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Previously, a small, single-center, placebo-controlled trial found possible benefit for the acetylcholinesterase inhibitor donepezil in improving impaired memory in patients with multiple sclerosis (MS; Neurology 2004; 63:1579). Researchers have now tested this preliminary finding in a larger, multicenter, NIH-sponsored trial. In all, 120 MS patients (age range, 18–59) who scored at least half a standard deviation below the norm on the Rey Auditory Verbal Learning Test were randomized to receive placebo or donepezil (5 mg/day for 4 weeks, followed by 10 mg/day for another 20 weeks).
From baseline to week 24, donepezil recipients improved no more than placebo recipients either on measures of verbal learning and memory, as assessed by the Selective Reminding Test (a component of the Brief Repeatable Battery [BRB]), or on secondary neuropsychological measures of the BRB and other standard tests. In addition, donepezil and placebo recipients did not differ significantly on subjective improvement in memory or cognition, whether reported by the study participant, his or her partner, or the evaluating clinician.
Krupp LB et al. Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis. Neurology 2011 Apr 26; 76:1500.
Comment
In this large, multicenter trial, donepezil was no better than placebo for MS-related memory impairment, a finding consistent with the lack of benefit over placebo for the cholinesterase inhibitor rivastigmine in an earlier study of 60 MS patients (Can J Neurol Sci 2008; 35:476). For now, treatment with cholinesterase inhibitors appears not to be the answer to the common problem of cognitive impairment in patients with MS.