The association between antidepressant treatment and suicidal thoughts and behavior in children and adolescents has been the topic of recent debate. Much of our knowledge about treatment emergent risks associated with antidepressant treatment in youth derive from short-term, randomized, controlled trials (RCTS). These trials are limited in detecting adverse effects of medications due to the relatively small number of participants required to test primary efficacy end points. The proposed R03 small grant project will address gaps in knowledge by determining the relative safety and tolerability of antidepressant medications in the acute treatment of childhood anxiety, based on a secondary analysis of individual patient-level data of all available randomized controlled trials (RCTs) comparing antidepressants and placebo for generalized anxiety disorder, separation anxiety disorder, and social phobia. Outcomes will include treatment emergent adverse events (TEAEs) and treatment-induced changes in vital signs, cardiovascular effects, height, weight, and clinical laboratory parameters. The study also aims to identify patient subgroups at highest risk of adverse outcomes during acute treatment. This work will build on the PI's existing databases of antidepressant RCTs for pediatric depression, OCD, and non-OCD anxiety disorders. Meta-analysis of individual patient data (MAP) has been proposed as the most rigorous empirical method available to determine the relative efficacy and safety of treatments. This study is novel in that MAP allows for statistically powerful time-to-event analysis, identification of subgroups of patients at differential risk of adverse outcomes, and adjustment for variables that may have confounded the original treatment comparisons. We will therefore be able to examine questions of safety and tolerability otherwise unanswerable by a single trial, a multi-center RCT, or a traditional study-level meta- analysis. The feasibility of this project is supported by existing commitments from PIs and industry sponsors to provide our team with the patient-level data necessary to accomplish the goals of this application. These findings will be of benefit to clinicians who manage and treat anxious youth with these medications. This preliminary research will also build the foundation for future work examining the treatment emergent risks and side effects burden of psychotropic medications in other psychiatric disorders, including MDD, OCD, and bipolar disorder. ? ? ?
