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Isaacson SH, Nasrallah H, Pahwa R, Alva G, Kremens D, Stahl SM. Management of Parkinson's disease psychosis: first-line antipsychotic selection and rationale for continuing, combining, or switching. Expert Opin Pharmacother 2025; 26:707-717. [PMID: 40138188 DOI: 10.1080/14656566.2025.2481205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Accepted: 03/14/2025] [Indexed: 03/29/2025]
Abstract
INTRODUCTION 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. AREAS COVERED 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. EXPERT OPINION 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.
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Affiliation(s)
- Stuart H Isaacson
- Parkinson's Disease and Movement Disorders Center of Boca Raton, Boca Raton, FL, USA
| | - Henry Nasrallah
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA
| | - Rajesh Pahwa
- Parkinson's Disease and Movement Disorder Center, University of Kansas Medical Center, KS, USA
| | - Gustavo Alva
- Department of Neuroscience, University of California, Riverside, CA, USA
| | - Daniel Kremens
- Movement Disorders Program, Thomas Jefferson University, Philadelphia, PA, USA
| | - Stephen M Stahl
- University of California, San Diego, USA
- Neuroscience Education Institute, Carlsbad, CA, USA
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Gupta RK, Gothwal M, Lenka A, Kamble N, Yadav R, Arumugham SS, Pal PK, Hegde S. P300 Event-Related Potential: A Surrogate Marker of Cognitive Dysfunction in Parkinson's Disease Patients with Psychosis. Ann Indian Acad Neurol 2025; 28:92-98. [PMID: 39746843 DOI: 10.4103/aian.aian_687_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 10/29/2024] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND AND OBJECTIVES Psychosis is one of the major neuropsychiatric non-motor symptoms of Parkinson's disease (PD). Prolonged latency and decreased amplitude of the P300 event-related potential (ERP) is a potential neurophysiologic biomarker of deeper neurocognitive deficits in PD. We aimed to characterize electroencephalogram (EEG)/ERP parameters in PD patients with and without psychosis (PDP and PDNP, respectively), and to determine if such measures could act as endophenotypes for PD-associated psychosis (PDP). METHODS We recruited 40 PD patients (all males), 20 PDP patients and 20 PDNP patients, aged between 39 and 65 years. The cognitive composite scores for attention and working memory were calculated. EEG/ERP recording was carried out following this, with eyes-closed resting-state EEG followed by an auditory oddball P300 task. RESULTS The composite scores for both attention and working memory were significantly higher in the PDNP group compared to the PDP group. The mean reaction time during the oddball task in the PDP group was significantly higher than in the PDNP group. A trend of increased P300 amplitude was observed in the PDNP group compared to the PDP group; however, it was significant at CP4, P8, C4, TP8, T8, CZ, FC4, FT8, FZ, F4, and F8 electrode sites. Power spectral analysis indicated a significant increase in the EEG power of slow-frequency waves (delta, theta) across all the brain regions in the PDP group compared to the PDNP group. CONCLUSIONS Our results demonstrate the association between psychosis and the severity of neurocognitive deficits in PD patients assessed using electrophysiologic measures. P300 may be considered a potential neurophysiologic biomarker of psychosis in PD.
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Affiliation(s)
- Rajnish Kumar Gupta
- Department of Psychology, Manipal University Jaipur, Jaipur, Rajasthan, India
| | - Mohit Gothwal
- Department of Clinical Psychology, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India
| | - Abhishek Lenka
- Department of Neurology, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India
- Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Nitish Kamble
- Department of Neurology, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India
| | - Ravi Yadav
- Department of Neurology, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India
| | - Shyam Sundar Arumugham
- Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India
| | - Pramod Kumar Pal
- Department of Neurology, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India
| | - Shantala Hegde
- Department of Clinical Psychology, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India
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Wu J, Jin X, Xie W, Liu L, Wang F, Zhu L, Shen Y, Qiu L. Global research trends and hotspots in Parkinson's disease psychosis: a 25-year bibliometric and visual analysis. Front Aging Neurosci 2024; 16:1480234. [PMID: 39649718 PMCID: PMC11621064 DOI: 10.3389/fnagi.2024.1480234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 11/07/2024] [Indexed: 12/11/2024] Open
Abstract
Background Parkinson's disease psychosis (PDP) is one of the most severe and disabling non-motor symptoms in the progression of Parkinson's disease (PD), significantly impacting the prognosis of PD patients. In recent years, there has been an increase in literature on PDP. However, bibliometrics has rarely been applied to PDP research. This study provides an overview of the current state of PDP research and predicts future trends in this field. Methods The literature search was conducted using the Web of Science Core Collection, with the search terms (Parkinson* AND (psychotic* OR hallucination* OR illusion* OR delusion* OR misperception* OR psychosis OR psychoses)). VOSviewer and CiteSpace software were employed to perform bibliometric analysis and visual representation of the search results. Results A total of 603 articles were effectively included. Since 2017, there has been a significant upward trend in publications related to PDP. The United States, the United Kingdom, and Canada were the top three contributing countries in terms of publication volume, with France also having a strong influence in this field. Movement Disorders and King's College London included and published the most articles on PDP. The paper titled "Hallucinations in Parkinson's Disease: Prevalence, Phenomenology, and Risk Factors" received the highest number of citations and average citations. Cluster analysis results identified brain, prevalence, connectivity, and atypical antipsychotics as key hotspots in this field. High-frequency keywords were grouped into three themes: neurobiology, therapeutic strategies, and symptom research. Among them, pimavanserin, risk, and functional connectivity have been the most studied areas in the past 7 years and are likely to remain key topics in future research. Conclusion Research on PDP has garnered increasing attention. This study visualizes PDP research over the past 25 years to analyze global hotspots and trends. It offers researchers a valuable perspective for identifying key topics and understanding research trajectories in this expanding field.
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Affiliation(s)
- Jianhong Wu
- Affiliated Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, Jiangsu, China
| | - Xin Jin
- Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu, China
| | - Weiming Xie
- Affiliated Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, Jiangsu, China
| | - Liang Liu
- Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Fei Wang
- Affiliated Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, Jiangsu, China
| | - Ling Zhu
- Jiangyin People's Hospital, Wuxi, Jiangsu, China
| | - Yuan Shen
- Affiliated Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, Jiangsu, China
| | - Linghe Qiu
- Affiliated Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, Jiangsu, China
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Flanigan JL, Harrison MB, Patrie JT, Shah BB, Sperling SA, Wyman-Chick KA, Dalrymple WA, Barrett MJ. Clinical and cognitive features associated with psychosis in Parkinson's disease: a longitudinal study. Front Aging Neurosci 2024; 16:1463426. [PMID: 39574488 PMCID: PMC11579864 DOI: 10.3389/fnagi.2024.1463426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 10/14/2024] [Indexed: 11/24/2024] Open
Abstract
Background Parkinson's disease psychosis (PDPsy) is associated with increased nursing home placement and mortality and is closely linked with cognitive dysfunction. Objective Assess the clinical and cognitive features associated with PDPsy in patients without dementia. Methods We prospectively recruited people with Parkinson's disease (PwP) without dementia for a 3-year, longitudinal study at an outpatient movement disorders clinic. Participants completed annual visits involving assessment of motor and non-motor symptoms including neuropsychological testing. PDPsy was defined as the recurring presence of visual illusions, sense of presence, hallucinations, or delusions for at least 1 month. Using generalized estimating equations, we conducted two sets of analyses to separately assess the clinical and the cognitive predictors of PDPsy. Results We enrolled 105 participants. At baseline, mean age was 67.8 (SD = 8.0), median disease duration was 4.9 years (IQR: 3.4-7.7), and mean MoCA was 24.8 (SD = 2.3). Prevalence of PDPsy increased over 3 years from 31% (n = 32) to 39% (n = 26). Forty-five participants (43%) experienced PDPsy. Visual illusions were most common (70%, n = 84), followed by hallucinations (58.3%, n = 70). In multivariate analysis, of the clinical variables, only depressive symptoms [OR 1.09, 95% CI: (1.03, 1.16), p = 0.004] increased the odds of PDPsy; of the cognitive variables, only Trail Making Test B-A scores [OR 1.43, 95% CI: (1.06, 1.93), p = 0.018] significantly increased the odds of PDPsy. Conclusions In PwP without dementia, depressive symptoms were associated with increased risk of PDPsy. Executive/attentional dysfunction was also associated with PDPsy and may mark the transition from isolated minor hallucinations to more complex psychotic symptoms.
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Affiliation(s)
- Joseph L. Flanigan
- Department of Neurology, University of Virginia, Charlottesville, VA, United States
| | - Madaline B. Harrison
- Department of Neurology, University of Virginia, Charlottesville, VA, United States
| | - James T. Patrie
- Department of Public Health Sciences, University of Virginia, Charlottesville, VA, United States
| | - Binit B. Shah
- Department of Neurology, University of Virginia, Charlottesville, VA, United States
| | - Scott A. Sperling
- Center for Neurological Restoration, Department of Neurology, Cleveland Clinic, Cleveland, OH, United States
| | | | | | - Matthew J. Barrett
- Department of Neurology, Virginia Commonwealth University, Richmond, VA, United States
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Pisani S, Gosse L, Aarsland D, Ray Chaudhuri K, Ballard C, Ffytche D, Velayudhan L, Bhattacharyya S. Parkinson's disease psychosis associated with accelerated multidomain cognitive decline. BMJ MENTAL HEALTH 2024; 27:1-10. [PMID: 39043465 PMCID: PMC11268075 DOI: 10.1136/bmjment-2024-301062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 07/10/2024] [Indexed: 07/25/2024]
Abstract
BACKGROUND Cognitive deficits are associated with poor quality of life and increased risk of development of dementia in patients with Parkinson's disease (PD) psychosis. The trajectory of cognitive decline in PD psychosis remains however unclear. OBJECTIVE We examined this using data from the Parkinson's Progression Markers Initiative study. METHODS We analysed data from patients with drug-naïve PD (n=676) and healthy controls (HC, n=187) over 5 years, and examined all cognitive measures assessed at each time point. We classified patients with PD into those who developed psychosis over the course of the study (PDP) and those without psychosis throughout (PDnP) using the Movement Disorders Society Unified Parkinson's Disease Rating Scale part I hallucinations/psychosis item. We used linear mixed-effect models with restricted maximum likelihood. Age, sex, ethnicity, education and neuropsychiatric and PD-specific symptoms were entered as covariates of interest. FINDINGS There were no baseline cognitive differences between PD patient groups. There were differences in cognitive performance between PD and HC across the majority of the assessments.Patients with PDP exhibited greater cognitive decline over 5 years compared with PDnP across most domains even after controlling for sociodemographics, depression, sleepiness, rapid eye movement sleep behaviour disorder and motor symptom severity (immediate recall, b=-0.288, p=0.003; delayed recall, b=-0.146, p=0.003; global cognition, Montreal Cognitive Assessment, b=-0.206, p<0.001; visuospatial, b=-0.178, p=0.012; semantic fluency, b=-0.704, p=0.002; processing speed, b=-0.337, p=0.029). CONCLUSIONS Patients with PD psychosis exhibited decline in semantic aspects of language, processing speed, global cognition, visuospatial abilities and memory, regardless of sociodemographic characteristics, neuropsychiatric and motor symptoms. These cognitive domains, particularly semantic aspects of language may therefore play an important role in PD psychosis and warrant further investigation. TRIAL REGISTRATION NUMBER NCT01141023.
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Affiliation(s)
- Sara Pisani
- Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Luca Gosse
- Faculty of Medicine, Dentistry and Health, The University of Sheffield, Sheffield, UK
| | - Dag Aarsland
- Department of Psychological Medicine, Centre for Healthy Brain Ageing, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
- Centre for Age-Related Medicine (SESAM), Stavanger University Hospital, Stavanger, Norway
| | - K Ray Chaudhuri
- National Parkinson’s Foundation Centre of Excellence, King's College Hospital NHS Foundation Trust, London, UK
- Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Clive Ballard
- Faculty of Health and Life Sciences, University of Exeter, Exeter, UK
| | - Dominic Ffytche
- Department of Psychological Medicine, Centre for Healthy Brain Ageing, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Latha Velayudhan
- Department of Psychological Medicine, Centre for Healthy Brain Ageing, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Sagnik Bhattacharyya
- Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
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Spitschan M, Kervezee L, Lok R, McGlashan E, Najjar RP. Brighter future for light therapy: harmonising the reporting of light interventions in psychiatry. BMJ MENTAL HEALTH 2024; 27:1-2. [PMID: 39054044 PMCID: PMC11284921 DOI: 10.1136/bmjment-2024-301060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 05/30/2024] [Indexed: 07/27/2024]
Affiliation(s)
- Manuel Spitschan
- TUM School of Medicine and Health, Technical University of Munich, Munchen, Germany
- Translational Sensory and Circadian Neuroscience, Max Planck Institute for Biological Cybernetics, Tübingen, Baden-Württemberg, Germany
- TUM Institute for Advanced Study (TUM IAS), Technical University of Munich, Garching, Germany
| | - Laura Kervezee
- Department of Cellular and Chemical Biology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
| | - Renske Lok
- Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA
| | - Elise McGlashan
- Melbourne School of Psychological Sciences, University of Melbourne, Parkville, Victoria, Australia
| | - Raymond P Najjar
- Department of Ophthalmology, National University of Singapore, Singapore
- Singapore Eye Research Institute, Singapore
- Department of Biomedical Engineering, National University of Singapore, Singapore
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Kim JS, Hong SB, Park KW, Lee ATC. Psychotic Symptoms in Patients With Major Neurological Diseases. J Clin Neurol 2024; 20:153-165. [PMID: 38433485 PMCID: PMC10921039 DOI: 10.3988/jcn.2023.0501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 12/28/2023] [Accepted: 12/30/2023] [Indexed: 03/05/2024] Open
Abstract
Neurological diseases often manifest with neuropsychiatric symptoms such as depression, emotional incontinence, anger, apathy and fatigue. In addition, affected patients may also experience psychotic symptoms such as hallucinations and delusions. Various factors contribute to the development of psychotic symptoms, and the mechanisms of psychosis are similar, but still differ among various neurological diseases. Although psychotic symptoms are uncommon, and have been less well investigated, they may annoy patients and their families as well as impair the patients' quality of life and increase the caregiver burden. Therefore, we need to appropriately identify and treat these psychotic symptoms in patients with neurological diseases.
