Parkinson's disease psychosis management: an evidence based, experience informed, pragmatic approach.

INTRODUCTION: Psychotic symptoms in people with Parkinson's disease (PD) have attracted increasing. Recommendations on treating psychosis often fail to take into account what psychotic symptoms require treatment, which has been complicated by the increasing number of reports documenting the frequency of 'minor' hallucinations. AREAS COVERED: This article focuses both on the phenomenology of psychotic symptoms and their management. EXPERT OPINION: Understanding the nature and implications of the types of psychotic symptoms in PD is the key to proper treatment. Evidence and experience-based data on the effect of anti-psychotic medications will be reviewed and how the various clinical settings should determine the treatment approach. The evidence base consists of all reported blinded trials recorded in PubMed and the experience-based studies are those chosen by the author from PubMed as illustrative. Specific recommendations for the treatment of psychosis will be listed for specific situations. Pimavanserin is the first-line choice for mild symptoms; quetiapine for symptoms that require improvement in a short period and clozapine for urgent problems or those which fail the other approaches.

Psychotic symptoms are common in PD, affecting the majority of patients by the time of death. 'Minor hallucinations' rarely require treatment but formed hallucinations and delusions often do. The vast majority of patients requiring treatment are on medications for PD motor problems. Some patients can be treated with reduction of psychoactive medications that are unrelated to PD, and some may tolerate reductions in PD medications without intolerable worsening of motor function. The remainder require treatment with medications that reduce psychotic symptoms, which include cholinesterase inhibitors, clozapine, pimavanserin, and possibly quetiapine and electroconvulsive therapy. Only clozapine and pimavanserin have unequivocal evidence for efficacy and motor tolerance. Data will be reviewed in support of each of these medications will be reviewed and pragmatic suggestions based on a large experience on when each might be used, and in what order they may be tried if initial approaches fail.

The Clinician's Tardive Inventory (CTI): A New Clinical Tool for Documenting and Rating Tardive Dyskinesia.

Objective: Current clinician-rated tardive dyskinesia (TD) symptom scales have not addressed the expanding clinical signs and functional impact of TD. The study objective was to develop and test the reliability of a new integrated instrument.Methods: A movement disorder neurologist devised the outline of the rating scale. A Steering Committee (5 neurologists and 2 psychiatrists) provided revisions until consensus was reached. The Clinician's Tardive Inventory (CTI) assesses abnormal movements of the eye/eyelid/face, tongue/mouth, jaw, and limb/trunk; complex movements defined as complicated movements different from simple patterned movements or postures; and vocalizations. The CTI rates frequency of symptoms from 0 to 3 (ranging from absent to constant). Functional impairments, including activities of daily living (ADL), social impairment, symptom distress, and physical harm, are rated 0-3 (ranging from unawareness to severe impact). The CTI underwent interrater and test-retest reliability testing between February and June 2022 based on videos and accompanying vignettes, which were reviewed by 2 movement disorder specialists to determine adequacy. Four clinicians rated each video/vignette. Interrater agreement was analyzed via 2-way random-effects intraclass correlation (ICC), and test-retest agreement was assessed utilizing the Kendall tau-b.Results: Forty-five video/vignettes were assessed for interrater reliability and 16 for test-retest reliability. The most prevalent movements were those of the tongue and mouth (77.8%) and jaw (55.6%). ICCs for movement frequency for anatomic symptoms were as follows: anatomic symptom summary score 0.92, abnormal eye movement 0.89, abnormal tongue/mouth movement 0.91, abnormal jaw movement 0.89, abnormal limb movement 0.76, complex movement 0.87, and abnormal vocalization 0.77; ICCs for functional impairments were as follows: total impairment score 0.92, physical harm 0.82, social embarrassment 0.88, ADLs 0.83, and symptom bother 0.92; Retests were conducted a mean (SD) of 15 (3) days later with correlation coefficients ranging from 0.66 to 0.87.Conclusions: The CTI is a new integrated instrument with proven reliability in assessing TD signs and functional impacts. Future validation study is warranted.

