Donepezil for the Treatment of Agitation in Alzheimer's Disease
Open accessAbstract
BACKGROUND: Agitation is a common and distressing symptom in patients with Alzheimer's disease. Cholinesterase inhibitors improve cognitive outcomes in such patients, but the benefits of these drugs for behavioral disturbances are unclear. METHODS: We randomly assigned 272 patients with Alzheimer's disease who had clinically significant agitation and no response to a brief psychosocial treatment program to receive 10 mg of donepezil per day (128 patients) or placebo (131 patients) for 12 weeks. The primary outcome was a change in the score on the Cohen-Mansfield Agitation Inventory (CMAI) (on a scale of 29 to 203, with higher scores indicating more agitation) at 12 weeks. RESULTS: There was no significant difference between the effects of donepezil and those of placebo on the basis of the change in CMAI scores from baseline to 12 weeks (estimated mean difference in change [the value for donepezil minus that for placebo], -0.06; 95% confidence interval [CI], -4.35 to 4.22). Twenty-two of 108 patients (20.4%) in the placebo group and 22 of 113 (19.5%) in the donepezil group had a reduction of 30% or greater in the CMAI score (the value for donepezil minus that for placebo, -0.9 percentage point; 95% CI, -11.4 to 9.6). There were also no significant differences between the placebo and donepezil groups in scores for the Neuropsychiatric Inventory, the Neuropsychiatric Inventory Caregiver Distress Scale, or the Clinician's Global Impression of Change. CONCLUSIONS: In this 12-week trial, donepezil was not more effective than placebo in treating agitation in patients with Alzheimer's disease. (ClinicalTrials.gov number, NCT00142324 [ClinicalTrials.gov].).
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All activity studies were in care homes except one, in which some participants attended a day centre and others lived in a care home.
“All studies were in care homes except one, in which some participants attended a day centre and others lived in a care home. 27”
From Non-pharmacological interventions for agitation in dementia: systematic review of randomised controlled trials (2014) · cites this paper as [27]
Donepezil showed no benefit for clinically significant agitation over 12 weeks in a large RCT, or for overall change in neuropsychiatric inventory scores in a longer term trial with up to four years' follow-up.
“In addition, donepezil showed no benefit for clinically significant agitation over 12 weeks in a large RCT,147 or for overall change in neuropsychiatric inventory scores in a longer term trial with up to four years’ follow-up.98”
From Assessment and management of behavioral and psychological symptoms of dementia (2015) · cites this paper as [147]
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- Authors
- Howard, R. J., Juszczak, E., Ballard, C. G., Bentham, P., Brown, R. G., Bullock, R., Burns, A. S., Holmes, C., Jacoby, R., Johnson, T., Knapp, M., Lindesay, J., O'Brien, J. T., Wilcock, G., Katona, C., Jones, R. W., DeCesare, J., & Rodger, M.
- Affiliations
- King's College London (GB)
- University of Oxford (GB)
- Queen Elizabeth Hospital Birmingham (GB)
- Victoria Hospital (GB)
- University of Manchester (GB)
- University of Southampton (GB)
- University of Cambridge (GB)
- University of Leicester (GB)
- Newcastle University (GB)
- John Radcliffe Hospital (GB)
- University of Kent (GB)
- The Research Institute for the Care of Older People (GB)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2007-10-04
- Volume
- 357
- Issue
- 14
- Pages
- 1382-1392
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2136332296
- Cited by
- 327
- References
- 34
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 13 · 2023: 16 · 2022: 33 · 2021: 7 · 2020: 5 · 2019: 13 · 2018: 15 · 2017: 15 · 2016: 15 · 2015: 19 · 2014: 19 · 2013: 22 · 2012: 16
- FWCI
- 17.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Kent Academic Repository (University of Kent) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Medical Research Council
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- donepezil, Alzheimer's disease, agitation, cholinesterase inhibitors, Cohen-Mansfield Agitation Inventory, behavioral problems, placebo comparison, psychosocial interventions, caregiver distress, Neuropsychiatric Inventory
- MeSH terms
- Donepezil, Aged, Aged, 80 and over, Alzheimer Disease, Cholinesterase Inhibitors, Double-Blind Method, Female, Humans, Indans, Male, Piperidines, Psychomotor Agitation, Psychotherapy, Social Support, Treatment Failure
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