Deconstructing Pediatric Depression Trials: An Analysis of the Effects of Expectancy and Therapeutic Contact

ObjectiveThis study investigated how study type, mean patient age, and amount of contact with research staff affected response rates to medication and placebo in acute antidepressant trials for pediatric depression.MethodData were extracted from nine open, four active comparator, and 18 placebo-controlled studies of antidepressants for children and adolescents with depressive disorders. A multilevel meta-analysis examined how study characteristics affected response rates to antidepressants and placebo.ResultsThe primary finding was a main effect of study type across patient age and contact amount, such that the odds of medication response were greater in open versus placebo-controlled studies (odds ratio 1.87, 95% confidence interval 1.17–2.99, p = .012) and comparator studies (odds ratio 2.01, 95% confidence interval 1.16–3.48, p = .015) but were not significantly different between comparator and placebo-controlled studies. No significant main effects of patient age or amount of contact with research staff were found for analyses of response rates to medication and placebo. Response to placebo in placebo-controlled trials did significantly increase with the amount of therapeutic contact in older patients (age by contact; odds ratio 1.08, 95% confidence interval 1.01–1.15, p = .038).ConclusionsAlthough patient expectancy strongly influences response rates to medication and placebo in depressed adults, it appears to be less important in the treatment of children and adolescents with depression. Attempts to limit placebo response and improve the efficiency of antidepressant trials for pediatric depression should focus on other causes of placebo response apart from expectancy.