摘要:Background: Cognitive impairment is one of the debilitating consequences of multiple sclerosis (MS) with negative effects on daily life, individual and social activities, quality of life (QOL), and depression. No approved medication is introduced so far for affected individuals. We aimed to evaluate the efficacy of donepezil on cognitive performance, QOL, and depression in MS. Methods: This is a double-blinded randomized clinical trial conducted on 100 patients with MS during 2018. Patients were assessed prior to intervention abbreviated mental test (AMT), prospective and retrospective mental questionnaire (PRMQ), everyday memory questionnaire (EMQ), digit span test, Beck depression inventory (BDI), and MSQOL questionnaire. Then patients were randomly divided into two groups of treatment (daily regimen of 10 mg donepezil) and placebo for 3 months. Subjects were reassessed using the same instruments at the end of intervention. Results: Fifty patients remained in each group at the end of study. The mean age in donepezil and placebo groups was 31.9 ± 5.89 and 30.65 ± 5.43 years, respectively. EMQ, PRMQ, digit span test, MSQOL, and depression scores improved following donepezil therapy ( P 0.001) while no statistically significant difference was found in the placebo group ( P 0.05). Comparison of two groups also showed more favorable scores in donepezil group with respect to all assessment tools ( P 0.001). Conclusions: Donepezil could effectively improve cognitive impairment in MS patients. Also, its positive effect on QOL and depression could result in a smaller number of interventions in this group of patients.