Onset of response in relation to outcome in depressed outpatients with placebo and imipramine

Abstract

We have retrospectively analyzed the results of the pooled data from three 6-week placebo controlled double blind phase III clinical trials, initially designed to assess the efficacy of newer antidepressants, in order to study the relationship of early onset improvement with later outcome in 145 depressed outpatients receiving placebo (n = 98) or imipramine (n = 47). The early onset response was seen in a subgroup of subjects receiving either imipramine or placebo and appeared to be independent of treatment assignment. Furthermore, the early onset response predicted outcome for the duration of the trial and was not selective as defined by specific changes in subscales measuring insomnia, anxiety or endogenous features. Exclusion of early onset responders resulted in the augmentation of the difference in outcome with drug and placebo. We recommend that future placebo controlled trials assessing therapeutic efficacy of active treatments in depressed outpatients take into account the early onset response in the analysis of results.