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New drug improves outcomes when added to existing therapy for Alzheimer's disease

The JAMA Network Journals

The drug memantine lessens the decline in cognition and activities of daily living for patients with moderate to severe Alzheimer disease (AD) who are also receiving donepezil (another drug used to treat AD), according to a new study in the January 21 issue of The Journal of the American Medical Association (JAMA).

Alzheimer disease is a neurodegenerative disorder characterized by cognitive decline, impaired performance of activities of daily living, and behavioral and psychiatric signs and symptoms, according to background information in the article. Alzheimer disease affects approximately 4.5 million people in the United States. Memantine is the first member of a new class of medications (a low-to-moderate-affinity, uncompetitive N-methyl-D-aspartate [NMDA] receptor antagonist) showing clinical benefit and good tolerability in AD patients. It was approved by the Food and Drug Administration in October 2003 for the treatment of Alzheimer disease.

Pierre N. Tariot, M.D., from the University of Rochester Medical Center, Rochester, N.Y., and colleagues compared the efficacy and safety of memantine versus placebo (sugar pill) in patients with moderate to severe AD already receiving stable treatments with another AD drug, donepezil, a cholinesterase inhibitor. The study was conducted at 37 U.S. sites between June 11, 2001 and June 3, 2002. The 404 participants were randomized to receive memantine (starting dose 5 milligrams/day, increased to 20 mg/d, n=203) or placebo (n=201) for 24 weeks. A total of 322 patients (80 percent) completed the clinical trial. Cognitive, functional, and global outcome measures were obtained at the start of the study (baseline), and at the end of weeks 4, 8, 12, 18 and 24. The researchers looked at the change from baseline on the Severe Impairment Battery (SIB), a measure of cognition, such as memory, orientation, language, and attention, and in activities of daily living (such as bathing and dressing).

"Efficacy of memantine was significantly better than placebo for treatment of moderate to severe AD in community-dwelling patients," the researchers report. "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 MMSE [Mini-Mental State Examination] scores of 5 to 14 resulted in the maintenance of cognitive function (0.9 increase in SIB score compared with baseline), whereas treatment with placebo was associated with cognitive decline (2.5 decrease in SIB score compared with baseline)."

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

In conclusion the authors write, "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 AD."


(JAMA. 2004;291:317-324. Available post-embargo at

Editor's Note: Please see JAMA article for authors' financial disclosures. This study was supported by funding from Forest Laboratories, Inc.

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