirmed 4-week continuous quit rates by pooled dosage group for weeks 4 through 7 and 9 through 12 and the continuous abstinence rates for weeks 9 through 52. Results: Weeks 9 through 12 continuous quit rates were greater in the 1.0-mg group ( 49.4%) and the 0.5-mg group ( 44.0%) vs placebo ( 11.6%; P <. 001 vs both doses). Weeks 9 through 52 abstinence rates were greater in the 1.0-mg group ( 22.4%; P <. 001) and the 0.5-mg group ( 18.5%; P <. 001) vs placebo ( 3.9%). Varenicline was generally well tolerated, with nausea occurring in 16% to 42% of varenicline-treated subjects. Reports of nausea were lower for the titrated vs nontitrated dosing and infrequently led to medication discontinuation. Conclusion: Varenicline tartrate, 0.5 mg and 1.0 mg twice daily, is efficacious for smoking cessation.