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.

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.

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.

Aim: Risk of long-term care (LTC) admission (LTCA) associated with atypical antipsychotic (AAP) use among patients with Parkinson\'s disease psychosis (PDP) is a major concern. However, no comparative studies have examined the differences in risk of LTC admissions between pimavanserin (PIM), the only FDA-approved AAP for PDP, and other off-label AAPs including quetiapine (QUE). Objective: To examine all-cause LTCA rates and risk among PDP patients treated with AAPs such as QUE or PIM. Methods: Analysis of Parts A, B and D claims (100% Medicare sample; 2013-2019) of Medicare beneficiaries with PDP that initiate ≥12-month continuous PIM or QUE monotherapy from 1 January 2014 to 31 December 2018 (i.e., index date) without any AAP use in the 12-month pre-index period was conducted. Outcome assessments among 1:1 propensity score-matched (31 variables - age, sex, race, region and 27 Elixhauser comorbidities) beneficiaries on PIM versus QUE included risk of all-cause skilled nursing facility stays (SNF-stays), LTC-stays, and overall LTCA (i.e., SNF-stays or LTC-stays). All-cause LTCA rates and LTCA risk were compared using logistic regression and cox proportional hazards models, respectively, controlling for demographics, comorbidities and co-existing-dementia or insomnia. Results: Of the matched sample (n = 842 for each group) from total sample (n = 9652), overall all-cause LTCA and SNF-stay rates were 23.2 and 20.2% for PIM versus 33.8 and 31.4% for QUE, respectively (p < 0.05, for each). Hazard ratio (95% CI) for risk of SNF-stay and overall LTCA was 0.78 (0.61, 0.98) and 0.80 (0.66, 0.97), respectively, for PIM versus QUE beneficiaries (p < 0.05, for each). Conclusion: The 20% lower risk of LTCA (i.e., greater delay) with PIM versus QUE in this analysis may suggest that PIM should be started early for the treatment of PDP.

Pimavanserin is an antipsychotic that is approved for use in Parkinson\'s disease psychosis. Working as a serotonin 2A inverse agonist, pimavanserin allows patients to improve their psychotic symptoms without worsening the motor symptoms of Parkinson\'s. This mechanism is mediated via serotonin receptors and may allow for pimavanserin to be considered for use in other disease processes that present with psychosis. Here, the authors describe the case of a 75-year-old man with Lewy Body Dementia (LBD) who was started on pimavanserin. The response of the patient to the medication was measured over a six-week time course using the Scales for the Assessment of Positive Symptoms of Schizophrenia (SAPS). Overall, pimavanserin was shown to be effective in this patient with LBD. The authors also provide a review of the sparse literature attesting to other off-label uses for this unique antipsychotic.

UNASSIGNED: Pimavanserin, a serotonin 5HT-2A receptor inverse agonist is the first-line, FDA-approved treatment of hallucinations and delusions associated with Parkinson\'s Disease psychosis (PDP), which occurs in up to 50% of PD patients. The neurobiological mechanism underlying the therapeutic effectiveness of Pimavanserin in PDP remains unknown. Several earlier studies have shown that treatment with 5HT-2A antagonists and other drugs acting on the serotonergic system such as SSRIs increase Brain derived neurotrophic factor (BDNF) levels in rodents. BDNF is synthesized as the precursor proBDNF, that undergoes cleavage intra or extracellularly to produce a mature BDNF (mBDNF) protein. mBDNF is believed to play a key role in neuroplasticity and neurogenesis. The present study tested the hypothesis that treatment with Pimavanserin is associated with higher and sustained elevations of mBDNF.
UNASSIGNED: Adult Sprague-Dawley male rats were treated with Pimavanserin, Fluoxetine or vehicle for 4 weeks (chronic) or 2 h (acute). BDNF levels were determined by enzyme-linked Immunosorbent assay (ELISA).
UNASSIGNED: We found significant increases in plasma mBDNF levels in rats following chronic Pimavanserin treatment, but not in Fluoxetine-treated rats. No significant changes in mBDNF levels were found in the prefrontal cortex or hippocampus following Pimavanserin or Fluoxetine treatment.
UNASSIGNED: These findings suggest that increase in mBDNF levels could be a contributing mechanism for the neuroprotective potential of Pimavanserin.

Schizophrenia is a chronic neuropsychiatric syndrome that significantly impacts daily function and quality of life. All of the available guidelines suggest a combined treatment approach with pharmacologic agents and psychological interventions. However, one in three patients is a non-responder, the effect on negative and cognitive symptoms is limited, and many drug-related adverse effects complicate clinical management. As a result, discovering novel drugs for schizophrenia presents a significant challenge for psychopharmacology. This selective review of the literature aims to outline the current knowledge on the aetiopathogenesis of schizophrenia and to present the recently approved and newly discovered pharmacological substances in treating schizophrenia. We discuss ten novel drugs, three of which have been approved by the FDA (Olanzapine/Samidorphan, Lumateperone, and Pimavanserin). The rest are under clinical trial investigation (Brilaroxazine, Xanomeline/Trospium, Emraclidine, Ulotaront, Sodium Benzoate, Luvadaxistat, and Iclepertin). However, additional basic and clinical research is required not only to improve our understanding of the neurobiology and the potential novel targets in the treatment of schizophrenia, but also to establish more effective therapeutical interventions for the syndrome, including the attenuation of negative and cognitive symptoms and avoiding dopamine blockade-related adverse effects.

Parkinson\'s disease (PD) is the second-most common neurodegenerative disorder with a long-term 60% cumulative prevalence of PD psychosis. Medical treatment is limited to few atypical antipsychotic drugs with low affinity to dopamine D2 receptors. In 2016, pimavanserin, a selective 5-HT2A inverse agonist/antagonist, was approved by the US Food and Drug Administration (FDA) as the only treatment for PD psychosis (PDP). This article provides an overview of the epidemiology, pathophysiology, and treatment options for PDP and illuminates the mode of action and therapy options with pimavanserin and the current study data.