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Is there a future for donepezil therapy in the treatment of multiple sclerosis-related cognitive impairment?

Evaluation of: Krupp LB, Christodoulou C, Melville P et al. Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis. Neurology 76(17), 1500–1507 (2011). Cognitive impairment is a core feature of multiple sclerosis (MS), is detectable in up to 65% of patients and represents the most important predictor of the subject’s work and vocational status. The cognitive domains most frequently involved are attention, information processing speed, episodic memory and executive functions. To date, there is no approved drug or evidence-based strategy for the treatment of this disabling condition. Promising findings were provided in a monocentric randomized trial on donepezil – a reversible inhibitor of acetylcholinesterase – for the treatment of MS-related memory impairment. However, a larger multicentric trial failed to confirm any efficacy of donepezil on memory impairment in MS subjects. Possible implications of these findings are discussed in this article.