MONDAY, April 11 (HealthDay News) -- A drug commonly prescribed
for Alzheimer's disease, memantine (Namenda), appears to be
ineffective in treating the mild stage of the disease, a new study
While some studies suggest the drug is effective in treating
moderate to severe Alzheimer's disease, "in mild Alzheimer's
disease there is a lack of evidence that it works," said lead
researcher Dr. Lon S. Schneider, a professor of psychiatry,
neurology and gerontology at the University of Southern California
Keck School of Medicine.
Memantine is approved by the U.S. Food and Drug Administration
for use in patients with moderate to severe Alzheimer's disease --
indicated in the U.S. by a score of 14 or less on a diagnostic test
called the Mini-Mental State Examination -- but it is often
prescribed off-label for use in patients with mild Alzheimer's
The drug belongs to a class of drugs called NMDA receptor
antagonists, which help reduce abnormal activity in the brain by
binding to NMDA receptors on brain cells and blocking the activity
of the neurotransmitter glutamine. At normal levels, glutamate aids
in memory and learning, but if levels are too high, glutamate
appears to overstimulate nerve cells, killing off key brain
Memantine can help patients with severe Alzheimer's disease
think more clearly and perform daily activities more easily, but,
like other Alzheimer's drugs, it is not a cure and does not stop
progression of the disease, the researchers say.
"The drug is effective, but perhaps we should be more careful about using it in more mild Alzheimer's patients with respect to efficacy," said Schneider.
The report is published in the April 11 online edition of the
Archives of Neurology.
To determine whether memantine was effective in patients with
mild Alzheimer's disease, Schneider's team conducted a
meta-analysis. In this type of study, researchers pool and analyze
the results of published studies that may have data on the
particular issue they are interested in.
The researchers identified three trials that included a total of
431 patients with mild Alzheimer's disease and 697 patients with
moderate Alzheimer's disease. Using several measurements,
Schneider's group assessed cognition, changes in behavior and
ability to function.
When the researchers looked at each study individually or pooled
the data from the three studies, they found no significant
difference between people with mild Alzheimer's disease taking
memantine or a placebo.
Among patients with moderate AD, the researchers found no
significant difference between memantine and use of a placebo in
any individual trial, but there was a significant effect when the
three trials were statistically combined. Nonetheless, the authors
concluded that evidence for the effectiveness of memantine in
patients with moderate Alzheimer's disease was "meager."
Prospective trials are needed to better determine memantine's
effectiveness when used alone or in combination with other drugs in
earlier stages of Alzheimer's, they reported.
Commenting on the study, Alzheimer's disease expert Greg M.
Cole, a neuroscientist at the Greater Los Angeles VA Healthcare
System and associate director of the Alzheimer's Disease Research
Center at the University of California Los Angeles, said that "most
of my clinician colleagues are not very impressed with the efficacy
of memantine in mild to moderate Alzheimer's disease."
Most researchers believe Alzheimer's disease has stages in which
the responses to drugs differ, Cole said. "But this distinction is
easily lost in the frustration of both lay persons and physicians
who want to try whatever might help. So they try memantine in mild
Alzheimer's disease cases," he said.
One trouble with Alzheimer's disease is that some patients
appear to show better responses to memantine than others, Cole
"It is difficult to decide if this is just random variation or if patients are really different and some can respond to the [drug]," Cole said.
"Some mild Alzheimer's disease patients might also respond, but until we can identify subsets of patients who respond well, we have to work with the average responses," Cole added. "Unfortunately, this new study demonstrates that the average response with mild to moderate Alzheimer's disease is marginal at best."
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