Combined use of Donepezil and Memantine increases the probability of five-year survival of Alzheimer’s disease patients
Open accessAbstract
BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease. Studying the effects of drug treatments on multiple health outcomes related to AD could be beneficial in demonstrating which drugs reduce the disease burden and increase survival. METHODS: We conducted a comprehensive causal inference study implementing doubly robust estimators and using one of the largest high-quality medical databases, the Oracle Electronic Health Records (EHR) Real-World Data. Our work was focused on the estimation of the effects of the two common Alzheimer's disease drugs, Donepezil and Memantine, and their combined use on the five-year survival since initial diagnosis of AD patients. Also, we formally tested for the presence of interaction between these drugs. RESULTS: Here, we show that the combined use of Donepezil and Memantine significantly elevates the probability of five-year survival. In particular, their combined use increases the probability of five-year survival by 0.050 (0.021, 0.078) (6.4%), 0.049 (0.012, 0.085), (6.3%), 0.065 (0.035, 0.095) (8.3%) compared to no drug treatment, the Memantine monotherapy, and the Donepezil monotherapy respectively. We also identify a significant beneficial additive drug-drug interaction effect between Donepezil and Memantine of 0.064 (0.030, 0.098). CONCLUSIONS: Based on our findings, adopting combined treatment of Memantine and Donepezil could extend the lives of approximately 303,000 people with AD living in the USA to be beyond five-years from diagnosis. If these patients instead have no drug treatment, Memantine monotherapy or Donepezil monotherapy they would be expected to die within five years.
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For moderate-to-severe AD dementia, a combination of memantine and donepezil is approved.
“For moderate-to-severe AD dementia, a combination of a glutamate regulator (memantine) and a cholinesterase inhibitor (donepezil) is approved [127,128,129].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [127]
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- Authors
- Yaghmaei, E., Lu, H., Ehwerhemuepha, L., Zheng, J., Danioko, S., Rezaie, A., Sajjadi, S. A., & Rakovski, C.
- Affiliations
- Chapman University (US)
- University of North Carolina at Chapel Hill (US)
- Children's Hospital of Orange County (US)
- University of California, Irvine (US)
- Corresponding author
- Rakovski, Cyril
- ORCID
- Venue
- Communications Medicine
- Published
- 2024-05-23
- Volume
- 4
- Issue
- 1
- Pages
- 99-99
- ISSN
- 2730-664X (ISSN-L)
- PMC
- PMC11116549
- OpenAlex
- W4398237142
- Cited by
- 47
- References
- 30
- Citations by year
- 2026: 21 · 2025: 17 · 2024: 9
- FWCI
- 13.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Communications Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Chapman University Digital Commons (Chapman University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UNC Libraries
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Alzheimer's disease, donepezil, memantine, combination therapy, five-year survival, drug-drug interactions, causal inference, doubly robust estimation, electronic health records, real-world data, monotherapy comparison
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