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Affiliation(s)
- Jong S Kim
- Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea.
| | - Seung-Bong Hong
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Keun-Woo Park
- Department of Neurology, Korea University Anam Hospital, Seoul, Korea
| | - Allen T C Lee
- Department of Psychiatry, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China
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Rodriguez Salgado AM, Acosta I, Kim DJ, Zitser J, Sosa AL, Acosta D, Jimenez-Velasquez IZ, Guerra M, Salas A, Valvuerdi A, Llibre-Guerra JC, Jeyachandran C, Contreras RL, Hesse H, Tanner C, Llibre Rodriguez JJ, Prina M, Llibre-Guerra JJ. Prevalence and impact of neuropsychiatric symptoms in normal aging and neurodegenerative syndromes: A population-based study from Latin America. Alzheimers Dement 2023; 19:5730-5741. [PMID: 37427840 PMCID: PMC10776811 DOI: 10.1002/alz.13384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 05/23/2023] [Accepted: 06/16/2023] [Indexed: 07/11/2023]
Abstract
BACKGROUND Neuropsychiatric symptoms (NPSs) are common in neurodegenerative diseases; however, little is known about the prevalence of NPSs in Hispanic populations. METHODS Using data from community-dwelling participants age 65 years and older enrolled in the 10/66 study (N = 11,768), we aimed to estimate the prevalence of NPSs in Hispanic populations with dementia, parkinsonism, and parkinsonism-dementia (PDD) relative to healthy aging. The Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to assess NPSs. RESULTS NPSs were highly prevalent in Hispanic populations with neurodegenerative disease; approximately 34.3%, 56.1%, and 61.2% of the participants with parkinsonism, dementia, and PDD exhibited three or more NPSs, respectively. NPSs were the major contributor to caregiver burden. DISCUSSION Clinicians involved in the care of elderly populations should proactively screen for NPSs, especially in patients with parkinsonism, dementia, and PPD, and develop intervention plans to support families and caregivers. Highlights Neuropsychiatric symptoms (NPSs) are highly prevalent in Hispanic populations with neurodegenerative diseases. In healthy Hispanic populations, NPSs are predominantly mild and not clinically significant. The most common NPSs include depression, sleep disorders, irritability, and agitation. NPSs explain a substantial proportion of the variance in global caregiver burden.
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Affiliation(s)
- Ana M Rodriguez Salgado
- Global Brain Health Institute, University of San Francisco California, San Francisco, California, USA
| | - Isaac Acosta
- Laboratory of the Dementias, National Institute of Neurology and Neurosurgery, Mexico City, Mexico
- National Autonomous University of Mexico, Mexico City, Mexico
| | - Dani J Kim
- Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Jennifer Zitser
- Department of Neurology, Movement Disorders Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Ana Luisa Sosa
- Laboratory of the Dementias, National Institute of Neurology and Neurosurgery, Mexico City, Mexico
- National Autonomous University of Mexico, Mexico City, Mexico
| | - Daisy Acosta
- Universidad Nacional Pedro Henriquez Ureña (UNPHU), Internal Medicine Department, Geriatric Section, Santo Domingo, Dominican Republic
| | - Ivonne Z Jimenez-Velasquez
- Internal Medicine Department, Geriatrics Program, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico
| | - Mariella Guerra
- Instituto de la Memoria Depresion y Enfermedades de Riesgo IMEDER, Lima, Perú
| | - Aquiles Salas
- Medicine Department, Caracas University Hospital, Faculty of Medicine, Universidad Central de Venezuela, Caracas, Venezuela
| | | | | | | | - Ricardo López Contreras
- Memory Clinic, Neurology Service, Salvadoran Social Security Institute, San Salvador, El Salvador
| | - Heike Hesse
- Universidad Tecnológica Centroamericana, Tegucigalpa, Honduras
| | - Caroline Tanner
- Department of Neurology, Weill Institute for Neurosciences, University of California-San Francisco, San Francisco, California, USA
| | | | - Matthew Prina
- Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK
| | - Jorge J Llibre-Guerra
- Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
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Tripathi A, Nasrallah HA, Pillai A. Pimavanserin treatment increases plasma brain-derived neurotrophic factor levels in rats. Front Neurosci 2023; 17:1237726. [PMID: 37712092 PMCID: PMC10499044 DOI: 10.3389/fnins.2023.1237726] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Accepted: 08/04/2023] [Indexed: 09/16/2023] Open
Abstract
Background 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. Methods 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). Results 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. Conclusion These findings suggest that increase in mBDNF levels could be a contributing mechanism for the neuroprotective potential of Pimavanserin.
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Affiliation(s)
- Ashutosh Tripathi
- Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, United States
| | - Henry A. Nasrallah
- Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, United States
| | - Anilkumar Pillai
- Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, United States
- Department of Psychiatry and Health Behavior, Augusta University, Augusta, GA, United States
- Charlie Norwood VA Medical Center, Augusta, GA, United States
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Foley JA, Chen C, Paget A, Cipolotti L. A Bayesian predictive processing account of Othello syndrome in Parkinson's disease. Cogn Neuropsychiatry 2023; 28:269-284. [PMID: 37366042 DOI: 10.1080/13546805.2023.2229080] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 03/24/2023] [Indexed: 06/28/2023]
Abstract
Introduction: Although delusions in Parkinson's disease (PD) are rare, when they occur they frequently take the form of "Othello syndrome": the irrational belief that a spouse or partner is being unfaithful. Hitherto dismissed as either a by-product of dopamine therapy or cognitive impairment, there are still no convincing theoretical accounts to explain why only some patients fall prey to this delusion, or why it persists despite clear disconfirmatory evidence.Methods: We discuss the limitations of existing explanations of this delusion, namely hyperdopaminergia-induced anomalous perceptual experiences and cognitive impairment, before describing how Bayesian predictive processing accounts can provide a more comprehensive explanation by foregrounding the importance of prior experience and its impact upon computation of probability. We illustrate this new conceptualisation with three case vignettes.Results: We suggest that in those with prior experience of romantic betrayal, hyperdominergic-induced aberrant prediction errors enable anomalous perceptual experiences to accrue greater prominence, which is then maintained through Bayes-optimal inferencing to confirm cognitive distortions, eliciting and shaping this dangerous delusion.Conclusions: We propose the first comprehensive mechanistic account of Othello syndrome in PD and discuss implications for clinical interventions.
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Affiliation(s)
- Jennifer A Foley
- Department of Neuropsychology, National Hospital for Neurology and Neurosurgery, London, UK
- UCL Queen Square Institute of Neurology, London, UK
| | - Cliff Chen
- Department of Clinical Neuropsychology, Salford Royal NHS Foundation Trust, Salford, UK
| | - Andrew Paget
- Department of Neuropsychology, National Hospital for Neurology and Neurosurgery, London, UK
| | - Lisa Cipolotti
- Department of Neuropsychology, National Hospital for Neurology and Neurosurgery, London, UK
- UCL Queen Square Institute of Neurology, London, UK
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Zheng HB, Liu B, Shen J, Xie F, Ji QM, Zhu XY. Non-invasive brain stimulation for treating psychiatric symptoms in Parkinson’s disease: A systematic review and meta-analysis. J Clin Neurosci 2022; 106:83-90. [DOI: 10.1016/j.jocn.2022.10.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 09/30/2022] [Accepted: 10/12/2022] [Indexed: 11/07/2022]
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Abler V, Brain C, Ballard C, Berrio A, Coate B, Espay AJ. Motor- and cognition-related safety of pimavanserin in patients with Parkinson's disease psychosis. Front Neurol 2022; 13:919778. [PMID: 36277907 PMCID: PMC9580496 DOI: 10.3389/fneur.2022.919778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 09/07/2022] [Indexed: 12/01/2022] Open
Abstract
Background Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, is the only treatment approved by the US Food and Drug Administration for hallucinations and delusions associated with Parkinson's disease (PD) psychosis. Aim We aimed to evaluate motor- and cognition-related safety in pimavanserin-treated patients with PD psychosis. Methods This analysis included patients with PD psychosis treated with pimavanserin 34 mg from a pooled analysis of 3 randomized, double-blind, placebo-controlled, 6-week studies [NCT00477672 (study ACP-103-012), NCT00658567 (study ACP-103-014), and NCT01174004 (study ACP-103-020)] and a subgroup of patients with PD dementia with psychosis from HARMONY (NCT03325556), a randomized discontinuation study that included a 12-week open-label period followed by a randomized double-blind period of up to 26 weeks. Motor- and cognition-related safety were examined. Results The pooled analysis included 433 randomized patients (pimavanserin, 202; placebo, 231). Least squares mean (standard error [SE]) change from baseline to week 6 Unified Parkinson's Disease Rating Scale (UPDRS) II + III score was similar for pimavanserin [−2.4 (0.69)] and placebo [−2.3 (0.60)] (95% Confidence Interval [CI]:−1.9, 1.6). The change from baseline to week 6 for UPDRS II and UPDRS III scores was similar between groups. In the HARMONY open-label period, 49 patients with PD dementia with psychosis were treated with pimavanserin 34 mg, 36 of whom were randomized in the double-blind period (pimavanserin, 16; placebo, 20). In the open-label period, the mean (SE) change from baseline to week 12 (n = 39) Extra-Pyramidal Symptom Rating Scale (ESRS-A) score was −1.7 (0.74); in the double-blind period, the results were generally comparable between the pimavanserin and placebo arms. The change from baseline in Mini-Mental State Examination (MMSE) score was also comparable between pimavanserin- and placebo-treated patients in HARMONY [open-label (n = 37): mean (SE) change from baseline to week 12, 0.3 (0.66)]. Rates of motor- and cognition-related adverse events were similar between pimavanserin and placebo in both analyses. Conclusions Pimavanserin 34 mg was well tolerated and did not yield a negative impact on motor- or cognition-related function in patients with PD psychosis.
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Affiliation(s)
- Victor Abler
- Acadia Pharmaceuticals Inc, San Diego, CA, United States
| | - Cecilia Brain
- Acadia Pharmaceuticals Inc, San Diego, CA, United States
| | - Clive Ballard
- University of Exeter Medical School, Exeter, United Kingdom
| | - Ana Berrio
- Acadia Pharmaceuticals Inc, San Diego, CA, United States
| | - Bruce Coate
- Acadia Pharmaceuticals Inc, San Diego, CA, United States
| | - Alberto J. Espay
- Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, United States
- *Correspondence: Alberto J. Espay
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13
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Shaughnessy L, Brunton S, Chepke C, Farmer JG, Rosenzweig AS, Grossberg G. Using Telemedicine to Assess and Manage Psychosis in Neurodegenerative Diseases in Long-Term Care. J Am Med Dir Assoc 2022; 23:1145-1152. [PMID: 35032454 PMCID: PMC8752392 DOI: 10.1016/j.jamda.2021.12.033] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 10/29/2021] [Accepted: 12/11/2021] [Indexed: 11/04/2022]
Abstract
The coronavirus disease 2019 (COVID-19) epidemic has forced a sudden global implementation of telemedicine strategies, including in long-term care (LTC) facilities where many people with dementia and Parkinson disease (PD) reside. Telemedicine offers a unique set of advantages for residents in LTC facilities if effectively supported and implemented, including expanded access to specialists in rural or underserved areas or for people with dementia who cannot travel for off-site visits. Many medical and psychiatric organizations have recently issued new or updated guidelines on the use of telemedicine. On October 22, 2020, a multidisciplinary consensus panel was convened to collate a list of best practices for LTC facilities and specialists when conducting telemedicine with residents with dementia-related psychosis or PD-related psychosis (PDP). A collaborative effort between specialists, facility administrators, and facility staff is essential for the success of telemedicine in the LTC setting. Telemedicine in LTC facilities comes with increased administrative and technical challenges that fall heavily on the shoulders of the LTC facility administrators and staff. Specialists can ease this burden by maintaining flexibility and ensuring expression of empathy and thanks to the staff who are facilitating the visits. LTC staff can provide specialists with valuable information about their patients to aid in evaluation and diagnosis. Specialists can facilitate this exchange of information by speaking to staff who work closely with the resident about any signs of hallucinations or delusions they may have observed. Educational efforts can increase staff understanding of dementia and PDP and empower them to engage with, and facilitate the resident's treatment plan. Using these strategies to take advantage of the benefits of telemedicine, specialists and LTC staff can together expand and improve care for LTC facility residents with dementia-related psychosis or PDP.
