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Pimavanserin versus quetiapine for the treatment of psychosis in Parkinson's disease and dementia with Lewy bodies.

ABSTRACT: INTRODUCTION:Psychosis is common among patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Limited data exist on the most effective therapies. METHODS:Retrospective cohort study comparing patients with PD or DLB initiated on quetiapine or pimavanserin for psychosis. Primary outcome was time to discontinuation of pimavanserin or quetiapine using Kaplan-Meier survival analysis. We hypothesized the rate of antipsychotic discontinuation would be lower in the pimavanserin group. Subjects were included if the indication for treatment was psychosis and excluded if there was a history of major mental illness or no follow up data were available. RESULTS:Forty-seven patients were included in the quetiapine cohort and 45 in the pimavanserin cohort. Patients in the pimavanserin cohort were more likely to have a diagnosis of DLB (33% vs. 11%, P?=?0.01) and to have been prescribed an antipsychotic previously (62% vs. 6%, P??1 after day 43; P?=?0.04). There was no difference in mortality in the pimavanserin group compared to the quetiapine group (HR 0.37, 95% CI 0.06 to 2.45; P?=?0.88). More individuals had a documented secondary indication for taking quetiapine than pimavanserin (38% vs. 4%; P?=?0.001). CONCLUSION:Accounting for efficacy, safety and tolerability, pimavanserin may be more clinically useful for promptly managing psychosis, while quetiapine may confer additional secondary benefits long-term.

SUBMITTER: Horn S

PROVIDER: S-EPMC7061324 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Pimavanserin versus quetiapine for the treatment of psychosis in Parkinson's disease and dementia with Lewy bodies.

Horn Sarah S Richardson Hayley H Xie Sharon X SX Weintraub Daniel D Dahodwala Nabila N

Parkinsonism & related disorders 20191111

<h4>Introduction</h4>Psychosis is common among patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Limited data exist on the most effective therapies.<h4>Methods</h4>Retrospective cohort study comparing patients with PD or DLB initiated on quetiapine or pimavanserin for psychosis. Primary outcome was time to discontinuation of pimavanserin or quetiapine using Kaplan-Meier survival analysis. We hypothesized the rate of antipsychotic discontinuation would be lower in the pi ...[more]

PMID: 31751863

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Project description:As the differential diagnosis of dementias based on established clinical criteria is often difficult, biomarkers for applicable diagnostic testing are currently under intensive investigation. Amyloid plaques deposited in the brain of patients suffering from Alzheimer's disease, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) mainly consist of carboxy-terminally elongated forms of amyloid-beta (Abeta) peptides, such as Abeta1-42. Absolute Abeta1-42 levels in CSF have shown diagnostic value for the diagnosis of Alzheimer's disease, but the discrimination among Alzheimer's disease, DLB and PDD was poor. A recently established quantitative urea-based Abeta-sodium-dodecylsulphate-polyacrylamide-gel-electrophoresis with Western immunoblot (Abeta-SDS-PAGE/immunoblot) revealed a highly conserved Abeta peptide pattern of the carboxy-terminally truncated Abeta peptides 1-37, 1-38, 1-39 in addition to 1-40 and 1-42 in human CSF. We used the Abeta-SDS-PAGE/immunoblot to investigate the CSF of 23 patients with Alzheimer's disease, 21 with DLB, 21 with PDD and 23 non-demented disease controls (NDC) for disease-specific alterations of the Abeta peptide patterns in its absolute and relative quantities. The diagnostic groups were matched for age and severity of dementia. The present study is the first attempt to evaluate the meaning of Abeta peptide patterns in CSF for differential diagnosis of the three neurodegenerative diseases--Alzheimer's disease, DLB and PDD. The Abeta peptide patterns displayed disease-specific variations and the ratio of the differentially altered Abeta1-42 to the Abeta1-37 levels subsequently discriminated all diagnostic groups from each other at a highly significant level, except DLB from PDD. Additionally, a novel peptide with Abeta-like immunoreactivity was observed constantly in the CSF of all 88 investigated patients. The pronounced percentage increase of this peptide in DLB allowed a highly significant discrimination from PDD. Using a cut-off point of 0.954%, this marker yielded a diagnostic sensitivity and specificity of 81 and 71%, respectively. From several lines of indication, we consider this peptide to represent an oxidized alpha-helical form of Abeta1-40 (Abeta1-40*). The increased abundance of Abeta1-40* probably reflects a disease-specific alteration of the Abeta1-40 metabolism in DLB. We conclude that Abeta peptide patterns reflect disease-specific pathophysiological pathways of different dementia syndromes as distinct neurochemical phenotypes. Although Abeta peptide patterns failed to fulfil the requirements for a sole biomarker, their combined evaluation with other biomarkers is promising in neurochemical dementia diagnosis. It is noteworthy that DLB and PDD exhibit distinct clinical temporal courses, despite their similar neuropathological appearance. Their distinct molecular phenotypes support the view of different pathophysiological pathways for each of these neurodegenerative diseases.

Project description:Swallowing dysfunction is an increasingly recognized problem in patients with dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), which can result in aspiration pneumonia and death. Few studies have examined potential ways of improving swallowing function in this fragile patient group. The aim of this study was to evaluate swallowing dysfunction and carbonated liquid using videofluoroscopy in DLB and PDD patients.A total of 48 patients with DLB and PDD were referred for a clinical examination with videofluoroscopy. Descriptive overall assessments were provided at the time of the examination regarding swallowing function and the effects of different modifications, including carbonated thin liquid (CTL). Additionally, a repeated measures quantitative retrospective analysis has been performed comparing 1) thin liquids; 2) thickened liquids and 3) CTLs, with regard to the quantitative variables 1) pharyngeal transit time (PTT); 2) pharyngeal retention and 3) tracheal penetration.In all, 40/48 (83%) of the patients had a swallowing dysfunction, which was confirmed on videofluoroscopy, with 34/40 (85%) patients having a pharyngeal-type dysfunction. A total of 14/40 (35%) patients with an objective swallowing impairment did not have any subjective swallowing symptoms. Out of the patients with swallowing dysfunction, 87% had an overall improved swallowing function with carbonated liquid. PTT for carbonated liquid (median 633 ms, interquartile range [IQR] 516-786 ms) was quicker than for thin liquid (760 ms, IQR 613-940 ms, P=0.014) and thickened liquid (880.0 ms, IQR 600-1,500 ms, P<0.001). No significant effect was seen in residue or penetration.The majority of patients with DLB or PDD had a swallowing dysfunction, sometimes without subjective swallowing symptoms, which improved with carbonated liquid. This highlights the importance of investigating patients with videofluoroscopy and to carry out a prospective interventional study to further evaluate carbonated liquid, also addressing the effects on quality of life, aspiration and mortality.

Dataset Information

Pimavanserin versus quetiapine for the treatment of psychosis in Parkinson's disease and dementia with Lewy bodies.

Publications

Pimavanserin versus quetiapine for the treatment of psychosis in Parkinson's disease and dementia with Lewy bodies.

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