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Antidepressant treatment and the risk of fatal and non-fatal self harm in first episode depression: nested case-control study

BMJ 2005; 330 doi: (Published 17 February 2005) Cite this as: BMJ 2005;330:389
  1. Carlos Martinez, epidemiologist (carlos.martinez{at},
  2. Stephan Rietbrock, epidemiologist1,
  3. Lesley Wise, epidemiologist2,
  4. Deborah Ashby, professor of medical statistics3,
  5. Jonathan Chick, consultant psychiatrist4,
  6. Jane Moseley, epidemiologist2,
  7. Stephen Evans, professor of pharmacoepidemiology5,
  8. David Gunnell, professor of epidemiology6
  1. 1 General Practice Research Database Division, Medicines and Healthcare products Regulatory Agency, London SW8 5NQ
  2. 2 Post-Licensing Division, Medicine and Healthcare products Regulatory Agency
  3. 3 Wolfson Institute of Preventive Medicine, Queen Mary, University of London
  4. 4 Department of Psychiatry, University of Edinburgh, Edinburgh
  5. 5 Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London
  6. 6 Department of Social Medicine, University of Bristol, Bristol BS8 2PR
  1. Correspondence to: C Martinez
  • Accepted 11 January 2005


Objective To compare the risk of non-fatal self harm and suicide in patients taking selective serotonin reuptake inhibitors (SSRIs) with that of patients taking tricyclic antidepressants, as well as between different SSRIs and different tricyclic antidepressants.

Design Nested case-control study.

Setting Primary care in the United Kingdom.

Participants 146 095 individuals with a first prescription of an antidepressant for depression.

Main outcome measures Suicide and non-fatal self harm.

Results 1968 cases of non-fatal self harm and 69 suicides occurred. The overall adjusted odds ratio of non-fatal self harm was 0.99 (95% confidence interval 0.86 to 1.14) and that of suicide 0.57 (0.26 to 1.25) in people prescribed SSRIs compared with those prescribed tricyclic antidepressants. We found little evidence that associations differed over time since starting or stopping treatment. We found some evidence that risks of non-fatal self harm in people prescribed SSRIs compared with those prescribed tricyclic antidepressants differed by age group (interaction P = 0.02). The adjusted odds ratio of non-fatal self harm for people prescribed SSRIs compared with users of tricylic antidepressants for those aged 18 or younger was 1.59 (1.01 to 2.50), but no association was apparent in other age groups. No suicides occurred in those aged 18 or younger currently or recently prescribed tricyclic antidepressants or SSRIs.

Conclusion We found no evidence that the risk of suicide or non-fatal self harm in adults prescribed SSRIs was greater than in those prescribed tricyclic antidepressants. We found some weak evidence of an increased risk of non-fatal self harm for current SSRI use among those aged 18 or younger. However, preferential prescribing of SSRIs to patients at higher risk of suicidal behaviour cannot be ruled out.


  • Contributors All authors contributed to the conception and design or the analysis and interpretation of the data. LW and CM developed the study protocol. DA, DG, JC, SR, SE, and JM contributed to study design and data interpretation. CM and SR were responsible for data extraction and analysis. CM and SR reviewed notes for non-fatal self harm, and CM and DG reviewed notes for potential suicides. DG, LW, and CM wrote the paper with contributions from all authors. The final manuscript was approved by all authors. CM is the guarantor.

  • Funding Medicines and Healthcare products Regulatory Agency.

  • Competing interests The UK Committee on Safety of Medicines established an expert working group to conduct a review of the safety of SSRIs. No members of the expert working group have financial interests in any of the companies that hold marketing authorisations for SSRIs. The MHRA funded the study and professional staff at the MHRA, including JM and LW, have been acting as secretariat to or observers on the expert working group's review. Neither JM nor LW have any personal financial interests in any drug product. DG, JC, and DA are members of the MHRA's expert working group on the safety of SSRIs, and DA is a member of the Committee on Safety of Medicines. Both act as independent advisers, receiving travel expenses and a small fee for meeting attendance and reading materials in preparation for the meeting. DA has spoken on the methodology of adverse drugs reactions in HIV at a scientific meeting attended by several pharmaceutical companies and sponsored by GlaxoSmithKline (GSK). A honorarium was paid to her department. SE has no personal interests to declare. His department receives funding from many pharmaceutical companies, including GSK, but mainly for methodological research. SE has no direct involvement in any of this. The General Practice Research Database Division receives funding for services, including the conduct of commissioned research, from a wide range of public sector bodies and the pharmaceutical industry. Neither CM nor SR have any competing interests.

  • Ethical approval General Practice Research Database Scientific and Ethical Advisory Group.

  • Accepted 11 January 2005
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