DELAYED-ONSET OF ACTION OF ANTIDEPRESSANT DRUGS - SURVEY OF RESULTS OF ZURICH METAANALYSES

The onset of action of antidepressant drugs was investigated on the ba sis of two independent, multicenter, double-blind studies, comparing a mitriptyline (N = 120), oxaprotiline (N = 120), imipramine (N = 506) a nd moclobemide (N = 580) with placebo (N = 189 /+ 191). Highly signifi cant differences between the active drugs and placebo were found with respect to the total number of improvers and the total number of respo nders. In addition, significant differences between treatment modaliti es showed up in both the percentage rate and the time distribution of premature withdrawals. However, among improvers, the distribution of t ime spans to onset of improvement was found to be independent of treat ment modality, indicated by virtual ly identical cumulative percentage s of improvers over the whole observation period. This picture of trea tment-independent improvement rates was essentially the same for the H AMD, HAMA and ZUNG assessments, except for a significant time lag betw een observerratings and selfratings. Specifically, our analyses reveal ed no evidence for a delayed onset of action of various antidepressant s with large biochemical and pharmacological differences when compared to placebo. The early onset of improvement was highly predictive of l ater outcome: on average, 70% of patients showing improvement within t he first 14 days became responders. Differences between active treatme nts and placebo emerged within the first five days and reached a point of maximum distinction around day 14. After this time point, differen ces between treatment modalities remained constant until the end of th e observation period. Not more than 20 - 25% of patients were, on aver age, ''true'' drug responders, thus suggesting that the therapeutic qu alities of antidepressants do not lie in the suppression of symptoms, but rather relate to their ability to elicit and maintain certain cond itions which enable recovery in a subgroup of patients who would other wise remain nonresponders.