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

BACKGROUND: There is controversy about the implications of relatively small average drug-placebo differences observed in randomised controlled trials of antidepressant medications. AIMS: To investigate whether efficacy is better understood as a large effect in a subgroup of patients. METHOD: The 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. RESULTS: The 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. CONCLUSIONS: This 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.