Effectiveness of adding memantine to an Alzheimer dementia treatment regimen which already includes stable donepezil therapy: a critically appraised topic.

Background: Alzheimer dementia (AD) is a major cause of debility and economic strain in aging societies around the world. The only 2 medication classes approved specifically for the treatment of AD are the cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and memantine. Evidence that the use of memantine in a patient already on cholinesterase inhibitor therapy can provide a clinically significant benefit is limited.

Objective: To review the evidence supporting the addition of memantine therapy in patients with moderate-to-severe AD who are already receiving treatment with a cholinesterase inhibitor.

Methods: The objective was addressed through the development of a critically appraised topic which included a clinical scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Included were neurology consultants and residents, a medical librarian, clinical epidemiologists, and content experts in the field of behavioral neurology.

Results: One article was selected for review. Patients receiving memantine for 24 weeks experienced a statistically significant change from baseline on a modified 19-item AD Cooperative Study-Activities of Daily Living Inventory (P=0.03) and on the Severe Impairment Battery (P=0.001) when compared with placebo. The change in mean scores in the memantine group versus placebo on the 19-item AD Cooperative Study-Activities of Daily Living Inventory were -2.0 versus -3.4 and on the Severe Impairment Battery 0.9 versus -2.5 which indicate improved performance or reduced deterioration in the memantine group. The number needed to treat and the effect size could not be calculated from the data provided.

Conclusions: The addition of memantine to donepezil in patients with moderate-to-severe AD provides a statistically significant improvement in several AD-oriented outcome measures, however, the clinical relevance of this benefit remains unclear.