Combination therapy for all stages of Alzheimer's
March 3, 2009. Memantine is marketed for moderate-to-severe Alzheimer's, but two recent studies suggest it is effective for all stages of the disease when used in combination with any one of the older Alzheimer's drugs. While there's no cure, some doctors say a two-drug cocktail including memantine is the best way to slow deterioration in quality of life.
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Alzheimer's disease is often treated by a class of drugs called cholinesterase inhibitors, which help boost levels of a brain chemical called acetylcholine. Memantine, sold in the U.S. under the brand name Namenda by Forest Laboratories Inc. of New York, counteracts abnormal brain activity caused by another chemical called glutamate.
The drug is approved by the Food and Drug Administration to treat moderate-to-severe Alzheimer's, but the agency declined to allow the company to market it for mild cases of the disease, citing lack of convincing evidence.
There is still scant evidence that memantine alone works well for those patients. However, two recent studies from Harvard University and the University of Pittsburgh suggest combination therapy with memantine is the most effective treatment for all stages of the disease. The multiyear studies, both done with funding from the National Institutes of Health, found the combination therapy worked better than either a placebo or cholinesterase inhibitors alone.
"The results are encouraging," says Barry Reisberg, director of the Fisher Alzheimer's Disease Program at New York University School of Medicine in New York. "There will be a new debate" on when and how to prescribe memantine, adds Dr. Reisberg, who has received research funding from Forest and other pharmaceutical companies that sell Alzheimer's drugs. Some physicians, including Dr. Reisberg, begin combination therapy even in patients with mild Alzheimer's. Others prefer to wait a year or two -- or until the patient progresses further in the disease -- to prescribe memantine.
Both studies looked at a varied group of patients, from mild to severe cases, and didn't break out results separately based on severity. The Pittsburgh work, a 943-patient study published Feb. 9 in the online edition of the Journal of Neurology, Neurosurgery and Psychiatry, found that patients getting combination therapy were a third less likely than those taking cholinesterase inhibitors alone to be admitted to a nursing home during the average follow-up time of five years.
A 382-patient Harvard study, published late last year, found combination therapy slowed decline in daily-life activities and cognitive function. For example, patients who took combination therapy for two years correctly answered an average of two more questions in a battery of 37 simple questions than patients who got a cholinesterase inhibitor alone, says Harvard instructor Alireza Atri, director of the Special Dementia Unit at the Edith Nourse Rogers Memorial Veterans Hospital in Bedford, Mass. After four years, the combination-therapy patients got nearly five more questions right, adds Dr. Atri, who does paid consulting for Forest and other drug makers.
The new studies "lend some support" to adding memantine to the mix earlier, says Mayo Clinic physician Ronald C. Petersen, chairman of the nonprofit Alzheimer Association's Medical and Scientific Advisory Council. Dr. Petersen, though, remains cautious about early-stage use of memantine. One reason is its high cost -- some $1,800 a year or more, which may not be covered by insurance for mild Alzheimer's.
Forest, which wasn't involved in the two new studies, says it "applauds" any research that further informs the medical community. The company adds that it doesn't endorse the use of memantine for mild Alzheimer's.
Memantine doesn't typically cause gastrointestinal side effects linked to cholinesterase inhibitors. The drug can cause dizziness, insomnia and occasionally increased confusion, Dr. Petersen says.
