PMID- 34518459
OWN - NLM
STAT- MEDLINE
DCOM- 20211206
LR  - 20211214
IS  - 1421-9824 (Electronic)
IS  - 1420-8008 (Linking)
VI  - 50
IP  - 3
DP  - 2021
TI  - 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.
PG  - 289-295
LID - 10.1159/000518470 [doi]
AB  - BACKGROUND: Donepezil 23 mg is considered for Alzheimer's disease (AD) to 
      optimize cognitive benefits; however, increased adverse events (AEs) can 
      negatively influence drug adherence. We investigated whether body weight (BW) 
      differs based on the presence of AEs, and which baseline 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 10 mg/day of donepezil, and the daily dose was 
      escalated to 23 mg with/without dose titration. Dose titration indicates 15 
      mg/day of donepezil before escalation or 10 mg and 23 mg/day on alternate days 
      before escalation during the first 4 weeks. The patients were divided into 2 
      groups based on occurrence of AEs of special interest (AESIs) to compare baseline 
      characteristics. We also assessed relationships between BW and AESIs. RESULTS: 
      Among the 160 participants in the safety population, the baseline BWs differed 
      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 prominent in the no-dose titration group (p = 0.009) but absent 
      in the dose-titration groups (p > 0.05). CONCLUSIONS: BW is the most important 
      factor that 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 the occurrence of AEs ("Clinicaltrials.gov" 
      No. NCT02550665 registered on September 15, 2015).
CI  - (c) 2021 S. Karger AG, Basel.
FAU - Hong, Yun Jeong
AU  - Hong YJ
AD  - Neurology, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, 
      Seoul, Republic of Korea.
FAU - Han, Hyun Jeong
AU  - Han HJ
AD  - Neurology, Dementia and Neurocognitive Center, Myongji Hospital, Hanyang 
      University College of Medicine, Ilsan, Republic of Korea.
FAU - Youn, Young Chul
AU  - Youn YC
AD  - Neurology, Chung-Ang University Hospital, Seoul, Republic of Korea.
FAU - Park, Kyung Won
AU  - Park KW
AD  - Neurology, Dong-A University College of Medicine, Busan, Republic of Korea.
FAU - Yang, Dong Won
AU  - Yang DW
AD  - Neurology, The Catholic University of Korea, Seoul, Republic of Korea.
FAU - Kim, SangYun
AU  - Kim S
AD  - Neurology, Seoul National University College of Medicine & Neurocognitive 
      Behavior Center, Seoul National University Bundang Hospital, Seongnam, Republic 
      of Korea.
FAU - Kim, Hwa Jung
AU  - Kim HJ
AD  - Preventive Medicine, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, Republic of Korea.
FAU - Kim, Hyung-Ji
AU  - Kim HJ
AD  - Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Lee, Yoojin
AU  - Lee Y
AD  - Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Kwon, Miseon
AU  - Kwon M
AD  - Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Lee, Jae-Hong
AU  - Lee JH
AD  - Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
CN  - ODESA study (Optimal Dose Escalation Strategy to Successful Achievement of High 
      Dose Donepezil 23 mg)
LA  - eng
SI  - ClinicalTrials.gov/NCT02550665
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210910
PL  - Switzerland
TA  - Dement Geriatr Cogn Disord
JT  - Dementia and geriatric cognitive disorders
JID - 9705200
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Indans)
RN  - 0 (Piperidines)
RN  - 8SSC91326P (Donepezil)
SB  - IM
MH  - *Alzheimer Disease/drug therapy
MH  - Body Weight
MH  - Cholinesterase Inhibitors/adverse effects
MH  - Donepezil/adverse effects
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Humans
MH  - Indans/adverse effects
MH  - Piperidines/adverse effects
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Adverse events
OT  - Alzheimer's disease
OT  - Body weight
OT  - Donepezil
OT  - Dose-titration
OT  - Safety
EDAT- 2021/09/15 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/09/14 05:57
PHST- 2021/04/17 00:00 [received]
PHST- 2021/07/11 00:00 [accepted]
PHST- 2021/09/15 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/09/14 05:57 [entrez]
AID - 000518470 [pii]
AID - 10.1159/000518470 [doi]
PST - ppublish
SO  - Dement Geriatr Cogn Disord. 2021;50(3):289-295. doi: 10.1159/000518470. Epub 2021 
      Sep 10.