Assessing the ‘true’ effect of active antidepressant therapy v. placebo in major depressive disorder: use of a mixture model

Abstract

BackgroundThere is controversy about the implications of relatively small average drug–placebo differences observed in randomised controlled trials of antidepressant medications.AimsTo investigate whether efficacy is better understood as a large effect in a subgroup of patients.MethodThe mixture model was used to identify patient subgroups (patients benefiting or not benefiting from treatment) to directly model the skewness of Montgomery–åsberg Depression Rating Scale (MADRS) scores at week 8.ResultsThe MADRS scores improved by 15.9 points (95% CI 15.2–16.6) among patients who benefited from treatment. The proportion of patients who benefited from escitalopram and not from placebo treatment was 19.5%, corresponding to a number needed to treat of 5.ConclusionsThis model gave a considerably better fit to the data than the analysis of covariance model in which all patients were assumed to benefit from treatment. The small average antidepressant–placebo difference obscures a much larger effect in a clinically meaningful subgroup of patients.