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It has been argued recently that the drug-placebo difference is diminishing in clinical trials of depression. Recently a paper suggested that the placebo response in trials of antidepressant agents increased abruptly after 1991 and remained stable afterwards at the level of 35–40%.1 A possible explanation for this change could be the introduction of Diagnostic and Statistical Manual Third Edition (DSM)-III and DSM-III-Revised (R) and the change in paradigm concerning depression, which came with them since the early 1980s.2 ,3 With the introduction of operationalised diagnostic criteria, the concept of depression both changed and broadened. Neither the Hamilton Rating Scale for Depression (HAM-D) nor the Montgomry-Asberg Depression Rating Scale (MADRS) correspond to this new concept since they were both developed or last updated before 1980 and overall the properties of these scales are problematic.4
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