The efficacy of memantine in Alzheimer's disease ( AD) has been investigated in multiple randomised, placebo-controlled phase III trials. Recently, the indication label for memantine in Europe was extended to cover patients with moderate to severe AD, i.e. Mini-Mental State Exam total scores below 20. The efficacy data for memantine in this patient subgroup has been summarised by a meta-analysis of 1,826 patients in six trials. Efficacy was assessed using measures of global status ( Clinician's Interview-Based Impression of Change Plus Caregiver Input), cognition ( Alzheimer's Disease Assessment Scale - Cognitive Subscale, or Severe Impairment Battery), function ( Alzheimer's Disease Cooperative Study Activities of Daily Living 19- or 23-item scale), and behaviour ( Neuropsychiatric Inventory). Results ( without replacement of missing values) showed statistically significant effects for memantine ( vs. placebo) in each domain. Memantine was well tolerated, and the overall incidence rates of adverse events were comparable to placebo. This meta-analysis supports memantine's clinically relevant efficacy in patients with moderate to severe AD. Copyright (c) 2007 S. Karger AG, Basel.