Are Child and Adolescent Responses to Placebo Higher in Major Depression than in Anxiety Disorders? A Systematic Review of Placebo-Controlled Trials

Background: In a previous report, we hypothesized that responses to placebo were high in child and adolescent depression because of specific psychopathological factors associated with youth major depression. The purpose of this study was to compare the placebo response rates in pharmacological trials for major depressive disorder (MDD), obsessive compulsive disorder (OCD) and other anxiety disorders (AD-non-OCD). Methodology and Principal Findings: We reviewed the literature relevant to the use of psychotropic medication in children and adolescents with internalized disorders, restricting our review to double-blind studies including a placebo arm. Placebo response rates were pooled and compared according to diagnosis (MDD vs. OCD vs. AD-non-OCD), age ( adolescent vs. child), and date of publication. From 1972 to 2007, we found 23 trials that evaluated the efficacy of psychotropic medication ( mainly non-tricyclic antidepressants) involving youth with MDD, 7 pertaining to youth with OCD, and 10 pertaining to youth with other anxiety disorders (N = 2533 patients in placebo arms). As hypothesized, the placebo response rate was significantly higher in studies on MDD, than in those examining OCD and AD-non-OCD (49.6% [ range: 17-90%] vs. 31% [ range: 4-41%] vs. 39.6% [ range: 9-53], respectively, ANOVA F = 7.1, p = 0.002). Children showed a higher stable placebo response within all three diagnoses than adolescents, though this difference was not significant. Finally, no significant effects were found with respect to the year of publication. Conclusion: MDD in children and adolescents appears to be more responsive to placebo than other internalized conditions, which highlights differential psychopathology.