Do selective serotonin reuptake inhibitors cause suicide?

Editor—Gunnell et al offer figures for suicide with selective serotonin reuptake inhibitors (SSRIs).¹ However, in the expert working group's report on SSRIs,² the table for citalopram indicates no suicide in the placebo group. Data on paroxetine are not available from the report, but prior submissions indicate four suicides with paroxetine (CSM Expert Working Group on the Safety of SSRIs, unpublished data, 2003). Gunnell et al note three suicides in the placebo group during the withdrawal phase, but a 1991 review of the safety of paroxetine does not indicate that these happened in the withdrawal phase of placebo controlled trials.³ If Gunnell et al are relying on a company submission these figures must be in some doubt.

Figure 1.

Twelve suicides may have occurred in 23 804 patients taking SSRIs and six in 17 022 taking placebo, an odds ratio of 1.43; or possibly 12 suicides with SSRIs and three with placebo, an odds ratio of 2.86. Leaving paroxetine out, the figures become eight suicides in 15 323 patients taking SSRIs and three in 11 214 patients taking placebo, an odds ratio of 1.96. Adding in venlafaxine and mirtazapine gives 16 suicides in 23 885 patients taking antidepressant and three in 14 564 taking placebo, an odds ratio of 3.1.

If antidepressants reduce the risk of suicide in some patients an odds ratio of 1.0 for suicide points to a clear risk. A randomised controlled trial with a challenge-dechallenge design and a rating scale sensitive to suicidal ideation might need less than 100 patients to firm up on any risk of induced suicidality. Eli Lilly designed such a trial in conjunction with the US Food and Drug Administration in 1990.