doi: 10.1161/01.STR.0000020094.08790.49
(Stroke. 2002;33:1834.)
© 2002 American Heart Association, Inc.
Original Contributions |
Efficacy and Safety of Memantine in Patients With Mild to Moderate Vascular Dementia
A Randomized, Placebo-Controlled Trial (MMM 300)
From CHU Pellegrin, Bordeaux, France (J.-M.O.); Hôpital Broca, Paris, France (A.-S.R., F.F.); and Merz Pharmaceuticals, Frankfurt, Germany (A.S., H.-J.M.).
Correspondence to Professor J.-M. Orgogozo, CHU Pellegrin, 33076 Bordeaux, France. E-mail j.m.orgogozo{at}neuro.u-bordeaux2.fr
Background and Purpose— Based on the hypothesis of glutamate-induced neurotoxicity (excitotoxicity) in cerebral ischemia, this study examined the efficacy and tolerability of memantine, an uncompetitive N-methyl-D-aspartate antagonist, in the treatment of mild to moderate vascular dementia.
Methods— In this multicenter, 28-week trial carried out in France, 321 patients received 10 mg/d memantine or placebo twice a day; 288 patients were valid for intent-to-treat analysis. Patients had to meet the criteria for probable vascular dementia and have a Mini-Mental State (MMSE) score between 12 and 20 at inclusion. The 2 primary end points were the cognitive subscale of the Alzheimers Disease Assessment Scale (ADAS-cog) and the global Clinician’s Interview Based Impression of Change (CIBIC-plus).
Results— After 28 weeks, the mean ADAS-cog scores were significantly improved relative to placebo. In the intention-to-treat population, the memantine group mean score had gained an average of 0.4 points, whereas the placebo group mean score had declined by 1.6 points, ie, a difference of 2.0 points (95% confidence interval, 0.49 to 3.60). The response rate for CIBIC-plus, defined as improved or stable, was 60% with memantine compared with 52% with placebo (P=0.227, intention to treat). Among the secondary efficacy parameters, which were analyzed in the per-protocol subset, MMSE was significantly improved with memantine compared with deterioration with placebo (P=0.003). The Gottfries-Brane-Steen Scale intellectual function subscore and the Nurses’ Observation Scale for Geriatric Patients disturbing behavior dimension also showed differences in favor of memantine (P=0.04 and P=0.07, respectively). Memantine was well tolerated with a frequency of adverse events comparable to placebo.
Conclusions— In patients with mild to moderate vascular dementia, memantine 20 mg/d improved cognition consistently across different cognitive scales, with at least no deterioration in global functioning and behavior. It was devoid of concerning side effects.
Key Words: cerebral ischemia • dementia • glutamate • memantine • N-methyl-D-aspartate • randomized controlled trials
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