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Donepezil Improves Memory in Patients With Multiple Sclerosis

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NEW YORK (Reuters Health) Nov 08 - Donepezil, an acetylcholinesterase inhibitor used to treat Alzheimer's disease, seems to improve memory in patients with multiple sclerosis (MS), according to a report in the November 9th issue of Neurology.

"MS is not known to result in the reduction of acetylcholine," lead author Dr. Krupp, from the State University of New York at Stony Brook, said in a statement. "But evidence suggests that there is a decrease in cholinergic activity, likely resulting from the disruption of cholinergic pathways by the demyelination and axonal damage to the nerves that occurs in MS."

In the present study, Dr. Krupp's team used standard neuropsychological tests to assess the cognitive outcomes of 69 MS patients who were randomized to receive donepezil or placebo for 24 weeks. All of the subjects had cognitive impairment at baseline.

Donepezil-treated patients showed a significant improvement in memory performance compared with control patients (p = 0.043). Moreover, this apparent benefit for donepezil remained even after controlling for a variety of potential confounders, such reading ability and MS subtype.

Compared with placebo, treatment with donepezil doubled a patient's chances of experiencing memory improvement, the authors note (p = 0.006). By contrast, the drug was not linked to improvements on other aspects of cognition.

Treatment with donepezil appeared safe and was not associated with any serious side effects. However, patients treated with the drug were more likely to report unusual dreams than those who received placebo (p = 0.010).

Dr. Krupp's team has "now set the gold standard for the next generation of cognitive enhancer trials in MS," Dr. P. Murali Doraiswamy, from Duke University in Durham, North Carolina, and Dr. M. Rao, from the Medical College of Wisconsin in Milwaukee, note in a related editorial.

Still, the editorialists note that further studies are needed to answer some real world questions, such as "How long should we treat? How do we tell if the drug is no longer working? Are benefits lost once the drug is stopped? Are there withdrawal effects? Are there long-term risks? Is treatment cost-effective?"

Neurology 2004;63:1552-1553,1579-1585.