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IntroductionParkinson's disease (PD) is associated with increased mortality risk (MR), reflecting progression of motor and nonmotor symptoms. PD psychosis (PDP), a common nonmotor symptom, increases with prolonged disease and elevates the MR of PD even further. Pimavanserin is the only FDA-approved treatment for PDP. This review summarizes real-world evidence around the MR of patients with PDP treated with pimavanserin versus off-label atypical antipsychotics.MethodsA PubMed search was conducted using the following search terms: pimavanserin AND antipsychotic AND mortality AND Parkinson's disease AND psychosis. Inclusion criteria specified the entry of retrospective, observational, and open-label studies comparing pimavanserin to atypical antipsychotics or untreated controls.ResultsA total of 10 of the 32 articles met inclusion criteria. Among five comparisons of pimavanserin with atypical antipsychotics, two were large (n = 21,719; n = 21,975), representative, Medicare-database studies, which demonstrated comparable or lower all-cause pimavanserin MR. Among three pimavanserin versus control studies, two reported lower or comparable pimavanserin MR and one, long-term care study reported higher MR for pimavanserin versus non-pimavanserin treated patients with unknown PDP status. Two open-label extensions reported pimavanserin mortality rates of 6.45 and 18.8 deaths per 100 patient-years, which are comparable to, or lower than, mortality rates for PD, PDP, and other atypical antipsychotics. Most studies (70 %; 7 of 10) demonstrated pimavanserin's MR was lower than or similar to other atypical antipsychotics or untreated controls.ConclusionsPimavanserin did not increase the MR in PDP. Pimavanserin's MR appears to be comparable to or lower than other atypical antipsychotics prescribed for PDP, including quetiapine.

Multiple system atrophy (MSA) is a rare neurodegenerative disorder with substantial knowledge gaps despite recent gains in basic and clinical research. In order to make further advances, concerted international collaboration is vital. In 2014, an international meeting involving leaders in the field and MSA advocacy groups was convened in Las Vegas, Nevada, to identify critical research areas where consensus and progress was needed to improve understanding, diagnosis, and treatment of the disease. Eight topic areas were defined: pathogenesis, preclinical modeling, target identification, endophenotyping, clinical measures, imaging biomarkers, nonimaging biomarkers, treatments/trial designs, and patient advocacy. For each topic area, an expert served as a working group chair and each working group developed priority-ranked research recommendations with associated timelines and pathways to reach the intended goals. In this report, each groups' recommendations are provided.

Background: More than half of patients with Parkinson's disease will experience psychosis symptoms in the form of hallucinations or delusions at some point over the course of their disease. These symptoms can significantly impact patients' health-related quality of life, cognitive abilities, and activities of daily living (ADLs) and function. Clinical assessment of how psychosis impacts these measures is crucial; however, few studies have assessed this sufficiently, in part due to a lack of appropriate scales for comprehensively assessing function. Objective: The objective was to assess how symptoms of Parkinson's disease psychosis (PDP) impact ADLs and function, cognitive function, and health-related quality of life. Design: To address this unmet need, we utilized a modified version of the Functional Status Questionnaire (mFSQ) to measure the impact of psychosis on ADLs and function in patients with PDP treated with pimavanserin, a US Food and Drug Administration-approved medication to treat hallucinations and delusions associated with PDP. Methods: Eligible patients entered a 16-week, single-arm, open-label study of oral pimavanserin (34 mg) taken once daily. The primary endpoint was change from baseline to Week 16 on the mFSQ. Secondary endpoints included the Movement Disorders Society–modified Unified Parkinson's Disease Rating Scale (MDS-UPDRS) I and II; Schwab and England ADL; Clinical Global Impression–Severity of Illness (CGI-S), Clinical Global Impression–Improvement (CGI-I), and Patient Global Impression–Improvement (PGI-I), and were also measured as change from baseline to Week 16 using mixed-effects model for repeated measures (MMRM) and least-squares mean (LSM). Results: Our results in a proof-of-concept, 16-week, open-label clinical study in 29 patients demonstrated that an improvement in psychosis symptoms following treatment with pimavanserin was associated with improvements in multiple measures of ADLs and function. Notably, a significant improvement was found on the primary endpoint, change from baseline to Week 16 in mFSQ score [LSM [SE] 14.0 [2.50], n = 17; 95% CI (8.8, 19.3); p < 0.0001]. Conclusion: These findings highlight the potential for improvement in function with improvement of psychosis symptoms in patients with PDP and suggest that the mFSQ may be a measurement tool to evaluate the level of improvement in function. Trial registration: ClinicalTrials.gov Identifier: NCT04292223. [ABSTRACT FROM AUTHOR]

