Varenicline as a Cause of Suicidal Outcomes.

objectivePostmarketing analyses and case reports have associated varenicline use with suicidal behaviors. This article reviews postmarketing analyses, case reports, clinical trials, uncontrolled observational studies, controlled observational studies, and studies in smokers with psychiatric problems that have tested this association.

methodThe author searched the literature for relevant reports via computer and other searches to undertake a qualitative, systematic review.

resultsTwo pooled analyses of 10 and 17 placebo-controlled trials failed to find more suicidal outcomes in the varenicline condition. Seven large uncontrolled observational studies reported low rates of suicide outcomes in varenicline users (<0.1%), and 1 study reported a higher rate (6%). Five large controlled observational studies did not find more suicide outcomes in varenicline users than in those using prescribed bupropion or over-the-counter nicotine medications. Small placebo-controlled trials and observational studies of smokers with current psychiatric problems did not find varenicline was associated with suicidal outcomes.

conclusionsAmong the more valid study designs (pooled analyses of placebo controlled trials or large controlled observational studies), there is consistent evidence that varenicline either does not cause increased suicide outcomes, or if it does, the effect is very small. Warnings to consumers and clinicians should reflect, not just the results of postmarketing studies, but the results of the more valid research designs.