Donepezil does little to improve post–COVID-19 fatigue, psychological symptoms

Treatment with the acetylcholinesterase inhibitor donepezil hydrochloride falls short of improving post–COVID-19 conditions such as fatigue and psychological symptoms, as shown in a study from Japan.

The study included 110 adult patients (mean age 43 years, 58 percent female) within 52 weeks of the onset of COVID-19 and had a global binary fatigue score of at least 4 on the Chalder Fatigue Scale (CFS). These patients were randomly assigned to receive donepezil (n=55) or placebo (n=55) for 3 weeks. Donepezil was administered at 3 mg/day for the first week and then 5 mg/day for the second and third weeks.

Changes in the CFS score and the absolute score at the end of the treatment at week 3 were evaluated as the primary outcome. Secondary outcomes such as psychological symptoms and quality of life were assessed at 3 and 8 weeks.

Baseline characteristics were similar between the two treatment groups. At week 3, the mean CFS score was 14.6 in the donepezil group and 14.1 in the control group, with the difference in the estimated treatment effect of 0.34 (95 percent confidence interval [CI], −2.23 to 2.91) not reaching statistical significance (p=0.79).

Likewise, secondary outcomes were similar between the donepezil and placebo groups. No significant differences were noted for scores on the Hospital Anxiety and Depression Scale, Impact of Event Scale–Revised, EuroQol 5-Dimension 5-Level Version, Patient Health Questionnaire, and Daily Health Status at 3 and 8 weeks.

In terms of safety, none of the patients in either group had serious adverse events.