Antidepressants and suicide in children and adolescents: A storm in a teacup?
So have the regulatory authorities overstated the risks and underestimated the benefits of antidepressants in the treatment of depression in youth? Considering that existing data from clinical trials on suicidality appear contradictory and incomplete, more careful scrutiny of the risks and benefits is clearly needed. Better data and a cleaner, more systematic approach toward adverse event data reporting may be able to answer the question at hand. Risk benefit analyses in paediatric trials may be more complicated because of high placebo response rates which make it difficult to show statistically and clinically significant drug-placebo differences. For example, in two recent randomised controlled trials of sertraline in children and adolescents (aged 6 - 17) with DSM-IV defined major depressive disorder, undertaken at the request of the FDA, 69% of those who were taking sertraline were classified as responders compared with 59% of patients taking placebo. While these differences were statistically significant, the mean change in scores from baseline to endpoint on the primary outcome measure, the Children's Depression Rating Scale-Revised, between the groups was so small so as to be of minimal clinical significance. In addition to high placebo response rates, other problems include non-publication of negative findings, withholding of unfavourable data and under-reporting of adverse events. For now, monitoring child, adolescent, and adult patients closely for suicidal ideation during the first weeks of antidepressant therapy and during dose titrations of their medication should always be part of the armamentarium and standard of care of any good clinician.