Lines of evidence on the risks of suicide with selective serotonin reuptake inhibitors.
BACKGROUND
There has been a long-standing controversy about the possibility that selective serotonin reuptake inhibitor (SSRI) antidepressants might induce suicidality in some patients.


METHODS
Starting from the clinical studies that gave rise to this issue, this paper reviews an unselected cohort of randomized clinical trials (RCTs), a series of meta-analyses undertaken to investigate aspects of the problem, studies in recurrent brief depressive disorders, epidemiological studies and healthy volunteer studies using SSRIs to shed light on this issue.


RESULTS
The original clinical studies produced evidence of a dose-dependent link, present on a challenge, dechallenge and rechallenge basis, between SSRIs and both agitation and suicidality. Meta-analyses of RCTs conducted around this time indicate that SSRIs may reduce suicidal ideation in some patients. These same RCTs, however, yield an excess of suicides and suicide attempts on active treatments compared with placebos. This excess also appears in the best-controlled epidemiological studies. Finally, healthy volunteer studies give indications that SSRIs may induce agitation and suicidality in some individuals.


CONCLUSIONS
The data reviewed here, which indicate a possible doubling of the relative risk of both suicides and suicide attempts on SSRIs compared with older antidepressants or non-treatment, make it difficult to sustain a null hypothesis, i.e. that SSRIs do not cause problems in some individuals to whom they are given. 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.
Healy
David
D
North Wales Department of Psychological Medicine, University of Wales College of Medicine, Bangor, UK. healy_hergest@compuserve.com
D000928:Antidepressive Agents / Q000009:adverse effects*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D013405:Suicide / Q000706:statistics & numerical data
D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors