What happens when donepezil is suddenly withdrawn? An open label trial in dementia with Lewy bodies and Parkinson's disease with dementia

Minett, Thaís; Thomas, Alan; Wilkinson, Lucy; Daniel, Sarah; Sanders, Jonathan; Richardson, Jonathan L.; Littlewood, Elizabeth; Myint, Pat; Newby, Jane; McKeith, Ian G.

doi:10.1002/gps.995

Cited by 120 publications

(89 citation statements)

References 21 publications

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“…A pharmacological approach to the psychiatric symptoms in DLB is sometimes difficult due to neu- Nasogastric tubing roleptic supersensitivity. Although the acetylcholinesterase inhibitor donepezil (3)(4)(5), quetiapine (14) and Yi-Gan San (15) were reported to be beneficial on psychiatric symptoms in DLB, all of them were not effective in this case. We first administered amitriptyline to this patient.…”

Section: Discussionmentioning

confidence: 77%

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Amitriptyline and Lorazepam Improved Catatonia and Occipital Hypoperfusion in a Patient with DLB

Maeda

Ogawa

2011

Intern. Med.

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A 76-year-old woman presented with catatonia, refusal to eat due to delusion, and visual hallucination. Single photon emission computed tomography showed remarkable occipital hypoperfusion and frontal hyperperfusion.123 I metaiodobenzyl guanidine myocardial scintigraphy revealed decreased uptake. She was diagnosed as probable dementia with Lewy bodies (DLB). Intravenous or oral L-dopa had no effect on catatonia. Amitriptyline and lorazepam improved catatonia and visual hallucination. Cerebral blood flow of the frontal and occipital lobes seemed to be normalized. Occipital hypoperfusion is one of the features of DLB. Although the mechanism of perfusion abnormality in DLB remains to be clarified, our case suggested that it might be reversible.

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Section: Discussionmentioning

confidence: 77%

“…Neurolepic supersensitivity sometimes makes it difficult to treat these symptoms (2). Some studies have shown the usefulness of the acetylcholinesterase inhibitor donepezil on psychiatric symptoms in DLB (3)(4)(5). We herein present a woman with probable DLB who showed catatonia and refusal to eat.…”

Section: Introductionmentioning

confidence: 93%

Amitriptyline and Lorazepam Improved Catatonia and Occipital Hypoperfusion in a Patient with DLB

Maeda

Ogawa

2011

Intern. Med.

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“…Data were also reviewed demonstrating that (e) among AChEIs, Donepezil has performed well [18][19][20][21][22]; (f) a Cochrane database systematic review found that Donepezil produced consistent reduction in neurocognitive symptoms in patients with PD and NCDLB, without exacerbation of Parkinsonian features or other side effects [23]; (g) Donepezil has reduced constipation in nongeriatric affective patients [24]; and (h) Donepezil increased cholinergically mediated bowel contractions as much as 477% in patients suffering from severe intestinal dysmotility [25].…”

Section: Discussionmentioning

confidence: 99%

Donepezil for Lewy Body Constipation: A Six-Month Follow-up

Lepkowsky¹

2017

J Mol Genet Med

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In a previous case study, four patients at different stages of Parkinson's disease (PD) and Neurocognitive Disorder with Lewy Bodies (NCDLB) disease progression were treated with Donepezil, with the intention of mitigating Lewy body impairment of the cholinergic pathways in the myenteric plexus, increasing bowel motility, and reducing the symptom of constipation. In all four cases, the use of Donepezil was associated with significant reduction of the symptom of constipation. There was no exacerbation or instigation of other symptoms. The symptom status of the four patients was reviewed six months later. In none of the patients has there been exacerbation of the symptom of constipation, nor emergence of new symptoms. The findings suggest that Donepezil might have long-term efficacy for reducing constipation in patients with PD and NCDLB. Further research is recommended using larger numbers of subjects matched for diagnosis, age, gender, and other variables.

