Memantine's effects are small but "clinically noticeable" after patients take 20 milligrams of the drug daily for 28 weeks, according to Dr. Rupert McShane of the University of Oxford and colleagues. The effect of memantine was measured by a variety of tests that rate a patient's thinking skills, daily activity and mood.
While there is no evidence that the drug can treat agitation in Alzheimer's patients, it does appear to prevent the onset of agitation, the review finds.
The studies also hint at some cognitive benefits from the drug for patients with mild to moderate Alzheimer's and vascular dementia, which occurs when brain cells are starved of oxygen by blocked or diseased blood vessels. However, these changes were not clinically significant, and it remains unknown whether there is a true benefit in mild to moderate cases, McShane and colleagues write.
The Food and Drug Administration approved memantine for the treatment of moderate to severe Alzheimer's dementia in 2003. The European Agency for the Evaluation of Medical Products approved the drug for similar indications in 2002. Manufacturers of the drug in Europe and the United States have applied for approval of the drug for mild to moderate Alzheimer's dementia.
The review appears in the April issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.
The review included nine published studies comprising 2,339 participants, but three important trials have not yet been published.
To account for the missing data, the Cochrane researchers also gathered publicly available information on the unpublished memantine trials. McShane and colleagues then calculated how the best and worst possible outcomes of each unpublished study might affect the overall evidence for memantine use.
Even if the one relevant unpublished study was to find no effect of memantine on moderate to severe Alzheimer's dementia, the overall evidence from all studies would still tend in favor of the drug's use, the researchers concluded.
Two of the unpublished studies considered in the Cochrane review examine the drug's effect on mild cases of Alzheimer's dementia.
Although it appears that researchers finished collecting data for one of the studies in 2003, "the lack of any substantive reference to it suggests that the results may be less favorable than those in published studies," McShane says.
Dementia researchers caution that the drug does not protect brain cells from the disease.
"Memantine is a symptomatic treatment for Alzheimer's disease, not a cure for it," says Dr. Piero G. Antuono, a professor of neurology at the Medical College of Wisconsin. "It produces a delay in the progression of the disease for some time."
Memantine and other treatments for severe Alzheimer's disease "raise ethical issues," McShane says. "It is possible that the drug only extends the total time of deterioration without reducing the personal of social burden of the disease."
Alzheimer's disease is the most common cause of dementia. More than four million Americans have Alzheimer's, and the prevalence of the disease doubles every five years after age 65, according to the National Institute on Aging.
Vascular dementia is the second most common cause of dementia in western societies. In both types of dementia, there are no therapies proven to reverse the brain damage.
Becky Ham, Science Writer Health Behavior News Service
FOR MORE INFORMATION
A. Areosa Sastre et al. Memantine for dementia. The Cochrane Database of Systematic Reviews 2005, Issue 2.
The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit: http://www.