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.


METHODS
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.


CONCLUSIONS
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.
East Kent NHS and Social Care Partnership Trust, Kent Institute of Medicine and Health Sciences, University of Kent at Canterbury, UK. gfox@doctors.org.uk
Chris
C
Fox
Ian D
ID
Maidment
Malaz
M
Boustani
Cornelius
C
Katona