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SSRIs and Suicide Risk: A Concern for Adults, Too?

Perhaps, but failure to treat moderate-to-severe depression is also a concern; clinicians should continue to use SSRIs but should monitor patients closely.

Controversy about the safety of SSRIs in children has spurred concern that these medications might also increase the risk for suicide in adults, despite negative findings in individual studies and small, underpowered meta-analyses. Three more-recent large analyses and a comprehensive review provide important data and a novel perspective.

Fergusson et al. systemically reviewed 702 published, randomized, controlled trials on SSRIs and analyzed the 345 studies (involving over 36,000 subjects) that contained data on suicide attempts. SSRIs were associated with increased risk for suicide attempts, compared with placebo (odds ratio, 2.28) and other therapies (OR, 1.94) but not compared with tricyclic antidepressants. Risk for completed suicide (only 24 suicides were reported overall) did not increase for SSRIs compared with placebo, but did increase for SSRIs compared with TCAs (OR, 7.27).

Gunnell et al. performed a meta-analysis of all 477 published and unpublished, placebo-controlled, SSRI safety studies (involving over 40,000 individuals) that were submitted by pharmaceutical companies to the British drug regulatory agency. These researchers found no increased risk for completed suicide with SSRIs (n=16 suicides overall); did find modest, nearly significant evidence of increased risk for nonfatal self-harm (OR, 1.57; 95% confidence interval, 0.99-2.55); and estimated that one such event would occur for every 759 patients treated.

Martinez et al. conducted an observational, nested case-control study involving 146,000 patients in a U.K. family practice database. After adjustment for factors that increase risk (e.g., history of self-harm), risks for suicide or self-harm did not differ between patients prescribed SSRIs and those prescribed TCAs. However, among patients aged 18 or younger, risk for nonfatal self-harm increased with SSRIs, compared with TCAs. No differences in risks were found among different SSRIs.

In a comprehensive review of the issue, Licinio and Wong note that in four separate studies of completed suicides, only 15% to 20% of patients had been taking antidepressants. Thus, failure to treat depression may be a greater problem than adverse events (see also Journal Watch Psychiatry Mar 9 2005). The authors also note that the suicide rate in the U.S. decreased over the last 15 years while the use of these drugs increased.

Comment: The three studies highlight the value of large databases in evaluating the risk for extremely infrequent events. Martinez et al. note that suicide attempts occur in 3-4 per 1000 individuals; completed suicides are 1/30 as frequent. Gunnell et al. comment that even the large population they studied was not large enough to detect an increase of 20% in risk for suicide and self-harm. Still, given the numbers of people receiving SSRIs, even a small effect can have large public health repercussions. The trials reviewed in the first two studies were relatively short; clinically treated patients are exposed for a much longer time. Nonetheless, failure to treat depression may be a much greater problem than the small risk of adverse events, and, clearly, antidepressant-associated risk for suicide is not a unique property of SSRIs. It seems prudent to follow the recommendations given by editorialists in the British Medical Journal and by Licinio and Wong: Continue to prescribe SSRIs for adults with moderate-to-severe depression, but closely monitor them during the early phases of treatment.

— Peter Roy-Byrne, MD

Published in Journal Watch Psychiatry March 9, 2005

Citation(s):

Fergusson D et al. Association between suicide attempts and selective serotonin reuptake inhibitors: Systematic review of randomised controlled trials. BMJ 2005 Feb 19; 330:396. http://bmj.bmjjournals.com/cgi/reprint/330/7488/396.

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Gunnell D et al. 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. BMJ 2005 Feb 19; 330:385. http://bmj.bmjjournals.com/cgi/reprint/330/7488/385.

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Martinez C et al. Antidepressant treatment and the risk of fatal and non-fatal self harm in first episode depression: Nested case-control study. BMJ 2005 Feb 19; 330:389. http://bmj.bmjjournals.com/cgi/reprint/330/7488/389.

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Licinio J and Wong ML. Opinion: Depression, antidepressants and suicidality: A critical appraisal. Nat Rev Drug Discov 2005 Feb; 4:165-71.

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Cipriani A et al. Suicide, depression, and antidepressants. BMJ 2005 Feb 19; 330:373-4.

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