Clinical Citations: Varenicline: A more effective smoking cessation therapy?

November 1, 2006

Most established smoking cessation therapies are based on nicotine replacement therapy (NRT), which has shown only moderate effectiveness and been associated with health risks and compliance challenges. To date, the most widely used non-NRT treatment is the antidepressant bupropion hydrochloride. Now, however, another non-NRT agent, varenicline tartrate, has been developed specifically for smoking cessation. Two multicenter double-blind studies have demonstrated that this agent has both short- and long-term effectiveness.

Most established smoking cessation therapies are based on nicotine replacement therapy (NRT), which has shown only moderate effectiveness and been associated with health risks and compliance challenges. To date, the most widely used non-NRT treatment is the antidepressant bupropion hydrochloride. Now, however, another non-NRT agent, varenicline tartrate, has been developed specifically for smoking cessation. Two multicenter double-blind studies have demonstrated that this agent has both short- and long-term effectiveness.

In a 7-week randomized trial by Nides and associates, healthy adult smokers received either varenicline (0.3 mg daily; 1.0 mg once daily; or 1.0 mg twice daily for 6 weeks, then placebo for 1 week); bupropion (150 mg twice daily); or placebo. Results showed that 4-week continuous quit rates were higher for varenicline therapy (37.3% at 1.0 mg once daily and 48.0% at 1.0 mg twice daily) than for bupropion (33.3%) or placebo (17.1%). Carbon monoxide- confirmed quit rates from weeks 4 to 52 were also higher for varenicline (14.4%) than for bupropion (6.3%) or placebo (4.9%).

In another randomized placebo-controlled study over 52 weeks, Oncken and colleagues evaluated the efficacy of 4 varenicline regimens (titrated or nontitrated dosages of 0.5 mg twice daily or 1.0 mg twice daily) in 647 patients. Continuous quit rates for varenicline 0.5-mg titrated (40.8%) and nontitrated (47.3%) and for 1.0-mg titrated (54.6%) and nontitrated (44.2%) were higher than for placebo (11.6%). Abstinence rate results were also higher for varenicline therapy in the pooled 0.5-mg group (18.5%) and pooled 1.0-mg group (22.4%) than for placebo (3.9%).

In a related editorial, Johnson outlines some of the concerns about NRT, such as the potential for long-term NRT dependence and questions about its safety during pregnancy. These concerns, along with the relatively modest success rates achieved by both NRT and bupropion, have driven the interest in developing new therapies for nicotine dependence.

Johnson points out that by mimicking the dopamine agonist effects of nicotine, varenicline can help relieve the craving that smokers experience when they try to quit. Moreover, in the presence of nicotine, varenicline can suppress nicotine's reinforcing effects. Johnson argues that the advances in smoking cessation therapies leave no legitimate excuses for avoiding or delaying their implementation.