Pimavanserin (PIM) is the only FDA approved atypical antipsychotic treatment (AAP) for hallucinations and delusions associated with Parkinson's disease psychosis (PDP) among patients with or without coexisting dementia; however, Other-AAPs (i.e. quetiapine (QUE), risperidone, olanzapine, aripiprazole) are commonly prescribed off-label. Healthcare resource utilization (HCRU) patterns among patients with PDP and coexisting dementia (PDP+D) who newly initiate PIM versus (vs.) Other-AAPs (i.e. other AAP-mix) or QUE in real-world settings is limited.

A retrospective analysis of Parts A, B, and D claims from the 100% Medicare sample from 04/01/15 to 12/31/21 was conducted. AAP-naïve patients with PDP+D who initiated ≥12-month continuous monotherapy with PIM vs. Other-AAPs or vs. QUE during 04/01/16-12/31/20 were propensity score matched 1:1 on thirty-one variables (age, sex, race, region and 27 Elixhauser comorbidity characteristics). Adjusted log binomial regressions compared all-cause HCRU [(e.g. inpatient hospitalizations and by hospitalization-type [short-term stays (ST-stays), long-term stays (LT-stays), skilled nursing facility stays (SNF-stays)], and emergency room (ER) visits] risk between cohorts.

Of the 5,932 patients with PDP+D, matched cohorts (n = 1,294 in each) on continuous- monotherapy of PIM vs. Other-AAPs or QUE had similar demographics and comorbidities. Adjusted regression results showed those who initiated PIM vs. Other-AAPs had significantly lower relative risk (RR) of ≥1 all-cause inpatient hospitalizations (RR = 0.88, 95% CI: 0.80-0.97), ST-stays (RR = 0.86, 95% CI: 0.77-0.95), SNF-stays (RR = 0.79, 95% CI: 0.68-0.92), and ER visits (RR = 0.89, 95% CI: 0.84-0.94). PIM vs. QUE also experienced significantly lower RR for ≥1 all-cause IP hospitalizations (RR = 0.88, 95% CI: 0.80-0.96), ST-stays (RR = 0.85, 95% CI: 0.77-0.95), SNF-stays (RR = 0.81, 95% CI: 0.70-0.94), and ER visits (RR = 0.88, 95% CI: 0.83-0.94).

Patients initiating PIM-monotherapy for PDP+D experienced 12% lower all-cause inpatient hospitalizations vs. Other-AAPs or QUE. These results are consistent with prior real-world research in PDP with or without dementia.

The past decade has seen a paradigm shift in the evaluation and management of Parkinson's disease psychosis (PDP), with the first approval of an antipsychotic in the US in 2016. An evidence-based review by the Movement Disorder Society found pimavanserin and clozapine to be clinically useful, (low-dose) quetiapine to be possibly useful, and all other antipsychotics to be avoided due to motor worsening. Clozapine and quetiapine use can be limited by provoking Parkinson's disease (PD) nonmotor symptoms of somnolence and hypotension. Quetiapine may also be limited by its risk in cognitive impairment. Pimavanserin is not associated with these symptoms. Despite advances in the understanding of PDP and the approval of pimavanserin in the US, clinical questions concerning patient selection, treatment timing, switch strategies, and combination therapy remain.

To develop a consensus on first-line and subsequent treatment strategies for PDP, a panel of experts reviewed the clinical presentation and course of PDP, then discussed clinical trial evidence and experience.

PDP is a common but still undertreated sequela of PD progression. Pimavanserin is recommended as a first-line antipsychotic therapy based on its established safety and efficacy. While switching strategies are suggested, further study is needed to assess combination antipsychotic therapy.

Parkinson's disease psychosis (PDP) is a prevalent non-motor symptom associated with Parkinson's disease. The treatment options for PDP are limited, and its pharmacological management remains ambiguous. This study aimed to evaluate the existing evidence in relation to clinical practice.

This multi-methods study consisted of a systematic review of reviews, adhering to the PRISMA guidelines. The review was registered with PROSPERO. Following data extraction and assessment using the AMSTAR 2 tool, a narrative synthesis was performed. In the second phase of the study, a questionnaire was developed, validated, piloted, and distributed to the heads of specialized PD clinics in Germany and Austria.

