Pharmacotherapy of depressed children and adolescents: current issues and potential directions.

The recent deliberations by the U.S. Food and Drug Administration (FDA) regarding the relationship between antidepressants and suicidality in children have incited debates about the safety of these medications for the treatment of pediatric depression. In light of these events, this review discusses four issues pertaining to pharmacotherapy for pediatric depression. First, we summarize pertinent data from randomized controlled trials of antidepressants for pediatric depression. These data provide strong support for fluoxetine and modest support for the other antidepressants. Second, we examine the outcome of the FDA meta-analysis of the data on antidepressant-induced suicidality, with specific emphasis on the methodological limitations of this analysis. Third, we consider the collective implications of the antidepressant efficacy and suicidality data on clinical practice. Specifically, we present several compelling arguments that justify the continued use of antidepressants for pediatric depression, despite the inherent limitations of these medications. Finally, we review several pathophysiological factors that might provide insights into treatment response and impact the design of future pharmacotherapy studies of depression. These factors relate to diagnostic heterogeneity, developmental consistency, and psychobiology. Potentially novel pharmacotherapies are also discussed.