Is There a Delay in the Antidepressant Effect? A Meta-Analysis

Objectives: It has long been thought that there is a delay of several weeks before a true antidepressant effect occurs, although this theory has increasingly come into question. The goals of this meta-analysis were to determine whether significant drug-placebo separation occurs during the first 2 weeks of treatment and to ascertain whether the timing of response to antidepressant medication and placebo is distinct.

Data Sources: Seventy-six double-blind, placebo-controlled trials conducted between 1981 and 2000, included in a recently published meta-analysis that evaluated placebo response rates in depressed outpatients, were reviewed. In addition, each issue of 6 psychiatric journals from January 1992 through December 2001 was reviewed.

Study Selection: Forty-seven studies that evaluated antidepressant medications with established efficacy, performed weekly or biweekly (every other week) evaluations, and presented the time course of improvement as measured by the Hamilton Rating Scale for Depression were included in our meta-analysis.

Data Synthesis: The time course of improvement on active medication and placebo was nearly identical, as 60.2% and 61.6% of the improvement that occurred on active medication and placebo, respectively, took place during the first 2 weeks of treatment. Drug-placebo differences were not only present but were most pronounced during the first 2 weeks of treatment and diminished in a stepwise fashion thereafter. A series of subanalyses confirmed that this early drug-placebo separation was clinically observable and represented a true drug effect.

Conclusion: These results challenge the notion that a delay exists before a true antidepressant effect occurs.