The search resulted in the inclusion of eleven reviews. The quality of eight of these reviews was rated as high (n = 7) or moderate (n = 1). The reviews indicated that clozapine and pimavanserin demonstrated the highest efficacy and tolerability. Other antipsychotic medications either failed to alleviate PDP symptoms or resulted in distinct motor complications. The survey findings also favored clozapine for its efficacy in managing PDP and improving quality of life, although quetiapine was regarded as effective and pimavanserin was not available. Clinicians reported initiating antipsychotic treatment at various stages of PDP, with a tendency to reduce the dosage or discontinue D2 agonists or anticholinergics.

The reviewed literature and the survey results consistently favored clozapine for its efficacy and tolerability in treating PDP. It may be considered the first-line treatment, with pimavanserin as an alternative option.

Reducing falls and fractures remains an important clinical goal in managing older residents with Parkinson's disease psychosis (PDP) in long-term care/nursing home (LTC/NH) settings.

This analysis examined risk of all-cause falls or fractures among PDP residents on continuous monotherapy with pimavanserin (PIM) versus (i) other atypical antipsychotics (AAPs) [quetiapine (QUE), risperidone (RIS), olanzapine (OLA), aripiprazole (ARI)] and (ii) QUE.

A retrospective analysis of parts A, B, and D claims from a 100% Medicare sample (2013-2019) in LTC/NH settings was conducted. LTC/NH residents in the USA initiating continuous monotherapy (PIM versus other AAPs; PIM versus QUE) for ≥ 6 months between 01 January 2014 and 31 December 2018 were 1:1 propensity score matched (PSM) on 31 variables (age, sex, race, region, and 27 Elixhauser comorbidities). Outcomes included three measures: risks of falls only, fractures only, and falls/fractures during 6-months follow-up. Demographic characteristics were described using chi-square and t-tests. Generalized linear models were used to assess difference in risks of falls/fractures.

Of 7187 residents, 47.59% (n = 3420) were female and mean age was 78.8 (± 7.75) years. In total, 14% (n = 1005) were on PIM and 86% (n = 6182) were on other AAPs. After PSM, falls only among PIM residents (n = 1005) was 4.58% (n = 46) versus 7.66% (n = 77) for other AAPs (n = 1005) [relative risk (RR) = 0.63 (0.46, 0.86), p < 0.05] and 8.26% (n = 83) for QUE (n = 1005) residents (p < 0.05). Fractures only among PIM residents was 1.39% (n = 14) compared with 2.09% (n = 21) for other AAPs (p = 0.31) and 1.89% (n = 19) for QUE (p = 0.49), respectively. Taken together, falls/fractures among PIM residents were 5.67% (n = 57) versus 9.05% (n = 91) for other AAPs [RR = 0.63 (0.46, 0.86), p < 0.05] and 9.55% (n = 96) for QUE (p < 0.05), respectively.

In this analysis of LTC/NH residents with PDP, PIM had a 37% and 41% lower risk of all-cause falls/fractures versus other AAPs and versus QUE, respectively.

Parkinson's disease (PD) is associated with the development of psychosis (PDP), including hallucinations and delusions, in more than half of the patient population. Optimal PD management must therefore involve considerations about both motor and non-motor symptoms. Often, clinicians fail to diagnosis psychosis in patients with PD and, when it is recognized, treat it suboptimally, despite the availability of multiple interventions. In this paper, we provide a summary of the current guidelines and clinical evidence for treating PDP with antipsychotics. We also provide recommendations for diagnosis and follow-up. Finally, an updated treatment algorithm for PDP that incorporates the use of pimavanserin, the only US FDA-approved drug for the treatment of PDP, was developed by extrapolating from a limited evidence base to bridge to clinical practice using expert opinion and experience. Because pimavanserin is only approved for the treatment of PDP in the US, in other parts of the world other recommendations and algorithms must be considered.

