brand logo

Am Fam Physician. 2019;100(12):online

Clinical Question

Is augmentation of antidepressant treatment effective for patients with treatment-resistant depression?

Bottom Line

The available evidence that treatment-resistant depression (depression that is unresponsive to two different treatments of adequate dose and length) responds well to augmentation treatment (i.e., adding psychotherapy, lithium, or aripiprazole [Abilify] to current treatment) is weak. The available evidence shows no benefit with lithium and small benefit with psychotherapy or aripiprazole. (Level of Evidence = 1a–)


The authors searched two databases (but not the Cochrane Library) for randomized studies of augmentation treatment for patients who did not respond to at least two courses of treatment for major depressive disorder. Two authors selected studies for inclusion and independently extracted the data. Most of the 28 studies of 5,461 patients had low to moderate risk of bias (i.e., studies were of medium to high quality) and included both drug treatment and psychological therapies. Instead of comparing directly across treatments (the benefit in one group vs. the other), the authors compared the before-after change in results within each group. In three low-quality studies, psychological treatment showed a moderate benefit. In four studies of aripiprazole, there was a small likelihood of benefit after short-term treatment (effect size = 1.33; 95% CI, 1.23 to 1.44) compared with placebo. Lithium produced an effect size similar to placebo.

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.

For definitions of levels of evidence used in POEMs, see

To subscribe to a free podcast of these and other POEMs that appear in AFP, search in iTunes for “POEM of the Week” or go to

This series is coordinated by Natasha J. Pyzocha, DO, contributing editor.

A collection of POEMs published in AFP is available at

Continue Reading

More in AFP

More in PubMed

Copyright © 2019 by the American Academy of Family Physicians.

This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.  See permissions for copyright questions and/or permission requests.