title: Suicidal behavior and depression in smoking cessation treatments.
abstract: BACKGROUND
  Two treatments for smoking cessation--varenicline and bupropion--carry Boxed Warnings from the U.S. Food and Drug Administration (FDA) about suicidal/self-injurious behavior and depression. However, some epidemiological studies report an increased risk in smoking or smoking cessation independent of treatment, and differences between drugs are unknown.
  
  
  METHODS
  From the FDA's Adverse Event Reporting System (AERS) database from 1998 through September 2010 we selected domestic, serious case reports for varenicline (n = 9,575), bupropion for smoking cessation (n = 1,751), and nicotine replacement products (n = 1,917). A composite endpoint of suicidal/self-injurious behavior or depression was defined as a case with one or more Preferred Terms in Standardized MedDRA Query (SMQ) for those adverse effects. The main outcome measure was the ratio of reported suicide/self-injury or depression cases for each drug compared to all other serious events for that drug.
  
  
  RESULTS
  Overall we identified 3,249 reported cases of suicidal/self-injurious behavior or depression, 2,925 (90%) for varenicline, 229 (7%) for bupropion, and 95 (3%) for nicotine replacement. Compared to nicotine replacement, the disproportionality results (OR (95% CI)) were varenicline 8.4 (6.8-10.4), and bupropion 2.9 (2.3-3.7). The disproportionality persisted after excluding reports indicating concomitant therapy with any of 58 drugs with suicidal behavior warnings or precautions in the prescribing information. An additional antibiotic comparison group showed that adverse event reports of suicidal/self-injurious behavior or depression were otherwise rare in a healthy population receiving short-term drug treatment.
  
  
  CONCLUSIONS
  Varenicline shows a substantial, statistically significant increased risk of reported depression and suicidal/self-injurious behavior. Bupropion for smoking cessation had smaller increased risks. The findings for varenicline, combined with other problems with its safety profile, render it unsuitable for first-line use in smoking cessation.
authors.affiliation: Institute for Safe Medication Practices, Alexandria, Virginia, United States of America. tmoore@ismp.org
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Moore
authors.forename: Curt D
authors.initials: CD
authors.lastname: Furberg
authors.forename: Joseph
authors.initials: J
authors.lastname: Glenmullen
authors.forename: John T
authors.initials: JT
authors.lastname: Maltsberger
authors.forename: Sonal
authors.initials: S
authors.lastname: Singh
mesh_terms: D000328:Adult; D001552:Benzazepines / Q000009:adverse effects*; D016642:Bupropion / Q000009:adverse effects*; D003863:Depression / Q000139:chemically induced* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000009:adverse effects*; D018722:Nicotinic Agonists / Q000009:adverse effects; D011810:Quinoxalines / Q000009:adverse effects*; D016540:Smoking Cessation / Q000379:methods*; D013405:Suicide / Q000523:psychology*; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D016642:Bupropion; D009538:Nicotine; D000068580:Varenicline
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