Varenicline and suicidal behaviour: a cohort study based on data from the General Practice Research Database

OBJECTIVE To determine whether varenicline, a recently licensed smoking cessation product, is associated with an increased risk of suicide and suicidal behaviour compared with alternative treatments bupropion and nicotine replacement therapy. DESIGN Cohort study nested within the General Practice Research Database. SETTING Primary care in the United Kingdom. PARTICIPANTS 80,660 men and women aged 18-95 years were prescribed a new course of a smoking cessation product between 1 September 2006 and 31 May 2008; the initial drugs prescribed during follow-up were nicotine replacement products (n=63 265), varenicline (n=10 973), and bupropion (n=6422). MAIN OUTCOME MEASURES Primary outcomes were fatal and non-fatal self harm, secondary outcomes were suicidal thoughts and depression, all investigated with Cox's proportional hazards models. RESULTS There was no clear evidence that varenicline was associated with an increased risk of fatal (n=2) or non-fatal (n=166) self harm, although a twofold increased risk cannot be ruled out on the basis of the upper limit of the 95% confidence interval. Compared with nicotine replacement products, the hazard ratio for self harm among people prescribed varenicline was 1.12 (95% CI 0.67 to 1.88), and it was 1.17 (0.59 to 2.32) for people prescribed bupropion. There was no evidence that varenicline was associated with an increased risk of depression (n=2244) (hazard ratio 0.88 (0.77 to1.00)) or suicidal thoughts (n=37) (1.43 (0.53 to 3.85)). CONCLUSION Although a twofold increased risk of self harm with varenicline cannot be ruled out, these findings provide some reassurance concerning its association with suicidal behaviour.