Successful Use of Donepezil for the Treatment of Psychotic Symptoms in Patients With Parkinson's Disease

Bergman, Joseph; Lerner, Vladimir

doi:10.1097/00002826-200203000-00009

Cited by 143 publications

(73 citation statements)

References 33 publications

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“…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]. Donepezil has also been shown to reduce Lewy pathology cholinergic impairment including hallucinations and delusions and psychotic symptoms in PD patients, without apparent side effects or exacerbation of Parkinsonian symptoms [78][79]. Although an early study suggested that treatment of NCDLB with Donepezil was sometimes associated with an increase in Parkinsonian features, a Cochrane database systematic review of previous research using cholinergic agonists to treat PD & NCDLB found that Donepezil produced consistent reduction in neurocognitive symptoms without exacerbation of Parkinsonian features or other side effects [87,88].…”

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%

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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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Section: Symptom Treatment Of Cholinergic Lewy Pathologymentioning

confidence: 99%

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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“…Cholinesterase inhibitors, including donepezil [53][54][55] and rivastigmine, 56 have been shown to improve symptoms of PDP in case reports and small openlabel studies; however, larger controlled studies are necessary to determine if these agents may be beneficial for PDP. A case report has suggested a potential benefit of mirtazapine for PDP; 57 however, antidepressants have been shown to induce or exacerbate psychotic symptoms, [58][59] so further research is necessary to determine if this is a reasonable treatment option for PDP.…”

Section: Other Pharmacologic Approachesmentioning

confidence: 99%

A New Perspective in the Treatment of Parkinson’s Disease Psychosis

Pahwa¹,

Lyons²

2016

US Neurology

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N europsychiatric symptoms, such as psychosis, are well described in Parkinson's disease (PD); most appear to be due to disease pathology with exacerbation caused by dopaminergic treatment. More than 50% of patients with PD develop psychosis at some point throughout their disease course. Clinicians need to routinely assess patients with PD for psychotic symptoms, particularly hallucinations. Treatment of psychotic symptoms in PD is an unmet need as there are currently no US Food and Drug Administration (FDA) approved medications specifically for PD psychosis (PDP). Current treatments for PDP have been adapted from dopamine antagonists used to treat psychosis in other conditions, such as schizophrenia. Typical antipsychotics, as well as some atypical antipsychotics, worsen PD motor symptoms due to blockade of dopamine D2 receptors. Quetiapine and clozapine have been studied in PDP and are the most commonly used treatments for PDP. Clozapine has been shown to be effective; however, regular bloodwork is required, while data for quetiapine are inconsistent. Pimavanserin, a highly selective serotonin (5HT2A subtype) receptor inverse agonist, is not associated with motor worsening in PDP patients due to the absence of dopamine blockade. In a double-blind, placebo-controlled study, pimavanserin showed significant improvement in moderate to severe psychosis compared to placebo, with good tolerability and without worsening of PD motor symptoms. These data suggest that pimavanserin is a safe and efficacious treatment for PDP psychosis and could be a potential new treatment option for PDP.

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“…Since the clinical manifestations of DLB and PDP seem very close, if not identical, other than the obvious difference that many of the PDP patients are not demented, it would seem reasonable that they may also be helpful in PDP. The effects of CEI in PDP have been the subject of only a few open label trials [105][106][107][108][109], showing good tolerance and some benefit. One problem with such an approach is the long lag time between drug initiation and clinical response.…”

Section: Managementmentioning

confidence: 99%

Parkinson Disease Psychosis: Update

Friedman

2013

Behavioural Neurology

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Abstract. Psychotic symptoms are common in drug treated patients with Parkinson's disease (PD). Visual hallucinations occur in about 30% and delusions, typically paranoid in nature, occur in about 5%. These problems, particularly the delusions, cause great distress for patient and caregivers, and are among the most important precipitants for nursing home placement. Psychotic symptoms carry a poor prognosis. They often herald dementia, and are associated with increased mortality. These symptoms often abate with medication reductions, but this may not be tolerated due to worsened motor function. Only clozapine has level A evidence to support its use in PD patients with psychosis (PDP), whether demented or not. While quetiapine has been recommended by the American Academy of Neurology for "consideration," double blind placebo controlled trials have demonstrated safety but not efficacy. Other antipsychotic drugs have been reported to worsen motor function and data on the effectiveness of cholinesterase inhibitors is limited. PDP remains a serious problem with limited treatment options.

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Successful Use of Donepezil for the Treatment of Psychotic Symptoms in Patients With Parkinson's Disease

Cited by 143 publications

References 33 publications

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

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

A New Perspective in the Treatment of Parkinson’s Disease Psychosis

Parkinson Disease Psychosis: Update

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