Suicidal Behavior and Depression in Smoking Cessation Treatments

Abstract

BackgroundTwo 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.MethodologyFrom 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.ResultsOverall 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.ConclusionsVarenicline 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.

Varenicline Is a Potent Partial Agonist at α6β2* Nicotinic Acetylcholine Receptors in Rat and Monkey Striatum

“…However, smoking relapse rates remain high even with varenicline treatment (McNeil et al, 2010;Raupach and van Schayck, 2011). In addition, varenicline is not without side effects, including nausea and serious psychiatric problems (Jorenby et al, 2006;Moore et al, 2011;Williams et al, 2011).…”

Varenicline for smoking cessation and reduction in people with severe mental illnesses: systematic review and meta-analysis

“…For example, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) Yellow Card reports state that varenicline had the highest reported rate of depression disorders, and the secondhighest rate of non-fatal suicidal behaviour compared with other drugs in the MHRA study [55]. Similarly, Moore and colleagues studied the FDA's Adverse Event Reporting System (AERS) database from 1998 to September 2010 and found that varenicline substantially increased the risk of reported depression and suicidal/self-injurious behaviour [27].…”

“…Nicotine in cigarettes is an addictive drug, and nicotine withdrawal produces a wide range of withdrawal symptoms such as headaches, nausea, anxiety, and depression. Previous smoking cessation studies have reported similar symptoms among smokers treated with bupropion, as well as with other nicotine replacement therapies [20,27].…”

“…The U.S. Food and Drug Administration then issued a black box warning for varenicline regarding neuropsychiatric events in 2009 [27]. The adverse neuropsychiatric effects reported in patients taking varenicline include depression, hostility, aggression, psychosis, thoughts of self-harm, suicide and suicidal behaviour, erratic behaviour, and drowsiness.…”

Varenicline: the risks of over-the-counter sales in Brazil

“…Moore et al assert that varenicline use is associated with an increased risk of suicidal/self-injury behavior and depression in smokers attempting to quit. 5 Data for this study were drawn from case reports of adverse drug events received by the FDA from 1998 to 2010. The authors identified 3,249 cases of suicidal behavior and depression, with varenicline accounting for 90% of reports.…”