Treatment of Parkinson's disease psychosis.
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ABSTRACT:
SUBMITTER: Black KJ
PROVIDER: S-EPMC6103448 | biostudies-literature | 2017 Dec
REPOSITORIES: biostudies-literature
Publications
Early in the course of Parkinson disease (PD), treatment usually goes well. However, after five to ten years, things start to change as treatment requires higher doses of medications and side effects become more problematic. One of the most difficult problems is the development of hallucinations or delusions. Throughout the 20th century, treatment options were unproven and unsatisfactory, but the past 20 years have brought important changes. Two medications that are well tolerated in PD have now ...[more]
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Project description:OBJECTIVE:To examine the nature of the association between affective disorders and psychosis in Parkinson's disease (PD). BACKGROUND:In PD, psychosis and affective disorders are common and independently impact quality of life and mortality. Both depression and psychosis are correlated with the occurrence of cognitive dysfunction, suggesting that they may share neurobiological substrates. Anxiety has not been examined as a correlate of psychosis. METHODS:144 PD subjects were evaluated with the Schedule for Assessment of Positive Symptoms to assess psychotic features, while depression and anxiety were examined by the Structured Clinical Interview for DSM-IV-TR (SCID) and self-assessment scales Beck Depression Inventory II (BDI-II) and Beck Anxiety Inventory (BAI). Correlational analyses assessed associations between hallucinations and delusions with depression and anxiety. RESULTS:A diagnosis of anxiety (SCID) was significantly (p=.015) associated with hallucinations (OR=4.81, CI=1.36-16.99). Severity of anxiety (BAI) significantly predicted (p=.03) the presence of hallucinations (OR=1.08, CI=1.01-1.15) and delusions (OR=1.09, CR=1.01-1.17). Current depression (SCID) was significantly (p=.001) associated with the presence of hallucinations (OR=6.12, CI=2.04-18.39) and delusions (OR=7.14, CI=2.23-22.93). Multiple linear regressions revealed that severity of anxiety remained an independent predictor (p<.05) of both the number of types of hallucinations (t=3.06, p=.003) and delusions (t=2.87, p=.005). Severity of depression was a significant predictor of the total number of delusions (t=2.28, p=.024). CONCLUSIONS:This study demonstrates an association between depression and psychosis and, for the first time, an association between anxiety and psychosis. These associations may have implications on pathophysiology and treatment of psychosis in PD.
| S-EPMC5608273 | biostudies-other
Project description:Psychosis is a common non-motor symptom of Parkinson's disease whose pathogenesis remains poorly understood. Parkinson's disease in conjunction with psychosis has been shown to induce injury to extracorticospinal tracts as well as within some cortical areas. In this study, Parkinson's disease patients with psychosis who did not receive antipsychotic treatment and those without psychosis underwent diffusion tensor imaging. Results revealed that in Parkinson's disease patients with psychosis, damage to the left frontal lobe, bilateral occipital lobe, left cingulated gyrus, and left hippocampal white-matter fibers were greater than damage to the substantia nigra or the globus pallidus. Damage to white-matter fibers in the right frontal lobe and right cingulate gyrus were also more severe than in the globus pallidus, but not the substantia nigra. Damage to frontal lobe and cingulate gyrus white-matter fibers was more apparent than that to occipital or hippocampal fiber damage. Compared with Parkinson's disease patients without psychosis, those with psychosis had significantly lower fractional anisotropy ratios of left frontal lobe, bilateral occipital lobe, left cingu-lated gyrus, and left hippocampus to ipsilateral substantia nigra or globus pallidus, indicating more severe damage to white-matter fibers. These results suggest that psychosis associated with Par-kinson's disease is probably associated with an imbalance in the ratio of white-matter fibers be-tween brain regions associated with psychiatric symptoms (frontal lobe, occipital lobe, cingulate gyrus, and hippocampus) and those associated with the motor symptoms of Parkinson's disease (the substantia nigra and globus pallidus). The relatively greater damage to white-matter fibers in psychiatric symptom-related brain regions than in extracorticospinal tracts might explain why chosis often occurs in Parkinson's disease patients.
| S-EPMC4145938 | biostudies-other
Project description:Background: Parkinson's disease psychosis (PDP) is a common nonmotor symptom that affects up to 60% of patients. Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, is approved for treating hallucinations and delusions associated with PDP.Objective: Evaluate the efficacy and tolerability of pimavanserin in an open-label extension (OLE) study.Methods: Patients completing a pivotal 6-week placebo-controlled trial (Core Study) could enroll in the OLE. All patients pimavanserin 34?mg once daily, blinded to previous treatment allocation. Prespecified blinded assessments at Week 4 were the Scale for the Assessment of Positive Symptoms (SAPS) PD version and SAPS H?+?D scales, Caregiver Burden Scale (CBS), and Clinical Global Impression (CGI) Improvement and Severity scales.Results: Of 171 who entered the OLE, 148 (87%) completed Week 4. Among patients who received placebo in the Core Study, mean (SD) change from OLE baseline to OLE Week 4 for the SAPS-PD was - 3.4 (6.3); p?<?0.0001. Mean change from Core Study baseline to OLE Week 4 for SAPS-PD was similar among prior pimavanserin- and placebo-treated patients (-6.9 vs. -6.3). Improvement was similar with CGI-I, CGI-S, CBS, and SAPS-H?+?D in patients previously treated with placebo. Adverse events occurred in 92 (53.8%) patients during the 4-week OLE.Conclusion: Improvements at OLE Week 4 from pretreatment baseline were similar with placebo and pimavanserin in the Core Study. The beneficial effects observed with pimavanserin in the 6-week Core Study were maintained for 4 weeks in the blinded OLE, supporting the durability of response with pimavanserin 34?mg for PDP over 10 weeks.
| S-EPMC7683065 | biostudies-literature
Project description:Pimavanserin (PMV) is the first approved drug for treating hallucinations and delusions in Parkinson's disease (PD) psychosis. Psychosis is one of the leading causes of nursing home placement in people with PD. Furthermore, hallucinations are a more frequent cause of institutionalization than motor disability or dementia related to PD. The management of PD psychosis involves antipsychotic medications. Most of the drugs in this class directly block dopamine D2 receptors, leading to significantly worsening motor symptoms in patients with PD. The most commonly used medications for managing PD psychosis are quetiapine, clozapine, and PMV. This literature review aims to study pimavanserin's history, mechanism, clinical trials, and post-marketing experience. PMV is a potent 5-HT2A receptor antagonist/inverse agonist. Moreover, this drug can interact with 5-HT2C receptors. We calculated some physicochemical descriptors and pharmacokinetic properties of PMV. Eight clinical trials of PMV and PD psychosis are registered on ClinicalTrials.gov. Only four of them have complete results already published. Meta-analytic results showed that PMV efficacy is inferior to clozapine. However, PMV has a significantly lower number of side-effects for managing psychosis in PD. Medicare database assessment revealed 35% lower mortality with PMV compared to other atypical antipsychotics. Moreover, sensitive statistical analysis demonstrated that PMV is a protective factor for the risk of falls in individuals with PD.
| S-EPMC9599742 | biostudies-literature
Project description:INTRODUCTION:Psychosis is common among patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Limited data exist on the most effective therapies. METHODS:Retrospective cohort study comparing patients with PD or DLB initiated on quetiapine or pimavanserin for psychosis. Primary outcome was time to discontinuation of pimavanserin or quetiapine using Kaplan-Meier survival analysis. We hypothesized the rate of antipsychotic discontinuation would be lower in the pimavanserin group. Subjects were included if the indication for treatment was psychosis and excluded if there was a history of major mental illness or no follow up data were available. RESULTS:Forty-seven patients were included in the quetiapine cohort and 45 in the pimavanserin cohort. Patients in the pimavanserin cohort were more likely to have a diagnosis of DLB (33% vs. 11%, P?=?0.01) and to have been prescribed an antipsychotic previously (62% vs. 6%, P?<?0.01); otherwise, the groups were similar. Time to discontinuation analysis, which accounts for efficacy, safety and tolerability, revealed a lower early pimavanserin discontinuation rate and a higher late pimavanserin discontinuation rate (HR?<?1 before day 43, HR?>?1 after day 43; P?=?0.04). There was no difference in mortality in the pimavanserin group compared to the quetiapine group (HR 0.37, 95% CI 0.06 to 2.45; P?=?0.88). More individuals had a documented secondary indication for taking quetiapine than pimavanserin (38% vs. 4%; P?=?0.001). CONCLUSION:Accounting for efficacy, safety and tolerability, pimavanserin may be more clinically useful for promptly managing psychosis, while quetiapine may confer additional secondary benefits long-term.
| S-EPMC7061324 | biostudies-literature
Project description:Psychotic symptoms frequently occur in Parkinson's disease (PD), but their pathophysiology is poorly understood. According to the National Institute of Health RDoc programme, the pathophysiological basis of neuropsychiatric symptoms may be better understood in terms of dysfunction of underlying domains of neurocognition in a trans-diagnostic fashion. Abnormal cortico-striatal reward processing has been proposed as a key domain contributing to the pathogenesis of psychotic symptoms in schizophrenia. This theory has received empirical support in the study of schizophrenia spectrum disorders and preclinical models of psychosis, but has not been tested in the psychosis associated with PD. We, therefore, investigated brain responses associated with reward expectation and prediction error signaling during reinforcement learning in PD-associated psychosis. An instrumental learning task with monetary gains and losses was conducted during an fMRI study in PD patients with (n = 12), or without (n = 17), a history of psychotic symptoms, along with a sample of healthy controls (n = 24). We conducted region of interest analyses in the ventral striatum (VS), ventromedial prefrontal and posterior cingulate cortices, and whole-brain analyses. There was reduced activation in PD patients with a history of psychosis, compared to those without, in the posterior cingulate cortex and the VS during reward anticipation (p < 0.05 small volume corrected). The results suggest that cortical and striatal abnormalities in reward processing, a putative pathophysiological mechanism of psychosis in schizophrenia, may also contribute to the pathogenesis of psychotic symptoms in PD. The finding of posterior cingulate dysfunction is in keeping with prior results highlighting cortical dysfunction in the pathogenesis of PD psychosis.
| S-EPMC5402044 | biostudies-literature
Project description:BackgroundUp to 60 percent of patients with Parkinson's disease (PD) develop Parkinson's disease psychosis (PDP). PDP is associated with a significant economic burden. The management of PDP has been divided into two approaches-one focuses on decreasing the doses of anti-Parkinsonian medications and the other involves prescribing atypical antipsychotics. Of these atypical antipsychotics, pimavanserin is United States (US) Food and Drug Administration (FDA)-approved specifically for the treatment of PDP.ObjectiveThe goal was to evaluate the safety and efficacy of pimavanserin in the treatment of PDP based on data from randomized clinical trials.MethodsAll the articles, which assessed pimavanserin's effect on the treatment of PDP, were retrieved from Google Scholar, PubMed, and abstracts from annual scientific sessions. The data on dose, therapy duration, patient numbers, and study duration were collected. These data were analyzed with random effect modeling using the inverse variance method and the Mantel-Haenszel method.ResultsFour studies comparing pimavanserin to a placebo provided data on 680 patients (263 placebo, 417 pimavanserin). Treatment with pimavanserin was associated with a significant reduction in scores using the Scale of Assessment of Positive Symptoms, Hallucinations, and Delusion (SAPS-H+D) (mean difference [MD]: -1.55 [-2.71, -0.379], p=0.009). The groups had similar composite scores for Unified Parkinson's Disease Rating Scale II and III (UPDRS II and III) (MD: 0.093 [-1.28, 1.46], p=0.89). Interestingly, pimavanserin was protective against orthostatic hypotension (risk ratio: 0.33 [0.30, 0.37], p<0.001). All other adverse events were similarly distributed across both groups.ConclusionThere was a significant improvement in psychosis symptoms in patients with PD who took pimavanserin. Pimavanserin was also shown to be protective against orthostatic hypotension.