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Affiliation(s)
- Lynn Shaughnessy
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
| | - Stephen Brunton
- Primary Care Education Consortium, Winnsboro, SC, USA; Touro University, Vallejo, CA, USA
| | - Craig Chepke
- Excel Psychiatric Associates and University of North Carolina School of Medicine, Huntersville, NC, USA
| | - Jill G Farmer
- Parkinson's Disease and Movement Disorder Program, Center for Neurosciences, Robert Wood Johnson University Hospital Hamilton, Lawrenceville, NJ, USA; Drexel College of Medicine, Philadelphia, PA, USA
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14
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Oh M, Kim JW, Lee SM. Delusional parasitosis as premotor symptom of parkinson’s disease: A case report. World J Clin Cases 2022; 10:2858-2863. [PMID: 35434114 PMCID: PMC8968791 DOI: 10.12998/wjcc.v10.i9.2858] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 12/16/2021] [Accepted: 01/23/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Delusional parasitosis is characterized by a false belief of being infested with parasites, insects, or worms. This illness is observed in patients with Parkinson’s disease and is usually related to dopaminergic treatment. To our knowledge, no cases of delusional parasitosis have been reported as a premotor symptom or non-motor symptom of Parkinson’s disease.
CASE SUMMARY A 75-year-old woman presented with a complaint of itching that she ascribed to the presence of insects in her skin, and she had erythematous plaques on her trunk, arms, buttocks, and face. These symptoms started two months before the visit to the hospital. She took medication, including antipsychotics, with a diagnosis of delusional parasitosis, and the delusion improved after three months. A year later, antipsychotics were discontinued, and anxiety and depression were controlled with medication. However, she complained of bradykinesia, masked face, hand tremor, and mild rigidity, and we performed fluorinated N-3-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane positron emission tomography (PET), which showed mildly decreased DAT binding in the right anterior putamen and caudate nucleus. Parkinson’s disease was diagnosed on the basis of PET and clinical symptoms.
CONCLUSION In conclusion, delusional parasitosis can be considered a non-motor sign of Parkinson’s disease along with depression, anxiety, and constipation.
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Affiliation(s)
- Miae Oh
- Department of Psychiatry, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul 02447, South Korea
| | - Jong Woo Kim
- Department of Psychiatry, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul 02447, South Korea
| | - Sang-Min Lee
- Department of Psychiatry, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul 02447, South Korea
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15
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Abstract
Cognitive impairment affects up to 80% of patients with Parkinson's disease (PD) and is associated with poor quality of life. PD cognitive dysfunction includes poor working memory, impairments in executive function and difficulty in set-shifting. The pathophysiology underlying cognitive impairment in PD is still poorly understood, but there is evidence to support involvements of the cholinergic, dopaminergic, and noradrenergic systems. Only rivastigmine, an acetyl- and butyrylcholinesterase inhibitor, is efficacious for the treatment of PD dementia, which limits management of cognitive impairment in PD. Whereas the role of the serotonergic system in PD cognition is less understood, through its interactions with other neurotransmitters systems, namely, the cholinergic system, it may be implicated in cognitive processes. In this chapter, we provide an overview of the pharmacological, clinical and pathological evidence that implicates the serotonergic system in mediating cognition in PD.
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16
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Chendo I, Fabbri M, Godinho C, Moiron Simões R, Severiano Sousa C, Coelho M, Voon V, Ferreira JJ. High frequency of psychosis in late-stage Parkinsońs disease. Clin Park Relat Disord 2022; 5:100119. [PMID: 34988427 PMCID: PMC8710406 DOI: 10.1016/j.prdoa.2021.100119] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 11/10/2021] [Accepted: 11/17/2021] [Indexed: 12/31/2022] Open
Abstract
55.4% of late-stage Parkinsońs disease (LSPD) patients have psychotic symptoms. 72.5% of LSPD patients present a comorbid psychiatric diagnosis. Clinical diagnostic interview increases detection of psychosis. Background Psychosis is a frequent non-motor symptom in Parkinson’s disease (PD). Estimates of the frequency of Parkinsońs disease psychosis (PDP) vary widely. Knowledge about the frequency and phenomenology of psychosis in late-stage (LS) PD patients is limited. This study aimed to determine the frequency of psychosis in LSPD patients through clinical diagnostic interview (CDI) (gold standard), according to NINDS/NIMH diagnostic criteria for PDP. The secondary objectives were to characterize the phenomenology, to test selected instruments and assess their adequacy in comparison to CDI, and to assess the psychiatric comorbidities. Methods A cross-sectional study including LSPD patients (patients with ≥ 7 years from symptoms onset and Hoehn and Yahr scale score > 3 or a Schwab and England scale score < 50% in the ON condition) was conducted. Patients were subjected to psychiatric, neurological, and neuropsychological evaluations. Each patient was interviewed by a psychiatrist who performed a CDI. Results 92 LSPD patients were included. 55.4% experienced psychotic symptoms according to NINDS/NIMH diagnostic criteria for PDP. Hallucinations were present in 94.1% and delusions in 29.4% of the psychotic patients. Visual hallucinations were the most common (88.23%) psychotic symptom. 72.5% of LSPD patients with psychotic symptoms had at least one comorbid psychiatric diagnosis. Lower frequency of psychosis was found when the assessment was performed only through selected instruments rather than CDI. Conclusions A high frequency (55.4%) of psychotic symptoms and comorbid psychiatric (72.5%) diagnosis were found in LSPD patients. The use of CDI, in addition to structured scales may increase the sensitivity of detecting psychotic symptoms.
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Affiliation(s)
- Inês Chendo
- Psychiatry Department, Department of Neurosciences, Hospital de Santa Maria, Lisbon, Portugal.,Clínica Universitária de Psiquiatria e de Psicologia Médica, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.,CNS - Campus Neurológico, Torres Vedras, Portugal
| | - Margherita Fabbri
- Instituto de Medicina Molecular João Lobo Antunes, Lisbon, Portugal.,Department of Neurosciences, Clinical Investigation Center CIC 1436, Parkinson Toulouse Expert Center, NS-Park/FCRIN Network and NeuroToul COEN Center, Toulouse University Hospital, INSERM, University of Toulouse 3, Toulouse, France
| | - Catarina Godinho
- Grupo de Patologia Médica, Nutrição e Exercício Clínico (PaMNEC) do Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), Escola Superior de Saúde Egas Moniz, Almada, Portugal
| | - Rita Moiron Simões
- CNS - Campus Neurológico, Torres Vedras, Portugal.,Neurology Department, Hospital Beatriz Ângelo, Loures, Portugal
| | - Catarina Severiano Sousa
- Instituto de Medicina Molecular João Lobo Antunes, Lisbon, Portugal.,Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Miguel Coelho
- Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.,Neurology Service, Department of Neurosciences, Hospital Santa Maria, Lisbon, Portugal
| | - Valerie Voon
- Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
| | - Joaquim J Ferreira
- CNS - Campus Neurológico, Torres Vedras, Portugal.,Instituto de Medicina Molecular João Lobo Antunes, Lisbon, Portugal.,Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
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17
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Diederich NJ. [Causes of visual hallucinations in Parkinson's disease]. DER NERVENARZT 2022; 93:392-401. [PMID: 34342675 PMCID: PMC9010390 DOI: 10.1007/s00115-021-01165-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 05/17/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Visual hallucinations (VH) have mainly been considered as late symptoms of Parkinson's disease (PD); however, minor forms of VH also occur in early stages of the disease. Initially dopaminergic overstimulation was discussed as the cause and later on VH have been considered as an early red flag of dementia in PD. OBJECTIVE The present study analyzed whether the pathophysiological concept of VH has been enlarged in recent years. MATERIAL AND METHODS Clinical, pharmacological, neuropathological as well as functional magnetic resonance imaging studies dealing with VH were reviewed. A systematic classification in monomodal and multimodal models of VH is proposed. The applicability to various forms of VH and various triggering situations is critically examined. RESULTS Reduction of the visual information input, erroneous visual processing, attention deficits, and dysfunctional connectivity between various cerebral networks have been shown. There is partial overlapping with the Lhermitte syndrome and the Charles Bonnet syndrome. No model is able to fully explain all VH variants. Not all VH have the same pathogenesis and the same poor prognosis. CONCLUSION The chain of causes underlying VH is complex and can vary from patient to patient. So far the therapeutic applications are largely unexplored; however, there is preliminary evidence that beside adjustment of the medication, improvement of visual acuity, active involvement of the partner, and possibly, individually adaptable coping strategies could be successfully implemented.
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Affiliation(s)
- Nico J. Diederich
- Abteilung für Neurologie, Centre Hospitalier de Luxembourg, 4, rue Barblé, 1210 Luxemburg-Stadt, Luxemburg
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18
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Zhong M, Wu Z, Jiang X, Shen B, Zhu J, Zhang L. Knowledge domain and emerging trends in visual hallucination research: A scientometric analysis. World J Psychiatry 2021; 11:491-506. [PMID: 34513610 PMCID: PMC8394690 DOI: 10.5498/wjp.v11.i8.491] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 03/29/2021] [Accepted: 07/05/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Visual hallucination (VH) refers to a spontaneous visual perception without corresponding external stimuli and often occurs in ophthalmological and neuropsychiatric disorders. It is associated with poor quality of life, and increased patient hospitalization and nursing home admission. To date, a scientometric analysis of research on VH is lacking.
AIM To objectively summarize the features of VH research and gain insights into the emerging trends in research on VH.
METHODS CiteSpace V was used in this article. Publication outputs, document types, geographic distributions, co-authorship status, research hotspots, and co-citation status were analyzed. A total of 2176 original articles and 465 reviews were included in the database downloaded from the Web of Science Core Collection. We selected the top 50 most cited or occurring articles or items to create a visualized network with a 1-year interval. In the document co-citation analysis stage, we performed clustering analysis on co-cited references, and log likelihood tests were used to name the clusters.
RESULTS The results showed that most publications can be classified into neurology, sports, and ophthalmology studies. In addition, North America, Europe, Asia and Australia published the most documents. Some well-known authors have always had a leading role in this field; meanwhile, new authors keep emerging. A relatively stable cooperation has been formed among many authors. Furthermore, neuropsychiatric symptom and functional connectivity are the top hotspots. Research on VH in dementia with Lewy bodies and Parkinson’s disease (PD) have received much attention. Studies on VH in PD are likely to be the new emerging trends in the future, especially the mechanisms of VH.
CONCLUSION Research on VH has formed a complete system. More large-scale clinical and in-depth basic research are required to better understand the mechanisms underlying VH, which will contribute to our understanding of the pathophysiology and therapeutic options for VH.
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Affiliation(s)
- Min Zhong
- Department of Geriatric Neurology, Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Zhuang Wu
- Department of Geriatric Neurology, Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Xu Jiang
- Department of Geriatric Neurology, Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Bo Shen
- Department of Geriatric Neurology, Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Jun Zhu
- Department of Geriatric Neurology, Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Li Zhang
- Department of Geriatric Neurology, Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
- Institute of Neuropsychiatric Diseases, Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
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19
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Radojević B, Dragašević-Mišković NT, Marjanović A, Branković M, Dobričić V, Milovanović A, Tomić A, Svetel M, Petrović I, Jančić I, Stanisavljević D, Savić MM, Kostić VS. Clinical and Genetic Analysis of Psychosis in Parkinson's Disease. JOURNAL OF PARKINSONS DISEASE 2021; 11:1973-1980. [PMID: 34151861 DOI: 10.3233/jpd-212716] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Recent studies explored polymorphisms of multiple genes as contributing to genetic susceptibility to psychosis in Parkinson's disease (PDP). OBJECTIVE We aimed to examine the association of seven selected polymorphisms of genes related to dopamine pathways with PDP development. At the same time, demographic and clinical correlates of PDP were assessed. METHODS PD patients (n = 234), treated with levodopa for at least two years, were genotyped for the rs4680 in COMT, rs6277, rs1076560, and rs2283265 in DRD2, and rs1800497 and rs2734849 polymorphisms in ANKK1 genes. Also, variable number of tandem repeats polymorphism in the DAT gene was examined. Each patient underwent comprehensive neurological examination, assessment of psychosis, as defined by the NINDS/NIMH criteria, as well as screening of depression, anxiety, and cognitive status. RESULTS Diagnostic criteria for PDP were met by 101 (43.2%) patients. They had longer disease duration, were taking higher doses of dopaminergic agents, and had higher scores of the motor and non-motor scales than the non-PDP group. Multivariate regression analysis revealed LEDD≥900 mg, Unified Parkinson's Disease Rating Scale III part score, the Hamilton Depression Rating Scale score≥7, the Hamilton Anxiety Rating Scale score > 14,and GG homozygotes of rs2734849 ANKK1 as independent predictors of the onset of PDP. CONCLUSION Besides previous exposure to dopaminergic drugs, impairment of motor status, depression and anxiety, as well-established clinical risk factors for the development of PDP, GG rs2734849 ANKK1 could also be a contributing factor, which requires addressing by future longitudinal studies.
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Affiliation(s)
| | | | - Ana Marjanović
- Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia
| | - Marija Branković
- Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia
| | - Valerija Dobričić
- Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), Institutes of Neurogenetics & Cardiogenetics, University of Lübeck, Lübeck, Germany
| | - Andona Milovanović
- Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia
| | - Aleksandra Tomić
- Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia
| | - Marina Svetel
- Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia
| | - Igor Petrović
- Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia
| | - Ivan Jančić
- Faculty of Pharmacy, University of Belgrade, Serbia
| | - Dejana Stanisavljević
- Institute Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Serbia
| | | | - Vladimir S Kostić
- Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia
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20
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Terravecchia C, Mostile G, Rascunà C, Arabia G, Barone P, Marconi R, Morgante L, Quattrone A, Nicoletti A, Zappia M. Does an association between cigarette smoking and Parkinson's Disease-related psychosis exist? Insights from a large non-demented cohort. J Neurol Sci 2021; 427:117509. [PMID: 34082149 DOI: 10.1016/j.jns.2021.117509] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 05/14/2021] [Accepted: 05/21/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Parkinson's Disease-related Psychosis (PDP) encompasses a spectrum of symptoms ranging from "minor" hallucinations to formed hallucinations and delusions. Notably, cognitive impairment has been recognized as the strongest risk factor for PDP. Several evidences suggest a possible role of cigarette smoking in both cognition and psychotic syndromes. OBJECTIVES To evaluate the possible independent association between cigarette smoking and PDP in a large cohort of non-demented PD patients. METHODS A cohort of non-demented PD patients was selected from the FRAGAMP study population. All participants underwent a standardised structured questionnaire to assess demographic, clinical and environmental exposure data. Clinical features were assessed using UPDRS, HY stage, AIMS, MMSE and Hamilton Rating Scale for Depression. Presence of psychotic symptoms was assessed using UPDRS-I.2 score. Diagnosis of PDP was made according to NINDS/NIMH criteria. RESULTS Four hundred eighty-five non-demented PD patients were enrolled [292 men (60.2%); mean age ± SD 65.6 ± 9.8]. Among them, 28 (5.8%) had PDP. Multivariate analysis, adjusting by HY stage, MMSE and LED, shown an independent association between PDP and "nightmares-abnormal movements during sleep" and current smoking [adjOR 7.39 (95%CI 1.45-37.69; P-value 0.016)]. CONCLUSIONS Our findings provide interesting insights about the possible role of current smoking in facilitating the occurrence of psychotic symptoms in PD.
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Affiliation(s)
- Claudio Terravecchia
- Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, Catania, Italy
| | - Giovanni Mostile
- Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, Catania, Italy; Oasi Research Institute-IRCCS, Troina, Italy
| | - Cristina Rascunà
- Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, Catania, Italy
| | - Gennarina Arabia
- Institute of Neurology, University "Magna Graecia", Catanzaro, Italy
| | - Paolo Barone
- Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Salerno, Italy
| | | | | | - Andrea Quattrone
- Institute of Neurology, University "Magna Graecia", Catanzaro, Italy
| | - Alessandra Nicoletti
- Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, Catania, Italy
| | - Mario Zappia
- Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, Catania, Italy.
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21
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Abstract
Acute presentation of new movement disorders and acute decompensation of chronic movement disorders are uncommon but potentially life-threatening. Inadvertent or purposeful overdose of many psychiatric medications can result in acute life-threatening movement disorders including serotonin syndrome, neuroleptic malignant syndrome, and malignant catatonia. Early withdrawal of potentiating medications, treatment with benzodiazepines and other diagnosis-specific drugs, and providing appropriate supportive care including airway and breathing management, hemodynamic stabilization, fluid resuscitation, and renal support including possible hemodialysis are the mainstays of acute management. Many of these conditions require admission to the neurologic intensive care unit.
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22
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Mantri S, Edison B, Alzyoud L, Albert SM, Daeschler M, Kopil C, Marras C, Chahine LM. Knowledge, Responsibilities, and Peer Advice From Care Partners of Patients With Parkinson Disease Psychosis. Front Neurol 2021; 12:633645. [PMID: 33597918 PMCID: PMC7882678 DOI: 10.3389/fneur.2021.633645] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 01/04/2021] [Indexed: 01/09/2023] Open
Abstract
Introduction: Care partners (CPs) of individuals with Parkinson disease psychosis (PDP) experience increased strain and rely on informal support networks. The objective of this study was to characterize CP responsibilities, sources of support, and peer advice. Methods: This was a mixed-methods cross-sectional study. The sample was recruited from the online Fox Insight study cohort. CPs who indicated their care recipient suffered hallucinations and/or delusions were administered a questionnaire regarding their caregiving experience to person with PDP. A free-text question asked CPs to give advice to a hypothetical peer CP. Responses to multiple-choice questions were tabulated; responses to the free-text question were grouped into advice categories. Results: 145 CP of individuals with PDP were included in this analysis, mean age (standard deviation, SD) 66.4 (9.4) years; 110 (75.9%) were women. Most (115, 79.3%) provided caregiving on a daily basis, with a range of responsibilities. Only 16 (11%) learned about PDP from a physician; communication challenges included perceived embarrassment or having to prioritize other issues in a limited appointment time. The most common peer advice was to alert the care recipient's neurologist (n = 38, 30.4%); only 8 (6.4%) suggested medication changes. Conclusion: CPs face challenges with clinician communication and learn about psychosis from a variety of informal sources. Few CPs advocate for medications to control PDP, instead preferring non-pharmacological management strategies. Peer advice favored alerting the care recipient's physician, suggesting that CPs do desire more information from the medical team.
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Affiliation(s)
- Sneha Mantri
- Department of Neurology, Duke University, Durham, NC, United States
| | - Briana Edison
- Department of Neurology, University of Pittsburgh, Pittsburgh, PA, United States
| | - Lamees Alzyoud
- Department of Neurology, University of Pittsburgh, Pittsburgh, PA, United States
| | - Steven M Albert
- Department of Behavioral and Community Sciences, University of Pittsburgh, Pittsburgh, PA, United States
| | - Margaret Daeschler
- The Michael J Fox Foundation for Parkinson's Research, New York, NY, United States
| | - Catherine Kopil
- The Michael J Fox Foundation for Parkinson's Research, New York, NY, United States
| | - Connie Marras
- The Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada
| | - Lana M Chahine
- Department of Neurology, University of Pittsburgh, Pittsburgh, PA, United States
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23
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Huang KH, Kuo WY, Kuan YH, Chang YC, Tsai TH, Lee CY. Risk of Pneumonia is associated with Antipsychotic Drug Use among older patients with Parkinson's Disease: A Case-control Study. Int J Med Sci 2021; 18:3565-3573. [PMID: 34522183 PMCID: PMC8436093 DOI: 10.7150/ijms.63246] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 08/09/2021] [Indexed: 12/14/2022] Open
Abstract
Objective: To investigate the risk of pneumonia associated with the use of antipsychotic drugs in older-adult patients with Parkinson's disease (PD) in Taiwan. Methods: This case-control study was based on data from the longitudinal health insurance database in Taiwan. We analyzed the data of 51,158 older patients with PD for the period between 2001 and 2016. To reduce the potential confounding caused by unbalanced covariates in nonexperimental settings, we used propensity score matching to include older patients without pneumonia to serve as the control group. Results: Compared with patients who had never taken antipsychotics, current (adjusted odds ratios [aOR] =1.63, 95% confidence interval [CI] = 1.51-1.75), recent (aOR = 1.63, 95% CI = 1.52-1.74), and past (aOR = 1.89, 95% CI = 1.80-2.00) users of antipsychotics had a higher risk of incident pneumonia. Among typical and atypical antipsychotics, haloperidol and clozapine were associated with higher risks of incident pneumonia, respectively. By contrast, aripiprazole was not associated with a higher risk of pneumonia. Conclusion: Older patients with PD receiving typical antipsychotics or atypical antipsychotics had a higher risk of pneumonia. Among these antipsychotics, clozapine had the highest risk of pneumonia. Clinicians should pay attention to the risk of pneumonia in older patients with PD who receive typical antipsychotics and atypical antipsychotics.
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Affiliation(s)
- Kuang-Hua Huang
- Department of Health Services Administration, China Medical University, Taichung, Taiwan
| | - Wei-Yin Kuo
- Department of Health Services Administration, China Medical University, Taichung, Taiwan
| | - Yu-Hsiang Kuan
- Department of Pharmacology, Chung Shan Medical University, Taichung, Taiwan.,Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Yu-Chia Chang
- Department of Healthcare Administration, Asia University, Taichung, Taiwan.,Department of Long Term Care, National Quemoy University, Kinmen, Taiwan
| | - Tung-Han Tsai
- Department of Health Services Administration, China Medical University, Taichung, Taiwan
| | - Chien-Ying Lee
- Department of Pharmacology, Chung Shan Medical University, Taichung, Taiwan.,Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan
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Orayj K. Impact of Antidepressants on Cardiac Events and All-Cause Mortality in Parkinson's Disease: A National Data-Linkage Study. Neuropsychiatr Dis Treat 2021; 17:2499-2510. [PMID: 34354357 PMCID: PMC8331107 DOI: 10.2147/ndt.s325521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 07/27/2021] [Indexed: 12/03/2022] Open
Abstract
PURPOSE This study investigated the 1-year risk of ischemic heart disease (IHD), all cardiovascular events, and all-cause mortality among newly diagnosed Parkinson's disease (PD) patients who used antidepressants compared to those who did not. PATIENTS AND METHODS Patients with PD aged 40 years or older were identified using data from 2000 through 2016 held within the Welsh Secure Anonymized Information Linkage (SAIL) databank. Antidepressant users were propensity-score matched 1:1 with non-users, adjusting for patients' demographics, socioeconomic status, and multiple comorbidities. Cox proportional hazard regression analyses were performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between the antidepressants and the study outcomes. The follow-up period was 1 year after the initial prescription of antidepressants. RESULTS The study group comprised a total of 3364 participants, with numbers split equally between the antidepressant-user and non-user groups, based on the propensity score-matching process. Overall, the propensity score-adjusted model showed that antidepressant usage in PD patients was not significantly associated with the risk of IHD (HR = 1.05; 95% CI 0.63-1.75) or all cardiovascular events (HR = 1.01; 95% CI 0.71-1.45) compared to non-users. The propensity score-adjusted model also showed that the use of any antidepressant, regardless of its category, was not statistically significantly associated with all-cause mortality (HR = 0.81; 95% CI 0.65-1.02). However, this association reached statistical significance in the multivariate adjusted model (HR = 0.67; 95% CI 0.54-0.84). CONCLUSION There was no evidence that antidepressant use was associated with an increased risk of IHD or all cardiovascular events in newly diagnosed PD patients who suffered from depression. Furthermore, antidepressant use might reduce the mortality rate in PD patients during the first year after initiation.
