Memantine
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Memantine A Viewpoint by Anne-Sophie Rigaud ˆ Hopital Broca, CHU Cochin Port-Royal, Universit´e Ren´e Descartes, Paris, France
Memantine is an uncompetitive antagonist of NMDA receptors. As excitotoxicity is a major pathophysiological mechanism involved in neurodegenerative and vascular disorders, memantine is considered a promising neuroprotective drug for the treatment of dementia, of both vascular and Alzheimer’s origin. Placebo-controlled trials with memantine have shown some cognitive benefit in patients with vascular dementia, especially those with dementia associated with ‘small vessel disease’ (white matter lesions and/or lacunae). However, more information is still needed on the efficacy and especially the long-term effectiveness of the drug in this pathological condition. In double-blind, randomised studies, the efficacy of memantine has been shown on cognition and activities of daily living in patients with moderate to severe Alzheimer’s disease (AD) with few adverse effects recorded. However, effects especially on activities of daily living, are not fully convincing yet. These studies, and the differences in interpretation
by clinicians and researchers, might be an opportunity to reopen the debate on the best outcome variables in anti-dementia drug trials. Approval of memantine in the European Community for the treatment of patients with moderately severe to severe AD is a new step in the treatment of this pathological condition. It broadens the number of treated patients, as only AD patients with mild to moderately severe stages have been eligible for prescription of an anticholinesterase drug so far. It also broadens the number of pharmacological drugs and classes available in this disease and therefore raises several issues that should be addressed in the coming years:
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when to shift from the prescription of an anticholinesterase drug to that of memantine?
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when to combine memantine with an anticholinesterase drug, as there appears to be no negative interaction between the two classes?
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when to stop the prescription of memantine in the later stages of AD?
Furthermore, the results of ongoing trials should provide more information on the efficacy of memantine on less impaired stages of AD and in other pathological conditions such as vascular and mixed dementia. ▲
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