Brief commentary: Under-recognition of underuse of clozapine in treating psychotic symptoms in Parkinson's disease.

Clozapine is an important drug in the treatment of Parkinson's disease (PD). It has proven efficacy in treating PD psychosis without worsening motor function, as well as in treating tremor refractory to L-Dopa, yet it is severely underused in the United States. Unlike the situation of treatment resistant schizophrenia, this underuse is underrecognized.

Amantadine for Refractory Tremor in Parkinson Disease and Other Indications: A Chart Review With Long-Term Follow-up.

OBJECTIVES: The aim of this study was to determine how amantadine was used in a movement disorders clinic and how effective it was. METHODS: A chart review over a 2-month period in 2022 of all patients in a movement disorders clinic who had ever taken amantadine was undertaken. RESULTS: One hundred six charts were included. Amantadine was initiated primarily for tremor and secondly for l -dopa-induced dyskinesias (LIDs). Sixty-two percent of tremor patients improved and tolerated amantadine; 74% of those with LID improved and tolerated the drug. Hallucinations occurred in 23%. Initiating amantadine as a syrup allowed a more conservative titration than other formulations, which is attractive given the high percentage of hallucinations that may occur. Patients who tolerated drug initiation were generally kept on the drug for many years. CONCLUSIONS: Amantadine should be considered as adjunctive therapy in Parkinson disease patients with refractory tremor as well as for LIDs.

Dopamine Transporter Scan (DAT) in Parkinsonism - a Short Review for Non-Neurologists.

The Dopamine Transporter Scan (DaT) is a radionuclear imaging technique which was approved by the FDA to differentiate essential tremor (ET) from Parkinson's disease (PD). The scan is a crude indicator of the number of dopamine-secreting cells and is abnormal in presynaptic parkinsonian syndromes. In this article we review this and other possible clinical situations in which a DaT scan may be useful.

Inpatient Mortality in Parkinson's Disease.

Introduction: Although a majority of the American public prefer to die at home, a large percentage of Parkinson's disease patients die in acute care hospitals. We examine trends in the clinical and demographic characteristics of Parkinson's disease patients who die in a hospital to identify populations potentially vulnerable to unwanted inpatient mortality. Methods: Patients with Parkinson's disease admitted to a hospital from 2002-2016 were identified from the National Inpatient Sample (n = 710,013) along with their associated clinical and demographic characteristics. The main outcome examined was mortality during inpatient admission. From these data, logistic regression models were estimated to obtain the odds ratios of inpatient mortality among clinical and demographic attributes, and their change over time. Results: Characteristics significantly associated with increased odds of inpatient mortality included increased age (OR = 1.70 for 55-65, 2.52 for 66-75, 3.99 for 76-85, 5.72 for 86+, all P < 0.001), length of stay ≤5 days (reference; 6 + days OR = 0.37, P < 0.001), white race or ethnicity (reference; Black OR = .84 P < .001, Hispanic OR = 0.91 P = 0.01), male (reference; female OR = 0.93 P < 0.001), hospitalization in Northeast (reference; Midwest OR = 0.78, South 0.84, West OR = 0.82; all P < 0.001), higher severity of illness (moderate OR = 1.50, major OR = 2.32, extreme OR = 5.57; all P < 0.001), and mortality risk (moderate OR = 2.88, major OR = 10.92, extreme OR = 52.30; all P < 0.001). Fitted probabilities overall declined over time. Conclusion: Differences exist among PD patient populations regarding likelihood of in-hospital mortality that are changing with time. Insight into which PD patients are most at risk for inpatient mortality may enable clinicians to better meet end-of-life care needs.

Klinefelter's Syndrome with Tremors, Ataxia and Parkinsonism.

Klinefelter's syndrome (KS) is the most common cause of hypogonadism in men. Essential tremor (ET) and parkinsonism have been reported in KS, but ataxia, which has been commonly reported with other causes of hypogonadism, is very rare in KS. Orthostatic tremor has not been reported. We present a case with multiple movement disorders, including gait ataxia, essential-type tremor, rest tremor, orthostatic tremor and parkinsonism.