Predictors of placebo response in randomized controlled trials of psychotropic drugs for children and adolescents with internalizing disorders.
OBJECTIVE
The aim of this study was to assess predictors of placebo response in all available short-term, placebo-controlled trials of psychotropic drugs for children and adolescents with internalizing disorders, major depressive disorder (MDD), obsessive compulsive disorder (OCD,) and anxiety disorders (ANX) exclusive of OCD and posttraumatic stress disorder (PTSD).


METHODS
We reviewed the literature relevant to the use of psychotropic medication in children and adolescents with internalizing disorders, restricting our review to double-blind studies including a placebo arm. Placebo response, defined according to each trial's primary response outcome variable and Clinical Global Impressions-Improvement, when available, and potential predictive variables were extracted from 40 studies.


RESULTS
From 1972 to 2007, we found 23 trials that evaluated the efficacy of psychotropic medication involving youth with MDD, 7 pertaining to youths with OCD, and 10 pertaining to youths with ANX (N = 2,533 patients in placebo arms). For all internalizing disorders combined, predictors of nonresponse to placebo were the percentage of Caucasian patients included in the study and the duration of the disorder: Both variables were negatively correlated with the percent of placebo responders. The type of disorder was found to predict the robustness of placebo response: (OCD < ANX < MDD). For a subset of MDD studies, we found that baseline illness severity tended to be negatively correlated with placebo response. Finally, trial "success" was significantly associated with lower placebo response rate.


CONCLUSIONS
Predictors of placebo response in internalizing disorders of youths parallel those in adult studies, with the exception of race. These predictors should be considered when designing placebo-controlled trials in youths to enhance findings of true drug-placebo differences.
Cohen
David
D
Department of Child and Adolescent Psychiatry, Université Pierre et Marie Curie, GH Pitié-Salpétrière, AP-HP, Paris, France.
Consoli
Angèle
A
Bodeau
Nicolas
N
Purper-Ouakil
Diane
D
Deniau
Emmanuelle
E
Guile
Jean-Marc
JM
Donnelly
Craig
C
D000293:Adolescent; D001008:Anxiety Disorders / Q000188:drug therapy*; D002648:Child; D003865:Major Depressive Disorder / Q000188:drug therapy*; D006801:Humans; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy*; D015990:Placebo Effect; D011619:Psychotropic Drugs / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy*; D016896:Treatment Outcome
D011619:Psychotropic Drugs