Measuring onset of antidepressant action in clinical trials: an overview of definitions and methodology.

This article discusses 4 critical questions that must be addressed in any valid analysis of comparative onset of therapeutic effect among antidepressant drugs: (1) how is onset defined, (2) how is onset measured, (3) how can the treatment groups be compared statistically with regard to onset of effect, and (4) how do these issues affect protocol design? A rigorous study of differential onset of effect should include an estimation of the portion of patients that respond, the timing of the onset of response, and the duration of response and an examination of the dynamic process of the onset of action. Methods for measuring symptom severity changes over time also will be reviewed.