Antidepressants and Suicide: Risk-benefit Conundrums

There has been a long-standing controversy about the possibility that selective serotonin reuptake inhibitor (SSRI) antidepressants might induce suicidality in some patients. To shed light on this issue, this paper reviews available randomized controlled trials (RCTs), meta-analyses of clinical trials and epidemiological studies that have been undertaken to investigate the issue further. The original clinical studies raising concerns about SSRIs and suicide induction produced evidence of a dose-dependent link on a challenge-dechallenge and rechallenge basis between SSRIs and both agitation and suicidality. Meta-analyses of RCTs conducted around this time indicated that SSRIs may reduce suicidal ideation in some patients. These same RCTs, however, revealed an excess of suicidal acts on active treatments compared with placebo, with an odds ratio of 2.4 (95; confidence interval 1.6-3.7). This excess of suicidal acts also appears in epidemiological studies. The data reviewed here make it difficult to sustain a null hypothesis that SSRIs do not cause problems in some individuals. Further studies or further access to data are indicated to establish the magnitude of any risk and the characteristics of patients who may be most at risk.