A Meta-Analysis of Randomized Placebo Controlled Trials of Antidepressant Medications in Depressed Children: Small Benefits, Large Stakes

Abstract

Background: Depression has been estimated to affect up to one-quarter of children and adolescents prior to adulthood. Although most youngsters still do not receive an intervention, the introduction of antidepressant medications has drastically affected the manner in which children and adolescents suffering with depression are treated. Questions have been raised about the empirical support for using SSRIs in this population. Likewise, important concerns regarding the safety of these medications have been increasingly considered by scientific, clinical, and government communities. Thus, the aim of the current study was to quantify the actual benefit to children and adolescents derived from the use of antidepressant medication. Methods: To secure studies appropriate for the meta-analysis, we searched three electronic bibliographic databases (MEDLINE, PubMed, and PsycINFO) using the search terms “antidepressant” and “child[ren]” or “adolescents.” Our search yielded 14 published antidepressant trials. Data from an additional 5 unpublished trials were requested from the FDA and MHRA websites. Within the 19 total studies, we evaluated 11 SSRI-placebo comparisons and 9 tricyclic-placebo comparisons. Findings: A statistically significant difference in depressive symptoms was reported in only 1 of the 9 tricyclic-placebo comparisons, 5 of the 6 published SSRI-placebo comparisons, and 1 of the 5 unpublished SSRI-placebo comparisons. Furthermore, it was determined that 84% of the response to the medications examined in these studies was duplicated by placebo, leaving a maximum of 16% attributable to a true drug effect. Conclusions: Results indicating an overall benefit of SSRI medications compared to placebo for children and adolescents should be interpreted with caution given widely held concerns over publication biases toward positive medication results, high rates of placebo response, and lack of documented clinical (as opposed to statistical) advantage of such medications. Nevertheless, instead of telling parents what to do and how to weigh the evidence of benefit and risk, an alternative strategy involves educating parents about benefits and risk and letting them decide for themselves how to proceed with their depressed children. For those who choose it, children and their families may be offered alternative interventions such as exercise, interpersonal psychotherapy, and cognitive behavioral therapy that have been found to produce therapeutic effects in depressed children without the medical side effects and associated risk.