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“…Donepezil has been shown to produce significant improvements in cognition and behavior which disappeared when Donepezil was withdrawn, but treatment gains were restored on recommencement of Donepezil [75]. Donepezil has been shown to improve cognition for up to 52 weeks in longterm treatment of NCDLB patients, without increasing the risk of Parkinsonian features or other clinically significant safety events [76,77].…”

Section: Symptom Treatment Of Cholinergic Lewy Pathologymentioning

confidence: 99%

“…Based on researchdemonstrating Donepezil's efficacy in treating cholinergic impairment in patients with PD and NCDLB, and its effectiveness in reducing constipation and increasing bowel motility in non geriatric patients [73][74][75][76][77][78][79][88][89][90]93,94]. Donepezil has been used specifically to treatconstipation in PD and NCDLB patients, with consequent significant reduction of the symptom of constipation, without exacerbation or instigation of other symptoms [39].…”

Section: Symptom Treatment Of Cholinergic Lewy Pathology In the Ensmentioning

confidence: 99%

Mechanisms of α‐Synuclein Pathology and Treatment in the Enteric Nervous System

Lepkowsky¹

2017

IJGS

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Abstractα-synuclein (Lewy Body) pathology is commonly found in the enteric nervous system (ENS) of patients diagnosed with Neurocognitive Disorder with Lewy Bodies (NCDLB) and Parkinson's Disease (PD). Lewy pathology in the ENS can produce symptoms of bowel immotility, including constipation, obstipation, and bowel impaction. These symptoms significantly reduce the quality of life for the patient, producing hardship for the patient and care providers. In Lewy body patients, medical intervention using acetylcholinesterase inhibitors (AChEIs) can significantly reduce or alleviate bowel immotility. The specific mechanism through which the cholinergic agonist Donepezil mitigates Lewy Body bowel immotility is explained. Practice, 1143 Deer Trail Lane, Solvang, California 93463, USA, Tel: 805-688-1229 Fax: 805-686-9382; E-mail: clepkowsky@gmail.com of α-synuclein aggregates in the MP predates cognitive and motor functional manifestations of Lewy body diseases so consistently that it has been nominated as a potential biomarker for Lewy pathology [10,17,30]. Symptomatic Manifestations of Cholinergic Lewy Pathology in the ENSLewy body cholinergic impairment in the ENS manifests symptomatically as gastric immotility and constipation [13,[31][32][33][34][35][36][37][38][39][40][41]. Increased colonic transit time and impaired gastric emptying are frequently found in PD patients [35,42]. The prevalence of constipation in PD is at least three times that of the general population, leading some researchersto suggest that constipation might be a universal feature of PD [47,48]. Bowel immotility can occur 20 years before diagnosis of PD or NCDLB, suggesting that it might be a prodromal symptom for both disorders [5,19,36,44,[49][50][51][52].As α-synuclein pathology advances in the ENS, symptoms of gastric immotility advance from constipation to obstipation and impaction. Escalating gastric immotility in PD and NCDLB can interfere with mobility, sleep, cognition, and mood, increasing the cost of care, and potentially debilitating and/or dramatically reducing the quality of life for patients. [4,34,36,[53][54][55][56] Potential Exacerbation of ENS Symptoms by AntiParkinson MedicationLPD and NCDLB patients with significant Parkinsonian motoric/gait features are often prescribed L-dopa agents like Carbidopa-Levodopa (known also by the brand names Sinemet and Stalevo) in order to preserve gait, balance, and other basic motor functions [40,57,58]. Carbidopa-Levodopa's potential side effects include constipation [59]. which can complicate or exacerbate gastric immotility due to ENS Lewy pathology. Medications frequently used for the treatment of resting tremor in PD and NCDLB includeTrihexyphenidyl (marketed as Artane or Trihex) and Benztropinemesylate (marketed as Cogentin), identified as definite anticholinergics that can also exacerbate gastric immotility through suppression of the cholinergic neurotransmitter pathways innervating the ENS [58,[60][61][62].

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What happens when donepezil is suddenly withdrawn? An open label trial in dementia with Lewy bodies and Parkinson's disease with dementia

Cited by 120 publications

References 21 publications

Amitriptyline and Lorazepam Improved Catatonia and Occipital Hypoperfusion in a Patient with DLB

Amitriptyline and Lorazepam Improved Catatonia and Occipital Hypoperfusion in a Patient with DLB

Donepezil for Lewy Body Constipation: A Six-Month Follow-up

Mechanisms of α‐Synuclein Pathology and Treatment in the Enteric Nervous System

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