Question: For people with Alzheimer's or mixed dementia how effective are cholinesterase inhibitors augmented with memantine compared to cholinesterase inhibitors (ChEI) alone / placebo in achieving improved outcomes in terms of cognition, function, delay to institution, and carer burden / stress?


Two systematic reviews, of moderate to high quality, provided evidence to inform this summary. The reviews were only able to identify a small number of RCTs (a total of four different studies, with two RCTs being common to both reviews). Both reviews reported some evidence of a small benefit from adding memantine to donepezil in patients with moderate to severe Alzheimer's disease; outcomes assessed included clinical global score, cognition, function, and behaviour and mood. When patients with mild Alzheimer's disease were included in the analyses (one review), only function was significantly improved by the addition of memantine. The authors of both reviews concluded that it is currently unclear clinically significant outcomes can be achieved using combination therapy. These conclusions are a reasonable interpretation of the available evidence and are likely to be reliable.

Further studies are needed to confirm the findings of the two systematic reviews included in this assessment. More data are particularly needed for patients with mild Alzheimer's disease and for patients with other dementias; no studies which included participants with any other dementia types were identified. Studies assessing combination therapy using memantine and ChEIs other than donepezil may also be useful.

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