| S-EPMC8970241 | biostudies-literature
Project description:Parkinson's disease (PD) is caused by progressive degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), resulting in the deficiency of DA in the striatum. Thus, symptoms are developed, such as akinesia, rigidity and tremor. The aetiology of neuronal death in PD still remains unclear. Several possible mechanisms of the degeneration of dopaminergic neurons are still elusive. Various mechanisms of neuronal degeneration in PD have been proposed, including formation of free radicals, oxidative stress, mitochondrial dysfunction, excitotoxicity, calcium cytotoxicity, trophic factor deficiency, inflammatory processes, genetic factors, environmental factors, toxic action of nitric oxide, and apoptosis. All these factors interact with each other, inducing a vicious cycle of toxicity causing neuronal dysfunction, atrophy and finally cell death. Considerable evidence suggests that free radicals and oxidative stress may play key roles in the pathogenesis of PD. However, currently, drug therapy cannot completely cure the disease. DA replacement therapy with levodopa (L-Dopa), although still being a gold standard for symptomatic treatment of PD, only alleviates the clinical symptoms. Furthermore, patients usually experience severe side effects several years after the L-Dopa treatment. Until now, no therapy is available to stop or at least slow down the neurodegeneration in patients. Therefore, efforts are made not only to improve the effect of L-Dopa treatment for PD, but also to investigate new drugs with both antiparkinsonian and neuroprotective effects. Here, the advantages and limitations of current and future therapies for PD were dicussed. Current therapies include dopaminergic therapy, DA agonists, MAO-B inhibitor, COMT inhibitors, anticholinergic drugs, surgical procedures such as pallidotomy and more specifically deep brain stimulation of the globus pallidus pars interna (GPi) or subthalamic nucleus (STN), and stem cell transplantation.
| S-EPMC5552548 | biostudies-other
Project description:BackgroundParkinson's disease psychosis (PDP) has a major impact on quality of life and care partner burden; however, little is known about the lived experiences of care partners in managing PDP.ObjectiveTo understand how care partners of individuals with PDP experience their role and articulate their needs related to psychosis.MethodsThis was a qualitative study of semi-structured telephone interviews. Recruitment was conducted online via the clinical study matching tool, Fox Trial Finder; study activities took place remotely via telephone interviews. Transcripts of the phone interviews were analyzed by grounded theory methods, and a codebook of key themes that emerged from the analysis was developed.ResultsNine care partners (all female) were interviewed. Discussion topics in the codebook included (1) care partner burden and guilt; (2) communication with medical professionals; (3) coping strategies; (4) emotional reactions of the care partner to psychosis; (5) sources of knowledge about PD psychosis; (6) attitudes towards medications for PDP; (7) strategies to care for loved ones with psychosis; (8) psychosis triggers.ConclusionsThis qualitative analysis uncovers important aspects of the care partner experience, including challenges in navigating the medical system and communicating with professionals. Providers treating patients with PDP should be aware of these constraints and provide added support for strained care partners.
| S-EPMC7978339 | biostudies-literature
Project description:PurposeTo assess the present evidence regarding the efficiency, safety, and potential risks of pharmacotherapy used for Parkinson's disease psychosis (PDPsy) treatment.Patients and methodsWe searched the following databases: PubMed, the Cochrane Library, ISI Web of Science, and Embase using the following terms: atypical antipsychotics, pimavanserin, olanzapine, quetiapine, clozapine, Parkinson's disease and psychosis. We systematically reviewed all randomized placebo-controlled trials comparing an atypical antipsychotic with a placebo.ResultsA total of 13 randomized placebo-controlled trials for a total 1142 cases were identified involving pimavanserin (n=4), clozapine (n=2), olanzapine (n=3), and quetiapine (n=4). For each atypical antipsychotic, a descriptive synthesis and meta-analyses was presented. Pimavanserin was associated with a significant improvement in psychotic symptoms compared to a placebo without worsening motor function. Clozapine was efficacious in alleviating psychotic symptoms and did not exacerbate motor function either. Quetiapine and Olanzapine did not demonstrate significant differences in reducing psychotic symptoms but may aggravate motor function.ConclusionsThere is strong evidence that pimavanserin is effective for the treatment of PDPsy. Clozapine is also recommended but should be used with caution due to its side effects. In the future, more well-designed randomized controlled trials (RCTs) are needed to confirm and update the findings reported in this meta-analysis.
| S-EPMC6677378 | biostudies-literature