How long to onset of antidepressant action: a meta-analysis of patients treated with fluoxetine or placebo.

The onset of action of antidepressant medications is commonly believed to require three or more weeks based on clinical observation and corollary receptor-based hypotheses. However, this is not congruent with early published observations with the tricyclic antidepressants and has been recently challenged. Time to response has implications for treatment compliance, dose adjustment, patient well-being, and the associated economic costs of depression. Weekly improvement on the 21-item Hamilton Depression Rating Scale (HAMD21) from baseline and time to response for fluoxetine- and placebo-treated patients were compared. Data from six double-blind clinical trials of 6-7 weeks' duration, in which 1447 patients with DSM-III-R major depression had been randomly allocated to fluoxetine (n = 962) or placebo (n = 485), were pooled. Analysis of variance was used to evaluate HAMD21 improvement and the Kaplan-Meier estimate was used to evaluate time to response (> or = 50% improvement in HAMD21). Improvement in HAMD21 was statistically significantly greater for fluoxetine than placebo beginning at Week 1 and continuing throughout all weeks of therapy. However, Week 1 and 2 results varied among the individual studies. HAMD factors of cognition and psychomotor status revealed the most rapid changes for fluoxetine-treated compared with placebo-treated patients. The probability of achieving a clinical response, defined as a HAMD21 score reduction from baseline of at least 50%, was similar for both fluoxetine (0.043) and placebo (0.049) at the end of Week 1. However, by Week 2 and thereafter the probability of a response was greater for fluoxetine than placebo.(ABSTRACT TRUNCATED AT 250 WORDS)