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Evidence Lacking for Efficacy of Memantine in Treating Mild Alzheimer Disease

CHICAGO, April 11, 2011—An analysis of studies involving the drug memantine finds a lack of evidence for benefit when the drug is used to treat patients with mild Alzheimer disease and mild cognitive impairment, according to a report posted online today that will appear in the August print issue of Archives of Neurology, one of the JAMA/Archives journals.

"Memantine, indicated for moderate to severe Alzheimer disease (AD), is frequently prescribed off-label [for uses other than those approved by the FDA] either alone or with a cholinesterase inhibitor for mild AD and mild cognitive impairment," the authors write as background information in the article. Cholinesterase inhibitors are drugs that increase levels of a brain chemical called acetylcholine. Increasing acetylcholine levels appears to slow mental decline in people with AD.

Lon S. Schneider, M.D., M.S., of the University of Southern California Keck School of Medicine, Los Angeles, and colleagues systematically searched manufacturer-sponsored meta-analyses, registries, presentations, and publications for randomized, placebo-controlled, parallel-group clinical trials of memantine in patients with mild to moderate AD. Three trials were identified that included 431 patients with mild AD and 697 patients with moderate AD. Using several different scales, the researchers assessed cognition, global change, functional activities, and behavior.

"There were no significant differences between memantine and placebo on any outcome for patients with mild AD, either within any trial or when data were combined," the authors report.

Among patients with moderate AD, there was no significant difference between memantine and placebo in any individual trial, although there was a significant effect when the three trials were statistically combined.

"Despite its frequent off-label use, evidence is lacking for a benefit of memantine in mild AD, and there is meager evidence for its efficacy in moderate AD," the authors conclude. "Prospective trials are needed to further assess the potential for efficacy of memantine either alone or added to cholinesterase inhibitors in mild and moderate AD."
(Published online April 11, 2011. Arch Neurol. 2011;doi:10.1001/archneurol.2011.69. Available pre-embargo to the media at

Editor's Note: Please see the article for additional information, including other authors, financial contributions and affiliations, financial disclosures, funding and support, etc.

For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail

Media Advisory: To contact Lon S. Schneider, M.D., M.S., call Leslie Ridgeway at 323-442-2823 or email

Posted: April 2011