Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review

Abstract

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.

Figure 1

Forest plots of suicide, non-fatal self harm, and suicidal thoughts in placebo controlled trials of SSRIs