Psychological Medicine


Is the antidepressive effect of second-generation antidepressants a myth?

P. Becha1 c1

a1 Psychiatric Research Unit, Frederiksborg General Hospital, Hillerød, Denmark

Two recent meta-analyses on second-generation antidepressants versus placebo in mild to moderate forms of major depression, based on data on all randomized clinical trials using the Hamilton Depression Scale (HAMD) submitted to FDA, have shown an effect size of 0.30 in favour of antidepressants in the acute therapy of major depression. The clinical significance of an effect size at this level was found to be so poor that these meta-analyses have subscribed to the myth of an exclusively placebo-like effect of second-generation antidepressants. A re-allocation of HAMD items focusing on those items measuring severity of clinical depression, the HAMD6, has identified effect sizes of 0.40 for second-generation antidepressants in placebo-controlled trials for which even a dose–response relationship can be demonstrated. In the relapse-prevention phase during continuation therapy of patients with major depression, the advantage of second-generation antidepressants over placebo was as significant as in the acute therapy phase. To explore a myth is not to deny the facts but rather to re-allocate them.

(Received September 16 2008)

(Revised April 07 2009)

(Accepted April 29 2009)

(Online publication June 03 2009)


c1 Address for correspondence: P. Bech, MDSci., Professor of Psychiatry and Applied Psychometrics, Psychiatric Research Unit, Frederiksborg General Hospital, 3400 Hillerød, Denmark. (Email: