Management Of Parkinson's Disease Psychosis Research Articles

Low continuation of antipsychotic therapy in Parkinson disease \u2013 intolerance, ineffectiveness, or inertia?

BackgroundAntipsychotics are used in Parkinson disease (PD) to treat psychosis, mood, and behavioral disturbances. Commonly used antipsychotics differ substantially in their potential to worsen motor symptoms through dopaminergic receptor blockade. Recent real-world data on the use and continuation of antipsychotic therapy in PD are lacking. The objectives of this study are to (1) examine the continuation of overall and initial antipsychotic therapy in individuals with PD and (2) determine whether continuation varies by drug dopamine receptor blocking activity.MethodsWe conducted a retrospective cohort study using U.S. commercially insured individuals in Optum 2001–2019. Adults aged 40 years or older with PD initiating antipsychotic therapy, with continuous insurance coverage for at least 6 months following drug initiation, were included. Exposure to pimavanserin, quetiapine, clozapine, aripiprazole, risperidone, or olanzapine was identified based on pharmacy claims. Six-month continuation of overall and initial antipsychotic therapy was estimated by time to complete discontinuation or switching to a different antipsychotic. Cox proportional hazards models evaluated factors associated with discontinuation.ResultsOverall, 38.6% of 3566 PD patients in our sample discontinued antipsychotic therapy after the first prescription, 61.4% continued with overall treatment within 6 months of initiation. Clozapine use was too rare to include in statistical analyses. Overall therapy discontinuation was more likely for those who initiated medications with known dopamine-receptor blocking activity (adjusted hazard ratios 1.76 [95% confidence interval 1.40–2.20] for quetiapine, 2.15 [1.61–2.86] for aripiprazole, 2.12 [1.66–2.72] for risperidone, and 2.07 [1.60–2.67] for olanzapine), compared with serotonin receptor-specific pimavanserin. Initial antipsychotic therapy discontinuation also associated with greater dopamine-receptor blocking activity medication use – adjusted hazard ratios 1.57 (1.28–1.94), 1.88 (1.43–2.46), 2.00 (1.59–2.52) and 2.03 (1.60–2.58) for quetiapine, aripiprazole, risperidone, and olanzapine, respectively, compared with pimavanserin. Similar results were observed in sensitivity analyses.ConclusionsOver one-third of individuals with PD discontinued antipsychotic therapy, especially if the initial drug has greater dopamine-receptor blocking activity. Understanding the drivers of antipsychotic discontinuation, including ineffectiveness, potentially inappropriate use, clinician inertia, patient adherence and adverse effects, is needed to inform clinical management of psychosis in PD and appropriate antipsychotic use in this population.

Treatment Patterns With Antipsychotics in Long-Term Care Patients With Parkinson's Disease Psychosis.

This study assessed treatment change patterns in Parkinson's disease psychosis (PDP) residents receiving antipsychotic (AP) therapies in U.S. long-term care (LTC) facilities. Residents with PDP in LTC between 01/01/13 and 06/30/16 were identified with ≥1 claim of psychosis, hallucinations, or delusions after PD diagnosis. Treatment patterns were evaluated during the 12 months post index. We identified 864 PDP residents: 408 (47.2%) on AP therapy and 456 (52.8%) on no AP therapy. A total of 335 residents (82.1%) continued, 13 (3.2%) discontinued, 11 (2.7%) switched, and 49 (12.0%) augmented (used ≥2 APs) their index AP therapy. Based on the multivariate regression analysis, younger age, male gender, anemia, anxiolytic use or anxiety, sedatives/hypnotic use, bladder disorders including urinary tract infections, coronary conditions, diabetes, hypertension, and dementia were associated with a higher likelihood of treatment change. Understanding the factors associated with treatment change may inform ways to improve management of PDP in the U.S. LTC setting.

