A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500)

Int Clin Psychopharmacol. 2002 Nov;17(6):297-305. doi: 10.1097/00004850-200211000-00005.


The aim of the reported trial was to investigate the safety and efficacy of memantine in mild to moderate vascular dementia (VaD). This was a 28-week, double-blind, parallel, randomized controlled trial of memantine 20 mg daily versus placebo which was conducted in 54 centres in the UK. Memantine is a uncompetitive, moderate affinity N-methyl-D-aspartate receptor antagonist. Patients with a diagnosis of probable VaD and Mini Mental State Examination total scores between 10 and 22 were eligible for inclusion. Primary efficacy parameters were the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) and the Clinical Global Impression of Change (CGI-C). A total of 579 patients were randomized and 548 patients with at least one post-baseline efficacy assessment qualified for the intent-to-treat analysis. At endpoint, memantine was shown to improve cognition relative to placebo in VaD: the change of ADAS-cog from baseline differed by a mean of -1.75 points (95% confidence intervals -3.023 to -0.49) and a median of 2 points between the two groups, while CGI-C ratings showed no significant differences between treatment groups. A total of 77% of all memantine-treated patients experienced adverse event, versus 75% of the placebo-treated patients, dizziness being the most frequent adverse event (11% versus 8%, respectively). Memantine was well tolerated and safe.

Publication types

  • Clinical Trial
  • Meta-Analysis
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / pharmacology*
  • Cognition
  • Dementia, Vascular / drug therapy*
  • Dementia, Vascular / pathology
  • Dizziness / chemically induced
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Memantine / adverse effects
  • Memantine / pharmacology*
  • Mental Status Schedule
  • Placebos
  • Treatment Outcome


  • Antiparkinson Agents
  • Placebos
  • Memantine