Memantine combined with an acetyl cholinesterase inhibitor - hope for the future?

Background: Memantine and cholinesterase inhibitors (ChEI) have distinct pharmacological actions, and interest in the use of combination therapy for Alzheimer's disease (AD) is increasing.

Objective: To assess the available data on the use of memantine-ChEI combination and to develop evidence-based recommendations.

Method: A systematic literature review with detailed discussion of the current evidence base.

Results: AVAILABLE DATA ARE LIMITED: five studies of which two were randomized, double-blind, placebo-controlled trials. One study indicated that memantine-ChEI combination is not significantly more effective than placebo-ChEI in mild to moderate AD, but data were published in abstract and poster form only. A second study indicated that the memantine-ChEI combination is significantly more effective than placebo-ChEI in moderate to severe AD. The calculated effect sizes of 0.36 on cognition and 0.12 on function, which were the primary outcomes, were small, indicating a clinically minimal effect on cognition and no effect on function. No data are available on whether combination treatment is more effective than memantine monotherapy.

Conclusion: The available data do not justify the use of combination therapy. Future studies should include three arms (memantine-placebo, placebo-ChEI, and memantine-ChEI), be of an adequate size and duration, and use pragmatic measures. Clinicians should have full access to data from any future trials.