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Arch Gen Psychiatry. 2006 Nov;63(11):1217-23.

Early onset of selective serotonin reuptake inhibitor antidepressant action: systematic review and meta-analysis.

Authors:

Taylor MJ , Freemantle N , Geddes JR , Bhagwagar Z .

Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, England.

Matthew. Taylor@psych.ox. Ac.uk

Context:

Selective serotonin reuptake inhibitors (SSRIs) are often described as having a delayed onset of effect in the treatment of depression. However, some trials have reported clinical improvement as early as the first week of treatment.

Objectives:

To test the alternative hypotheses of delayed vs early onset of antidepressant action with SSRIs in patients with unipolar depression.

Data Sources:

Trials identified by searching CENTRAL, The Cochrane Collaboration database of controlled trials (2005), and the reference lists of identified trials and other systematic reviews.

Study Selection:

Randomized controlled trials of SSRIs vs placebo for the treatment of unipolar depression in adults that reported outcomes for at least 2 time points in the first 4 weeks of treatment (50 trials from >500 citations identified). Trials were excluded if limited to participants older than 65 years or specific comorbidities.

Data Extraction:

Data were extracted on trial design, participant characteristics, and outcomes by a single reviewer.

Data Synthesis:

Pooled estimates of treatment effect on depressive symptom rating scales were calculated for weeks 1 through 6 of treatment. In the primary analysis, the pattern of response seen was tested against alternative models of onset of response. The primary analysis incorporated data from 28 randomized controlled trials (n=5872). A model of early treatment response best fit the experimental data. Treatment with SSRIs rather than placebo was associated with clinical improvement by the end of the first week of use. A secondary analysis indicated an increased chance of achieving a 50% reduction in Hamilton Depression Rating Scale scores by 1 week (relative risk, 1.64; 95% confidence interval, 1.2-2.25) with SSRI treatment compared with placebo.

Conclusions:

Treatment with SSRIs is associated with symptomatic improvement in depression by the end of the first week of use, and the improvement continues at a decreasing rate for at least 6 weeks.

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