FPIN's Help Desk Answers

Alzheimer Disease: Monotherapy vs. Combination Therapy


Am Fam Physician. 2017 Apr 1;95(7):452.

Clinical Question

Is the combination of memantine with donepezil more effective in the treatment of Alzheimer disease than either drug alone?

Evidence-Based Answer

Combination treatment with memantine and donepezil results in a small improvement in cognitive function that is of uncertain clinical significance in patients with moderate to severe Alzheimer disease, but no improvement in patients with mild to moderate disease. (Strength of Recommendation: B, based on a meta-analysis of randomized controlled trials.)

Evidence Summary

A meta-analysis of three double-blind randomized controlled trials evaluated the use of combination therapy with memantine plus donepezil (two studies) or memantine plus donepezil, galantamine, or rivastigmine in patients with Alzheimer disease.1 Data were analyzed for 1,043 patients

Author disclosure: No relevant financial affiliations.

Address correspondence to Amber Avila, MD, at aavila@siumed.edu. Reprints are not available from the authors.


1. Muayqil T, et al. Systematic review and meta-analysis of combination therapy with cholinesterase inhibitors and memantine in Alzheimer's disease and other dementias. Dement Geriatr Cogn Dis Extra. 2012;2(1):546–572.

2. Gareri P, et al. Retrospective study on the benefits of combined Memantine and cholinEsterase inhibitor treatMent in AGEd Patients affected with Alzheimer's disease. J Alzheimers Dis. 2014;41(2):633–640.

Help Desk Answers provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (http://www.cebm.net/?o=1025).

The complete database of evidence-based questions and answers is copyrighted by FPIN. If interested in submitting questions or writing answers for this series, go to http://www.fpin.org or e-mail: questions@fpin.org.

Copyright Family Physicians Inquiries Network. Used with permission.

This series is coordinated by John E. Delzell Jr., MD, MSPH, Assistant Medical Editor.

A collection of FPIN's Help Desk Answers published in AFP is available at http://www.aafp.org/afp/hda.


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May 1, 2017

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