No Evidence for Benefit of Memantine in Mild Alzheimer’s Disease

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’s disease.”Memantine, indicated for moderate to severe Alzheimer’s disease is frequently prescribed off-label [for uses other than those approved by the FDA] either alone or with a cholinesterase inhibitor for mild Alzheimer’s disease 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 Alzheimer’s disease.Lon S. Schneider 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 Alzheimer’s disease. Three trials were identified that included 431 patients with mild Alzheimer’s disease and 697 patients with moderate Alzheimer’s disease. 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 Alzheimer’s disease, either within any trial or when data were combined,” the authors report.

Among patients with moderate Alzheimer’s disease, 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 Alzheimer’s disease, and there is meager evidence for its efficacy in moderate Alzheimer’s disease,” 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 Alzheimer’s disease.”

1. Lon S. Schneider, et al. Lack of Evidence for the Efficacy of Memantine in Mild Alzheimer Disease. Archives of Neurology, 2011; DOI: 10.1001/archneurol.2011.69