The drug varenicline shows effectiveness in helping smokers quit and abstain from smoking when compared to placebo and the smoking cessation medication bupropion, according to three studies in the July 5 issue of Journal of the American Medical Association.
Although nearly 41 percent of smokers try to quit smoking each year, relapse is common, and only about 10 percent achieve and maintain abstinence. The negative effects of nicotine withdrawal account, in part, for low success rates, according to background information in the article. Approved pharmacotherapies to treat nicotine dependence (e.g., nicotine replacement therapy and bupropion) have had important, but moderate efficacy, with reported rates of quitting generally twice those of placebo. Additional and more effective therapies are needed.
David Gonzales, Ph.D., of Oregon Health & Science University, Portland, and colleagues with the Varenicline Phase 3 Study Group evaluated the efficacy of varenicline compared with placebo and sustained-release (SR) bupropion in generally healthy adult smokers. Varenicline is a non-nicotine drug that is thought to be beneficial for smoking cessation by stimulating the release of the chemical dopamine in the brain to reduce craving and withdrawal while simultaneously blocking the reinforcing effects of smoked nicotine. Most other smoking cessation pharmacotherapies are nicotine replacement products.
Participants in the study were 1,025 smokers (10 cigarettes or more per day) with fewer than 3 months of smoking abstinence in the past year. The randomized, double-blind, phase 3 clinical trial was conducted at 19 U.S. centers from June 2003 to April 2005. Participants were randomly assigned to receive brief counseling plus either varenicline twice per day (n = 352), bupropion SR twice per day (n = 329), or placebo (n = 344) orally for 12 weeks, with 40 weeks of nondrug follow-up.
The carbon monoxide–confirmed 4-week continuous abstinence rate for weeks 9 through 12 was superior for varenicline (44.0 percent) vs. placebo (17.7 percent) and vs. bupropion SR (29.5 percent). Bupropion SR was also superior to placebo. The continuous abstinence rate for weeks 9 to 24 was superior for varenicline (29.5 percent) vs. placebo (10.5 percent) and vs. bupropion SR (20.7 percent). The continuous abstinence rate for weeks 9 through 52 was significantly greater for varenicline (21.9 percent) than for placebo (8.4 percent) but no longer significant compared with bupropion SR (16.1 percent).
Varenicline reduced craving and withdrawal and, for those who smoked while receiving study drug, also reduced smoking satisfaction. No sex differences in efficacy for varenicline were observed. Varenicline was safe and generally well tolerated, with study drug discontinuation rates similar to those for placebo. The most common adverse events for participants receiving active-drug treatment were nausea for varenicline and insomnia for bupropion SR.
"Varenicline is an efficacious therapy for smoking cessation. In this trial, varenicline was more efficacious than placebo at all time points and more efficacious than bupropion SR at the end of 12 weeks of treatment and at 24 weeks," the authors write.