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Affiliation(s)
- Khalid Orayj
- Clinical Pharmacy Department, School of Pharmacy, King Khalid University, Abha, Saudi Arabia
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25
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Pennington C, Duncan G, Ritchie C. Altered awareness of cognitive and neuropsychiatric symptoms in Parkinson's disease and Dementia with Lewy Bodies: A systematic review. Int J Geriatr Psychiatry 2021; 36:15-30. [PMID: 32869379 DOI: 10.1002/gps.5415] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 08/09/2020] [Accepted: 08/14/2020] [Indexed: 01/29/2023]
Abstract
OBJECTIVES Altered awareness of cognitive and neuropsychiatric symptoms is a common feature of neurodegeneration, which can significantly impact on quality of life, medication concordance and personal safety. Elucidating how awareness is affected by common alpha-synucleinopathies therefore has significant clinical relevance. We performed a systematic review of the literature on awareness of cognitive and neuropsychiatric symptoms in Parkinson's disease and Dementia with Lewy Bodies. METHODS Searches of PubMed and Web of Science were carried out, using keywords and MeSH subheadings, limited to papers in English dealing with humans. The terms "Parkinson's" or "Lewy body" were used to denote the disease of interest, combined with either "agnosia", "anosognosia", "insight", "metacognition", or "neuropsychology" to denote the neuropsychological area of interest. RESULTS 21 publications investigating awareness of cognitive symptoms, and 18 publications on awareness of neuropsychiatric symptoms were identified. The large majority focused on Parkinson's disease rather than Dementia with Lewy Bodies. Cognitively intact people with Parkinson's disease may over-report cognitive symptoms, whilst those with cognitive impairment under-report symptoms. Awareness of neuropsychiatric symptoms is likely to decline over time, particularly in those with progressive cognitive impairment. CONCLUSIONS Altered awareness of cognitive and neuropsychiatric symptoms is common in Parkinson's disease. Symptom awareness varies significantly between individuals, and appears to be influenced by mood and global cognitive functioning, with executive functioning specifically implicated. There are gaps in our understanding of how dopaminergic medications influence symptom awareness, and a need for longitudinal studies of how awareness changes over time in Parkinson's disease and Dementia with Lewy Bodies.
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Affiliation(s)
- Catherine Pennington
- Edinburgh Dementia Prevention, University of Edinburgh, Edinburgh, UK
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
| | - Gordon Duncan
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
| | - Craig Ritchie
- Edinburgh Dementia Prevention, University of Edinburgh, Edinburgh, UK
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
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26
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Abstract
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.
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Affiliation(s)
- Alice Powell
- ForeFront Parkinson's Disease Research Clinic, Brain and Mind Centre, School of Medical Sciences, the University of Sydney, Camperdown, Australia.,Department of Geriatric Medicine, Prince of Wales Hospital, Randwick, Australia
| | - Elie Matar
- ForeFront Parkinson's Disease Research Clinic, Brain and Mind Centre, School of Medical Sciences, the University of Sydney, Camperdown, Australia
| | - Simon J G Lewis
- ForeFront Parkinson's Disease Research Clinic, Brain and Mind Centre, School of Medical Sciences, the University of Sydney, Camperdown, Australia
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27
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Kurita A, Koshikawa H, Akiba T, Seki K, Ishikawa H, Suzuki M. Visual Hallucinations and Impaired Conscious Visual Perception in Parkinson Disease. J Geriatr Psychiatry Neurol 2020; 33:377-385. [PMID: 31808354 DOI: 10.1177/0891988719892318] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Visual hallucinations (VHs) are common in patients with Parkinson disease (PD), especially those with dementia, whereas auditory hallucinations are quite rare. Recent studies have revealed the involvement of several regions along the visual information-processing system that contribute to the pathophysiological mechanism of VHs: the eyes and retina, retinofugal projection, lateral geniculate nucleus, striate cortex, ventral pathways in the temporal cortices, and frontal and parietal cortices. In addition, the concurrent involvement of other systems in the brainstem and basal forebrain further modify VHs in PD. In this review, we discuss the pathophysiological association between the regional involvement of these areas and VHs.
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Affiliation(s)
- Akira Kurita
- Department of Neurology, 26403Teikyo University Chiba Medical Center, Ichihara, Japan
| | - Hiroaki Koshikawa
- Department of Neurology, 26403Teikyo University Chiba Medical Center, Ichihara, Japan
| | - Takeshi Akiba
- Department of Neurology, 26403Teikyo University Chiba Medical Center, Ichihara, Japan
| | - Kanako Seki
- Department of Neurology, 26403Teikyo University Chiba Medical Center, Ichihara, Japan
| | - Hiroaki Ishikawa
- Department of Neurology, 26403Teikyo University Chiba Medical Center, Ichihara, Japan
| | - Megumi Suzuki
- Department of Neurology, 26403Teikyo University Chiba Medical Center, Ichihara, Japan
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28
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Weintraub D. Management of psychiatric disorders in Parkinson's disease : Neurotherapeutics - Movement Disorders Therapeutics. Neurotherapeutics 2020; 17:1511-1524. [PMID: 32514891 PMCID: PMC7851231 DOI: 10.1007/s13311-020-00875-w] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Affective disorders (depression and anxiety), psychosis, impulse control disorders, and apathy are common and sometimes disabling psychiatric conditions in Parkinson disease (PD). Psychiatric aspects of PD are associated with numerous adverse outcomes, yet in spite of this and their high frequency, there remains incomplete understanding of epidemiology, presentation, risk factors, neural substrate, and management strategies. Psychiatric features are typically co- or multimorbid, and there is great intra- and interindividual variability in presentation [1]. The neuropathophysiological changes that occur in PD, as well as the association between PD treatment and particular psychiatric disorders, suggest a neurobiological contribution to many psychiatric symptoms. There is evidence that psychiatric disorders in PD are still under-recognized and undertreated, and although psychotropic medication use is common, randomized controlled trials demonstrating efficacy and tolerability are largely lacking. Future research on neuropsychiatric complications in PD should be oriented toward determining modifiable correlates or risk factors, and most importantly, establishing efficacious and well-tolerated treatment strategies.
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Affiliation(s)
- Daniel Weintraub
- Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
- Parkinson's Disease Research, Education and Clinical Center (PADRECC), Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA.
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29
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Knolle F, Garofalo S, Viviani R, Justicia A, Ermakova AO, Blank H, Williams GB, Arrondo G, Ramachandra P, Tudor-Sfetea C, Bunzeck N, Duezel E, Robbins TW, Barker RA, Murray GK. Altered subcortical emotional salience processing differentiates Parkinson's patients with and without psychotic symptoms. NEUROIMAGE-CLINICAL 2020; 27:102277. [PMID: 32540629 PMCID: PMC7298672 DOI: 10.1016/j.nicl.2020.102277] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Revised: 03/30/2020] [Accepted: 05/05/2020] [Indexed: 01/03/2023]
Abstract
Emotional salience processing differentiates PD patients with and without psychosis. Enhanced striatal, hippocampal and midbrain responses in PD patients with psychosis. Indication for ‘jumping to conclusions’ bias in the same PD patients with psychosis. Aberrant top-down and salience processing associated with PD psychosis. Similar deficits as proposed in ‘aberrant salience hypothesis’ of schizophrenia. Objective Current research does not provide a clear explanation for why some patients with Parkinson’s Disease (PD) develop psychotic symptoms. The ‘aberrant salience hypothesis’ of psychosis has been influential and proposes that dopaminergic dysregulation leads to inappropriate attribution of salience to irrelevant/non-informative stimuli, facilitating the formation of hallucinations and delusions. The aim of this study is to investigate whether non-motivational salience is altered in PD patients and possibly linked to the development of psychotic symptoms. Methods We investigated salience processing in 14 PD patients with psychotic symptoms, 23 PD patients without psychotic symptoms and 19 healthy controls. All patients were on dopaminergic medication for their PD. We examined emotional salience using a visual oddball fMRI paradigm that has been used to investigate early stages of schizophrenia spectrum psychosis, controlling for resting cerebral blood flow as assessed with arterial spin labelling fMRI. Results We found significant differences between patient groups in brain responses to emotional salience. PD patients with psychotic symptoms had enhanced brain responses in the striatum, dopaminergic midbrain, hippocampus and amygdala compared to patients without psychotic symptoms. PD patients with psychotic symptoms showed significant correlations between the levels of dopaminergic drugs they were taking and BOLD signalling, as well as psychotic symptom scores. Conclusion Our study suggests that enhanced signalling in the striatum, dopaminergic midbrain, the hippocampus and amygdala is associated with the development of psychotic symptoms in PD, in line with that proposed in the ‘aberrant salience hypothesis’ of psychosis in schizophrenia.
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Affiliation(s)
- F Knolle
- Department of Psychiatry, University of Cambridge, Cambridge, UK; Department of Neuroradiology, Technical University Munich, Munich, Germany.
| | - S Garofalo
- University of Bologna, Department of Psychology, Bologna, Italy
| | - R Viviani
- Institute of Psychology, University of Innsbruck, Innsbruck, Austria; Psychiatry and Psychotherapy Clinic III, University of Ulm, Ulm, Germany
| | - A Justicia
- Department of Psychiatry, University of Cambridge, Cambridge, UK; IMIM (Hospital del Mar Medical Research Institute), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
| | - A O Ermakova
- Faculty of Natural Sciences, Imperial College London, UK
| | - H Blank
- Institute of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - G B Williams
- Department of Clinical Neuroscience and WT-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
| | - G Arrondo
- Department of Psychiatry, University of Cambridge, Cambridge, UK
| | - P Ramachandra
- Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK
| | - C Tudor-Sfetea
- Department of Psychiatry, University of Cambridge, Cambridge, UK
| | - N Bunzeck
- Institute of Psychology I, University of Lübeck, Lübeck, Germany
| | - E Duezel
- Otto-von-Guericke University Magdeburg, Institute of Cognitive Neurology and Dementia Research, Magdeburg, Germany; German Centre for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
| | - T W Robbins
- Department of Psychology, University of Cambridge, Cambridge, UK
| | - R A Barker
- Department of Clinical Neuroscience and WT-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
| | - G K Murray
- Department of Psychiatry, University of Cambridge, Cambridge, UK
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30
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Hommel ALAJ, Meinders MJ, Lorenzl S, Dodel R, Coelho M, Ferreira JJ, Laurens B, Spampinato U, Meissner W, Rosqvist K, Timpka J, Odin P, Wittenberg M, Bloem PhD BR, Koopmans RT, Schrag A. The Prevalence and Determinants of Neuropsychiatric Symptoms in Late-Stage Parkinsonism. Mov Disord Clin Pract 2020; 7:531-542. [PMID: 32626798 DOI: 10.1002/mdc3.12968] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 04/04/2020] [Indexed: 01/10/2023] Open
Abstract
Background Late-stage parkinsonism and Parkinson's disease (PD) are insufficiently studied population. Although neuropsychiatric symptoms (eg, psychosis, depression, anxiety, behavioral problems) are frequently present, their prevalence and clinical predictors remain unknown. Objective To determine the prevalence and predictors of neuropsychiatric symptoms in late-stage PD. Methods We conducted a multinational study of patients with PD with ≥7 years disease duration and either a Hoehn and Yahr stage ≥4 or a Schwab and England score ≤ 50% in the on stage. Neuropsychiatric symptoms were assessed through interviews with carers using the Neuropsychiatric Inventory, with a frequency × severity score ≥ 4, indicating clinically relevant symptoms. The determinants analyzed were demographic characteristics, medication, and motor and nonmotor symptoms. Univariate and multivariate logistic analyses were performed on predictors of clinically relevant neuropsychiatric symptoms. Results A total of 625 patients were recruited in whom the Neuropsychiatric Inventory could be completed. In 92.2% (576/625) of the patients, at least 1 neuropsychiatric symptom was present, and 75.5% (472/625) had ≥1 clinically relevant symptom. The most common clinically relevant symptoms were apathy (n = 242; 38.9%), depression (n = 213; 34.5%), and anxiety (n = 148; 23.8%). The multivariate analysis revealed unique sets of predictors for each symptom, particularly the presence of other neuropsychiatric features, cognitive impairment, daytime sleepiness. Conclusion Neuropsychiatric symptoms are common in late-stage PD. The strongest predictors are the presence of other neuropsychiatric symptoms. Clinicians involved in the care for patients with late-stage PD should be aware of these symptoms in this specific disease group and proactively explore other psychiatric comorbidities once a neuropsychiatric symptom is recognized.
