Evidence lacking for efficacy of memantine in treating mild Alzheimer's disease

An analysis of studies involving the drug memantine finds a lack of evidence for benefit when the drug is used to treat patients with mild Alzheimer disease, according to a report posted online today that will appear in the August print issue of Archives of Neurology.

12 april 2011--"Memantine, indicated for moderate to severe Alzheimer disease (AD), is frequently prescribed off-label [for uses other than those approved by the FDA] either alone or with a cholinesterase inhibitor for mild AD and mild cognitive impairment," the authors write as background information in the article. Cholinesterase inhibitors are drugs that increase levels of a brain chemical called acetylcholine. Increasing acetylcholine levels appears to slow mental decline in people with AD.

Lon S. Schneider, M.D., M.S., of the University of Southern California Keck School of Medicine, Los Angeles, and colleagues systematically searched manufacturer-sponsored meta-analyses, registries, presentations, and publications for randomized, placebo-controlled, parallel-group clinical trials of memantine in patients with mild to moderate AD. Three trials were identified that included 431 patients with mild AD and 697 patients with moderate AD. Using several different scales, the researchers assessed cognition, global change, functional activities, and behavior.

"There were no significant differences between memantine and placebo on any outcome for patients with mild AD, either within any trial or when data were combined," the authors report.

Among patients with moderate AD, there was no significant difference between memantine and placebo in any individual trial, although there was a significant effect when the three trials were statistically combined.

"Despite its frequent off-label use, evidence is lacking for a benefit of memantine in mild AD, and there is meager evidence for its efficacy in moderate AD," the authors conclude. "Prospective trials are needed to further assess the potential for efficacy of memantine either alone or added to cholinesterase inhibitors in mild and moderate AD."

More information: Arch Neurol. Published online April 11, 2011. doi:10.1001/archneurol.2011.69

Provided by JAMA and Archives Journals

Anti-dementia drugs effective over long-term
By Martha KerrFri Oct 12, 8:33 PM ET
Although the patient's family may not notice, individuals with Alzheimer's disease maintain a sustained response to anti-dementia medications, investigators reported here this week.
The initial effects of the anti-dementia drugs on symptoms of Alzheimer's disease wane over time, but remain beneficial by slowing disease progression, Dr. Susan D. Rountree, of Baylor University in Houston, reported at the 132nd annual meeting of the American Neurological Association.
Guidelines addressing duration of therapy have not been established for donepezil, galantamine, rivastigmine and memantine, Rountree said. She and her colleagues evaluated cumulative drug exposure, calculated as years of drug use and disease duration, in 643 patients with probable Alzheimer's disease.
The investigators conducted neuropsychiatric testing when the study began and annually for an average of more than 3 years up to 10 years.
"There was a persistently slower rate of decline on all the cognitive measures and basic activities of daily living," Rountree told Reuters Health. Treatment did not affect the rate of decline on the more complex tasks, but the magnitude of the initial reduction in dementia with treatment initiation was retained over time, she added.
"Benefits were seen even in those with advanced disease," Rountree said. The findings suggest that patients who use anti-dementia drugs persistently derive more benefits from therapy than those who use these drugs less persistently.
These results should be of value to the families of Alzheimer's disease patients, who become discouraged with what they perceive to be a wearing-off of the effectiveness of these drugs, she commented.