EXAMINING PARKINSON'S DISEASE PSYCHOSIS TREATMENT OUTCOMES IN THE REAL WORLD: INTERIM YEAR 1 FINDINGS FROM THE INSYTE OBSERVATIONAL STUDY

Introduction Parkinson's disease is the second most common neurodegenerative disease, and over half of patients diagnosed will experience the symptoms of psychosis at some point during the course of the disease. Despite the prevalence of Parkinson's disease psychosis (PDP), longitudinal studies have not evaluated treatment modalities and outcomes in actual medical practice, and a considerable gap exists in our understanding of the extent to which outcomes achieved in controlled clinical trials can be replicated in the general population. Healthcare providers managing PDP currently utilize a wide range of antipsychotics (AP) off-label, including those that primarily block postsynaptic dopamine receptors, a practice that goes against specific recommendations from evidence-based reviews. Minimal data are available on AP therapy in PDP, regarding mitigating the burden of PDP by reducing hospitalizations and long-term care facility entry, or in improving other outcomes such as activities of daily living and sleep. Additionally, absent such “real world” data, factors that may be predictive of best clinical, economic, and/or humanistic outcomes cannot be fully ascertained. The goal of the INSYTE Study – Management of Parkinson's Disease Psychosis in Actual Practice – is to examine real-world management of PDP and its treatment outcomes, including the role of medication adjustments and AP usage, as well as the impact of PDP on healthcare resource utilization. The study also evaluates treatment decisions and their effect on humanistic measures, including quality of life, treatment satisfaction, sleep quality, activities of daily living, and patient and caregiver burden. Methods The INSYTE Study is enrolling up to 750 patients and their caregivers, from up to 100 sites in the United States. To achieve the study objectives, a prospective, observational design has been implemented to accommodate and describe standard medical practice associated with PDP management. Patients participating in the INSYTE Study will have a diagnosis of PDP prior to enrollment, or else will meet the symptomatic criteria for the condition (for example, Parkinson's disease with a history of delusions and/or hallucinations). INSYTE employs validated assessment instruments, although as an observational study, it does not impose a predefined visit schedule, medical tests, laboratory tests, procedures, or interventions. The INSYTE Study will compile clinical assessments and other data at follow-up visits for up to three years from enrollment. Results Preliminary baseline findings from 55 enrolling sites indicate that investigators at the majority (75%) of enrolling sites are neurologists, of whom 44% are in private practices, as opposed to academic or hospital-based centers. Baseline findings from 334 enrolled patients indicate that most are Caucasian (95%), male (63%), retired (76%), married (75%), and live in a private residence (92%). Most patients (86%) are participating in INSYTE with a caregiver. Average patient age is 74.7 years. Mean duration since PD and PDP diagnosis were 8.8 and 2.6 years, respectively. At baseline, 12% had no cognitive impairment, 50% had slight or mild impairment, and 38% had moderate or severe impairment. At enrollment, 33% of patients were utilizing an AP: of those, 82% were utilizing AP as monotherapy (primarily pimavanserin [50%] and quetiapine [25%]). Pimavanserin+quetiapine was the most frequently employed combination AP therapy (15%); other combinations ( Conclusions The INSYTE Study is the largest observational study to date to explore PDP treatments and patient outcomes in a real-world (clinical practice) setting. Results from this study will better inform the scientific community on current practices and potentially support updates to treatment guidelines and standards of care for the management of PDP. The findings to date reflect the enrollment of approximately half (n=334) of the planned patients from 55 actively participating sites. These data represent baseline characteristics of the enrolled patients (and caregivers, when present). The currently enrolled patients represent 0–38 years since their PD diagnosis, but an average of 8.8 years, and an average of 2.6 years since PDP symptom onset. Patients were also on a wide array of PDP treatments. To date, patients and caregivers have responded well to various questionnaires, as have healthcare professionals from participating sites. These clinical, economic, and humanistic findings will be updated to reflect year 1 interim analyses in Q1 2019. This research was funded by The INSYTE Observational Study is funded by ACADIA Pharmaceuticals, Inc. (San Diego, CA, USA).

Parkinson's disease psychosis: presentation, diagnosis and management.

Parkinson's disease is a neurodegenerative disorder characterized by motor and nonmotor symptoms. Psychosis is a common feature of Parkinson's disease. Parkinson's disease psychosis (PDP) encompasses minor phenomena (illusions, passage hallucinations and presence hallucinations), visual and nonvisual hallucinations and delusions. PDP is associated with reduced function and quality of life. The initial management approach should focus on identification and treatment of any contributory medical factors, reduction or discontinuation of medications with potential to induce or worsen psychosis, nonpharmacological strategies and consideration of acetylcholinesterase inhibitor treatment in the setting of dementia. Pimavanserin, quetiapine and clozapine may all be considered for use in PDP. In this review, we discuss the presentation, diagnosis and management of PDP.

