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

Neurologist. 2011 Mar;17(2):121-3. doi: 10.1097/NRL.0b013e31820aa383.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / drug therapy*
  • Cholinesterase Inhibitors / therapeutic use*
  • Databases, Factual
  • Donepezil
  • Dopamine Agents / therapeutic use*
  • Drug Therapy, Combination
  • Humans
  • Indans / therapeutic use*
  • Male
  • Memantine / therapeutic use*
  • Nootropic Agents / therapeutic use
  • Piperidines / therapeutic use*
  • Placebos
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • Cholinesterase Inhibitors
  • Dopamine Agents
  • Indans
  • Nootropic Agents
  • Piperidines
  • Placebos
  • Donepezil
  • Memantine