Is drug–placebo difference in short-term antidepressant drug trials on unipolar major depression much greater than previously believed?

A pooled analysis of randomized placebo-controlled short-term antidepressant trials on unipolar major depression shows that the rate of antidepressant and placebo responders is 50% and 30% respectively. The traditional calculation of antidepressant–placebo difference (50–30 = 20%) in these drug trials is based on the assumption that all placebo responders should be antidepressant responders, a postulation that has been never investigated and proved. Further studies are needed investigating directly the relationship of placebo response in relation to antidepressant response/nonresponse. If a substantial part of placebo responders were antidepressant nonresponders, the drug–placebo differences in all short-term antidepressant drug trials on unipolar major depression are much more than 20%, and the previously published data on antidepressant–placebo difference should be re-calculated.