The drug memantine lessens the decline in cognition and activities of daily living for patients with moderate to severe Alzheimer disease who are also taking donepezil, according to an article in the January 21st issue of The Journal of the American Medical Association.

Memantine is the first member of a new class of medications called low-to-moderate-affinity, uncompetitive N-methyl-D-aspartate [NMDA] receptor antagonists to demonstrate clinical benefit and good tolerability in this population of patients. It was approved for use in the U.S. in October 2003.

In the current study, Pierre N. Tariot, MD, and his American colleagues compared the efficacy and safety of memantine with that of placebo in patients with moderate to severe disease who were already receiving treatment with donepezil, a cholinesterase inhibitor. The multicenter study was conducted between June 11, 2001 and June 3, 2002; a total of 404 participants were randomized to memantine (203 patients, starting dose 5 mg/day, increased to 20 mg/day) or placebo (201 patients) for 24 weeks. A total of 322 patients (80 percent) completed the clinical trial.

Cognitive, functional, and global outcome measures were obtained at baseline and at the end of weeks 4, 8, 12, 18, and 24. The researchers looked at the change from baseline with use of the Severe Impairment Battery, a measure of cognition, such as memory, orientation, language, and attention, and activities of daily living.

"Efficacy of memantine was significantly better than placebo for treatment of moderate to severe Alzheimer’s disease in community-dwelling patients," wrote the researchers. "Specifically, measures of cognitive function, activities of daily living, behavior, and clinical global status were significantly improved with memantine compared with placebo. Treatment with memantine during the six-month trial in patients with Mini-Mental State Examination scores of 5 to 14 resulted in the maintenance of cognitive function (0.9 increase in Severe Impairment Battery score compared with baseline), whereas treatment with placebo was associated with cognitive decline (2.5 decrease in Battery score compared with baseline)."

The 19-item Alzheimer Disease Cooperative Activities of Daily Living Inventory declined 2 points in the memantine group compared with 3.4 points in the placebo group.

The authors concluded, "Although the specific mechanisms and interactions between these therapies have not yet been defined, this and other studies demonstrate that memantine alone or together with a cholinesterase inhibitor results in significantly better outcomes than placebo in patients with moderate to severe Alzheimer’s disease."