Memantine Approved to Treat Late-Stage Alzheimer's Symptoms

A drug that helps slow the advance of late stage Alzheimer's disease has been approved for sale in the US after having been used in Germany since the 1980s to treat a variety of brain disorders.

Memantine, which is scheduled to be available in pharmacies this month under the brand name Namenda, is the first drug shown to have some impact on late Alzheimer's symptoms. The four other medications approved specifically for treating Alzheimer's work more specifically on symptoms that occur during the early stages of the disease.

"Memantine is a symptomatic treatment for Alzheimer's disease, not a cure for it," said Piero G. Antuono, MD, Medical College of Wisconsin Professor of Neurology. "It produces a delay in the progression of the disease for some time. It's a different drug from similar cognitive enhancers we have in the market in the way that it acts to modulate the response of brain cells to glutamate, which is the most common neurotransmitter in the brain.

"This is extremely important for memory because we know that some typical electric responses of brain cells which are an indication of learning, of storing new information, are modulated through this chemical called glutamate. What happens in Alzheimer's disease, and possibly also in other degenerative diseases, is that as brain cells die there is an increased release of glutamate which may hyper-stimulate healthy brain cells, causing them to be 'exhausted' or to die."

There is currently no known way to prevent Alzheimer's. The brain disorder remains incurable, robbing victims of memory while destroying physical and mental function to very severe degrees. Demand for memantine has been understandably high for some time, and many people have already been buying the drug overseas via the Internet.

Research Leads to Go-Ahead
When the Food and Drug Administration approved memantine as a treatment for Alzheimer's in October of 2003, FDA spokespeople joined other experts in cautioning families against expecting miracles from the medication. Still, research including a major study published in 1999 provided the FDA with sufficient evidence that memantine can be of use in improving quality of life for those with moderate or severe Alzheimer's.

Some patients in US memantine studies showed improvements in memory, according to the FDA. More prevalent were indications that the agent "slowed the pace of deterioration" and enabled people to do better on cognitive tests and in daily functions such as using the bathroom, bathing and dressing themselves.

"The medication kicks in only if there is a higher than normal activation of the neuron," said Dr. Antuono. "Rather than the membrane becoming more permeable to calcium and fluid getting in and the cells dying, memantine protects the cells from having this cascade of effects by limiting sensitivity to all of the glutamate that's been released."

Doctors will be able to use memantine in combination with the other drugs because it works on a different chemical in the brain.

"That's interesting because there are already drugs available to treat, very well, cognitive signs of dementia, said Dr. Antuono. "One of the pivotal studies used by the FDA was a combination study looking at the drug aracept plus memantine. The results showed that, compared to people on aracept alone, people (on the combination therapy) did better."

Earlier Use Probable
Although the FDA approved memantine for use in advanced Alzheimer's dementia, Dr. Antuono said that he expects it also to be used "off-label" for other dementias including early dementias.

"Medically it does not make sense to just use the medication when the disease is far gone," he said. "We don't treat diabetes when the person has renal failure and stroke. We treat diabetes when there's the first sign of something wrong with the blood glucose. The same thing with Alzheimer's disease. Probably, this drug will be used in combination and much earlier."

The Medical College has participated in a study looking at memantine in relation to early Alzheimer's disease, Dr. Antuono said. The results of that study have not yet been released.

"I think that with memantine we have yet another way of helping people who, for instance, do not respond to the medications we already have," said Dr. Antuono. "We have a hope to introduce a longer plateau in the unavoidable progression of the disease.

"I just saw a patient who has been on the drug for seven months. They had it shipped from Germany. The last time I saw this patient was a year and a half ago, and today their memory value measures are exactly like they were a year and a half ago. Alzheimer's doesn't behave like that. We could (in the past) predict the decline on this memory test every six months."

Combination Extends Functionality
While stressing that not all patients will experience remarkable results, Dr. Antuono said that adding memantine to the therapy mix is a big step forward by generally prolonging the time period during which patients can function with minimized Alzheimer's symptoms.

"Hopefully, with the combination of medication we can improve quality of life," said Dr. Antuono. "The patient is still home, still talking, still doing something. That's really what we try to do with most medical conditions.

"If you have a diagnosis of heart disease you may die of heart disease, but before that you may still be able to walk five blocks instead of one, still be able to travel instead of being bed-ridden. Realistically, we're doing now in some neurological diseases things unthinkable five or ten years ago because we're doing things that were unthinkable in medicine in general."

Dan Ullrich
HealthLink Contributing Writer

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.