PMID- 26226884
OWN - NLM
STAT- MEDLINE
DCOM- 20160114
LR  - 20181202
IS  - 1421-9824 (Electronic)
IS  - 1420-8008 (Linking)
VI  - 40
IP  - 3-4
DP  - 2015
TI  - Effects of Donepezil on Extrapyramidal Symptoms in Patients with Dementia with 
      Lewy Bodies: A Secondary Pooled Analysis of Two Randomized-Controlled and Two 
      Open-Label Long-Term Extension Studies.
PG  - 186-98
LID - 10.1159/000433524 [doi]
AB  - BACKGROUND/AIMS: The aim of this study was to clarify the effects of donepezil on 
      extrapyramidal symptoms in patients with dementia with Lewy bodies (DLB). 
      METHODS: Using pooled datasets from phase 2 and 3, 12-week randomized, 
      placebo-controlled trials (RCT, n = 281) and 52-week open-label long-term 
      extension trials (OLE, n = 241) of donepezil in DLB, the effects of donepezil on 
      the incidence of extrapyramidal adverse events (AEs) and on the Unified 
      Parkinson's Disease Rating Scale (UPDRS) part III were assessed, and potential 
      baseline factors affecting the AEs were explored. RESULTS: The RCT analysis did 
      not show significant differences between the placebo and active (3, 5, and 10 mg 
      donepezil) groups in extrapyramidal AE incidence (3.8 and 6.5%, p = 0.569) and 
      change in the UPDRS (mean +/- SD: -0.2 +/- 4.3 and -0.6 +/- 6.5, p = 0.562). In the OLE 
      analysis (5 and 10 mg donepezil), the incidence did not increase chronologically; 
      all AEs leading to a dose reduction or discontinuation except one were relieved. 
      The UPDRS was unchanged for 52 weeks. An exploratory multivariate logistic 
      regression analysis of the RCTs revealed that donepezil treatment was not a 
      significant factor affecting the AEs. Baseline severity of parkinsonism was a 
      predisposing factor for worsening of parkinsonism without significant 
      interactions between donepezil and baseline severity. CONCLUSION: DLB can safely 
      be treated with donepezil without relevant worsening of extrapyramidal symptoms, 
      but treatment requires careful attention to symptom progression when administered 
      to patients with relatively severe parkinsonism.
CI  - (c) 2015 The Author(s) Published by S. Karger AG, Basel.
FAU - Mori, Etsuro
AU  - Mori E
AD  - Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University 
      Graduate School of Medicine, Sendai, Japan.
FAU - Ikeda, Manabu
AU  - Ikeda M
FAU - Nakagawa, Masaki
AU  - Nakagawa M
FAU - Miyagishi, Hideaki
AU  - Miyagishi H
FAU - Yamaguchi, Hideo
AU  - Yamaguchi H
FAU - Kosaka, Kenji
AU  - Kosaka K
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150723
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  - Aged
MH  - Aged, 80 and over
MH  - Cholinesterase Inhibitors/adverse effects/*therapeutic use
MH  - Datasets as Topic
MH  - Disease Progression
MH  - Donepezil
MH  - Female
MH  - Humans
MH  - Indans/adverse effects/*therapeutic use
MH  - Lewy Body Disease/*drug therapy
MH  - Logistic Models
MH  - Longitudinal Studies
MH  - Male
MH  - Neuropsychological Tests
MH  - Piperidines/adverse effects/*therapeutic use
EDAT- 2015/08/01 06:00
MHDA- 2016/01/15 06:00
CRDT- 2015/08/01 06:00
PHST- 2015/05/22 00:00 [accepted]
PHST- 2015/08/01 06:00 [entrez]
PHST- 2015/08/01 06:00 [pubmed]
PHST- 2016/01/15 06:00 [medline]
AID - 000433524 [pii]
AID - 10.1159/000433524 [doi]
PST - ppublish
SO  - Dement Geriatr Cogn Disord. 2015;40(3-4):186-98. doi: 10.1159/000433524. Epub 
      2015 Jul 23.