- David Gunnell (), professor of epidemiology1,
- Julia Saperia, research assistant2,
- Deborah Ashby, professor of medical statistics2
- 1 Department of Social Medicine, University of Bristol, Bristol BS8 2PR
- 2 Wolfson Institute of Preventive Medicine, Queen Mary, University of London, London EC1M 6BQ
- Correspondence to: D Gunnell
- Accepted 20 January 2005
Objective To investigate whether selective serotonin reuptake inhibitor (SSRI) antidepressants are associated with an increased risk of suicide related outcomes in adults.
Design Meta-analysis of randomised controlled trials of SSRIs compared with placebo in adults submitted by pharmaceutical companies to the safety review of the Medicines and Healthcare products Regulatory Agency (MHRA).
Participants Over 40 000 individuals participating in 477 randomised controlled trials.
Main outcome measures Suicide, non-fatal self harm, and suicidal thoughts.
Results An estimated 16 suicides, 172 episodes of non-fatal self harm, and 177 episodes of suicidal thoughts were reported. We found no evidence that SSRIs increased the risk of suicide, but important protective or hazardous effects cannot be excluded (odds ratio 0.85, 95% credible interval 0.20 to 3.40). We found weak evidence of an increased risk of self harm (1.57, 0.99 to 2.55). Risk estimates for suicidal thoughts were compatible with a modest protective or adverse effect (0.77, 0.37 to 1.55). The relative frequency of reported self harm and suicidal thoughts in the trials compared with suicide indicates non-fatal end points were under-recorded.
Conclusion Increased risks of suicide and self harm caused by SSRIs cannot be ruled out, but larger trials with longer follow up are required to assess the balance of risks and benefits fully. Any such risks should be balanced against the effectiveness of SSRIs in treating depression. When prescribing SSRIs, clinicians should warn patients of the possible risk of suicidal behaviour and monitor patients closely in the early stages of treatment.
Contributors DG and DA conceived the idea for the paper. JS carried out the data analysis. DG initially drafted the paper, and all authors have contributed to further drafting. DG is the guarantor.
Competing interests DG and DA were members of the MHRA's expert working group on the safety of SSRIs. They acted 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. An honorarium was paid to her department. JS has no competing interests.
- Accepted 20 January 2005