A comparison of the efficacy of donepezil in Parkinson's disease with Dementia and Dementia with Lewy bodies

Thomas, Alan; Burn, David J.; Rowan, Elise; Littlewood, Elizabeth; Newby, Jane; Cousins, David Andrew; Pakrasi, Sanjeet; Richardson, Jonathan L.; Sanders, Jonathan; McKeith, Ian G.

doi:10.1002/gps.1381

Cited by 92 publications

(67 citation statements)

References 36 publications

(33 reference statements)

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“…[51] Arguing against a role for the cholinergic system in depression is the lack of robust evidence for a significant impact of cholinesterase inhibitors on mood in PD (e.g. [52]), although, to date, there have been no randomized trials with depression as a primary outcome. A second possible mechanism underpinning an association between axial symptoms and depression is white matter change.…”

Section: Discussionmentioning

confidence: 99%

Parkinson's disease motor subtypes and mood

et al. 2011

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Section: Discussionmentioning

confidence: 99%

Parkinson's disease motor subtypes and mood

et al. 2011

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“…For these reasons, it is suggested that cholinesterase inhibitors (ChEIs) may be effective for treating DLB. In fact, usefulness of ChEIs such as galantamine, rivastigmine, and donepezil in the treatment of DLB symptoms has been reported in several open-label studies [5,6,7,8,9] and two randomized controlled trials [10,11]. Their usefulness has also been reported in several clinical trials of Parkinson's disease dementia, which is considered to fall into same category as DLB [12,13].…”

Section: Introductionmentioning

confidence: 88%

Long-Term Safety and Efficacy of Donepezil in Patients with Dementia with Lewy Bodies: Results from a 52-Week, Open-Label, Multicenter Extension Study

Ikeda

Mori

Kosaka

et al. 2013

Dement Geriatr Cogn Disord

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Background/Aims: To investigate the safety and efficacy of long-term administration (52 weeks) of donepezil in patients with dementia with Lewy bodies (DLB). Methods: This was a 52-week, multicenter, open-label extension study. Up to 8 weeks after the completion of the preceding randomized, placebo-controlled trial (RCT), patients started treatment with 3 mg of donepezil daily for 2 weeks, followed by 5 mg daily for the remaining 50 weeks. Cognitive function, behavioral and psychiatric symptoms, cognitive fluctuations, and caregiver burden were assessed using the Mini-Mental State Examination, Neuropsychiatric Inventory, Cognitive Fluctuation Inventory, and the Zarit Caregiver Burden Interview, respectively. Safety parameters were monitored throughout. Results: In total, 108 patients were enrolled in the study. Cognitive function and dementia-related behavioral symptoms, including cognitive fluctuations, were improved after the start of donepezil treatment, and improvement was maintained for 52 weeks. Reduction in caregiver burden observed in the preceding RCT returned to the baseline level at 52 weeks. There was no significant imbalance in the incidence of adverse events (AEs) by onset time, and delayed AE onset induced by the long-term administration of donepezil was unlikely to appear. Conclusion: The long-term administration of donepezil at 5 mg/day was well tolerated in patients with DLB and is expected to exhibit lasting effects, improving impaired cognitive function and psychiatric symptoms up to 52 weeks.

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“…The cholinergic loss and a choline acetyltransferase activity deficit with preserved postsynaptic cortical muscarinic and nicotinic receptors [3,4,5] rationalizes the use of cholinesterase inhibitors (ChEIs) in DLB. The favorable potential of ChEls such as galantamine, rivastigmine, and donepezil has been demonstrated in previous studies [6,7,8,9,10,11]. The phase 2 and 3 trials of donepezil in patients with DLB have added to the accumulating evidence of the efficacy and safety of donepezil in terms of cognitive, behavioral, and global function in DLB, even for long durations, without increasing the risk of clinically significant safety events [12,13,14,15].…”

Section: Introductionmentioning

confidence: 99%

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

Mori

Ikeda

Nakagawa

et al. 2015

Dement Geriatr Cogn Disord

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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.

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A comparison of the efficacy of donepezil in Parkinson's disease with Dementia and Dementia with Lewy bodies

Cited by 92 publications

References 36 publications

Parkinson's disease motor subtypes and mood

Parkinson's disease motor subtypes and mood

Long-Term Safety and Efficacy of Donepezil in Patients with Dementia with Lewy Bodies: Results from a 52-Week, Open-Label, Multicenter Extension Study

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

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