Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Research Article Dement Geriatr Cogn Disord 2007;24:20–27 DOI: 10.1159/000102568 Memantine in Moderate to Severe Alzheimer’s Disease: a Meta-Analysis of Randomised Clinical Trials Bengt Winblad a Roy W. Jones b Yvonne Wirth c Albrecht Stöffler c Hans Jörg Möbius c a Karolinska Institutet, Stockholm, Sweden; b Research Institute for the Care of the Elderly, Bath, UK; c Merz Pharmaceuticals GmbH, Frankfurt, Germany Introduction Alzheimer’s disease (AD) is a progressive neurodegen- erative disorder that usually starts with memory loss and other cognitive deficits. At the time of clinical diagnosis, most patients are already in the moderate to severe stages of AD. Although there is no specific consensus definition of moderate to severe AD [1], patients with Mini-Mental State Exam (MMSE) scores between 10 and 20 are usu- ally considered as having moderate AD and in a recent paper [2] MMSE scores were shown to be a useful surro- gate for the staging of dementia. The moderate stage of AD is characterised by a rapid decline of cognitive function and the occurrence of neu- ropsychiatric (behavioural) symptoms. In the severe stages of disease, patients develop major cognitive, func- tional, and behavioural difficulties that eventually result in complete dependence on carer support. Therefore, im- provements or stabilisation in cognitive performance, daily function and/or behavioural symptoms have the potential to raise and extend the independence levels of the person with AD and, through this, the quality of life for both patient and carer. Memantine is a moderate-affinity, uncompetitive, voltage-dependent NMDA receptor antagonist with fast on-off kinetics [3] . Clinical studies have demonstrated that memantine can produce significant improvement Key Words Memantine  Alzheimer’s disease, moderate to severe  Meta-analysis  Cognition  Function  Global status Abstract The efficacy of memantine in Alzheimer’s disease (AD) has been investigated in multiple randomised, placebo-con- trolled phase III trials. Recently, the indication label for me- mantine 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 pa- tient subgroup has been summarised by a meta-analysis of 1,826 patients in six trials. Efficacy was assessed using mea- sures of global status (Clinician’s Interview-Based Impres- sion of Change Plus Caregiver Input), cognition (Alzheimer’s Disease Assessment Scale – Cognitive Subscale, or Severe Impairment Battery), function (Alzheimer’s Disease Cooper- ative Study Activities of Daily Living 19- or 23-item scale), and behaviour (Neuropsychiatric Inventory). Results (with- out replacement of missing values) showed statistically sig- nificant 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 effi- cacy in patients with moderate to severe AD. Copyright © 2007 S. Karger AG, Basel Accepted: March 6, 2007 Published online: May 10, 2007 Yvonne Wirth Merz Pharmaceuticals GmbH Eckenheimer Landstr. 100 DE–60318 Frankfurt/Main (Germany) Tel. +49 69 1503 507, Fax +49 69 1503 803, E-Mail yvonne.wirth@merz.de © 2007 S. Karger AG, Basel 1420–8008/07/0241–0020$23.50/0 Accessible online at: www.karger.com/dem