Atypical antipsychotics currently constitute the first-line medication for schizophrenia, with quetiapine being one of the most commonly prescribed representatives of the group. Along with its specific affinity for multiple receptors, this compound exerts other biological characteristics, among which anti-inflammatory effects are strongly suggested. Simultaneously, published data indicated that inflammation and microglial activation could be diminished by stimulation of the CD200 receptor (CD200R), which takes place by binding to its ligand (CD200) or soluble CD200 fusion protein (CD200Fc). Therefore, in the present study, we sought to evaluate whether quetiapine could affect certain aspects of microglial activity, including the CD200-CD200R and CX3CL1-CX3CR1 axes, which are involved in the regulation of neuron-microglia interactions, as well as the expression of selected markers of the pro- and anti-inflammatory profile of microglia (Cd40, Il-1β, Il-6, Cebpb, Cd206, Arg1, Il-10 and Tgf-β). Concurrently, we examined the impact of quetiapine and CD200Fc on the IL-6 and IL-10 protein levels. The abovementioned aspects were investigated in organotypic cortical cultures (OCCs) prepared from the offspring of control rats (control OCCs) or those subjected to maternal immune activation (MIA OCCs), which is a widely implemented approach to explore schizophrenia-like disturbances in animals. The experiments were performed under basal conditions and after additional exposure to the bacterial endotoxin lipopolysaccharide (LPS), according to the "two-hit" hypothesis of schizophrenia. The results of our research revealed differences between control and MIA OCCs under basal conditions and in response to treatment with LPS in terms of lactate dehydrogenase and nitric oxide release as well as Cd200r, Il-1β, Il-6 and Cd206 expression. The additional stimulation with the bacterial endotoxin resulted in a notable change in the mRNA levels of pro- and anti-inflammatory microglial markers in both types of OCCs. Quetiapine diminished the influence of LPS on Il-1β, Il-6, Cebpb and Arg1 expression in control OCCs as well as on IL-6 and IL-10 levels in MIA OCCs. Moreover, CD200Fc reduced the impact of the bacterial endotoxin on IL-6 production in MIA OCCs. Thus, our results demonstrated that quetiapine, as well as the stimulation of CD200R by CD200Fc, beneficially affected LPS-induced neuroimmunological changes, including microglia-related activation.

Pimavanserin is the only approved drug for Parkinson's disease psychosis (PDP) and is an increasingly used therapy where available. Clozapine has proven efficacy for PDP but is much less commonly used secondary to frequent blood tests to monitor for agranulocytopenia. We identified 27 patients with PDP (72 ± 7.3 years, 11 (41%) female), with an inadequate response to pimavanserin, who subsequently started clozapine. The final mean daily dose of clozapine was 49.5 mg [range 25-100] at night, and mean duration of follow-up was 17 months [range: 2-50 months]. Patients reported clozapine to be markedly effective in 11 (41%), moderately effective in 6 (22%), somewhat effective in 5 (18%). No patient reported that it was ineffective, but 5 (19%) had inadequate follow-up. Clozapine should be considered in pimavanserin refractory psychosis.

Parkinson's disease (PD) is the second most common neurodegenerative disease. Psychosis is one of the common psychiatric presentations in the natural course of PD. PD psychosis is an important non-motor symptom, which is strongly correlated with a poor prognosis. Increasing attention is being given to PD psychosis. In this opinion review, we summarized and analyzed the identification, screening, epidemiology, mechanisms, risk factors, and therapeutic approaches of PD psychosis based on the current clinical evidence. PD psychosis tends to have a negative effect on patients' quality of life and increases the burden of family caregiving. Screening and identification in the early stage of disease is crucial for establishing tailored therapeutic strategies and predicting the long-term outcome. Development of PD psychosis is believed to involve a combination of exogenous and endogenous mechanisms including imbalance of neurotransmitters, structural and network changes, genetic profiles, cognitive impairment, and antiparkinsonian medications. The therapeutic strategy for PD psychosis includes reducing or ceasing the use of dopaminergic drug, antipsychotics, cholinesterase inhibitors, and non-pharmacological interventions. Ongoing clinical trials are expected to provide new insights for tailoring therapy for PD psychosis. Future research based on novel biomarkers and genetic factors may help inform individualized therapeutic strategies.

Aim: The objective was to determine the prevalence of the potentially inappropriate antipsychotics and anticholinergics used in patients with Parkinson's disease. Materials & methods: A cross-sectional study identified the prescription of antipsychotics, anticholinergics and drugs for the treatment of Parkinson's disease. The anticholinergic burden was evaluated, and quetiapine and clozapine were considered to be adequate antipsychotics. Results: 2965 patients with Parkinson's disease were identified. The presence of psychiatric disorders and other neurological pathologies was associated with a greater probability of receiving potentially inappropriate antipsychotic prescriptions. The presence of greater number of comorbidities was associated with a greater probability of receiving anticholinergics. Conclusion: Older age and associated comorbidities, especially psychiatric and neurological comorbidities, increase the likelihood of patients with Parkinson's disease being prescribed antipsychotics and anticholinergics.

