title: 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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Etsuro
authors.initials: E
authors.lastname: Mori
authors.forename: Manabu
authors.initials: M
authors.lastname: Ikeda
authors.forename: Masaki
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyagishi
authors.forename: Hideo
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Kosaka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D066264:Datasets as Topic; D018450:Disease Progression; D000077265:Donepezil; D005260:Female; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D020961:Lewy Body Disease / Q000188:drug therapy*; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil