Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials

Abstract

Objective: To establish whether an association exists between use of selective serotonin reuptake inhibitors (SSRIs) and suicide attempts.

Design: Systematic review of randomised controlled trials.

Data sources: Medline and the Cochrane Collaboration's register of controlled trials (November 2004) for trials produced by the Cochrane depression, anxiety, and neurosis group.

Selection of studies: Studies had to be randomised controlled trials comparing an SSRI with either placebo or an active non-SSRI control. We included clinical trials that evaluated SSRIs for any clinical condition. We excluded abstracts, crossover trials, and all trials whose follow up was less than one week.

Results: Seven hundred and two trials met our inclusion criteria. A significant increase in the odds of suicide attempts (odds ratio 2.28, 95% confidence 1.14 to 4.55, number needed to treat to harm 684) was observed for patients receiving SSRIs compared with placebo. An increase in the odds ratio of suicide attempts was also observed in comparing SSRIs with therapeutic interventions other than tricyclic antidepressants (1.94, 1.06 to 3.57, 239). In the pooled analysis of SSRIs versus tricyclic antidepressants, we did not detect a difference in the odds ratio of suicide attempts (0.88, 0.54 to 1.42).

Discussion: Our systematic review, which included a total of 87 650 patients, documented an association between suicide attempts and the use of SSRIs. We also observed several major methodological limitations in the published trials. A more accurate estimation of risks of suicide could be garnered from investigators fully disclosing all events.

Fig 1

Identification and inclusion of trials

Fig 2

Fatal and non-fatal suicide attempts in SSRI trials and placebo trials

Fig 3

Fatal and non-fatal suicide attempts in SSRI trials and trials studying tricyclic antidepressants

Fig 4

Fatal and non-fatal suicide attempts in SSRI trials and trials studying other therapies

Fig 5

Cumulative meta-analysis of fatal and non-fatal suicide attempts in placebo controlled trials