The cholinesterase inhibitors like Aricept (i.e., donepezil) have been available for treatment of dementias such as Alzheimer’s disease for two decades. It is clear that long-term use of these medications slows the progression of Alzheimer’s disease (in those who tolerate them) and that discontinuing these medications after extended use produces a risk of more rapid decline even in those who are in middle and late stage dementia.

The standard of care for use of medications to treat Alzheimer’s related dementias recommends use of a cholinesterase inhibitor (donepezil, Exelon, and galantamine) starting in Mild Cognitive Impairment and early stage dementia. Namenda (i.e., memantine) has been available to treat middle and late stage (but not early stage) dementia for over a decade. A recent study (Cumulative, additive benefits of memantine and donepezil combination over component monotherapies in moderate to severe dementia: a pooled under the curve analysis (how’s that for a title?), Alzheimer’s Research and Therapy, 2015, 7, 28 PMID 25991927) indicates that adding memantine to donepezil improves outcome over either medication used alone.

The study combined results from 4 randomized clinical trials (RTCs) conducted over 6 months for a total study population of 1408 participants in middle to late stage Alzheimer’s disease (MMSE scores of 3-14 of a possible 30). There were 4 treatment conditions: placebo, memantine only, donepezil only, or combination of memantine and donepezil. Scores on standardized cognitive, functional, and behavioral scales were used to assess outcome.

The results indicated that:
 All participants who were treated with placebo declined on all outcome measures compared to either combined treatment or monotherapies (i.e., donepezil or memantine alone).
 Donepezil treatment alone was more effective than treatment with memantine alone.
 The combination of donepezil and memantine together was clearly the most effective treatment and “clinically significant.”
 The actions of the two medications were additive but not synergetic as has sometimes been stated by some.

These results make it clear that currently available medications for middle and late stage Alzheimer’s like dementias remain effective even into late stage disease. Furthermore, adding memantine to donepezil (and presumably other cholinesterase inhibitors) improves outcome over either treatment alone.