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Memantine Reduces Behavioural Symptoms Associated With Alzheimer's Disease: Presented at AAN

By Jill Stein

MIAMI, FL -- April 13, 2005 -- Memantine significantly improves behavioural symptoms across the spectrum in both mild to moderate Alzheimer's disease (AD) and moderate to severe AD, researchers said here on April 12^th at the American Academy of Neurology 57^th Annual Meeting.

Memantine is a low-moderate affinity, uncompetitive antagonist of the N-methyl-d-aspartate receptor.

Jeffrey L. Cummings, MD, director, Alzheimer's Disease Center, University of California, Los Angeles, California, United States, and associates evaluated the effect of memantine on behavioural symptoms using data from 2 24-week, double- blind, placebo-controlled trials.

One trial (MEM-MD-02) included 404 patients with moderate to severe AD on stable therapy with the acetylcholinesterase inhibitor donepezil who were randomised to memantine or placebo. The other trial (MEM-MD-10) enrolled 403 patients with mild to moderate AD randomised to memantine monotherapy or placebo.

In both trials, researchers used the Neuropsychiatric Inventory (NPI) to evaluate behavioural symptoms. In addition to assessing overall psychotropic effects of treatment, the researchers used the NPI to examine whether treatment prevented the emergence of behavioural symptoms or reduced existing symptoms.

There were statistically significant differences in favour of memantine at endpoint, as measured by NPI total score (P =.002, study MEM-MD-02; P =.011, study MEM-MD-10).

Several NPI domains demonstrated statistically significant treatment differences in favour of memantine. For study MEM-MD-02, these domains were agitation/aggression, irritability/lability, and appetite/eating change; in study MEM-MD-10, the score for delusions favored memantine, with statistical trends for irritability, aberrant motor behaviour, and appetite/eating change.

When patients who were symptom free at baseline were examined, significantly fewer memantine patients in study MEM-MD-02 demonstrated the onset of agitation/aggression, irritability/lability, and nighttime behavioural disturbances at endpoint compared with placebo patients.

In study MEM-MD-10, significantly fewer memantine patients exhibited emergence of delusions and irritability/lability at endpoint compared with placebo patients.

Patients in study MEM-MD-02 who were symptomatic at baseline showed significantly less deterioration compared with placebo with respect to agitation/aggression, apathy, and irritability at endpoint. For study MEM-MD-10, significant domains were delusions and apathy.

"Behavioural abnormalities comprise an important component of the overall symptomatology of AD," and reduction and management of behavioural disturbances therefore represent an important treatment goal," Dr. Cummings commented. "In addition to other benefits, our results support the use of memantine in treating behavioural symptoms associated with AD"

The study was supported by Forest Laboratories, Inc.


[Presentation title: Effect of Memantine on Behavioral Outcomes in Mild to Severe Alzheimer's Disease. Abstract P02.093]

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