Parkinson\'s disease (PD) is among the most common neurodegenerative diseases. Parkinson\'s disease psychosis (PDP) is a potential psychiatric manifestation of PD that is associated with increased morbidity and mortality. The treatment of PD with concomitant PDP is challenging as standard-of-care medication to improve motor symptoms can cause or exacerbate PDP. In this case report, we present an atypical presentation of a 70-year-old female who developed PDP only four years after her initial PD diagnosis, much earlier than the established average. Treatment was particularly complex as her PDP symptoms were refractory to PD medication reduction and oral antipsychotics, yet her PD motor symptoms were well controlled with a deep brain stimulator (DBS). We discuss a combination of pimavanserin and maintenance electroconvulsive therapy (ECT) as a safe and efficacious treatment modality which has led to remission of her PDP while DBS continues to provide adequate management of her PD symptoms. This case improves upon the early recognition of PDP and outlines a unique treatment modality not well described in the literature. This is the only case that demonstrates the efficacy of combining pimavanserin and ECT for refractory PDP in a patient with a DBS.

OBJECTIVE: Pimavanserin, a novel 5-HT2A receptor antagonist, has been approved for the treatment of Parkinson\'s disease psychosis (PDP). This study aims to conduct a comprehensive analysis of the adverse events (AEs) of pimavanserin by analyzing the FDA\'s Adverse Event Reporting System (FAERS) database.
METHODS: AE reports related to pimavanserin in the FAERS database from the second quarter of 2016 to the fourth quarter of 2023 were mined. Signal detection methods, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), were employed to identify and classify AEs.
RESULTS: The study collected 12,839,687 AE reports, with 30,997 reports primarily suspecting pimavanserin, identifying 166 Preferred Terms (PTs) across 27 System Organ Classes (SOCs). The data showed that males reported more frequently than females, with the highest reporting in patients aged 75 and above. Reports increased over time, with a significant rise in 2023 compared to 2016. Major categories of AEs included hallucination, death, product dose omission issue, and confusional state, with death being notably the second most reported issue. Strong and new potential AEs were identified, including sleep-related issues like somnolence, insomnia, and sleep talking; cognitive and behavioral issues such as alexithymia, belligerence, and aggression; dose-related issues like prescribed underdose and underdose; and other AEs like nonspecific reactions.
CONCLUSIONS: This study reveals potential AEs of pimavanserin, including sleep disorders and cognitive changes, underscoring the importance of careful monitoring and personalized treatment in managing PDP.

Aim: Real-world healthcare resource use (HCRU) burden among patients with Parkinson\'s disease psychosis (PDP) treated with pimavanserin (PIM) versus other atypical antipsychotics (other-AAPs) including quetiapine (QUE) in long term care (LTC) and nursing home (NH) settings are lacking. This analysis examines HCRU differences among residents in LTC/NH settings who initiate PIM versus QUE or other-AAPs. Methods: A retrospective analysis of LTC/NH residents with PDP from the 100% Medicare claims between 1 April 2015 and 31 December 2021 was conducted. Treatment-naive residents who initiated ≥6 months continuous monotherapy with PIM or QUE or other-AAPs between 04/01/16 and 06/30/2021 were propensity score matched (PSM) 1:1 using 31 variables (age, sex, race, region and 27 Elixhauser comorbidity characteristics). Post-index (i.e., 6 months) HCRU outcomes included: proportion of residents with ≥1 all-cause inpatient (IP) hospitalizations and emergency room (ER) visits. HCRU differences were assessed via log binomial regression and reported as relative risk ratios (RR) and 95% confidence intervals after controlling for dementia, insomnia and index year. Results: From a total of PIM (n = 1827), QUE (n = 7770) or other-AAPs (n = 9557), 1:1 matched sample (n = 1827) in each cohort were selected. All-cause IP hospitalizations (PIM [29.8%]) versus QUE [36.7%]) and ER visits (PIM [47.3%] versus QUE [55.8%]), respectively, were significantly lower for PIM. PIM versus QUE cohort also had significantly lower RR for all-cause IP hospitalizations and ER visits, respectively, (IP hospitalizations RR: 0.82 [0.75. 0.9]; ER visits RR: 0.85 [0.8. 0.9]). PIM versus other-AAPs also had lower likelihood of HCRU outcomes. Conclusion: In this analysis, LTC/NH residents on PIM monotherapy (versus QUE) had a lower likelihood of all-cause hospitalizations (18%) and ER (15%) visits. In this setting, PIM also had lower likelihood of all-cause HCRU versus other-AAPs.

