Varenicline: Fewer Psychiatric Adverse Effects Than Previously Thought

Postmarketing surveillance of the smoking-cessation drug varenicline suggested a high rate of adverse neuropsychiatric events such as worsened depression and suicidality, and the medication received an FDA black-box warning in 2009. To examine this issue more closely, investigators with funding from the National Institute of Mental Health reviewed two kinds of study data on depression, aggression/agitation, and suicidal events. Overall, 13% of participants had current or past psychiatric illness.

The investigators reviewed manufacturer-supplied data from 17 industry-sponsored, randomized, controlled trials involving varenicline (n= 4823 patients), bupropion (n=795), and placebo (n=3204). Analyses showed no differences between varenicline and placebo for suicidal thoughts and behaviors, depression, or aggression/agitation, regardless of whether patients had histories of psychiatric illness. However, varenicline patients reported more nausea (studied as a “positive control”) than placebo recipients (odds ratio, 3.69).

The researchers also reexamined a Department of Defense observational study of adverse events measured at 30 and 60 days following initiation of varenicline (N=19,933) or nicotine-patch (N=15,867) treatment; the study predated the black-box warning. Analyses adjusted results by “propensity scores” that matched varenicline- and nicotine-patch–treated patients by demographics, comorbid psychiatry and medical illnesses, and concurrent psychiatric and smoking-cessation medications. Adverse events were greater for nicotine patch than varenicline.