IMAGE DESCRIPTION: An image of tablets that represent Donepezil. The title reads: Long Covid treatment trial: Donepezil hydrochloride. The ME Association Logo (bottom right).

Research: Long Covid treatment trial: Donepezil hydrochloride

The effect of donepezil hydrochloride on post-COVID memory impairment: A randomized controlled trial


Background: Post-Coronavirus Disease (COVID-19) condition, known as “post-COVID syndrome,” is associated with a range of complications persisting even after recovery. Among these complications, cognitive dysfunction, including memory impairment, has been relatively common observed, impacting executive function and quality of life. To date, no approved treatment exists for this specific complication. Therefore, the present clinical trial aimed to investigate the impact of Donepezil Hydrochloride on post-COVID memory impairment.

Methods: A randomized, controlled trial (Approval ID: IRCT20210816052203N1) was conducted, enrolling 25 patients with post-COVID memory impairment. Participants with a history of hospitalization were randomly assigned to either the drug group (n = 10) or the control group (n = 15). Memory indices were assessed at baseline, one month, and three months later using the Wechsler Memory Scale-Revised test. SPSS software and appropriate statistical tests were employed for data analysis.

Results: The statistical analysis revealed no significant difference in WMS-R subtest and index scores between the drug and control groups at the 4-week and 12-week follow-up periods. However, within the drug group, there was a notable increase in the visual reproduction I and verbal paired associates II subtests during the specified time intervals.

Conclusion: While donepezil 5 mg did not exhibit a significant overall increase in memory scales compared to the control group over time, our findings suggest that this medication may exert a positive effect on specific memory subtests. Further research and exploration are warranted to better understand the potential benefits of donepezil in managing post-COVID-related memory impairment.

MEA Comment

Dr Charles Shepherd, Honorary Medical Adviser to the ME Association says:

These are disappointing results from a small clinical trial which has assessed the use of a drug – donepezil hydrochloride (brand name Aricept) –  which can sometimes be of some help in slowing memory decline in Alzheimer's disease.

The findings are not surprising given the fact that memory decline in dementia does not normally involve the same sort of problems with short-term working memory and attention span that occurs in ME/CFS and Long Covid.  And the underlying cause of many cases of dementia, involving the progressive build-up of harmful amyloid plaques in the brain, is almost certainly very different to the cause of very acute onset of cognitive dysfunction in ME/CFS and Long Covid.

In our current state of knowledge, it does not therefore appear that drugs that are being used to treat dementia are going to be helpful for cognitive dysfunction in ME/CFS and Long Covid.

More information on Donepezil

Dr Charles Shepherd,
Trustee and
Hon. Medical Adviser
to the ME Association.
Member of the 2018-2021 NICE Guideline Committee.
Member of the 2002 Independent Working Group on ME/CFS.

Dr Charles Shepherd
Shopping Basket