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

Etsuro Mori, Manabu Ikeda, Masaki Nakagawa, Hideaki Miyagishi, Hideo Yamaguchi, Kenji Kosaka

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)186-198
Number of pages13
JournalDementia and geriatric cognitive disorders
Volume40
Issue number3-4
DOIs
Publication statusPublished - 2015 Sep 2

Keywords

  • Cholinesterase inhibitors
  • Dementia
  • Lewy body disease
  • Parkinson's disease
  • Pharmacology

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Cognitive Neuroscience
  • Psychiatry and Mental health

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