Donepezil as an adjuvant to constraint-induced therapy for upper-limb dysfunction after stroke: An exploratory randomized clinical trial

Donepezil, a primarily central acetylcholinesterase inhibitor, could potentiate learning in subjects with stroke by amplifying cholinergic input to the cerebral cortex from the nucleus basalis of Meynert. We tested this possible adjuvant effect of donepezil in a prospective randomized, double-blind, placebo-controlled, parallel-group study of 20 subjects I or more years following stroke undergoing constraint-induced therapy (CIT) for upper-limb dysfunction. CIT had substantial and significant effects on both primary outcome measures, the Wolf Motor Function Test (WMFT) and the Motor Activity Log (amount), and all secondary measures, including the Box and Block Test, the Actual Amount of Use Test, the Fugl-Meyer Motor Scale-Upper Extremity, and the Caregiver Strain Index. Subjects receiving donepezil achieved differential gains on the WMFT approaching statistical significance (p = 0.067, corrected for multiple comparisons), but not on other measures. This study is inconclusive, but a larger randomized controlled trial with adequate statistical power should be pursued because of the potential benefits of the treatment to stroke survivors.