Second Edition Editors

Much confusion has been generated by the sharply differing perspectives of the various stakeholders on the benefit to risk assessment of selective serotonin reuptake inhibitors (SSRIs). To make these issues clearer, this chapter aims to provide a review and critique of the following topics: (1) published randomized clinical trials on the efficacy of SSRIs for the treatment of major depressive disorder (MDD); (2) meta-analysis of related published and unpublished trials; (3) safety of SSRIs from clinical trial analyses and published clinical trial reports; (4) safety of SSRIs from observational studies; (5) suggestions for new studies to assess suicidality and related treatmentemergent adverse drug events, for example hostility,aggression and activation; (6) improving the safetyinfrastructure to assess drug safety in children andadolescents and (7) recent consequences of Foodand Drug Administration (FDA) black box warnings.From this review, the reader should have a moredetailed knowledge base from which to assess clinicaldecisions related to the safety of the SSRIs for thetreatment of depression in youth and to build consen-sus on future research and policy.