Do antidepressants really take several weeks to show effect?

Conventional repeated measurements analysis of variance suggests that response to antidepressants is slow, and that differences between antidepressants and placebo do not normally reach statistical significance until the 3rd or 4th week of treatment. This statistical “response lag” has finally led to the “delayed onset of action” hypothesis, although response-to-treatment and onset-of-action represent two principally different concepts that relate to different aspects of efficacy of antidepressant drug therapy. While response-to-treatment has its main focus on the proportion of patients in whom antidepressants induce a clinically relevant change, onset-of-action refers to the speed at which symptoms reduce under antidepressants in comparison to placebo. Standard drug trial procedures tend to obscure differences in onset of action across drugs, as well as across patients, because such procedures rely upon mean depression scores derived from studies which amalgamate separate depressive subgroups, rapid and slow remitters, as well as partial remitters, non-remitters and premature withdrawals (Parker, 1996a; Stassen et al., 1998).