Donepezil Treatment in Patients With Depression and Cognitive Impairment on Stable Antidepressant Treatment: A Randomized Controlled Trial
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Objective Depression and cognitive impairment are often comorbid in older adults, but optimal treatment strategies remain unclear. In a two-site study, the efficacy and safety of add-on donepezil versus placebo were compared in depressed patients with cognitive impairment receiving stable antidepressant treatment.Methods A randomized, double-blind, placebo-controlled trial was conducted in older adults with depression and cognitive impairment (https://clinicaltrials.gov/ct2/show/NCT01658228; NCT01658228). Patients received open-label antidepressant treatment for 16 weeks, initially with citalopram and then with venlafaxine, if needed, followed by random assignment to add-on donepezil 5-10 mg daily or placebo for another 62 weeks. Outcome measures were neuropsychological test performance (Alzheimer's Disease Assessment Scale-Cognitive subscale [ADAS-Cog] and Selective Reminding Test [SRT] total immediate recall) and instrumental activities of daily living (Functional Activities Questionnaire).Results Of 81 patients who signed informed consent, 79 patients completed the baseline evaluation. Open antidepressant treatment was associated with improvement in depression in 63.93% responders by week 16. In the randomized trial, there were no treatment group differences between donepezil and placebo on dementia conversion rates, ADAS-Cog, SRT total immediate recall, or FAQ. Neither baseline cognitive impairment severity nor apolipoprotein E e4 genotype influenced donepezil efficacy. Donepezil was associated with more adverse effects than placebo.Conclusion The results do not support adjunctive off-label cholinesterase inhibitor treatment in patients with depression and cognitive impairment. The findings highlight the need to prioritize discovery of novel treatments for this highly prevalent population with comorbid illnesses.
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Another study failed to confirm the benefit of donepezil in reducing conversion to dementia.
“However, another study failed to confirm the benefit of donepezil in reducing conversion to dementia135.”
From Mechanisms and treatment of late-life depression (2019) · cites this paper as [135]
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- Authors
- Devanand, D. P., Pelton, G. H., D'Antonio, K., Ciarleglio, A., Scodes, J., Andrews, H., Lunsford, J., Beyer, J. L., Petrella, J. R., Sneed, J., Ciovacco, M., & Doraiswamy, P. M.
- Affiliations
- Columbia University Irving Medical Center (US)
- Duke Medical Center (US)
- New York State Psychiatric Institute (US)
- Corresponding author
- Devanand, Davangere P.
- ORCID
- Venue
- The American Journal of Geriatric Psychiatry
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 26
- Issue
- 10
- Pages
- 1050-1060
- ISSN
- 1064-7481 (ISSN-L)
- PMC
- PMC6396676
- OpenAlex
- W2809791546
- Cited by
- 47
- References
- 44
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 7 · 2023: 7 · 2022: 9 · 2021: 8 · 2020: 7 · 2019: 2
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- American Journal of Geriatric Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG040093, R01AG041795)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- donepezil, depression, cognitive impairment, older adults, cholinesterase inhibitors, adjunctive therapy, antidepressant treatment, citalopram, venlafaxine, conversion to dementia, apolipoprotein E e4, functional activities of daily living, neuropsychological performance
- MeSH terms
- Donepezil, Aged, Aged, 80 and over, Cholinesterase Inhibitors, Depressive Disorder, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Comorbidity, Outcome Assessment, Health Care, Antidepressive Agents, Second-Generation, Off-Label Use, Cognitive Dysfunction
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