Factors Related to Placebo Response in Randomized, Double-Blind Clinical Trials of Antidepressants in Children and Adolescents: A Meta-regression Analysis

Background and ObjectiveMany randomized clinical trials (RCTs) for antidepressants in children and adolescents have failed to demonstrate efficacy due to a high placebo response. The aim of this study was to identify the potential factors affecting placebo response using meta-regression analysis of RCTs for antidepressants in children and adolescents using the Children's Depressive Rating Scale-Revised (CDRS-R) as the outcome.MethodsPubMed and ClinicalTrials.gov were searched for randomized, double-blind, placebo-controlled trials of antidepressants for the acute treatment of major depressive disorder in children and adolescents. The outcome used in the present study was the mean change of the CDRS-R total score from baseline to the last assessment for the primary efficacy in the placebo arm. Potential factors related to the placebo response, such as study design, operational, and patient factors, were explored using meta-regression.ResultsThe analyses included 23 trials. On multivariable meta-regression, setting up a placebo lead-in period was significantly associated with a smaller placebo response in the CDRS-R.ConclusionSetting up a placebo lead-in period should be considered in future clinical trials of antidepressants in adolescents and children.