The clinical significance of antidepressant treatment effects cannot be derived from placebo-verum response differences

Abstract

A placebo—verum difference in antidepressant response of at least three points on the Hamilton Depression Rating Scale has been proposed as the threshold for clinical significance in antidepressant trials. Given the considerable clinical and regulatory consequences of such a definition of clinical relevance it deserves a critical discussion. Eight arguments are presented indicating that using this definition as a criterion for assessing the clinical utility of antidepressants in daily practice would risk erroneously discarding treatments with a clear benefit for patients.