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Am Fam Physician. 2020;101(4):250

Clinical Question

Does a lack of early symptom improvement in patients treated for depression predict treatment failure?

Bottom Line

Do not be in a hurry to change treatment in patients with severe depression who do not respond to treatment within the first two weeks. Early response to treatment predicts eventual response or remission, but a lack of early response does not predict treatment failure. Approximately one-third of patients who do not show an early response will respond by six weeks. No individual symptom response predicts eventual improvement. (Level of Evidence = 1a)


The researchers used individual patient data derived from 30 studies of the treatment of severe major depressive disorder with a second-generation antidepressant. They had data on 2,184 patients who received a placebo and 6,058 who received an antidepressant. By six weeks of treatment, approximately 50% of treated patients had responded, with 32% achieving remission of symptoms. By 12 weeks, the rate was up to approximately 68% response with 49% achieving remission. Patients with early improvement— by two weeks—were likely to respond by six weeks, but almost 33% of patients without early improvement responded by six weeks, and 43% responded by 12 weeks. No individual symptom response predicted eventual response or remission.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Unknown/not stated

Setting: Various (meta-analysis)

Reference: de Vries YA, Roest AM, Bos EH, et al. Predicting antidepressant response by monitoring early improvement of individual symptoms of depression: individual patient data meta-analysis. Br J Psychiatry. 2019;214(1):4–10.

Editor’s Note: Dr. Shaughnessy is an assistant medical editor for AFP.

POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see Copyright Wiley-Blackwell. Used with permission.

For definitions of levels of evidence used in POEMs, see

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