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Affiliation(s)
- Adrianus L A J Hommel
- Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour Department of Neurology, Centre of Expertise for Parkinson & Movement Disorders Nijmegen the Netherlands.,Groenhuysen Organisation Roosendaal the Netherlands
| | - Marjan J Meinders
- Radboud University Medical Center Radboud Institute for Health Sciences Nijmegen the Netherlands
| | - Stefan Lorenzl
- Interdisziplinäres Zentrum für Palliativmedizin und Klinik für Neurologie Universität München-Klinikum Großhadern Munich Germany.,Institute of Nursing Science and Practice Salzburg Austria
| | - Richard Dodel
- Department of Geriatric Medicine University Hospital Essen Essen Germany
| | - Miguel Coelho
- University of Lisbon, Lisbon School of Medicine (FMUL), Laboratory of Clinical Pharmacology and Therapeutics, Lisbon, Portugal; and University of Lisbon Lisbon School of Medicine (FMUL), Instituto de Medicina Molecular Lisbon Portugal.,University of Lisbon Lisbon School of Medicine (FMUL), Instituto de Medicina Molecular Lisbon Portugal.,Department of Neurosciences Service of Neurology, Hospital Santa Maria Lisbon Portugal
| | - Joaquim J Ferreira
- University of Lisbon, Lisbon School of Medicine (FMUL), Laboratory of Clinical Pharmacology and Therapeutics, Lisbon, Portugal; and University of Lisbon Lisbon School of Medicine (FMUL), Instituto de Medicina Molecular Lisbon Portugal
| | - Brice Laurens
- Service de Neurologie CHU de Bordeaux 33000 Bordeaux France.,Univ. de Bordeaux, Institut des Maladies Neurodégénératives Bordeaux France
| | - Umberto Spampinato
- Service de Neurologie CHU de Bordeaux 33000 Bordeaux France.,Univ. de Bordeaux, Institut des Maladies Neurodégénératives Bordeaux France
| | - Wassilios Meissner
- Service de Neurologie CHU de Bordeaux 33000 Bordeaux France.,Univ. de Bordeaux, Institut des Maladies Neurodégénératives Bordeaux France.,Department of Medicine University of Otago Christchurch New Zealand.,New Zealand Brain Research Institute Christchurch New Zealand
| | - Kristina Rosqvist
- Department of Neurology, Department of Clinical Sciences Lund University Lund Sweden
| | - Jonathan Timpka
- Department of Neurology, Department of Clinical Sciences Lund University Lund Sweden
| | - Per Odin
- Department of Neurology, Department of Clinical Sciences Lund University Lund Sweden
| | - Michael Wittenberg
- Coordinating Centre for Clinical Trials Philipps University Marburg Marburg Germany
| | - Bas R Bloem PhD
- Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour Department of Neurology, Centre of Expertise for Parkinson & Movement Disorders Nijmegen the Netherlands
| | - Raymond T Koopmans
- Radboud University Medical Center Department of Primary and Community Care Nijmegen The Netherlands.,Joachim en Anna, Center for Specialized Geriatric Care Nijmegen The Netherlands
| | - Anette Schrag
- University College London, Queen Square Institute of Neurology, University College London London United Kingdom
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Seiler N, Nguyen T, Yung A, O'Donoghue B. Terminology and assessment tools of psychosis: A systematic narrative review. Psychiatry Clin Neurosci 2020; 74:226-246. [PMID: 31846133 DOI: 10.1111/pcn.12966] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Accepted: 12/05/2019] [Indexed: 12/20/2022]
Abstract
AIM Phenomena within the psychosis continuum that varies in frequency/duration/intensity have been increasingly identified. Different terms describe these phenomena, however there is no standardization within the terminology. This review evaluated the definitions and assessment tools of seven terms - (i) 'psychotic experiences'; (ii) 'psychotic-like experiences'; (iii) 'psychotic-like symptoms'; (iv) 'attenuated psychotic symptoms'; (v) 'prodromal psychotic symptoms'; (vi) 'psychotic symptomatology'; and (vii) 'psychotic symptoms'. METHODS EMBASE, MEDLINE, and CINAHL were searched during February-March 2019. Inclusion criteria included 1989-2019, full text, human, and English. Papers with no explicit definition or assessment tool, duplicates, conference abstracts, systematic reviews, meta-analyses, or no access were excluded. RESULTS A total of 2238 papers were identified and of these, 627 were included. Definitions and assessment tools varied, but some trends were found. Psychotic experiences and psychotic-like experiences were transient and mild, found in the general population and those at-risk. Psychotic-like symptoms were subthreshold and among at-risk populations and non-psychotic mental disorders. Attenuated psychotic symptoms were subthreshold but associated with distress, risk, and help-seeking. Prodromal psychotic symptoms referred to the prodrome of psychotic disorders. Psychotic symptomatology included delusions and hallucinations within psychotic disorders. Psychotic symptoms was the broadest term, encompassing a range of populations but most commonly involving hallucinations, delusions, thought disorder, and disorganization. DISCUSSION A model for conceptualizing the required terms is proposed and future directions needed to advance this field of research are discussed.
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Affiliation(s)
- Natalie Seiler
- Orygen, the National Centre of Excellence in Youth Mental Health, Parkville, Melbourne, Australia.,Centre for Youth Mental Health, University of Melbourne, Parkville, Melbourne, Australia.,The University of Melbourne, Parkville, Melbourne, Australia.,Orygen Youth Health, Parkville, Melbourne, Australia
| | - Tony Nguyen
- Orygen, the National Centre of Excellence in Youth Mental Health, Parkville, Melbourne, Australia.,Centre for Youth Mental Health, University of Melbourne, Parkville, Melbourne, Australia.,The University of Melbourne, Parkville, Melbourne, Australia.,Orygen Youth Health, Parkville, Melbourne, Australia
| | - Alison Yung
- Orygen, the National Centre of Excellence in Youth Mental Health, Parkville, Melbourne, Australia.,Centre for Youth Mental Health, University of Melbourne, Parkville, Melbourne, Australia.,Orygen Youth Health, Parkville, Melbourne, Australia
| | - Brian O'Donoghue
- Orygen, the National Centre of Excellence in Youth Mental Health, Parkville, Melbourne, Australia.,Centre for Youth Mental Health, University of Melbourne, Parkville, Melbourne, Australia.,Orygen Youth Health, Parkville, Melbourne, Australia
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32
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Li T, Shi J, Qin B, Fan D, Liu N, Ni J, Zhang T, Zhou H, Xu X, Wei M, Zhang X, Wang X, Liu J, Wang Y, Tian J. Increased substantia nigra echogenicity correlated with visual hallucinations in Parkinson's disease: a Chinese population-based study. Neurol Sci 2019; 41:661-667. [PMID: 31754876 PMCID: PMC7039836 DOI: 10.1007/s10072-019-04110-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Accepted: 10/15/2019] [Indexed: 01/03/2023]
Abstract
As a noninvasive technique, transcranial sonography (TCS) of substantia nigra (SN) has gradually showed its effectiveness not only in diagnosis but also in understanding clinical features of Parkinson’s Disease (PD). This study aimed to further evaluate TCS for clinical diagnosis of PD, and to explore the association between sonographic manifestations and visual hallucinations (VH). A total of 226 subjects including 141 PD patients and 85 controls were recruited. All participants received TCS. A series of rating scales to evaluate motor and non-motor symptoms were performed in PD patients. Results showed that 172 subjects were successfully assessed by TCS. The area of SN was greater in PD patients than that in controls (P < 0.001). As receiver-operating characteristic (ROC) curve analysis showed, the best cutoff value for the larger SN echogenicity size was 23.5 mm2 (sensitivity 70.3%, specificity 77.0%). Patients with VH had larger SN area (P = 0.019), as well as higher Non-Motor Symptoms Scale (NMSS) scores (P = 0.018). Moreover, binary logistic regression analysis indicated that SN hyperechogenicity (odds ratio = 4.227, P = 0.012) and NMSS scores (odds ratio = 0.027, P = 0.042) could be the independent predictors for VH. In conclusion, TCS can be used as an auxiliary diagnostic tool for Parkinson’s disease. Increased SN echogenicity is correlated with VH in Parkinson’s disease, possibly because the brain stem is involved in the mechanism in the onset of VH. Further studies are needed to confirm these findings.
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Affiliation(s)
- Ting Li
- The Neurology Center, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Jing Shi
- The Neurology Center, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Bin Qin
- Beijing Hospital, Beijing, 100730, China
| | - Dongsheng Fan
- Peking University Third Hospital, Beijing, 100191, China
| | - Na Liu
- Peking University Third Hospital, Beijing, 100191, China
| | - Jingnian Ni
- The Neurology Center, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Tianqing Zhang
- The Neurology Center, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Hufang Zhou
- The Neurology Center, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Xiaoqing Xu
- The Neurology Center, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Mingqing Wei
- The Neurology Center, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Xuekai Zhang
- The Neurology Center, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Xiangzhu Wang
- The Neurology Center, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Jianping Liu
- Center for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yongyan Wang
- Institute of Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Jinzhou Tian
- The Neurology Center, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
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Abstract
Psychotic and compulsive symptoms in Parkinson disease are highly prevalent and associated with poor outcomes and greater caregiver burden. When acute, delirium should be ruled out or treated accordingly. When chronic, comorbid systemic illnesses, dementia, and psychiatric disorders should be considered. Reduction and discontinuation of anticholinergics, amantadine, dopamine agonists, and levodopa as tolerated, as well as adjunctive clozapine or quetiapine are frequently effective to manage Parkinson disease psychosis. Pimavanserin appears effective but is not widely available, and more experience is needed. Dopamine agonist discontinuation is usually successful for impulse control disorders, but requires frequent monitoring, documentation, and caregiver involvement.
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34
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Weintraub D, Mamikonyan E. The Neuropsychiatry of Parkinson Disease: A Perfect Storm. Am J Geriatr Psychiatry 2019; 27:998-1018. [PMID: 31006550 PMCID: PMC7015280 DOI: 10.1016/j.jagp.2019.03.002] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 03/04/2019] [Accepted: 03/04/2019] [Indexed: 12/16/2022]
Abstract
Affective disorders, cognitive decline, and psychosis have long been recognized as common in Parkinson disease (PD), and other psychiatric disorders include impulse control disorders, anxiety symptoms, disorders of sleep and wakefulness, and apathy. Psychiatric aspects of PD are associated with numerous adverse outcomes, yet in spite of this and their frequent occurrence, there is incomplete understanding of epidemiology, presentation, risk factors, neural substrate, and management strategies. Psychiatric features are typically multimorbid, and there is great intra- and interindividual variability in presentation. The hallmark neuropathophysiological changes that occur in PD, plus the association between exposure to dopaminergic medications and certain psychiatric disorders, suggest a neurobiological basis for many psychiatric symptoms, although psychological factors are involved as well. There is evidence that psychiatric disorders in PD are still under-recognized and undertreated and although psychotropic medication use is common, controlled studies demonstrating efficacy and tolerability are largely lacking. Future research on neuropsychiatric complications in PD should be oriented toward determining modifiable correlates or risk factors and establishing efficacious and well-tolerated treatment strategies.
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Affiliation(s)
- Daniel Weintraub
- Perelman School of Medicine (DW, EM), University of Pennsylvania, Philadelphia; Parkinson's Disease Research, Education and Clinical Center (PADRECC) (DW), Philadelphia Veterans Affairs Medical Center, Philadelphia.
| | - Eugenia Mamikonyan
- Perelman School of Medicine (DW, EM), University of Pennsylvania, Philadelphia
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Lyons KE, Pahwa R, Hermanowicz N, Davis T, Pagan F, Isaacson S. Changing the treatment paradigm for Parkinson’s disease psychosis with pimavanserin. Expert Rev Clin Pharmacol 2019; 12:681-691. [DOI: 10.1080/17512433.2019.1623669] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Kelly E. Lyons
- Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA
| | - Rajesh Pahwa
- Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA
| | - Neal Hermanowicz
- Department of Neurology, University of California Irvine, Irvine, CA, USA
| | - Thomas Davis
- Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Fernando Pagan
- Department of Neurology, Georgetown University Medical Center, Washington, DC, USA
| | - Stuart Isaacson
- Parkinson’s Disease and Movement Disorders Center of Boca Raton, Boca Raton, FL, USA
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Sawada H, Oeda T, Kohsaka M, Umemura A, Tomita S, Park K, Mizoguchi K, Matsuo H, Hasegawa K, Fujimura H, Sugiyama H, Nakamura M, Kikuchi S, Yamamoto K, Fukuda T, Ito S, Goto M, Kiyohara K, Kawamura T. Early use of donepezil against psychosis and cognitive decline in Parkinson's disease: a randomised controlled trial for 2 years. J Neurol Neurosurg Psychiatry 2018; 89:1332-1340. [PMID: 30076270 PMCID: PMC6288700 DOI: 10.1136/jnnp-2018-318107] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Revised: 04/27/2018] [Accepted: 07/10/2018] [Indexed: 12/21/2022]
Abstract
OBJECTIVES Brain acetylcholine is decreased even in patients with cognitively preserved Parkinson's disease (PD). We investigated whether early and long-term use of donepezil prevents psychosis in non-demented PD patients. METHODS A double-blinded, placebo-controlled trial was conducted. A total of 145 non-demented PD patients were randomly assigned to receive 5 mg/day donepezil (n=72) or placebo (n=73) for 96 weeks. Medications for PD were not restricted, but antipsychotic drugs were not permitted throughout the study. The primary outcome measure was survival time to psychosis that was predefined by Parkinson's Psychosis Questionnaire (PPQ) B score ≥2 or C score ≥2. Secondary outcome measures included psychosis developing within 48 weeks, total PPQ score, Mini-Mental State Examination (MMSE), Wechsler Memory Scale (WMS) and subgroup analysis by apolipoprotein ε4 genotyping. RESULTS Kaplan-Meier curves for psychosis development were very similar between the two groups, and the Cox proportional hazard model revealed an adjusted HR of 0.87 (95%CI 0.48 to 1.60). The changes in MMSE and WMS-1 (auditory memory) were significantly better with donepezil than in placebo. In the subgroup analysis, donepezil provided an HR of 0.31 (0.11-0.86) against psychosis in 48 weeks for apolipoprotein ε4 non-carriers. CONCLUSIONS Although donepezil provided beneficial effects on PPQ, MMSE and auditory WMS score changes in 2 years, it had no prophylactic effect on development of psychosis in PD. Apolipoprotein ε4 may suppress the antipsychotic effect of donepezil. TRIAL REGISTRATION NUMBER UMIN000005403.
