Memantine: a review of its use in moderate to severe Alzheimer's disease.

Memantine is an uncompetitive, moderate-affinity NMDA receptor antagonist that is indicated for the treatment of moderate to severe Alzheimer's disease. In well designed trials in patients with moderate to severe Alzheimer's disease, oral memantine monotherapy improved outcomes in the area of functional ability more than placebo in one trial, but in a second trial, treatment differences did not reach significance. Memantine has a distinct mode of action compared with that of acetylcholinesterase (AChE) inhibitors, and in a well designed study, combination therapy with memantine plus donepezil improved outcomes more than donepezil plus placebo in all four domains (function, cognition, behaviour and global change). Memantine is generally well tolerated, with adverse events occurring with a similar incidence to that reported with placebo. In modelled cost-effectiveness analyses, memantine was dominant to no therapy in regard to cost per quality-adjusted life-year (QALY) gained, and the combination of memantine plus donepezil was dominant to donepezil therapy alone in regard to QALYs gained when treatment periods exceeded 1 year in patients with moderate to severe disease. Thus, in the management of patients with moderate to severe Alzheimer's disease, memantine provides an effective treatment option. To date, clinical trial support is greater for memantine use in combination with an AChE inhibitor, while more data are needed to confirm its efficacy as monotherapy.