Efficacy of memantine for agitation in Alzheimer's dementia: a randomized double-blind placebo controlled trial -- commentary and summary

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Namenda is known in Europe as Ebixa and generically as memantine. It is typically prescribed for mid-stage Alzheimer's disease.

According to a new study conducted by researchers from the U.K., U.S. and Norway, it helps with many symptoms, though it does not ease clinically significant agitation in patients, which was the main question the study addressed.

On the positive side, the new research found that memantine does improve cognitive functioning and neuropsychiatric symptoms such as delusion, mood and anxiety.

Regenstrief Institute investigator Malaz Boustani, M.D., MPH, said,

“Memantine is quite commonly prescribed for Alzheimer’s disease in the U.S. Despite the negative findings regarding agitation, this trial opens a door of hope.”

“Memantine does appear to help with other behavioral and psychological symptoms of Alzheimer’s disease.”

Dr. Boustani is a co-author of the study, as well as associate professor of medicine at the Indiana University School of Medicine and associate director of the IU Center for Aging Research. Dr. Boustani is also the medical and research director of the Healthy Aging Brain Center at Wishard Health Services.

This is the first randomized controlled trial designed to assess the effectiveness of memantine for significant agitation in Alzheimer’s patients. Previous studies suggested memantine could help reduce agitation and improve cognitive functions such as memory. Led by the University of East Anglia in the U.K., this study showed it is no more effective in reducing significant agitation than a placebo.

An estimated 5.4 million Americans have Alzheimer’s disease according to the Alzheimer’s Association. Many are agitated. They may, for example, pace continually, become physically or verbally aggressive or scream persistently. In addition to harming quality of life for the patient, agitation places enormous strain on relationships with family members and care providers, and often results in institutionalization.

Chris Fox, M.D., of Norwich Medical School at University of East Anglia, led the research. He commented,

“People who have mild symptoms [of agitation] often respond to changes in the environment or psychological treatment, but these methods are impractical in severe agitation."

"Our findings regarding memantine are disappointing with respect to severe agitation -- particularly as the alternative antipsychotic medications can have significant side effects such as increased rates of stroke and death. However, we hope our study will highlight the urgent need for investment in safe and effective new treatments for this growing disease.”

The team of researchers studied 153 nursing home residents and hospital inpatients with severe Alzheimer’s from September 2007 to May 2010. All the study participants displayed significant agitation requiring clinical treatment. Half were given memantine, and half received a placebo. The researchers reported signficant improvement in cognitive function and for overall neuropsychiatric symptoms for the group given memantine, but no statistically significant difference in terms of the severe agitation that was the primary focus of the study.

Memantine is approved by the U.S. Food and Drug Administration for Alzheimer’s disease. The trial was sponsored by East Kent Hospitals University National Health Service Foundation Trust in the U.K. The study was funded by Lundbeck, a manufacturer of memantine.

Anne Corbett, research manager at the Alzheimer’s Society of the U.K., was not involved in the research. She summed up the study results with,

“This research suggests that even though memantine can have real benefits for people in the later stages of Alzheimer’s, it may not have all the answers."

"However, prescribers should not see the only alternative as being to hand out antipsychotics. These overprescribed drugs double the risk of death and treble the risk of stroke and should always be a last resort for people with dementia.”