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Am Fam Physician. 2011;84(7):769

Author disclosure: Dr. Lin is an Associate Editor of Essential Evidence, published by John Wiley & Sons, Inc., who also publish The Cochrane Library.

Clinical Question

Does varenicline (Chantix) use improve smoking cessation rates, and how does its effectiveness and safety compare with other medications?

Evidence-Based Answer

Compared with placebo, varenicline more than doubles the chances of successful long-term smoking abstinence. In head-to-head trials, varenicline appears to be at least as effective as nicotine replacement therapy and bupropion (Zyban). The most common adverse effect is nausea, which decreases over time; a large cohort study found no increase in the likelihood of depression or suicidality. (Strength of Recommendation = A, based on consistent, good-quality patient-oriented evidence.)

Practice Pointers

The 2008 U.S. Public Health Service guideline on treating tobacco use and dependence recommended combining cessation counseling with nicotine replacement therapy, bupropion, and/or varenicline for nonpregnant adult smokers.1 Varenicline is a nicotine receptor partial agonist that was highly effective and well-tolerated in initial trials that led to U.S. Food and Drug Administration (FDA) approval.2 However, postmarketing reports of depressed mood, agitation, and suicide attempts in patients using varenicline led the FDA to require a boxed warning in July 2009.3 In June 2011, the FDA also warned of a link between varenicline use and increased risk of myocardial infarction in smokers with cardiovascular disease.4

In this Cochrane review, the authors searched multiple electronic databases for randomized controlled trials with a minimum follow-up period of six months that compared varenicline with placebo or other medications for smoking cessation. Fourteen trials were identified, containing more than 10,000 total participants. The pooled risk ratio (RR) for six-month smoking abstinence for varenicline versus placebo was 2.3 (95% confidence interval [CI], 2.0 to 2.7). In five head-to-head trials, varenicline was statistically more effective at one year than bupropion (RR = 1.5; 95% CI, 1.2 to 1.9) and as effective at six months as nicotine replacement therapy (RR = 1.1; 95% CI, 0.9 to 1.4). Although up to one-third of all patients taking varenicline initially reported mild to moderate nausea, only 1 to 8 percent discontinued the drug for this reason.

A cohort study of more than 80,000 adults in primary care practices in the United Kingdom found no association between varenicline use and depression, suicidal thoughts, or self-harm.5 Nonetheless, physicians should generally avoid prescribing varenicline for smokers with poorly controlled psychiatric disorders or a history of suicidality, and carefully weigh risks and benefits in smokers with known cardiovascular disease. If patients who use varenicline experience agitation or mood changes, they should be counseled to immediately report these conditions to their physician, discontinue the drug, and seek prompt medical evaluation.

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at

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