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Delayed Onset of Action of Antidepressants

Fact or Fiction?

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Summary

In standard drug trials comparing antidepressants with placebo, a period of typically 3 weeks is required before formal statistical significance between treatments is achieved. This delay has often been interpreted as indicating a delayed onset of action of antidepressants. However, detailed analyses of the time course of recovery from depression demonstrate that the ‘delayed onset’ hypothesis needs revision. The respective findings, now replicated across several differing antidepressant drug classes and placebo, suggest that: (i) among responders, the onset of improvement occurs in more than 70% of cases within the first 3 weeks of treatment; (ii) there is no evidence of a pronounced increase in improvement rates beyond this time point; and (iii) early improvement 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 maintain the conditions necessary for improvement, irrespective of their primary site of action within the monoaminergic systems. Differences between the efficacy of active drugs and placebo are reflected both by the total number of patients who improve, and by the number and time distribution of patients who withdraw prematurely. As a consequence, the therapeutic qualities of antidepressants may not lie in their suppression of symptoms, but rather in their ability to convert a percentage of ‘nonresponders’ to ‘responders’, triggering and maintaining the conditions necessary for improvement in the early stages of treatment.

Clearly, all these findings, which are at odds with the ‘delayed onset’ hypothesis, require further study to detail the extent to which antidepressants act non-specifically by ‘kick starting’ a remission in the early stages of treatment. In addition, the characteristics that distinguish ‘true’ drug responders from placebo responders remain to be clarified.

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Authors and Affiliations

  1. Research Department, Psychiatric University Hospital Zurich, PO Box 68, CH-8029, Zurich, Switzerland

    Hans H. Stassen &  Jules Angst

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  1. Hans H. Stassen
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  2. Jules Angst
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Correspondence to Jules Angst.

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Stassen, H.H., Angst, J. Delayed Onset of Action of Antidepressants. Mol Diag Ther 9, 177–184 (1998). https://doi.org/10.2165/00023210-199809030-00001

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  • DOI: https://doi.org/10.2165/00023210-199809030-00001

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