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Research article
Effects of Body Weight on the Safety of High-dose Donepezil in Alzheimer’s Disease: Post-hoc Analysis of a Multicenter, Randomized, Open-label, Parallel Design, Three-arm Clinical Trial
Jae-Hong Lee
University of Ulsan College of Medicine
Corresponding Author
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Background: Donepezil 23mg is considered for Alzheimer’s disease (AD) to optimize cognitive benefits; however, this increases adverse events (AEs), which can negatively influence drug adherence. We investigated whether baseline body weight (BW) differs based on the presence of AEs, and which factors were relevant to the safety of high-dose donepezil.
Methods: This study was a post-hoc analysis of a multicenter randomized trial between 2014 and 2016. We included patients with moderate to severe AD treated with donepezil 10mg/day and the daily dose was escalated to 23mg with/without dose titration. Dose titration indicates 15mg/day of donepezil before the escalation or 10mg and 23mg/day on alternate days before the escalation during the first 4 weeks. The patients were divided into two groups according to the occurrence of AEs of special interest (AESIs) to compare baseline characteristics. We also assessed relationships between BW and AESIs.
Results: Among 160 safety set population, baseline BWs were different between the AESI (+) (n=67) and AESI (-) (n=93) groups. Baseline BW was inversely correlated with the occurrence of AESIs (p=0.020), and this relationship was more prominent in the no-dose titration group (p=0.009) and disappeared in the dose titration groups (p>0.05).
Conclusions: BW was the most important factor which correlated with cholinergic AEs. Hence, stepwise dose-titration should be considered, particularly in patients with low BW, to minimize the inverse relationship between BW and AEs occurrence. (‘Clinicaltrials.gov’ number NCT02550665 registered on Sep. 15, 2015)
Keywords
Alzheimer’s disease, High dose donepezil, Safety, Body weight, Adverse events, Dose-titration
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CURRENT STATUS: Under Review
Version 1
Posted 21 Sep, 2020
No community comments so far
Review #1 received
Received 19 Oct, 2020
Reviewer #1 agreed
On 30 Sep, 2020
Editor assigned
On 25 Sep, 2020
Reviewers invited
Invitations sent on 25 Sep, 2020
Submission checks complete
On 18 Sep, 2020
Editor invited
On 16 Sep, 2020
First submitted
On 13 Sep, 2020
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Subject Areas
Geriatrics & Gerontology
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This preprint is under consideration at BMC Geriatrics. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Effects of Body Weight on the Safety of High-dose Donepezil in Alzheimer’s Disease: Post-hoc Analysis of a Multicenter, Randomized, Open-label, Parallel Design, Three-arm Clinical Trial
Jae-Hong Lee
University of Ulsan College of Medicine
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 21 Sep, 2020
No community comments so far
Review #1 received
Received 19 Oct, 2020
Reviewer #1 agreed
On 30 Sep, 2020
Editor assigned
On 25 Sep, 2020
Reviewers invited
Invitations sent on 25 Sep, 2020
Submission checks complete
On 18 Sep, 2020
Editor invited
On 16 Sep, 2020
First submitted
On 13 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Geriatrics & Gerontology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Donepezil 23mg is considered for Alzheimer’s disease (AD) to optimize cognitive benefits; however, this increases adverse events (AEs), which can negatively influence drug adherence. We investigated whether baseline body weight (BW) differs based on the presence of AEs, and which factors were relevant to the safety of high-dose donepezil.
Methods: This study was a post-hoc analysis of a multicenter randomized trial between 2014 and 2016. We included patients with moderate to severe AD treated with donepezil 10mg/day and the daily dose was escalated to 23mg with/without dose titration. Dose titration indicates 15mg/day of donepezil before the escalation or 10mg and 23mg/day on alternate days before the escalation during the first 4 weeks. The patients were divided into two groups according to the occurrence of AEs of special interest (AESIs) to compare baseline characteristics. We also assessed relationships between BW and AESIs.
Results: Among 160 safety set population, baseline BWs were different between the AESI (+) (n=67) and AESI (-) (n=93) groups. Baseline BW was inversely correlated with the occurrence of AESIs (p=0.020), and this relationship was more prominent in the no-dose titration group (p=0.009) and disappeared in the dose titration groups (p>0.05).
Conclusions: BW was the most important factor which correlated with cholinergic AEs. Hence, stepwise dose-titration should be considered, particularly in patients with low BW, to minimize the inverse relationship between BW and AEs occurrence. (‘Clinicaltrials.gov’ number NCT02550665 registered on Sep. 15, 2015)