Efficacy and tolerability of memantine in the treatment of dementia

Background: Until recently, acetylcholinesterase inhibitors were the only approved agents for the treatment of Alzheimer's disease (AD). These medications have also been used in the treatment of vascular dementia (VD). Memantine, the first N-methyl-d-aspartate (NMDA)-receptor antagonist to be well tolerated, has been approved for the treatment of moderate to severe AD. Objective: The aim of this study was to review the current literature on the efficacy and tolerability of memantine in the treatment of AD and VD. Methods: A MEDLINE search of the English-language literature from January 1970 to March 2004 was conducted to identify randomized, double-blind, placebo-controlled, parallel-group trials in which memantine was administered to patients with VD or AD. The search terms were memantine, NMDA inhibitor, and NMDA antagonist. Results: Excessive glutamate, the brain's major excitatory neurotransmitter, can cause excitotoxicity by allowing too much calcium to enter neuronal cells. Moderate-affinity NMDA-receptor antagonists such as memantine block pathologic activity of glutamate while allowing physiologic activity. Use of memantine has been associated with significant improvements in measures of cognition, function, and behavior in both VD and AD. Adverse events associated with memantine have been comparable to those with placebo, with the exception of an increased incidence of dizziness, constipation, cataracts, nausea, dyspnea, confusion, headache, and urinary incontinence. Conclusions: Memantine seems to be promising and well tolerated in the treatment of moderate to severe VD or AD, either as monotherapy or in combination with donepezil. It appears to be particularly effective in improving cognitive, functional, and global outcomes in moderate to severe AD and in improving cognitive end points in mild to moderate VD. More research is needed on important clinical questions, including whether memantine can prolong patients' ability to provide self-care and delay institutional placement.