Level 1: Likely reliable evidence

A systematic review of 50 published randomized placebo-controlled trials of selective serotonin reuptake inhibitors (SSRIs) evaluated their onset of efficacy in a total of 10,121 adults with unipolar depression (Arch Gen Psychiatry. 2006; 63:1217-1223). Included trials evaluated fluoxetine (Prozac), fluvoxamine (Luvox), citalopram (Celexa), sertraline (Zoloft), escitalopram (Lexapro), 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 involving 5,872 patients who were mainly female and mostly from outpatient or primary-care populations. Fifteen trials provided intention-to-treat analyses, with last observation carried forward.


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The weighted mean differences in average Hamilton Depression Rating Scale scores favored SSRIs over placebo, based on the pooling of 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).

Based on two trials with a total of 684 pateints, there was no significant advantage for SSRI therapy at one week. But after two to six weeks, there was a signficant 79% increased chance for remission among those receiving an SSRI compared with those receiving a placebo.