Alzheimer's Drug Shows Some Cognitive Benefits

New reviews of clinical trials data suggest that memantine (Namenda) is effective at slowing the progression of cognitive decline in patients with moderate to severe Alzheimer's disease. However, for most patients that effect may be small. After six months of treatment, patients given memantine had slightly less functional and cognitive decline and were less likely to become agitated compared with those given placebo.

A review by the Cochrane Collaboration in London of its Specialized Register of the Cochrane Dementia and Cognitive Improvement Group pooled clinical trials data and unpublished data of the drug's use in the treatment of patients with moderate to severe Alzheimer's, mild to moderate Alzheimer's, and mild to moderate vascular dementia. The review was published in the April Cochrane Database of Systematic Reviews.

The Cochrane team found that memantine can slow down the rate at which cognitive deterioration and loss of everyday functions typically occurs in patients with moderate to severe Alzheimer's disease.

While the effect is small, it is “clinically noticeable,” according to Rupert McShane, M.D., a professor of medicine at the University of Oxford and lead author of the Cochrane review.

The studies reviewed by the team suggest some cognitive benefits from the drug in patients with mild to moderate Alzheimer's or mild to moderate vascular dementia. However, these changes were not judged clinically significant in the studies reviewed, and “it remains unknown whether there is a true benefit in mild to moderate cases,” McShane and his colleagues wrote.

In addition, the authors noted, there was no evidence that memantine was effective for reducing agitation or aggression in dementia patients; nonetheless, patients on the drug had lower rates of agitation and aggression, which suggests a possible preventive effect.

Memantine is approved by the U.S. Food and Drug Administration only for the treatment of moderate to severe Alzheimer's. The European Union's Agency for the Evaluation of Medical Products approved the drug for a similar indication.

Both agencies are reviewing applications by Forest Laboratories, the drug's manufacturer, for approval of the drug for mild to moderate Alzheimer's.

The Cochrane review included nine studies with data on 2,339 patients. However, the reviewers noted that three additional large studies have yet to be published. Cochrane reviewers attempted to account for the data in those studies by including information that was publicly available from the three trials. They then calculated how the still unknown data would affect the overall review in worst-case and best-case scenarios.

McShane and his colleagues acknowledged that firm conclusions may need to await the full disclosure of the data and results of those additional trials. While one study finished collecting data in 2003, “the lack of any substantive reference to it suggests that the results may be less favorable than those in published studies.”

A second review, appearing in the May International Journal of Geriatric Psychiatry, was more limited in scope. That review, completed by Serge Gauthier, M.D., director of the Alzheimer and Cognitive Disorders Clinic of the McGill Centre for Studies in Aging at McGill University in Montreal, and colleagues compiled data from two randomized, controlled studies on patients with moderate to severe Alzheimer's. They analyzed only the data collected with the Neuropsychiatric Inventory (NPI).

The subjects received memantine in one study, and memantine and donepezil in the other. The control groups in both studies, which had a total of 656 subjects, received placebo, and all lived in the community.

“In both studies, the change in NPI total scores at endpoint was consistently in favor of memantine treatment, reaching statistical significance in the combination study,” reported the researchers.

Like the Cochrane reviewers, Gauthier and his colleagues noted that memantine was associated with statistically significant less agitation/aggression emerging in the subjects compared with those receiving placebo.

An abstract of the “Cochrane Review: Memantine for Dementia” is posted online at<www.mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD003154/abstract.html>.An abstract of “Effects of Memantine on Behavioural Symptoms in Alzheimer's Disease Patients: An Analysis of the Neuropsychiatric Inventory (NPI) Data of Two Randomised, Controlled Studies” is posted at<www3.interscience.wiley.com/cgi-bin/abstract/110478152/ABSTRACT>.▪