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.


METHODS
Cohort study nested within the General Practice Research Database.


METHODS
Primary care in the United Kingdom.


METHODS
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).


METHODS
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)).


CONCLUSIONS
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.
University of Bristol, Department of Social Medicine, University of Bristol, Bristol BS8 2PS. d.j.gunnell@bristol.ac.uk
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001552:Benzazepines / Q000009:adverse effects*; D016642:Bupropion / Q000009:adverse effects; D015331:Cohort Studies; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects*; D005194:Family Practice; D005260:Female; D005731:Ganglionic Stimulants / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000009:adverse effects; D011810:Quinoxalines / Q000009:adverse effects*; D016540:Smoking Cessation; D013405:Suicide / Q000706:statistics & numerical data*; D000068580:Varenicline; D055815:Young Adult
D001552:Benzazepines; D018765:Dopamine Uptake Inhibitors; D005731:Ganglionic Stimulants; D011810:Quinoxalines; D016642:Bupropion; D009538:Nicotine; D000068580:Varenicline