Memantine Is Not Effective for Mild Alzheimer Disease

Off-label use of memantine for mild AD is not supported by the findings of a meta-analysis that focused specifically on patients with mild disease.

Memantine is an N-methyl-d-aspartate receptor antagonist that has been approved in the U.S. and Europe as a treatment for moderate-to-severe Alzheimer disease (AD). It is also frequently used off-label for mild AD. To determine whether such use is warranted, researchers conducted a meta-analysis of randomized, double-blind, placebo-controlled, memantine trials that included patients with mild AD. They identified three such trials, each lasting 24 weeks: two U.S. studies of patients with Mini-Mental State Examination (MMSE) scores of 10 to 22 (1 study allowed concurrent use of cholinesterase inhibitors) and a European study of patients with MMSE scores of 11 to 23. Of the 1128 participants in these trials, 431 (38%) had mild AD (MMSE score, 20–23).

In none of the trials (either individually or combined) did patients specifically with mild AD derive a significant benefit from memantine over placebo in cognitive function, global functioning, activities of daily living, or observed behavior. Given that placebo recipients with mild AD tended to improve on cognitive measures and to remain stable on global measures, drug effects, if any, would have been difficult to discern in trials of this size and duration.

Comment

This study involved a clever re-examination of data from six memantine trials included in two previous manufacturer-funded meta-analyses that reported positive findings. A meta-analysis from Europe (Alzheimers Dement 2007; 3:7) specifically excluded patients with mild AD, and the other, from the U.S. (Dement Geriatr Cogn Disord 2007; 24:20), collectively analyzed patients at all disease stages. The current, non–industry-supported meta-analysis, which focused specifically on patients with mild AD, documented no advantage of memantine over placebo on any analyzed measures. Off-label use of memantine in patients with mild AD, which is common in clinical practice, is simply not supported by these newly published data.

Reviewing Author

Martin Rhys Farlow, MD

Citation(s):

Schneider LS et al. Lack of evidence for the efficacy of memantine in mild Alzheimer disease. Arch Neurol 2011 Apr 11; [e-pub ahead of print]. (http://dx.doi.org/10.1001/archneurol.2011.69)