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Cited by 1,200Dementia and Cognitive Impairment ResearchCholinesterase and Neurodegenerative DiseasesAlzheimer's disease research and treatments

Donepezil for dementia due to Alzheimer’s disease.

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Birks, Jacqueline S, Harvey, Richard J·2018·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd001190.pub3PMC PMC6513124
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Abstract

BACKGROUND: Alzheimer's disease is the most common cause of dementia in older people. One approach to symptomatic treatment of Alzheimer's disease is to enhance cholinergic neurotransmission in the brain by blocking the action of the enzyme responsible for the breakdown of the neurotransmitter acetylcholine. This can be done by a group of drugs known as cholinesterase inhibitors. Donepezil is a cholinesterase inhibitor.This review is an updated version of a review first published in 1998. OBJECTIVES: To assess the clinical efficacy and safety of donepezil in people with mild, moderate or severe dementia due to Alzheimer's disease; to compare the efficacy and safety of different doses of donepezil; and to assess the effect of donepezil on healthcare resource use and costs. SEARCH METHODS: We searched Cochrane Dementia and Cognitive Improvement's Specialized Register, MEDLINE, Embase, PsycINFO and a number of other sources on 20 May 2017 to ensure that the search was as comprehensive and up-to-date as possible. In addition, we contacted members of the Donepezil Study Group and Eisai Inc. SELECTION CRITERIA: We included all double-blind, randomised controlled trials in which treatment with donepezil was administered to people with mild, moderate or severe dementia due to Alzheimer's disease for 12 weeks or more and its effects compared with those of placebo in a parallel group of patients, or where two different doses of donepezil were compared. DATA COLLECTION AND ANALYSIS: One reviewer (JSB) extracted data on cognitive function, activities of daily living, behavioural symptoms, global clinical state, quality of life, adverse events, deaths and healthcare resource costs. Where appropriate and possible, we estimated pooled treatment effects. We used GRADE methods to assess the quality of the evidence for each outcome. MAIN RESULTS: Thirty studies involving 8257 participants met the inclusion criteria of the review, of which 28 studies reported results in sufficient detail for the meta-analyses. Most studies were of six months' duration or less. Only one small trial lasted 52 weeks. The studies tested mainly donepezil capsules at a dose of 5 mg/day or 10 mg/day. Two studies tested a slow-release oral formulation that delivered 23 mg/day. Participants in 21 studies had mild to moderate disease, in five studies moderate to severe, and in four severe disease. Seventeen studies were industry funded or sponsored, four studies were funded independently of industry and for nine studies there was no information on source of funding.Our main analysis compared the safety and efficacy of donepezil 10 mg/day with placebo at 24 to 26 weeks of treatment. Thirteen studies contributed data from 3396 participants to this analysis. Eleven of these studies were multicentre studies. Seven studies recruited patients with mild to moderate Alzheimer's disease, two with moderate to severe, and four with severe Alzheimer's disease, with a mean age of about 75 years. Almost all evidence was of moderate quality, downgraded due to study limitations.After 26 weeks of treatment, donepezil compared with placebo was associated with better outcomes for cognitive function measured with the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog, range 0 to 70) (mean difference (MD) -2.67, 95% confidence interval (CI) -3.31 to -2.02, 1130 participants, 5 studies), the Mini-Mental State Examination (MMSE) score (MD 1.05, 95% CI 0.73 to 1.37, 1757 participants, 7 studies) and the Severe Impairment Battery (SIB, range 0 to 100) (MD 5.92, 95% CI 4.53 to 7.31, 1348 participants, 5 studies). Donepezil was also associated with better function measured with the Alzheimer's Disease Cooperative Study activities of daily living score for severe Alzheimer's disease (ADCS-ADL-sev) (MD 1.03, 95% CI 0.21 to 1.85, 733 participants, 3 studies). A higher proportion of participants treated with donepezil experienced improvement on the clinician-rated global impression of change scale (odds ratio (OR) 1.92, 95% CI 1.54 to 2.39, 1674 participants, 6 studies). There was no difference between donepezil and placebo for behavioural symptoms measured by the Neuropsychiatric Inventory (NPI) (MD -1.62, 95% CI -3.43 to 0.19, 1035 participants, 4 studies) or by the Behavioural Pathology in Alzheimer's Disease (BEHAVE-AD) scale (MD 0.4, 95% CI -1.28 to 2.08, 194 participants, 1 study). There was also no difference between donepezil and placebo for Quality of Life (QoL) (MD -2.79, 95% CI -8.15 to 2.56, 815 participants, 2 studies).Participants receiving donepezil were more likely to withdraw from the studies before the end of treatment (24% versus 20%, OR 1.25, 95% CI 1.05 to 1.50, 2846 participants, 12 studies) or to experience an adverse event during the studies (72% vs 65%, OR 1.59, 95% 1.31 to 1.95, 2500 participants, 10 studies).There was no evidence of a difference between donepezil and placebo for patient total healthcare resource utilisation.Three studies compared don

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  • Clinical trials of donepezil, rivastigmine, and galantamine in participants with average MMSE score 19 for mild dementia stage demonstrated moderate reduction in cognitive decline over 6 months using the ADAS-cog scale.

    “Clinical trials of donepezil, rivastigmine, and galantamine of participants with the average MMSE score–19 for AD in mild dementia stage demonstrated moderate reduction in cognitive decline over 6 months (or 26 weeks) using the ADAS-cog scale.21–23”

    From A 2025 update on treatment strategies for the Alzheimer’s disease spectrum (2025) · cites this paper as [23]

  • Current FDA-approved treatments offer modest symptomatic benefit or partial slowing of progression but do not halt neurodegeneration or restore lost neuronal circuits.

    “Current FDA-approved treatments, including cholinesterase inhibitors, memantine, and anti-amyloid monoclonal antibodies, offer modest symptomatic benefit or partial slowing of progression but do not halt neurodegeneration or restore lost neuronal circuits.”

    From Reverse the progression of Alzheimer’s disease through Nano-ERASER-based adult neuroregeneration (2026) · cites this paper as [5]

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Authors
Birks, J. S., & Harvey, R. J.
Affiliations
  • University of Oxford (GB)
  • Deakin University (AU)
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2018-06-18
Volume
2018
Issue
6
Pages
CD001190-CD001190
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd001190.pub3
PMC
PMC6513124
OpenAlex
W1904458203
Cited by
1,200
References
11
Citations by year
2026: 45 · 2025: 93 · 2024: 103 · 2023: 81 · 2022: 89 · 2021: 101 · 2020: 230 · 2019: 59 · 2018: 26 · 2017: 27 · 2016: 31 · 2015: 24 · 2014: 29 · 2013: 35 · 2012: 32
FWCI
15.85
Type
journal article
Language
en
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
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, dementia, cholinesterase inhibitors, acetylcholinesterase inhibition, cognitive function, activities of daily living, behavioural symptoms, quality of life, adverse events, health care utilization, cost-effectiveness, dose comparison, slow-release formulation, publication bias, GRADE quality of evidence
MeSH terms
Donepezil, Alzheimer Disease, Cholinesterase Inhibitors, Cognition, Cognition Disorders, Humans, Indans, Piperidines, Randomized Controlled Trials as Topic, Nootropic Agents

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