Varenicline and Risk of Self-Harm: A Nested Case-Control Study

Background: Smoking remains a serious public health concern. Pharmacotherapy for smoking cessation, including bupropion and varenicline, are proven means to increase quit rates. Post-marketing reports describing suicidal behaviours have raised concerns about the safety of varenicline. However, whether varenicline imparts a higher risk of suicide relative to bupropion remains uncertain. Methods: A population-based nested case-control study in Ontario, Canada, from April 1, 2011 to March 31, 2015 was conducted. Subjects were residents of Ontario aged 18 years and older with publicly funded drug coverage receiving either bupropion or varenicline for smoking cessation. We defined cases were those with a hospitalization or emergency department visit for suicide or non-fatal self-harm within 90 days of treatment. For each case, we identified up to fifty controls from the same cohort matched on age, sex, history of self-harm, use of selected psychotropic medications, alcohol abuse and prior admission to a mental health unit. Adjusted odds ratio were used to compare the risk of suicide/self-harm of varenicline to bupropion. Results: We identified 331 cases and 5,346 matched-controls. Following adjustment for potential confounders, we found that varenicline was not associated with an increased risk of suicide/self-harm relative to bupropion (adjusted odds ratio 1.15; 95% confidence interval 0.71 to 1.87). Interpretation: Treatment with varenicline does not appear to significantly increase the risk of suicide or self-harm relative to bupropion.