 The recent Alva et al. Phase 3b study on pimavanserin use in older adults with neurodegenerative diseases (NDDs), specifically including Alzheimer\'s disease, vascular dementia, Parkinson\'s disease (with or without dementia), frontotemporal dementia, and dementia with Lewy bodies, provides important new data on its safety for managing neuropsychiatric symptoms in this population. This commentary on the study further examines the findings within the broader context of antipsychotic therapy as it has evolved from chlorpromazine to pimavanserin in a continuous search for greater safety. Comparing pimavanserin\'s safety and efficacy profile with historical data and regulatory milestones provides a nuanced perspective for clinicians regarding the significance of the drug\'s known advantages over prior antipsychotic treatments. More research is needed to determine the full potential of pimavanserin to improve neuropsychiatric symptoms in older adults with NDDs.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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].
UNASSIGNED: 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.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT04292223.

UNASSIGNED: Pimavanserin, a 5-HT2A receptor inverse agonist/antagonist, is the only medication approved by the FDA for the treatment of hallucinations and delusions associated with Parkinson\'s disease psychosis (PDP). Further expanding knowledge of the safety profile of pimavanserin in PDP and neurodegenerative diseases (NDD) such as Alzheimer\'s disease is of great interest for informing its use in patients with PDP (with or without dementia), given this population is highly sensitive to adverse effects following antipsychotic use.
UNASSIGNED: This trial evaluated the effects of pimavanserin compared to placebo in frail older adults and elderly patients with neuropsychiatric symptoms related to NDD, such as hallucinations and delusions, to better understand the safety of pimavanserin in this population.
UNASSIGNED: This was a phase 3b, 8-week treatment (study duration of up to 16 weeks), multicenter, randomized, double-blind, placebo-controlled, two-arm parallel-group trial (NCT03575052). The primary endpoint was safety and tolerability, measured by treatment-emergent adverse events (TEAEs). Secondary safety endpoints were change from baseline in motor and cognitive function; exploratory endpoints included suicidality, sleep quality, and neuropsychiatric symptoms.
UNASSIGNED: Incidences of TEAEs were similar between treatment groups; 29.8% reported ≥1 TEAE (pimavanserin: 30.4%; placebo: 29.3%), and 1.8% reported serious TEAEs (pimavanserin: 2.0%; placebo: 1.5%). Pimavanserin did not impact motor- or cognitive-related function.
UNASSIGNED: Pimavanserin was well tolerated and not associated with motor or cognitive impairment. Together, these findings highlight the manageable and generally favorable safety profile of pimavanserin in patients with NDD, contributing to our knowledge on the safety of pimavanserin as it generalizes to patients with PDP.

Parkinson\'s disease (PD) is a common, prevalent neurodegenerative disease. It is mainly characterized by motor symptoms such as rigidity, tremors, and bradykinesia, but it can also manifest with non-motor symptoms, of which depression is the most frequent. The latter can impair the quality of life, yet it gets overlooked and goes untreated because of the significant overlap in their clinical features, hence making the diagnosis difficult. Furthermore, there is limited data on the availability of appropriate criteria for making the diagnosis of depression in PD patients, as it can occur with varying expressions throughout the course of PD or it can also precede it. This review article has included a brief discussion on the diagnosis of depression in PD patients and their overlapped clinical manifestations. Understanding the mechanisms underlying the disease processes of PD and depression and the pathways interconnecting them gives better knowledge on devising treatment options for the patients. Only studies from Pubmed were included and all other databases were excluded. Studies from the last 50 years were included. Suitable references included in these studies were also extracted. Thus, depression in PD and PD in depression, along with their pharmacological and non-pharmacological treatment options, have been discussed.

UNASSIGNED: Psychotic symptoms in people with Parkinson\'s disease (PD) have attracted increasing. Recommendations on treating psychosis often fail to take into account what psychotic symptoms require treatment, which has been complicated by the increasing number of reports documenting the frequency of \'minor\' hallucinations.
UNASSIGNED: This article focuses both on the phenomenology of psychotic symptoms and their management.
UNASSIGNED: Understanding the nature and implications of the types of psychotic symptoms in PD is the key to proper treatment. Evidence and experience-based data on the effect of anti-psychotic medications will be reviewed and how the various clinical settings should determine the treatment approach. The evidence base consists of all reported blinded trials recorded in PubMed and the experience-based studies are those chosen by the author from PubMed as illustrative. Specific recommendations for the treatment of psychosis will be listed for specific situations. Pimavanserin is the first-line choice for mild symptoms; quetiapine for symptoms that require improvement in a short period and clozapine for urgent problems or those which fail the other approaches.
Psychotic symptoms are common in PD, affecting the majority of patients by the time of death. ‘Minor hallucinations’ rarely require treatment but formed hallucinations and delusions often do. The vast majority of patients requiring treatment are on medications for PD motor problems. Some patients can be treated with reduction of psychoactive medications that are unrelated to PD, and some may tolerate reductions in PD medications without intolerable worsening of motor function. The remainder require treatment with medications that reduce psychotic symptoms, which include cholinesterase inhibitors, clozapine, pimavanserin, and possibly quetiapine and electroconvulsive therapy. Only clozapine and pimavanserin have unequivocal evidence for efficacy and motor tolerance. Data will be reviewed in support of each of these medications will be reviewed and pragmatic suggestions based on a large experience on when each might be used, and in what order they may be tried if initial approaches fail.

暂无摘要。

BACKGROUND: Pimavanserin is FDA-approved to treat Parkinson\'s disease (PD) psychosis. We analyzed the effect of pimavanserin on psychosis in the PD dementia (PDD) subgroup from the phase 3 HARMONY trial.
METHODS: This subgroup analysis included PDD patients enrolled in an international, multicenter, randomized discontinuation study of pimavanserin for dementia-related psychosis. PDD patients with moderate-to-severe psychosis, age 50-90 years, received pimavanserin 34 mg/day for 12 weeks (open-label period). Those with a sustained psychosis response to pimavanserin at weeks 8 and 12 were randomized during the double-blind period to continue pimavanserin or receive placebo. Primary efficacy endpoint was time to psychosis relapse as measured by the SAPS-H + D and CGI-I. Safety was assessed, as were effects on motor symptoms and cognitive abilities using the ESRS-A and MMSE.
RESULTS: 392 patients were enrolled in HARMONY (mean age: 72.6 years; 38.8 % female): 59 had PDD; 49/59 remained on pimavanserin during the open-label period (safety analysis set), and 36/49 were randomized to pimavanserin (n = 16) or placebo (n = 20) in the double-blind phase (intent-to-treat analysis set). Risk of psychosis relapse was lower with pimavanserin 34 mg compared with placebo in the double-blind phase (HR = 0.052; 95 % CI 0.016-0.166; 1-sided nominal p < 0.001). During the open-label period, 46.9 % experienced a treatment-emergent adverse event; event incidence was similar across arms in the double-blind period. Pimavanserin did not adversely affect motor or cognitive function in either treatment phase.
CONCLUSIONS: Pimavanserin significantly reduced risk of psychosis relapse in patients with PDD, was well tolerated, and did not worsen motor or cognitive function.