Introduction: Patient-reported outcomes (PROs) are increasingly collected in clinical trials and real-world studies as they provide valuable information on the impact of a treatment from the patient's perspective. Studies in Parkinson's disease psychosis (PDP) have focused on hallucination and delusions, however individuals with PDP also face functional limitations associated with worsening psychosis. Assessing activities of daily living (ADLs) and functioning of PDP patients can help inform PDP treatment. The International Parkinson and Movement Disorder Society has recommended the use of the Functional Status Questionnaire (FSQ) which has been infrequently utilized. Prior results were reported from a Phase 4 open-label study examining the impact of pimavanserin on ADLs and functioning in patients with PDP which utilized a modified version of the FSQ (mFSQ) as the primary outcome measure. In this analysis, we provide additional data on the patient-reported mFSQ within specific domains and correlation to the Schwab & England ADL scale. Methods: Eligible patients entered a 16-week single-arm, open-label study of once-daily oral pimvanserin (34mg). The 6 domain FSQ was modified to assess 5 domains by removing the work/performance domain since this was not applicable to the patients in this study. The mean change from baseline to week 16 was evaluated in mFSQ domains (Basic ADL, Intermediate ADL, Psychological Function, Quality of Interaction, Social Activity). In addition, correlation between Schwab & England ADL scale and observed mFSQ value across post-Baseline visits were evaluated. Results: A total of 29 patients were enrolled in the study, mean age (70.2 years), 62% males. The MMRM LSM (SE) for mSFQ from baseline to Week 16 were the following within each domain: Basic ADL (n=22), 8.1 (2.41), p=0.0031; Intermediate ADL (n=21), 7.0 (3.00), p=0.0286; Psychological Function (n=22), 13.3 (1.94), p <.0001; Quality of Interaction (n=22), 12.3(2.07), p <.0001; and Social Activity (n=18), 25.8 (7.52), p=0.0026. All mFSQ domains were showing improvement at 16 weeks from baseline; however, the largest change was seen in Social Activity. The correlation of mFSQ and the Schwab & England ADL scales resulted in a correlation coefficient of r=0.6 (p <.0001) for patient total score and r=0.5 (p<.0001) for caregiver total score. There was a consistent trend among both scales which was demonstrating improvement among patients and caregivers. Conclusions: This was the first open-label clinical trial to utilize the mFSQ in patients with PDP. In this small, proof-of-concept study, treatment with pimavanserin was associated with improvement across all mFSQ domains; most improvement was seen in social activity. Additionally, the mFSQ was significantly correlated with the Schwab & England ADL, thus this appears to be a promising scale deserving of further evaluation and use in clinical studies as well as in the clinic to complement other assessments. Funding: Acadia Pharmaceuticals, Inc. [ABSTRACT FROM AUTHOR]

Limited research is available on the real-world experiences of patients with dementia with Lewy bodies (DLB). This study evaluated clinical events, healthcare utilization, and healthcare costs of patients with DLB vs other dementia types with psychosis (ODP). Study patients included commercial and Medicare Advantage with Part D enrollees aged ≥40 years with evidence of DLB and ODP from 6/01/2015‒5/31/2019. Compared with patients with ODP, more patients with DLB had clinical events including anticholinergic effects, neurologic effects, and cognitive decline. Patients with DLB used more healthcare resources with greater dementia-related office and outpatient visits and psychosis-related inpatient stays and office, outpatient, and emergency visits compared with their ODP patient counterparts. Patients with DLB also incurred higher healthcare costs for all-cause and dementia-related office visits and pharmacy fills, and psychosis-related total costs. Understanding the clinical and economic impact of DLB and ODP is important to improve care for patients with dementia. [ABSTRACT FROM AUTHOR]