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Affiliation(s)
- Hideyuki Sawada
- Clinical Research Center and Department of Neurology, Utano National Hospital, Kyoto, Japan
| | - Tomoko Oeda
- Clinical Research Center and Department of Neurology, Utano National Hospital, Kyoto, Japan
| | - Masayuki Kohsaka
- Clinical Research Center and Department of Neurology, Utano National Hospital, Kyoto, Japan
| | - Atsushi Umemura
- Clinical Research Center and Department of Neurology, Utano National Hospital, Kyoto, Japan
| | - Satoshi Tomita
- Clinical Research Center and Department of Neurology, Utano National Hospital, Kyoto, Japan
| | - Kwiyoung Park
- Clinical Research Center and Department of Neurology, Utano National Hospital, Kyoto, Japan
| | - Kouichi Mizoguchi
- Department of Neurology, Shizuoka Medical Institute of Epilepsy and Neurological Disorders, Shizuoka City, Japan
| | - Hidenori Matsuo
- Department of Neurology, Nagasaki Kawatana Medical Center, Nagasaki, Japan
| | - Kazuko Hasegawa
- Department of Neurology, Sagamihara National Hospital, Sagamihara, Japan
| | - Harutoshi Fujimura
- Clinical Research Center and Department of Neurology, Toneyama National Hospital, Toyonaka, Japan
| | - Hiroshi Sugiyama
- Clinical Research Center and Department of Neurology, Utano National Hospital, Kyoto, Japan
- Department of Neurology, Minami-Kyoto National Hospital, Joyo, Japan
| | | | - Seishi Kikuchi
- Department of Neurology, Hokkaido Medical Center, Sapporo, Japan
| | - Kenji Yamamoto
- Clinical Research Center and Department of Neurology, Utano National Hospital, Kyoto, Japan
| | - Toshiaki Fukuda
- Clinical Research Center and Department of Neurology, Utano National Hospital, Kyoto, Japan
| | - Suminobu Ito
- Clinical Research Center, National Hospital Organization, Meguro, Japan
| | - Masashi Goto
- Division of General Internal Medicine, Kyoto Medical Center, Kyoto, Japan
| | - Kosuke Kiyohara
- Department of Public Health, Tokyo Women's Medical University, Shinjuku-ku, Japan
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Youdim MBH. Monoamine oxidase inhibitors, and iron chelators in depressive illness and neurodegenerative diseases. J Neural Transm (Vienna) 2018; 125:1719-1733. [PMID: 30341696 DOI: 10.1007/s00702-018-1942-9] [Citation(s) in RCA: 86] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Accepted: 10/11/2018] [Indexed: 12/11/2022]
Abstract
In early 1920s, tyramine oxidase was discovered that metabolized tyramine and in 1933 Blaschko demonstrated that this enzyme also metabolized adrenaline, noradrenaline and dopamine. Zeller gave it the name monoamine oxidase (MAO) to distinguish it from the enzyme that oxidatively deaminated diamines. MAO was recognized as an enzyme of crucial interest to pharmacologists because it catalyzed the major inactivation pathway for the catecholamines (and, later, 5-hydroxytryptamine, as well). Within the few decade, the inhibitors of MAO were discovered and introduced for the treatment of depressive illness which was established clinically. However, the first clinical use exposed serious side effects, pharmacological interest in, and investigation of, MAO continued, resulting in the characterization of two forms, distinct forms, MAO-A and -B, and selective inhibitors for them. Selective inhibitors of MAO-B (selegiline, rasagiline and safinamide) have found a therapeutic role in the treatment of Parkinson's disease and reversible inhibitors of MAO-A offered antidepressant activity without the serious side effects of the earlier nonselective MAO inhibitors. Subsequent molecular pharmacological have also generated the concept of neuroprotection, reflecting the possibility of slowing, halting and maybe reversing, neurodegeneration in Parkinson's or Alzheimer's diseases. Increased levels of oxidative stress through the accumulation of iron in the Parkinsonian and Alzheimer brains has been suggested to be critical for the initiation and progress of neurodegeneration. Selective inhibition of brain MAO could contribute importantly to lowering such stress, preventing the formation of hydrogen peroxide. Interaction of Iron with hydrogen peroxide and lead to Fenton reaction and production of the most reactive radical, namely hydroxyl radical. There are complex interactions between free iron levels in brain and MAO, and cascade of neurotoxic events may have practical outcomes for depressive disorders and neurodegenerative diseases. As consequence recent novel therapeutic drugs for neurodegenerative diseases has led to the development of multi target drugs, that possess selective brain MAO A and B inhibitory moiety, iron chelating and antioxidant activities and the ability to increase brain levels of endogenous neurotrophins, such as BDNF, GDNF VEGF and erythropoietin and induce mitochondrial biogenesis.
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Affiliation(s)
- Moussa B H Youdim
- Technion-Bruce Rappaport Faculty of Medicine, Rappaport Family Research Institute, Haifa, Israel. .,, Yokneam, Israel.
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Warren N, O'Gorman C, Hume Z, Kisely S, Siskind D. Delusions in Parkinson's Disease: A Systematic Review of Published Cases. Neuropsychol Rev 2018; 28:310-316. [PMID: 30073446 DOI: 10.1007/s11065-018-9379-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 06/25/2018] [Indexed: 01/16/2023]
Abstract
Delusions in Parkinson's disease (PD) are thought to be associated with disease progression and cognitive impairment. However, this symptom description is not consistent in the literature and there is a suggestion that different subgroups of psychotic patients occur in PD, which we aimed to clarify. Case reports were identified through a systematic search of databases (PUBMED, EMBASE, PsychInfo). Cases with isolated delusions were compared to those with both delusions and hallucinations. We identified 184 cases of delusions in PD. Delusions were primarily paranoid in nature (83%) and isolated in 50%. Those with isolated delusions had an earlier onset of PD (46 years vs 55 years), higher rates of impulse control disorders (40.2 vs 10.3%), dopamine dysregulation (29.9 vs 11.3%) and lower rates of cognitive impairment (8.0 vs 26.8%). There is unexpected heterogeneity amongst cases of delusional psychosis, that cannot adequately be explained by existing models of PD psychosis.
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Affiliation(s)
- Nicola Warren
- School of Medicine, University of Queensland, Brisbane, Australia.
- Metro South Addiction and Mental Health Service, Brisbane, Australia.
| | - Cullen O'Gorman
- School of Medicine, University of Queensland, Brisbane, Australia
- Department of Neurology, Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba, Brisbane, Qld, 4102, Australia
| | - Zena Hume
- Metro South Addiction and Mental Health Service, Brisbane, Australia
| | - Steve Kisely
- School of Medicine, University of Queensland, Brisbane, Australia
- Metro South Addiction and Mental Health Service, Brisbane, Australia
| | - Dan Siskind
- School of Medicine, University of Queensland, Brisbane, Australia
- Metro South Addiction and Mental Health Service, Brisbane, Australia
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de Freitas CM, Krum BN, Chiapinotto Ceretta AP, Schaffer LF, de Moraes Reis E, Schwerz JP, Barbosa CP, Soares FAA, Fachinetto R. Silymarin recovers 6-hydroxydopamine-induced motor deficits in mice. Food Chem Toxicol 2018; 118:549-556. [DOI: 10.1016/j.fct.2018.05.062] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 05/08/2018] [Accepted: 05/26/2018] [Indexed: 01/22/2023]
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Abstract
PURPOSE OF REVIEW We discuss features of Parkinson's disease psychosis (PDP) including symptomology and pathophysiology. Treatment options, including non-pharmacologic strategies, dose reduction of offending agents, and the addition of non-dopaminergic antipsychotics, are addressed. The efficacy of second-generation antipsychotics and novel agents is examined. RECENT FINDINGS Pimavanserin, a 5-HT2A/C receptor inverse agonist with no other receptor activity, has shown efficacy and tolerability and is now FDA approved for PDP treatment. Research into novel targets is ongoing. PDP is a morbid complication of Parkinson's disease with complex incompletely understood mechanisms. Treatment is directed towards mitigation of psychosis without worsening of motor features.
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Berardelli I, Bloise MC, Bologna M, Conte A, Pompili M, Lamis DA, Pasquini M, Fabbrini G. Cognitive behavioral group therapy versus psychoeducational intervention in Parkinson's disease. Neuropsychiatr Dis Treat 2018; 14:399-405. [PMID: 29416341 PMCID: PMC5790090 DOI: 10.2147/ndt.s152221] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
OBJECTIVE The aim of the current study was to evaluate whether cognitive behavioral group therapy has a positive impact on psychiatric, and motor and non-motor symptoms in Parkinson's disease (PD). METHODS We assigned 20 PD patients with a diagnosis of psychiatric disorder to either a 12-week cognitive behavioral therapy (CBT) group or a psychoeducational protocol. For the neurological examination, we administered the Unified Parkinson's Disease Rating Scale and the non-motor symptoms scale. The severity of psychiatric symptoms was assessed by means of the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Brief Psychiatric Rating Scale, and the Clinical Global Impressions. RESULTS Cognitive behavioral group therapy was effective in treating depression and anxiety symptoms as well as reducing the severity of non-motor symptoms in PD patients; whereas, no changes were observed in PD patients treated with the psychoeducational protocol. CONCLUSION CBT offered in a group format should be considered in addition to standard drug therapy in PD patients.
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Affiliation(s)
- Isabella Berardelli
- Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, Sant’Andrea Hospital, Sapienza University of Rome, Rome
| | | | - Matteo Bologna
- Department Human Neurosciences, Sapienza University of Rome, Rome
- Neuromed Institute (IRCCS), Pozzilli (IS), Italy
| | - Antonella Conte
- Department Human Neurosciences, Sapienza University of Rome, Rome
- Neuromed Institute (IRCCS), Pozzilli (IS), Italy
| | - Maurizio Pompili
- Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, Sant’Andrea Hospital, Sapienza University of Rome, Rome
| | - Dorian A Lamis
- Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | - Massimo Pasquini
- Department Human Neurosciences, Sapienza University of Rome, Rome
| | - Giovanni Fabbrini
- Department Human Neurosciences, Sapienza University of Rome, Rome
- Neuromed Institute (IRCCS), Pozzilli (IS), Italy
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Abstract
Psychotic symptoms in elderly people can be seen in a variety of conditions. This article reviews treatment strategies (both pharmacological and non-pharmacological) for such symptoms in schizophrenia and neurodegenerative disorders in this population. Traditionally, antipsychotics have been the most commonly used treatment for psychotic symptoms. Their usefulness in treating schizophrenia, both chronic and late onset, is well established and the atypical antipsychotics, which have a better side-effect profile, are more suitable for elderly people. More recently, there have been increasing concerns about their safety in psychoses due to dementia. The debate about whether an absolute ban on their use is required is still ongoing, but it has highlighted the need for adopting and developing non-pharmacological interventions.
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Turjanski N, Lloyd GG. Psychiatric side-effects of medications: recent developments. ACTA ACUST UNITED AC 2018. [DOI: 10.1192/apt.11.1.58] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Medications often induce neuropsychiatric side-effects. This article reviews psychiatric side-effects that are well known and describes those induced by recently developed medications. Therapeutic innovations have been prominent in the treatment of HIV infection, Parkinson's disease and epilepsy and therefore psychiatric side-effects caused by these agents are described in more detail.
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Schneider RB, Iourinets J, Richard IH. Parkinson's disease psychosis: presentation, diagnosis and management. Neurodegener Dis Manag 2017; 7:365-376. [DOI: 10.2217/nmt-2017-0028] [Citation(s) in RCA: 87] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
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.
