• Elaine R Peskind, Steven G Potkin, Nunzio Pomara, Brian R Ott, Stephen M Graham, Jason T Olin, and Scott McDonald.
• Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine and Veterans Affairs Northwest Network Mental Illness Research, Education, and Clinical Center, Seattle, WA 98108, USA. peskind@u.washington.edu
• Am J Geriatr Psychiatry. 2006 Aug 1;14(8):704-15.

ObjectiveThe 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).MethodThis 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.ResultsMost (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.ConclusionsThese results support the safety and efficacy of memantine for the treatment of mild to moderate AD.

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