Clinical Newswire Jan 20, 2004 - Two drugs that act differently on the brain's chemistry have demonstrated a remarkable interaction that may delay the symptoms of Alzheimer's disease according to a new study published in the Jan. 21 issue of the Journal of the American Medical Association (JAMA).
The combination of donepezil (Aricept) with memantine (Namenda) provided greater cognitive, functional, global and behavioural benefits to patients with moderate to severe Alzheimer’s disease than treatment with donepezil alone.
Current treatments for Alzheimer’s, which only slow progression of the disease, include cholinesterase inhibitors like donepezil (Aricept), which increase the level of acetylcholine in the brain, improving memory and learning. Previous studies had shown that patients who received donepezil once-a-day could keep doing daily tasks longer than those on a placebo.
Memantine (Namenda) is the first of a new class of drugs, called N-methyl-D-aspartate (NMDA)-receptor antagonists, which counteract the abnormal overproduction of the neurotransmitter glutamate. Overexpression of glutamate can lead to pathogenic excitotoxic effects.
The recent report in JAMA demonstrated beneficial results when donepezil is used in combination with memantine. Though the interaction between the drugs was not clear, "to find a new medication that can provide substantial benefit to patients at this stage of the disease, either alone or in combination with another Alzheimer's drug, is certainly good news," study author Pierre Tariot of the University of Rochester Medical Center, Rochester, N.Y., said in a statement.
In a year-long study, Tariot and his colleagues gave 404 people with moderate-to-severe Alzheimer's disease already receiving stable treatment with donepezil for at least three months, either memantine (starting dose 5 milligrams/day, increased to 20 mg/d, n=203) or a placebo for a minimum of 24 weeks. The study participants were from 37 different areas across the United States, they were mostly white, and their average age was 75. Cognition, Function, Global Status and Behavior measures were obtained at the start of the study (baseline), and at the end of weeks 4, 8, 12, 18 and 24.
A significantly greater percent of patients in the Namenda/donepezil group (85% vs. 75%) completed the study compared to the placebo/donepezil group (p=0.011). In all, 322 patients reached completion.
"Efficacy of memantine was significantly better than placebo for treatment of moderate-to-severe AD in community-dwelling patients," the researchers reported.
Addition of memantine was associated with significant improvements in measures of cognitive function (p=0.001), while patients receiving donepezil and placebo declined relative to their baseline status. Treatment with memantine during the six-month trial in patients with MMSE [Mini-Mental State Examination] scores of 5 to 14 resulted in the maintenance of cognitive function (0.9 increase in the Severe Impairment Battery (SIB) score compared with baseline), whereas treatment with placebo was associated with cognitive decline (2.5 decrease in SIB score compared with baseline).
Daily living was also improved, with a decline of 2 points in the memantine group versus 3.4 in the placebo group (p=0.028) using the 19-item Alzheimer Disease Cooperative Activities of Daily Living Inventory. The findings suggest that people on the combination of Namenda and donepezil may be better able to perform basic activities necessary for independence and personal care.
Patients treated with Namenda/donepezil also performed better in an assessment of global status, based on the Clinician's Interview-Based Impressions of Change-Plus (CIBIC- Plus) compared to the study's control group (p=0.03).
"The results clearly show that patients with moderate to severe Alzheimer's disease treated with the combination of Namenda and donepezil perform better on measures of intellectual and daily functioning compared to those patients taking donepezil and a sugar pill." Said Dr. Tariot.
Namenda is expected to be of greatest use to patients having reached the moderate stage of the disease, as well as to those who have progressed into severe stages.
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