An update expert opinion on management and research strategies in Parkinson's disease psychosis

Introduction: Psychosis, a frequent complication in Parkinson's disease (PD), contributes significantly to morbidity, mortality, nursing-home placement and quality of life. Medication side effects, issues of trial design and negative outcomes have limited clinical advances of new treatments for PD psychosis. Evidence-based medicine maintains clozapine as the most effective antipsychotic in PD without motor worsening, despite risk of agranulocytosis. Safe, effective treatments that improve psychosis without exacerbating parkinsonism are urgently needed.Areas covered: This article reviews the: i) phenomenology of PD psychosis, ii) pharmacological rationale for antipsychotics in PD; iii) clinical trials of antipsychotics in PD; iv) novel research strategies such as neuroimaging, genetics and animal models; and v) associated challenges in studying and treating PD psychosis. Preparation of this review included an extensive literature search using PubMed.Expert opinion: Management of PD psychosis is complex. Challenges pertaining to study design, rating scales, subject recruitment and completion have limited PD psychosis treatment trials. Novel research strategies focus on nondopaminergic systems and incorporate neuroimaging, genetic associations and animal models. These strategies also have challenges but have the potential to enhance our understanding of PD psychosis and advance the development of agents that can ultimately be tested in well-designed, randomized, controlled trials.

Treatment of behavioural symptoms and dementia in Parkinson's disease

Behavioural symptoms such as anxiety, depression and psychosis are common in Parkinson's disease (PD), and dementia occurs in about 90% of the patients. These symptoms can be more disabling than the motor dysfunction and they negatively impact quality of life, increase caregiver distress and are more frequently associated with nursing home placement. Depression can be treated with counselling and pharmacotherapy. Tricyclic antidepressants or selective serotonin reuptake inhibitors are widely used, but there is still need for controlled clinical trials. Management of psychosis in PD is complex and includes elimination of identifiable risk factors, reduction of polypharmacy and administration of atypical neuroleptics, which can alleviate psychotic symptoms without worsening motor functions. Clozapine is the best documented atypical neuroleptic shown to be effective against psychosis in PD patients. Cholinesterase inhibitors may prove additional benefit in psychotic PD patients. Recent evidence from small double-blind and open-label trials suggests that cholinesterase inhibitors may be effective in the treatment of dementia associated with PD.

Psychosis in Parkinson's disease.

Psychosis is a disabling nonmotor complication of Parkinson's disease (PD). Visual hallucinations are the most common clinical manifestation and have been observed in up to 40% of patients with advanced disease in hospital-based series. Age, cognitive dysfunction, depression, as well as severity and duration of disease have all been identified as risk factors in multiple studies. All major antiparkinsonian drugs can induce psychosis in at-risk patients. Early drug-induced psychosis has been observed in up to 16% of patients treated with dopamine agonists and has been associated with increased risk for the development of dementia later on. Management of psychosis in PD is complex and includes control of potential triggers and reductions of polypharmacy as well as the addition of atypical antipsychotics. Cholinesterase inhibitors may prove an additional option in psychotic PD patients with dementia.

MANAGEMENT OF PSYCHOSIS IN PARKINSON'S DISEASE

SUMMARYPsychosis is one of the most disabling complications associated with Parkinson's disease (PD) and occurs in up to 30% of PD patients treated chronically with antiparkinsonian drugs. Visual hallucinations, with or without delirium and paranoid delusions, are the most frequent symptoms. Psychosis complicating PD can be more disabling than the motor symptoms of PD; it frequently poses a serious threat to the patient's ability to maintain independence and is the single greatest risk factor for nursing home placement. Choosing an antipsychotic drug for a PD patient is a common clinical dilemma. The conventional antipsychotic drugs are poorly tolerated in PD because of their predictable and at times profound worsening in parkinsonian motor symptoms. The recent availability of atypical antipsychotic drugs that can control psychotic symptoms without compromising motor function has led to significant advances in therapeutic strategies in the management of PD psychosis in the community. This article reviews data on the use of atypical antipsychotics in patients with PD and the current recommendations on their use in the management of PD psychosis.