BMJ  2005;330:1149 (14 May), doi:10.1136/bmj.330.7500.1149-a

Letter

Do selective serotonin reuptake inhibitors cause suicide?

Let's keep it in perspective

EDITOR—The news media's preoccupation with whether antidepressants provoke suicidal behaviour has generated apprehension in the general public, and clinicians increasingly see patients resistant to taking selective serotonin reuptake inhibitors (SSRIs) even though they might benefit. The meta-analysis by Fergusson et al reported an excess of suicidal attempts with SSRIs v placebo and, initially, an alarming sevenfold odds ratio for fatalities compared with tricyclic antidepressants [subsequently corrected to 1.08 (0.28 to 4.09), see correction 19 March, p 653].¹

A statistical excess of suicidal attempts in studies of SSRIs v placebo has been previously reported and was reasonably explained in the accompanying editorial by Cipriani et al.^{2 3} However, the whole debate loses sight of the fact that the underlying trials were never designed to assess suicidality as an outcome but to satisfy regulatory agencies about efficacy. Retrospective counts of incidents of deliberate self harm or attempted suicide are extremely unreliable in such studies; fatalities obviously less so (but no excess has surfaced among these). The randomisation process in smaller trials may be questioned, and heterogeneity could have precluded some of the trials in the current meta-analysis. Prospective studies with suicidality as the outcome variable are needed to lay such issues to rest, but these have rarely been done, for valid reasons.⁴

In any case, odds ratios (or other ratios) alone do not give an indication of absolute risk: the number needed to harm (NNH) should also be examined. In the current meta-analysis, an NNH of 708 compares quite favourably with others in medicine—for example, 179 in the CAPRIE trial (comparing clopidogrel with aspirin for stroke patients).⁵

University of Toronto, CAMH-Clarke Site, 250 College Street, Toronto, ON, Canada M5T 1R8 isaac.sakinofsky{at}utoronto.ca

Kunin-Lunenfeld Applied Research Unit, Baycrest Centre for Geriatric Care, Toronto, ON, Canada M6A 2E1

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Competing interests: None declared.

References

1. Fergusson D, Doucette S, Cranley Glass K, Shapiro S, Healy D, Hebert P, et al. Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials. BMJ 2005;330: 396. (19 February.)[Abstract/Free Full Text]
2. Khan A, Warner HA, Brown WA. Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials. An analysis of the Food and Drug Administration database. Arch Gen Psychiatry 2000;57: 311-7.[Abstract/Free Full Text]
3. Cipriani A, Barbui C, Geddes J. Suicide, depression, and antidepressants. BMJ 2005;330: 373-4. (19 February.)[Free Full Text]
4. Gunnell D, Saperia J, Ashby D. Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo-controlled randomized controlled trials submitted to the MHRA's safety review. BMJ 2005;330: 385-8. (19 February.)[Abstract/Free Full Text]
5. CAPRIE Steering Committee. A randomized blinded trial of clopidogrel versus aspirin in patients at risk of ischaemic events. Lancet 1996;348: 1329-39.[CrossRef][ISI][Medline]

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