Onset of action under antidepressant treatment.

The issues of timing in antidepressant treatment are of great theoretical and practical relevance, even more so since recent meta-analyses yielded no evidence for a specific mode of action of antidepressants, which, according to the theory of delayed onset of action, is expected to emerge after 2 weeks of therapy. To address the issues of timing on a methodologically sound basis, future trials should adapt a 'longitudinal' rather than 'cross-sectional' design, standardized with respect to a washout period, baseline and first 2 week assessments. With this in mind, special attention should be paid to parameters which potentially enable the identification of placebo responders, true drug responders and patients at risk of non-improvement. Results and methods of the Zurich meta-analyses may serve as a starting point for further steps in this direction.