Drug Memantine Ineffective for Mild Alzheimer's, Study Finds

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 finds.

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 disease.

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 cells.

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 said.

“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.”

More information

For more information on Alzheimer’s disease, visit the Alzheimer’s Association.