The findings from two reviews of trial data suggest that it would be premature to conclude that selective serotonin reuptake inhibitor (SSRI) use does not have some effect on suicide risk. Moreover, results from a case-control study support a weak link between SSRI use and self harm among pediatric users.

All three reports appear in the February 19th issue of the British Medical Journal.

In the first study, Dr. Dean Fergusson, from the Ottawa Health Research Institute in Canada, and colleagues analyzed data from more than 87,000 patients enrolled in 702 trials that compared the effects of an SSRI with that of placebo or an active non-SSRI control.

SSRI-treated patients were 2.28-times more likely to attempt suicide than were placebo users. Similarly, SSRI use nearly doubled the risk of suicide attempts compared with use of non-tricyclic antidepressant agents.

Dr. David Gunnell, from the University of Bristol in the UK, and colleagues conducted a meta-analysis involving over 40,000 patients enrolled in 477 randomized, controlled trials. Although the authors found no evidence that SSRI use raised the risk of suicide, they note that “important protective or hazardous effects cannot be excluded.” However, there was weak evidence that these drugs increased the risk of self-harm.

Lastly, Dr. Carlos Martinez, from the Medicines and Healthcare products Regulatory Agency in London, and colleagues conducted a case-control study of 146,095 depressed individuals to assess the suicide risk seen with SSRI use compared with tricyclic antidepressant use.

Among adults, there was no evidence that SSRI use raised the risk of suicide or non-fatal self-harm to a greater extent than tricyclic antidepressants. In children and adolescents, by contrast, SSRI use increased the risk of non-fatal self-harm by 59%. No suicides were observed in this younger age group.

In a related editorial, Dr. Andrea Cipriani, from the University of Verona in Italy, and colleagues comment that in adults, clinicians “need to balance the benefits and harms” of prescribing SSRIs. By contrast, in children and adolescents, the risks generally outweigh the benefits and such drugs should not be prescribed on a routine basis.

BMJ 2005;330:373-374,385-393,396-399.