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Affiliation(s)
- Ruth B Schneider
- Department of Neurology, University of Rochester School of Medicine & Dentistry, 265 Crittenden Blvd, Box MIND, Rochester, NY 14642, USA
| | - Julia Iourinets
- Department of Neurology, University of Rochester School of Medicine & Dentistry, 919 Westfall Rd, Bldg C, Rochester, NY 14618, USA
| | - Irene H Richard
- Department of Neurology, University of Rochester School of Medicine & Dentistry, 919 Westfall Rd, Bldg C, Rochester, NY 14618, USA
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Predictors of onset of psychosis in patients with Parkinson's disease: Who gets it early? Parkinsonism Relat Disord 2017; 44:91-94. [PMID: 28928050 DOI: 10.1016/j.parkreldis.2017.09.015] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2017] [Revised: 08/20/2017] [Accepted: 09/13/2017] [Indexed: 01/24/2023]
Abstract
INTRODUCTION Psychosis is one of the common non-motor symptoms of PD, which substantially worsens the quality of life. Hence, it is important to identify factors that are associated with early onset of psychosis in PD. In order to identify those factors, the current study aims to compare various demographic and clinical features of PD patients with early and late onset psychosis. METHODOLOGY In this prospective case-control study, 51 consecutive patients with PD having psychosis (PDP) were recruited. Median of the latency of onset of psychotic symptoms from the onset of motor symptoms was calculated (5.5 years) and after doing a median split, the cohort of PDP was divided into early onset PDP (EOP, n = 25) and late onset PDP (LOP, n = 26). Both the groups were compared for several demographic and clinical characteristics. RESULTS Compared to those with LOP, patients with EOP had poor scores on frontal assessment battery (13.8 ± 2.0 vs 15.3 ± 1.8, p = 0.007), more frequently had Rapid Eye movement sleep Behavior Disorder (RBD) (80% vs 46.2%, p = 0.02), Postural Instability with Gait Difficulty (PIGD) phenotype (72% vs 26.9%, p = 0.002), and excessive daytime sleepiness (Epworth Sleepiness Scale: 8.04 ± 3.7 vs 3.9 ± 3.1). Patients with LOP were older (63.4 ± 7.0 years vs 56.5 ± 8.1 years, p = 0.002) and had higher Levodopa equivalent dose/day (LEDD: 819.1 ± 365.8 vs 608.5 ± 356.3, p = 0.04) compared to those with EOP. CONCLUSION Presence of RBD, excessive daytime sleepiness, frontal lobe dysfunction, and PIGD phenotype of PD may be associated with early onset of psychosis in PD. Higher LEDD may not trigger early occurrence of psychosis in PD.
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Holiday KA, Pirogovsky‐Turk E, Malcarne VL, Filoteo JV, Litvan I, Lessig SL, Song D, Schiehser DM. Psychometric Properties and Characteristics of the North-East Visual Hallucinations Interview in Parkinson's Disease. Mov Disord Clin Pract 2017; 4:717-723. [PMID: 28435846 PMCID: PMC5396180 DOI: 10.1002/mdc3.12479] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Revised: 12/31/2016] [Accepted: 01/29/2017] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Visual Hallucinations (VH) are a common symptom experienced by individuals with Parkinson's disease (PD); however, a validated measure of VH has yet to be established for this population. The North-East Visual Hallucinations Interview (NEVHI), a promising VH measure, has not been well validated in PD. The aim of this study was to evaluate the convergent and discriminant validity of the NEVHI as well as the proportional identification and characteristics of VH in PD. METHODS One hundred seventeen individuals with PD completed the NEVHI as well as evaluations of psychological, cognitive, motor, and visual functioning as measures of convergent and divergent validity. The hallucination items from the Neuropsychiatric Inventory (NPI) and the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Scale (MDS-UPDRS) were used to assess convergent validity. RESULTS The NEVHI identified 20.5% of PD patients with VH, which consisted of all individuals detected by the MDS-UPDRS and NPI and nine additional individuals not detected by the other measures. The NEVHI was strongly correlated with the MDS-UPDRS hallucinations item, and weakly correlated with the NPI VH item. Weak to non-significant correlations were found between the NEVHI and measures of psychological, cognitive, motor, visual, and demographic characteristics. DISCUSSION The NEVHI identified a greater number of individuals with VH than either the MDS-UPDRS or NPI. Results demonstrated good convergent validity between the NEVHI and a clinician-administered-to-patient-report measure of VH and excellent divergent validity, supporting the NEVHI as a valid and preferable measure for assessing the presence of VH in PD.
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Affiliation(s)
- Kelsey A. Holiday
- Research ServiceVeterans Affairs (VA) San Diego Healthcare SystemSan DiegoCalifornia
- San Diego State University/University of California San Diego Joint Doctoral Program in Clinical PsychologySan DiegoCalifornia
- Department of PsychiatryUniversity of California San DiegoSan DiegoCalifornia
| | - Eva Pirogovsky‐Turk
- Research ServiceVeterans Affairs (VA) San Diego Healthcare SystemSan DiegoCalifornia
- Department of PsychiatryUniversity of California San DiegoSan DiegoCalifornia
| | - Vanessa L. Malcarne
- San Diego State University/University of California San Diego Joint Doctoral Program in Clinical PsychologySan DiegoCalifornia
- Universisty of California San Diego Moores Cancer CenterSan DiegoCalifornia
| | - J. Vincent Filoteo
- Research ServiceVeterans Affairs (VA) San Diego Healthcare SystemSan DiegoCalifornia
- Department of PsychiatryUniversity of California San DiegoSan DiegoCalifornia
| | - Irene Litvan
- Department of NeurosciencesUniversity of California San DiegoSan DiegoCalifornia
| | - Stephanie L. Lessig
- Department of NeurosciencesUniversity of California San DiegoSan DiegoCalifornia
- Neurology ServiceVA San Diego Healthcare SystemSan DiegoCalifornia
| | - David Song
- Department of NeuroscienceUniversity of CaliforniaRiversideCalifornia
| | - Dawn M. Schiehser
- Research ServiceVeterans Affairs (VA) San Diego Healthcare SystemSan DiegoCalifornia
- Department of PsychiatryUniversity of California San DiegoSan DiegoCalifornia
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Abstract
Parkinson disease psychosis (PDP) is a common phenomenon in Parkinson disease (PD) patients treated with dopaminergic drugs, and is associated with high morbidity and mortality. It also correlates with depression and dementia, and can contribute to considerable caregiver stress and burnout. While symptoms can be relieved by decreasing doses or number of anti-PD medications, this may lead to an unacceptable worsening of motor function. When general medical or psychiatric conditions have been ruled out, and decreasing dopaminergic agents is not effective in treating psychosis, therapies include atypical antipsychotics, primarily clozapine and quetiapine. Of these, clozapine is effective but is associated with a poor side-effect profile and the necessity for frequent blood draws. Clinicians prefer quetiapine for its theoretically better safety profile, although there is no evidence for efficacy in treating psychosis. All atypical antipsychotics are associated with increased mortality in this patient population. Cholinesterase inhibitors can ameliorate psychosis symptoms. The serotonin 5-HT2A receptor inverse agonist pimavanserin was recently approved by the US FDA for the treatment of PDP and may prove to be a more targeted therapy without the downsides of atypical antipsychotics.
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Factor SA, McDonald WM, Goldstein FC. The role of neurotransmitters in the development of Parkinson's disease-related psychosis. Eur J Neurol 2017; 24:1244-1254. [PMID: 28758318 DOI: 10.1111/ene.13376] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 06/27/2017] [Indexed: 01/29/2023]
Abstract
Psychotic symptoms are common, disabling non-motor features of Parkinson's disease (PD). Despite noted heterogeneity in clinical features, natural history and therapy response, current dogma posits that psychosis generally progresses in a stereotypic manner through a cascade of events that begins with minor hallucinations and evolves to severe hallucinations and delusions. Further, the occurrence of psychotic symptoms is believed to indicate a poor prognosis. Here we propose a classification scheme that outlines the pathogenesis of psychosis as it relates to dysfunction of several neurotransmitter systems. We hypothesize that several subtypes exist, and that PD psychosis is not consistently indicative of a progressive cascade and poor prognosis. The literature was reviewed from 1990 to 2017. An overview of the features of PD psychosis is followed by a review of data indicating the existence of neurotransmitter-related subtypes of psychosis. We found that ample evidence exists to demonstrate the presence of multiple subtypes of PD psychosis, which are traced to dysfunction of the following neurotransmitter systems: dopamine, serotonin and acetylcholine. Dysfunction of each of these systems is recognizable through their clinical features and correlates, and the varied long-term prognoses. Identifying which neurotransmitter system is dysfunctional may help to develop targeted therapies. PD psychosis has various subtypes that differ in clinical features, underlying pathology and pathophysiology, treatment response and prognosis. A novel classification scheme is presented that describes the clinical subtypes with different outcomes, which could lead to the development of targeted therapies. Future research should focus on testing the viability of this classification.
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Affiliation(s)
- S A Factor
- Department of Neurology, Emory University School of Medicine, Atlanta, GA
| | - W M McDonald
- Department of Psychiatry, Emory University School of Medicine, Atlanta, GA, USA
| | - F C Goldstein
- Department of Neurology, Emory University School of Medicine, Atlanta, GA
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Barrett MJ, Smolkin ME, Flanigan JL, Shah BB, Harrison MB, Sperling SA. Characteristics, correlates, and assessment of psychosis in Parkinson disease without dementia. Parkinsonism Relat Disord 2017; 43:56-60. [PMID: 28735797 DOI: 10.1016/j.parkreldis.2017.07.011] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Revised: 06/16/2017] [Accepted: 07/15/2017] [Indexed: 01/13/2023]
Abstract
INTRODUCTION Considering that psychosis in Parkinson disease (PD) is associated with worse outcomes, including dementia, we aimed to study the characteristics, correlates, and assessment of PD psychosis in those without dementia. METHODS 101 PD subjects without dementia (Montreal Cognitive Assessment ≥21/30) were recruited to participate in a study of neuropsychiatric symptoms in PD. This study included a baseline standard neurological exam and common PD symptom assessments. Using the Scale for the Assessment of Positive Symptoms (SAPS) and separate assessment of visual illusions and sense of presence, NINDS-NIMH criteria for PD psychosis were applied. RESULTS Of the 33 (32.7%) PD subjects who met diagnostic criteria for psychosis in PD, visual illusions were most common (72.7%), followed by visual hallucinations (39.4%). Adjusted for presence of REM sleep behavior disorder (RBD) (p = 0.097), use of dopamine agonists (OR = 3.7, p = 0.012) and greater autonomic symptom burden (OR = 1.1 (per 1-unit change in score on SCOPA-AUT), p = 0.012) were associated with greater risk of psychosis. Use of dopamine agonists (OR = 5.0, p = 0.007), higher MDS-UPDRS Part II score (OR = 1.1, p = 0.010), and presence of RBD (OR = 4.8, p = 0.012) were independent predictors of visual hallucinations and visual illusions. MDS-UPDRS item 1.2 score ≥1 had highly correlated with the SAPS score (r = 0.65, p < 0.0001), but was 42% sensitive and 96% specific for identifying psychosis. CONCLUSION This study confirms the association between dopamine agonists and psychosis in PD patients without dementia. The association of RBD, autonomic symptoms, and MDS-UPDRS Part II scores with psychosis underscore its link to brainstem dysfunction and greater PD motor symptom severity.
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Affiliation(s)
- Matthew J Barrett
- Department of Neurology, University of Virginia, Charlottesville, VA, USA.
| | - Mark E Smolkin
- Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
| | - Joseph L Flanigan
- Department of Neurology, University of Virginia, Charlottesville, VA, USA.
| | - Binit B Shah
- Department of Neurology, University of Virginia, Charlottesville, VA, USA.
| | | | - Scott A Sperling
- Department of Neurology, University of Virginia, Charlottesville, VA, USA.
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Lenka A, Herath P, Christopher R, Pal PK. Psychosis in Parkinson's disease: From the soft signs to the hard science. J Neurol Sci 2017; 379:169-176. [PMID: 28716235 DOI: 10.1016/j.jns.2017.06.011] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Revised: 05/30/2017] [Accepted: 06/11/2017] [Indexed: 01/06/2023]
Abstract
Patients with Parkinson's disease (PD) may develop a wide spectrum of non-motor symptoms during the course of illness. Psychosis is one such commonly observed non-motor symptoms of PD. Although several studies based on neuroimaging, genetics, retinal imaging, and neuropsychological evaluations have explored the pathogenesis of psychosis in PD; exact neural correlates are yet to be understood. Identification of factors related to psychosis in PD is important, as psychosis has been reported to be associated with higher rates of mortality, caregiver distress, and nursing home placements. This review highlights the potential of the previous studies to gain further insights into the soft signs and hard science related to psychosis in PD. Studies based on neuropsychological evaluations have revealed significant dysfunction in attention, executive and visuospatial functions in patients with PD and psychosis. Neuroimaging studies reveal grey matter atrophy in regions of the brain corresponding to both dorsal and ventral visual pathways, hippocampus, and cholinergic structures. Meanwhile, functional imaging studies suggest existence of an aberrant top-to-bottom visual processing system, which dominates the normal bottom-to-top system in patients with PD and visual hallucinations. Although nucleotide polymorphisms of several genes have been studied in PD patients with psychosis, those on -45C>T polymorphisms of cholecystokinin gene (CCK) have shown the greatest promise because of its association with psychosis in PD. All these taken together, cohesively unfold the current status of research in patients with PD and psychosis. This paper also highlights the missing links and discusses the approach to future research in this field.
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Affiliation(s)
- Abhishek Lenka
- Department of Clinical Neurosciences, National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore, India; Department of Neurology, National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore, India
| | - Priyantha Herath
- Department of Neurology, University of South Carolina School of Medicine, Columbia, SC, USA
| | - Rita Christopher
- Department of Neurochemistry, National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore, India
| | - Pramod Kumar Pal
- Department of Neurology, National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore, India.
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