Varenicline: Fewer Psychiatric Adverse Effects Than Previously Thought

Summary and Comment |
October 8, 2013

Varenicline: Fewer Psychiatric Adverse Effects Than Previously Thought

  1. Joel Yager, MD

Regardless of prior psychiatric illness, varenicline recipients in two separate datasets show no increases in psychiatric adverse effects.

  1. Joel Yager, MD

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.


After reviewing the FDA data, the authors wondered whether the high number of safety signals reported for varenicline was due to “stimulated reporting” — i.e., reports that were snowballing because of heightened media coverage. These findings, together with the results of another recent, randomized, controlled trial, should assist clinicians and comfort patients considering varenicline to assist with smoking cessation, whether or not they have current or previous psychiatric illness.

Editor Disclosures at Time of Publication

  • Disclosures for Joel Yager, MD at time of publication Editorial boards Bulletin of the Menninger Clinic; Eating Disorders: Journal of Treatment and Research; Eating Disorders Review (Editor-in-Chief); Harvard Review of Psychiatry; International Journal of Eating Disorders; UpToDate Leadership positions in professional societies American Psychiatric Association (Chair, Steering Committee and Executive Committee on Practice Guidelines; Co-Chair, DSM5 Clinical and Public Health Committee; Chair, Council on Research and Quality Care)


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