Memantine treatment in mild to moderate Alzheimer disease: a 24-week randomized, controlled trial

Am J Geriatr Psychiatry. 2006 Aug;14(8):704-15. doi: 10.1097/01.JGP.0000224350.82719.83.


Objective: The objective of this study was to compare the efficacy and safety of the moderate-affinity, uncompetitive N-methyl-d-aspartate receptor antagonist, memantine, versus placebo in patients with mild to moderate Alzheimer disease (AD).

Method: This was a randomized, double-blind, placebo-controlled clinical trial conducted at 42 U.S. sites. Participants were 403 outpatients with mild to moderate AD and Mini-Mental State Examination scores of 10-22 randomized to memantine (20 mg/day; N=201) or placebo (N=202) for 24 weeks. Primary outcomes were change from baseline at 24 weeks on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), a measure of cognition, and on the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), a global measure. Secondary outcomes included change on the Neuropsychiatric Inventory (NPI) and the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL(23)), measures of behavior and function, respectively.

Results: Most (82.4%) participants completed the trial. Memantine resulted in significantly better outcomes than placebo on measures of cognition, global status, and behavior when based on the protocol-specified primary last observation carried forward imputation as well as a mixed-models repeated-measures approach applied to the continuous outcomes. Treatment discontinuations because of adverse events for memantine versus placebo were 19 (9.5%) and 10 (5.0%), respectively.

Conclusions: These results support the safety and efficacy of memantine for the treatment of mild to moderate AD.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / drug therapy*
  • Cognition / drug effects
  • Double-Blind Method
  • Drug-Related Side Effects and Adverse Reactions
  • Excitatory Amino Acid Antagonists / adverse effects
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Female
  • Humans
  • Male
  • Memantine / adverse effects
  • Memantine / pharmacology
  • Memantine / therapeutic use*
  • Neuropsychological Tests


  • Excitatory Amino Acid Antagonists
  • Memantine