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

Abstract

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.

Fig 1 Rate of suicide related adverse events reported for varenicline per million tablets prescribed in 2007-2008. (Data source MHRA yellow cards and data derived from IMS HEALTH Midas database)