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

BMJ 2009; 339 doi: (Published 01 October 2009) Cite this as: BMJ 2009;339:b3805
  1. D Gunnell, professor of epidemiology1,
  2. D Irvine, pharmacoepidemiologist2,
  3. L Wise, senior pharmacoepidemiologist2,
  4. C Davies, senior pharmacovigilance assessor2,
  5. R M Martin, professor of clinical epidemiology1
  1. 1University of Bristol, Department of Social Medicine, University of Bristol, Bristol BS8 2PS
  2. 2Vigilance and Risk Management of Medicines, Medicines and Healthcare products Regulatory Agency, London SW8 5NQ
  1. Correspondence to: D Gunnell d.j.gunnell{at}
  • Accepted 10 September 2009


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.


  • Contributors: All authors contributed to the study proposal, design of the analysis, and interpretation of the findings. DI was responsible for data extraction. DI undertook the analysis with input from DG, LW, and RMM. DG wrote the first draft of the paper, which was revised by all authors. DG and DI will act as guarantors.

  • Funding: Small grant from the Medicines and Healthcare Products Regulatory Agency (MHRA).

  • Competing interests: DG is a member of the Pharmacovigilance Expert Advisory Group of the MHRA. DI, LW, and CD are employees of the MHRA. RMM is a member of Independent Scientific Advisory Committee for MHRA database research (ISAC).

  • Ethical approval: Approval was given by the General Practice Research Database’s Independent Scientific Advisory Committee. The GPRD Group has obtained ethical approval from a multicentre research ethics committee for all purely observational research using GPRD data.

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