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• W2514012360 abstract "This virtual issue features 20 key and representative psychosis manuscripts published over the past decade in either Movement Disorders or Movement Disorders Clinical Practice. Although many important Parkinson's disease (PD) psychosis manuscripts have been published in other journals over this time period, the chosen manuscripts span the spectrum of key research that has occurred in this area, covering prevalence, course, psychiatric and cognitive comorbidity, overlap with related neurodegenerative diseases (dementia with Lewy bodies [DLB]), neurobiology, assessment instruments and diagnostic criteria, treatment excepted. Most are research articles, but some are expert reviews. Nearly all are authored by leaders in the field of PD psychosis (PD-P) research. By way of background, PD is still diagnosed on the basis of motor signs, but it is now recognized that a range of nonmotor symptoms (NMS) are both common and clinically significant. There is even evidence now that a range of NMS (e.g., rapid eye movement sleep behavior disorder [RBD], impaired olfaction, autonomic dysfunction, and depression and anxiety disorders) constitute a prodromal state for some patients who develop PD or related Lewy body disorders (DLB and multiple system atrophy).1-3 Included in the broad category of NMS are psychiatric disorders (e.g., psychosis, depression, anxiety, impulse-control disorders, and apathy) and cognitive impairment (e.g., mild cognitive impairment [MCI] and dementia with PD [PDD]). These disorders consistently are associated with lower quality of life, impaired function, worse long-term outcomes, increased caregiver burden, and even institutionalization in the case of psychosis.4, 5 Focusing specifically on PD-P, an important starting point is the need for consensus on terminology, symptomatology, and diagnostic criteria. An important step in this regard was the publication of diagnostic criteria for psychosis in PD, the product of a National Institutes of Health-sponsored workshop, which recognized illusions, false sense of presence, hallucinations, and delusions as possible presentations of psychosis in PD.6 Traditionally, the focus in PD-P has been on visual hallucinations specifically, but it is now recognized that auditory, tactile, and olfactory hallucinations are also relatively common.7 In addition, less severe psychosis (i.e., “minor” hallucinations [e.g., presence and passage phenomena, illusions], sometimes called “benign” hallucinations when insight is retained) is also common and has been shown to be a harbinger of more severe psychosis over the long term.8 PD-P was uncommonly reported before the introduction of dopamine-replacement therapy (DRT)9 and also was reported infrequently in de novo, untreated PD,10 and it increased in frequency only with the introduction of DRT.11 However, a recent and surprising study reported rates of minor hallucinations of approximately 40% in patients with newly diagnosed, untreated PD based on a detailed interview,12 findings that require replication. The occurrence of psychotic symptoms in a subset of patients with untreated PD is in keeping with recent research indicating that DRT does not fully explain the occurrence of PD-P13 and also with the fact that most patients with DLB, a disorder that has significant neuropathologic overlap with PD, have psychotic symptoms at the time of diagnosis and before the introduction of DRT.14 Many previous epidemiological studies have reported prevalence rates of PD-P that range from 20% to 30%.13 However, those studies were cross-sectional in design, and a recent prospective, longitudinal study that encompassed currently available treatments reported a 60% long-term cumulative prevalence of PD-P.15 Thus, over one-half of patients with PD can be expected to experience psychosis at some point during the course of their disease. Psychosis rarely occurs as a sole psychiatric or nonmotor disorder in PD. The majority of patients with PD-P also report disturbances of sleep and wakefulness, including RBD,16, 17 and other common correlates or risk factors are exposure to DRT and other PD medications,18 older age,19 and greater cognitive impairment, including dementia.20 Because some studies have found that the dose and duration of PD medications do not correlate with PD-P,19, 21 the etiology of PD-P evidently is complex and multifactorial. One possible neurobiological mechanism is that chronic DRT may lead to excessive stimulation or hypersensitivity of mesocorticolimbic dopamine (D2/D3) receptors.22 In addition, cholinergic deficits, serotonergic deficits, and serotonergic/dopaminergic imbalance, as determined by using a range of imaging modalities and other neural probes, have also been implicated as contributing to PD-P,22-24 particularly changes involving the primary visual system and dorsal/ventral visual association pathways.25-29 Finally, diffuse brain atrophy, implying widespread disease-related neurodegeneration of limbic, paralimbic, and neocortical gray matter, is associated with PD-P.30, 31 Screening questionnaires and rating scales are important in clinical care and research, including their use as outcome measures in clinical trials. A Movement Disorders Society task force reviewed psychosis rating scales used in PD and listed 4 instruments as “recommended” for use in PD as outcome measures in clinical trials.32 Since then, a “new” instrument was specifically developed for use in a PD-P clinical trial, a modification of the Schedule for the Assessment of Positive Symptoms (SAPS) called the SAPS-PD.33 And, in this series, we feature the development and validation of an even newer rating scale: the Psychosis and Hallucinations Questionnaire. The management of PD-D is complex, and controlled clinical trials have been few and far between; studies for the only antipsychotic shown to be efficacious for PD-P, clozapine, were conducted over 15 years ago.34, 35 The management of comorbid medical conditions and discontinuation or decreasing dosages of nonessential medications may be sufficient for some patients, at least in the short term.36 PD medications are usually discontinued sequentially and gradually, although this strategy is not evidence-based.37 Regarding the use of antipsychotics, although clozapine has demonstrated efficacy for PD-P, it is rarely used38 primarily because it requires routine blood monitoring. Several newer “atypical” antipsychotics, including risperidone, olanzapine, and aripiprazole, have been tried but are associated with adverse events, primarily worsening parkinsonism. Currently, quetiapine is the most commonly used antipsychotic in PD based on clinical experience and reasonable toleratibility,38 despite the fact that controlled clinical trials with reasonable sample sizes have been negative or uninterpretable.39-41 In addition to concerns about tolerability and lack of evidence for efficacy, recent pharmacoepidemiologic research suggests that antipsychotic use overall in PD is associated with increased mortality,42 as has also been reported in general dementia patients43 and which led to a boxed warning for antipsychotic use in patients with dementia. Fortunately, newer treatments are on the horizon; a recent controlled study of pimavanserin—a serotonin 2A receptor inverse agonist—for PD-P was positive,44 and plans are underway to study a similar compound (nelotanserin) for psychosis in PD and DLB. PD-P remains a challenging clinical disorder for patients, caregivers, and treatment providers. On the bright side, many significant advances have been made in the past decade in terms of epidemiology, neurobiology, and assessment. Additional prospective research is needed to more fully describe risk factors for the development of psychosis in unaffected patients as well as fully piecing together the complex neurobiology, which may involve multiple neurotransmitters, disease pathologies, and neural pathways. The largest unmet need for patients with PD-P remains adequate management strategies, both pharmacologic and nonpharmacologic. Hopefully, the next decade will be full of success stories in this regard." @default.
• W2514012360 created "2016-09-16" @default.
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• W2514012360 date "2016-08-11" @default.
• W2514012360 modified "2023-09-25" @default.
• W2514012360 title "Progress Regarding Parkinson's Disease Psychosis: It's No Illusion" @default.
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• W2514012360 doi "https://doi.org/10.1002/mdc3.12377" @default.
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