St. Louis, May 13, 1998 -- A new drug for Alzheimer patients appears to control psychiatric and behavioral disturbances as well as mental performance. People who took metrifonate were less likely to have hallucinations or be apathetic, depressed and agitated than people who took an inactive substance. Metrifonate also slowed the mental decline associated with Alzheimer's disease over the six-month study. The drug is under review by the Food and Drug Administration as a treatment for patients in the mild to moderate stages of the condition.
"There have been anecdotal reports that patients who take drugs in this class seem brighter, demonstrate more initiative and are easier to get along with in general," says John C. Morris, M.D., the Harvey A. and Dorismae Hacker Friedman Professor of Neurology at Washington University School of Medicine in St. Louis. "This is the first controlled study to document benefits for behavior as well as for memory and thinking, however."
Morris, who co-directs the medical school's Alzheimer's Disease Research Center, participated in the study. He is lead author of a paper in the May issue of the journal Neurology that presents the results. Bayer Corp. funded the clinical research at 24 sites in the United States, including Washington University School of Medicine. Morris reviewed the resulting data as an independent scientist, without compensation from Bayer.
Metrifonate belongs to a class of drugs called acetylcholinesterase (AChE) inhibitors. These drugs slow the breakdown of a chemical messenger called acetylcholine, which is in short supply in the Alzheimer brain. Two AChE inhibitors already are on the market for treatment of Alzheimer's: tacrine (Cognex) and donepezil (Aricept).
The 24 sites in the metrifonate study enrolled 408 mild-to-moderately demented patients. At this stage of the disorder, people usually are capable of dressing, grooming and feeding themselves but are unable to accomplish complex tasks such as balancing a checkbook or driving.
Of the 334 subjects who completed the study, 215 took metrifonate for 26 weeks, and 119 took an inactive substance. The patients didn't know which type of pill they were taking, and the researchers didn't know who was in which group.
Test scores during treatment were compared with those at the beginning of the study. One test, involving paper and pencil tasks, evaluated cognitive performance. Through interviews with subjects and caregivers, others evaluated daily function and psychiatric and behavioral disturbances. Test scores of the patients who took the inactive substance declined progressively during the study, whereas those of patients who took metrifonate remained steady.
"For the first time, aspects of behavior that can be most troublesome for many Alzheimer patients, such as hallucinations and agitation, were shown to benefit from metrifonate treatment," Morris says. "This drug appears to allow patients to maintain better control of their problem behaviors than if they didn't take it."
The study also assessed metrifonate's convenience, safety and side effects through patient reports, physical exams and blood tests. The drug was convenient to take just once a day and did not affect liver function. Only 12 percent of those who took it left the study because of nausea, diarrhea or other side effects.
"This metrifonate study shows that this class of drugs can benefit patients with mild or moderate Alzheimer's disease, at least temporarily. This means that Alzheimer's disease clearly is treatable," Morris says. "Unless there is a specific medical or other contraindication, I generally recommend that acetylcholinesterase (AChE) inhibitors be considered for Alzheimer patients in the mild or moderate stages of the disease."
He stresses that the drugs do not reverse Alzheimer symptoms or keep patients stable forever. "If people are cognitively impaired to the point where it no longer is safe for them to drive a car, for example, taking an AChE inhibitor won't restore them to a point where they will be able to resume driving," he says. "But eventually, we hope to have agents that can halt or even prevent the disease by protecting against nerve cell degeneration."
Morris JC, Cyrus PA, Orazem J, Mas J, Bieber F, Ruzicka BB, Gulanski B. Metrifonate benefits cognitive, behavioral, and global function in Alzheimer's disease patients. Neurology 50, 1222-1230, May 1998.
Disclosure: Although Morris was not paid to participate in this study, he is a paid consultant on a Bayer-supported medical education program on diagnosis and treatment of Alzheimer's disease.
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Neurology