DELAYED-ONSET OF ACTION OF ANTIDEPRESSANTS - FACT OR FICTION

In standard drug trials comparing antidepressants with placebo, a peri od of typically 3 weeks is required before formal statistical signific ance between treatments is achieved. This delay has often been interpr eted as indicating a delayed onset of action of antidepressants. Howev er, detailed analyses of the time course of recovery from depression d emonstrate that the 'delayed onset' hypothesis needs revision. The res pective findings, now replicated across several differing antidepressa nt drug classes and placebo, suggest that: (i) among responders, the o nset of improvement occurs in more than 70% of cases within the first 3 weeks of treatment; (ii) there is no evidence of a pronounced increa se in improvement rates beyond this time point; and (iii) early improv ement is highly predictive of better later outcome. Most notably, the time course of improvement appears to be independent of the treatment modality, and effective antidepressants seem to merely trigger and mai ntain the conditions necessary for improvement, irrespective of their primary site of action within the monoaminergic systems. Differences b etween the efficacy of active drugs and placebo are reflected both by the total number of patients who improve, and by the number and time d istribution of patients who withdraw prematurely. As a consequence, th e therapeutic qualities of antidepressants may not lie in their suppre ssion of symptoms, but rather in their ability to convert a percentage of 'nonresponders' to 'responders', triggering and maintaining the co nditions necessary for improvement in the early stages of treatment. C learly, all these findings, which are at odds with the 'delayed onset' hypothesis, require further study to detail the extent to which antid epressants act nonspecifically by 'kick starting' a remission in the e arly stages of treatment. In addition, the characteristics that distin guish 'true' drug responders from placebo responders remain to be clar ified.