Parkinson's disease psychosis (PDP) is a common, nonmotor symptom of Parkinson's disease (PD), which may affect up to 60% of patients and is associated with impaired quality of life, increased healthcare costs, and nursing home placement, among other adverse outcomes. Characteristic symptoms of PDP include illusions; visual, auditory, tactile, and olfactory hallucinations; and delusions. PDP symptoms typically progress over its course from being mild, infrequent, and often untroubling to complex, sometimes constant, and potentially highly disturbing. PDP has traditionally been treated with atypical antipsychotics (e.g., clozapine and quetiapine) although these are not approved for this indication and clozapine requires frequent white blood cell count monitoring due to the risk of agranulocytosis. Pimavanserin is a newer atypical antipsychotic with highly selective binding to serotonergic receptors, no evidence for worsening motor symptoms in PD, and no need for white blood cell count monitoring. It is currently the only approved medication indicated for PDP treatment. However, because it was approved relatively recently (2016), clinical experience with pimavanserin is limited. Case Presentations. A wide variety of representative clinical scenarios are presented, each with distinct variables and complications. Issues addressed include distinguishing PDP from similar symptoms caused by other disorders such as dementia, coordinating pimavanserin with other PD medications and with deep brain stimulation, adapting pimavanserin dosing for optimal benefit and tolerability, and recognizing variability of PDP symptoms due to patients' changing life circumstances.

These scenarios provide multiple insights regarding PDP management and the role of pimavanserin. Effective treatment of PDP may reduce disturbing symptoms of psychosis, thus improving patient function and quality of life. In addition, effective pharmacotherapy for PDP may also facilitate the use of other medications needed to treat neurological symptoms of PD (e.g., tremor, bradykinesia, and dyskinesia), although they may also have adverse effects that contribute to symptoms of PDP.

Introduction: Hallucinations in Parkinson's disease are common, can complicate medication management and significantly impact upon the quality of life of patients and their carers.Areas covered: This review aims to examine current evidence for the management of hallucinations in Parkinson's disease.Expert opinion: Treatment of hallucinations in Parkinson's disease should be both individualized and multifaceted. Screening, education, medication review and the avoidance of common triggers are important. For well-formed visual hallucinations, acetylcholinesterase inhibitors are recommended first-line. Refractory or severe symptoms may require the cautious use of atypical antipsychotics. Antidepressants may be beneficial in the appropriate setting. Unfortunately, current therapies for hallucinations offer only limited benefits and future research efforts are desperately required to improve the management of these challenging symptoms.

To reduce potentially inappropriate medications, the FORTA (Fit fOR The Aged) concept classifies drugs in terms of their suitability for geriatric patients with different labels, namely A (indispensable), B (beneficial), C (questionable), and D (avoid). The aims of our study were to assess the medication appropriateness in PD inpatients applying the FORTA list and drug-drug interaction software, further to assess the adequacy of FORTA list for patients with PD. We retrospectively collected demographic data, comorbidities, laboratory values, and the medication from the discharge letters of 123 geriatric inpatients with PD at the university hospital of Hannover Medical School. Patients suffered on average from 8.2 comorbidities. The majority of the medication was labeled A (60.6% of PD-specific and 40.9% of other medication) or B (22.3% of PD-specific and 26.9% of other medication). Administered drugs labeled with D were amantadine, clozapine, oxazepam, lorazepam, amitriptyline, and clonidine. Overall, 545 interactions were identified, thereof 11.9% severe interactions, and 1.7% contraindicated combinations. 81.3% of patients had at least one moderate or severe interaction. The FORTA list gives rational recommendations for PD-specific and other medication, especially for general practitioners. Considering the demographic characteristics and the common multimorbidity of geriatric PD patients, this study underlines the importance of awareness, education, and preventive interventions to increase drug safety.

Dementia with Lewy bodies (DLB) is the second most common form of dementia and is assumed to be often under- or misdiagnosed, especially in early stages. Here we present a complex case of probable DLB with major depression and alcohol and benzodiazepine dependence in which DLB was ruled out initially. This case highlights the challenging diagnostic workup of DLB patients. Core clinical features can be missing and indicative biomarkers can be negative, especially in early stages of the disease. Initially, Fluorodeoxyglucose positron emission tomography as well as neuropsychological assessment were suspicious for a possible DLB diagnosis in our patient while core clinical criteria were missing and the indicative biomarker 123I-FP-CIT SPECT was negative. Follow up was performed two years later and the patients showed several core and supportive clinical features of DLB and 123I-FP-CIT SPECT showed a pathological pattern. Extensive neuropsychological assessment in combination with PET imaging might provide crucial evidence for DLB even in early stages. If neuropsychology and PET imaging point to an early DLB diagnosis careful follow-up should be performed as core symptoms and indicative biomarkers might appear in later stages of the disease.