According to research published in the Archives of General Psychiatry, treatment with fluoxetine and venlafaxine decreased suicide risk in adult and elderly patients, and this appears to be related to the effect of treatment on depression severity. No evidence that fluoxetine increased risk of suicidal thoughts or behaviour in youths was found.

The authors note that the original black box warning for antidepressants and risk of suicide in children and adolescents issued by the FDA in 2004 was based on meta-analysis of adverse event reports (AERs) from company-sponsored randomised controlled trials (RCTs).  The extension of the warning to cover young adults was based on a second meta-analysis. 

The purpose of the current study was to determine what impact antidepressants have on the course of depression and suicidal thoughts and behaviour in different age groups, using intention-to-treat patient-level longitudinal data for RCTs of fluoxetine conducted by Eli Lilly, the Treatment for Adolescents With Depression Study of fluoxetine in children by the National Institute of Mental Health, and adult studies for venlafaxine hydrochloride conducted by Wyeth.  The authors note that their analyses substantially expand those conducted by the FDA in children, and provide similar analyses for adult and elderly populations, that were not previously reported by the FDA. 

The total number of studies included in the analysis were 12 adult (total n=2635), 4 elderly (n=960), and 4 youth (n=708) RCTs for fluoxetine hydrochloride, and 21 RCTs of venlafaxine in adults (n=2421 with immediate-release venlafaxine and n=2461 with extended-release venlafaxine).  All of the included studies were company-sponsored.  Researchers analysed the suicide items from the Children's Depression Rating Scale–Revised and the Hamilton Depression Rating Scale, as well as adverse event reports of suicide attempts and suicide during active treatment.

Overall, the authors report the following (taken from the abstract summary):

• Suicidal thoughts and behaviour decreased over time for adult and elderly patients randomised to fluoxetine or venlafaxine compared with placebo. 

• No differences were however found for youths, and there was no evidence of increased suicide risk observed in youths receiving active medication.

• In adults, reduction in suicide ideation and attempts occurred through a reduction in depressive symptoms.

• In all age groups, severity of depression improved with medication and was significantly related to suicide ideation or behaviour.

The authors say that their results clarify the relationship between suicidal thoughts and behaviour and antidepressant treatment, and emphasise the need to successfully treat episodes of major depressive disorder to lower the suicide risk.  They note that they did not replicate the FDA’s finding of an increased risk with antidepressant treatment in youths, but caution that their results apply only to fluoxetine, and that it remains to be determined whether they can be generalised to other antidepressants.

They go on to discuss the limitations of their analyses, and say that a number of unanswered questions remain, for example why was there no statistically significant effect of treatment on suicide in youths, despite a large overall reduction in depressive symptoms.