Suicidal behavior and depression in smoking cessation treatments

Thomas J. Moore, Curt D. Furberg, Joseph Glenmullen, John T. Maltsberger, Sonal Singh

Research output: Contribution to journalArticle

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. Methodology: 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.

Original languageEnglish (US)
Article numbere27016
JournalPLoS One
Volume6
Issue number11
DOIs
StatePublished - Nov 2 2011

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Withholding Treatment
Bupropion
Self-Injurious Behavior
Smoking Cessation
Depression
nicotine
drugs
Pharmaceutical Preparations
Nicotine
Drug Labeling
Tobacco Use Cessation Products
Drug therapy
suicide
United States Food and Drug Administration
endpoints
epidemiological studies
Suicide
drug therapy
Varenicline
Epidemiologic Studies

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Moore, T. J., Furberg, C. D., Glenmullen, J., Maltsberger, J. T., & Singh, S. (2011). Suicidal behavior and depression in smoking cessation treatments. PLoS One, 6(11), [e27016]. https://doi.org/10.1371/journal.pone.0027016

Suicidal behavior and depression in smoking cessation treatments. / Moore, Thomas J.; Furberg, Curt D.; Glenmullen, Joseph; Maltsberger, John T.; Singh, Sonal.

In: PLoS One, Vol. 6, No. 11, e27016, 02.11.2011.

Research output: Contribution to journalArticle

Moore, TJ, Furberg, CD, Glenmullen, J, Maltsberger, JT & Singh, S 2011, 'Suicidal behavior and depression in smoking cessation treatments', PLoS One, vol. 6, no. 11, e27016. https://doi.org/10.1371/journal.pone.0027016
Moore TJ, Furberg CD, Glenmullen J, Maltsberger JT, Singh S. Suicidal behavior and depression in smoking cessation treatments. PLoS One. 2011 Nov 2;6(11). e27016. https://doi.org/10.1371/journal.pone.0027016
Moore, Thomas J. ; Furberg, Curt D. ; Glenmullen, Joseph ; Maltsberger, John T. ; Singh, Sonal. / Suicidal behavior and depression in smoking cessation treatments. In: PLoS One. 2011 ; Vol. 6, No. 11.
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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. Methodology: 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.",
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