Abstract
Research question Do selective serotonin reuptake inhibitors take weeks to work?
Answer Probably not. Symptoms of depression improve during the first week of treatment
Why did the authors do the study? Patients with depression are often told to expect a delay of several weeks before their antidepressant starts to work. But the research on this issue is inconsistent. These authors wanted to find out if the rapid response reported by some trials of selective serotonin reuptake inhibitors (SSRIs) is real or just a placebo effect.
What did they do? They searched systematically through seven established research databases for published trials in any language that compared an SSRI with placebo in patients with depression. Their search included reference lists, conference proceedings, and abstracts. They included 50 trials in the final review and meta-analysis. The trials included 6153 patients treated with any SSRI licensed in the UK and 3968 controls treated with a placebo. Most of the patients were treated in primary care or psychiatric outpatient settings. They were at least moderately severely depressed at baseline.
The authors pooled data on depression rating scales for each of the first six weeks of treatment. They then matched their analysis against five models describing different patterns of response to treatment, including an early or a late start. They did further analyses of groups of trials reporting changes in scores from baseline or predefined response rates.
What did they find? In the primary analysis of 28 trials, the pooled data best fit a model describing an early response to treatment. In this model, patients' symptoms improved most during the first week of treatment and continued to improve, but more slowly, for the next six. In the secondary analyses, patients treated with an SSRI had significantly lower symptom scores (from the Hamilton or Montgomery-Asberg depression rating scales) than patients treated with placebo by the end of the first week. The difference increased with time, reaching −3.3 (95% CI −4.14 to −2.45) on the Hamilton scale by the end of six weeks. There was also a significant increase in the chance of a “response” during the first week for patients treated with an SSRI (relative risk 1.64 (1.2 to 2.25), number needed to treat=25). Response was usually defined as a 50% improvement in the Hamilton depression scores.
What does it mean? These analyses suggest that SSRI antidepressants work faster than previously thought. These authors found no evidence of a delay between the start of treatment and an effect, and their findings mean that patients can probably expect to feel at least a little better within a week or so. The full treatment effect, or remission, takes several weeks longer, but the authors estimate that patients in these trials had about a third of their eventual response to treatment during the first week. Since most were outpatients, the findings may not apply to patients with severe depression being treated in hospital.
References
- Taylor et al. Early onset of selective serotonin reuptake inhibitor antidepressant action: systematic review and meta-analysis. Archives of General Psychiatry 2006;63:1217-23 [DOI] [PMC free article] [PubMed] [Google Scholar]