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Early Onset of SSRI Antidepressant Action


Am Fam Physician. 2007 Sep 15;76(6):864-868.

Background: It has been stated that it takes two to three weeks before a response to an antidepressant medication is apparent. Studies supporting this predated the use of selective serotonin reuptake inhibitors (SSRIs). Some trials have shown that the delay in response to SSRIs is similar to other antidepressants. However, other studies have shown that SSRIs have a statistically significant improvement within as little as one week when compared with placebo. The early response to SSRIs may reflect a true effect or may be a chance event. To evaluate this issue, Taylor and colleagues performed a systematic review and meta-analysis of randomized trials to determine if there is an early response to SSRIs in the treatment of depression.

The Study: The authors searched the literature for randomized, placebo-controlled trials of fluoxetine (Prozac), fluvoxamine (Luvox), citalopram (Celexa), escitalopram (Lexapro), sertraline (Zoloft), and paroxetine (Paxil). The studies assessed these antidepressant medications in the treatment of unipolar depression. The authors used multiple databases for the literature search, and reviewed reference lists from the articles selected and related systematic reviews. Data extracted were trial design, participant characteristics, and outcomes. When reported, data from depression rating scores or changes in scores over the first six weeks of treatment were also extracted. Trials were eliminated if the participants were limited to adults 65 years and older or to those with specific comorbidities.

Results: The authors identified 28 trials that met inclusion criteria; these included 3,618 participants who received SSRIs and 2,254 in placebo groups. The pooled data were analyzed to assess the treatment effect of SSRIs compared with placebo for weeks 1 through 6 of treatment.

Patients treated with SSRIs were found to have greater clinical improvement by the end of week 1 compared with those in the placebo group. This improvement continued over time, but the increment of benefit decreased week by week. In those studies using the Hamilton Depression Rating Scale, treatment that resulted in a 50 percent reduction in this score at week 1 was significantly more likely to occur with SSRIs than with placebo (relative risk = 1.64; 95% confidence interval, 1.2 to 2.25). Those studies using the Montgomery-Asberg Depression Rating Scale showed similar results.

Conclusion: The authors conclude that symptomatic improvement in depression occurs with the use of SSRIs by week 1 and continues during the first six weeks of treatment, but at a declining rate. An early response to this class of antidepressants may represent a true response and not a placebo effect.


Taylor MJ, et al. Early onset of selective serotonin reuptake inhibitor antidepressant action: systematic review and meta-analysis. Arch Gen Psychiatry. November 2006;63:1217–23.

editor's note: During the course of our education, certain dogmas were taught that have grown to be accepted as fact over the years. The recent push to use evidence-based medicine to address some of these issues has brought changes in how we manage our patients. We have all seen a patient with depression respond rapidly to antidepressants, and we generally write it off to placebo effect. However, reviewing the literature pointed out that the dogma was based on two studies published in the 1980s.1,2 There have been substantial additions to our treatment options since then, yet the evidence did not support a change in our understanding. This study demonstrates that the early response that we thought was a placebo effect was in fact a response to SSRIs. We may now tell patients that they may get a response to SSRIs in as little as one week. —k.e.m.



1. Quitkin FM, Rabkin JD, Markowitz JM, Stewart JW, McGrath PJ, Harrison W. Use of pattern analysis to identify true drug response: a replication. Arch Gen Psychiatry. 1987;44:259–64.

2. Quitkin FM, Rabkin JG, Ross D, Stewart JW. Identification of true drug response to antidepressants: use of pattern analysis. Arch Gen Psychiatry. 1984;41:782–6.



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