Update on the use of memantine in Alzheimer's disease

Memantine is a low to moderate affinity N-methyl-D-aspartate receptor (NMDAR) antagonist. The effects of memantine in Alzheimer's disease (AD) have been studied in 7 randomized controlled trials in many post-hoc analyses. Three out of four RCTs in patients with moderate to severe AD (Mini Mental State Examination [MMSE] <14) showed a statistically significant but clinically small positive effect of memantine on cognition, global functioning, activities of daily living (ADL) and neuropsychiatric symptoms. No effects on these outcome measures could be found in the three RCTs studying patients with mild to moderate AD (MMSE 14-24). Two of these studies evaluated the effect of addition of memantine to donepezil. Only the study in patients with mild to moderate AD showed a positive effect of addition of memantine on cognition, ADL, global functioning and neuropsychiatric functioning. Cost-effectiveness of memantine therapy remains controversial. Post-hoc analyses and observational studies suggest some effects on agitation/aggression, delusions or hallucinations. Side effects of memantine are usually mild and seem to be comparable with placebo. In this review, an oversight of pharmacodynamics and pharmacokinetics of memantine is presented. Also, published data concerning efficacy and safety in patients with AD are presented.