Meta-Analysis: Pediatric Placebo Response in Depression Trials Does Not Replicate in Anxiety and Obsessive-Compulsive Disorder Trials.

Abstract

Background: Placebo response has been identified as an important factor influencing the success of adult antidepressant trials, yet little research of placebo response has been conducted in pediatric populations. Understanding disorder-specific and transdiagnostic predictors of pediatric placebo response is important in designing successful child psychopharmacological trials. Methods: A PubMed search was conducted for all pediatric antidepressant randomized controlled trials treating depression, anxiety, or obsessive-compulsive disorder (OCD). A random-effects model was utilized to examine the magnitude of placebo symptom improvement using standardized mean difference (SMD) and placebo response rates. Stratified subgroup analysis was performed by diagnostic indication. Meta-regression was utilized to search possible correlates of placebo symptom improvement and placebo response rate. Results: Thirty antidepressant trials involving 2911 participants receiving placebo were included in this meta-analysis. Magnitude of placebo improvement and placebo response rates varied significantly across disorders; being greater in depression (SMD\u2009=\u20091.44, 95% confidence interval [CI]: 1.18 to 1.71) than anxiety disorders (SMD\u2009=\u20091.09, 95% CI: 0.77 to 1.41) and the lowest in OCD (SMD\u2009=\u20090.71, 95% CI: 0.32 to 1.12). Different predictors were associated with placebo response in different indications. Conclusions: Both the magnitude and predictors of placebo response in pediatric depression trials do not replicate across anxiety and OCD. Based on our results, across disorders, minimizing the number of sites might significantly reduce placebo improvement. In addition to these, we could potentially decrease the placebo response in depression trials by increasing the number of subjects enrolled per study site, minimizing the number of study visits and conducting the studies in the United States. Further research is needed into the predictors of placebo response in pediatric anxiety and OCD.