Level 1: Likely reliable evidence

A systematic review of 50 randomized placebo-controlled trials of selective serotonin reuptake inhibitors (SSRIs) evaluated their onset of efficacy in 10,121 adults with unipolar depression (Arch Gen Psychiatry. 2006;63:1217-1223). Included trials evaluated fluoxetine (Prozac), fluvoxamine (Luvox), citalopram (Celexa), escitalopram (Lexapro), sertraline (Zoloft), and paroxetine (Paxil) and reported outcome measures at least twice in the first four weeks of treatment. Primary analyses were based on 28 randomized trials with 5,872 patients who were mainly female and mostly from outpatient or primary-care populations. Fifteen trials provided intention-to-treat analyses, with the last observation carried forward.

The weighted mean differences in Hamilton Depression Rating Scale scores favored SSRIs over placebo, based on 25 trials: -1.07 at one week (N=1,893) and -3.3 at six weeks (N=3,432). Based on five trials, the absolute difference in the rate of achieving a 50% reduction in Hamilton Depression Rating Scale scores was 4% at one week (NNT 25), 10% at two weeks (NNT 10), 9% at three weeks (NNT 11), 11% at four and five weeks (NNT 9), and 12% at six weeks (NNT 9) (N=1,203-1,428). The relative difference in the rate of achieving remission (Hamilton Depression Rating Scale scores <7-8) was 0.46 at one week (nonsignificant trend favoring placebo) and 1.79 at two to six weeks (significant benefit favoring SSRIs), based on two trials with 684 patients.