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Am Fam Physician. 2019;100(6):376

Clinical Question

What is the evidence for augmentation therapy in patients with treatment-resistant depression?

Bottom Line

There is weak research to guide treatment decisions for patients who have not responded to two adequate courses of antidepressant treatment. One study of cognitive behavior therapy showed benefit over placebo. Aripiprazole (Abilify) had a small effect, but neither antipsychotics nor lithium provided benefit over placebo. (Level of Evidence = 1a)


The investigators searched two databases (but not Cochrane CENTRAL) to identify randomized controlled trials that investigated the benefit of augmentation therapy in patients with depression despite two attempts at treatment of adequate duration. The authors followed PRISMA guidelines for conducting systematic reviews. They identified 28 studies. Twenty-five investigated additional pharmacotherapy and three investigated psychological therapies. The studies were of moderate to high quality. There was considerable heterogeneity across the study results attributed to different treatments, duration of study, and study quality. Cognitive behavior therapy was more effective than placebo in a single study, but other counseling interventions were not. Treatment with antipsychotics or lithium was not more effective than placebo. Aripiprazole had a small likelihood of producing benefit (effect size 1.33; 95% CI, 1.23 to 1.44).

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Setting: Various (meta-analysis)

Reference: Strawbridge R, Carter B, Marwood L, et al. Augmentation therapies for treatment-resistant depression: systematic review and meta-analysis. Br J Psychiatry. 2019;214(1):42–51.

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.

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