Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment

Neurology. 2006 Jul 11;67(1):57-63. doi: 10.1212/01.wnl.0000223333.42368.f1.


Objective: To investigate the behavioral effects of memantine in moderate to severe Alzheimer disease (AD).

Methods: The authors conducted a hypothesis-generating, exploratory analysis of a 24-week, double-blind, placebo-controlled trial comparing memantine (20 mg/day) with placebo in subjects with moderate to severe AD on stable donepezil treatment. They employed the Neuropsychiatric Inventory (NPI; 12-item), administered at baseline, week 12, and week 24, to assess the effects of memantine on behavior. Global, cognitive, and functional measures were collected and relationships between these assessments and changes in behavior were determined. The intent-to-treat population was examined using last-observation-carried-forward and observed-cases approaches.

Results: Patients treated with memantine had significantly lower NPI total scores than patients treated with placebo. Analyses of the 12 NPI domains revealed significant effects in favor of memantine on agitation/aggression, eating/appetite, and irritability/lability. Of patients who exhibited agitation/aggression at baseline, those treated with memantine showed significant reduction of symptoms compared with placebo-treated patients. Memantine-treated patients without agitation/aggression at baseline evidenced significantly less emergence of this symptom compared with similar patients receiving placebo. Caregivers of patients receiving memantine registered significantly less agitation-related distress. There were significant relationships between the NPI and the global rating scale and performance of activities of daily living, but not between changes in the NPI and cognition.

Conclusion: Treatment with memantine reduced agitation/aggression, irritability, and appetite/eating disturbances. Memantine reduced agitation/aggression in patients who were agitated at baseline and delayed its emergence in those who were free of agitation at baseline.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activities of Daily Living
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / complications
  • Alzheimer Disease / drug therapy*
  • Antiparkinson Agents / therapeutic use*
  • Behavioral Symptoms / drug therapy*
  • Behavioral Symptoms / etiology
  • Donepezil
  • Double-Blind Method
  • Female
  • Humans
  • Indans / therapeutic use
  • Male
  • Memantine / therapeutic use*
  • Mental Status Schedule
  • Middle Aged
  • Neuropsychological Tests / statistics & numerical data
  • Nootropic Agents / therapeutic use
  • Outcome Assessment, Health Care / methods
  • Piperidines / therapeutic use
  • Prospective Studies
  • Psychomotor Agitation / drug therapy
  • Psychomotor Agitation / etiology
  • Severity of Illness Index
  • Time Factors


  • Antiparkinson Agents
  • Indans
  • Nootropic Agents
  • Piperidines
  • Donepezil
  • Memantine