Coordinating Care Between Neurology and Psychiatry to Improve the Diagnosis and Treatment of Parkinson s Disease Psychosis Jeff Gelblum, MD Senior Attending Neurologist Mt. Sinai Medical Center Miami, FL
Jeff Gelblum, MD Disclosures Speakers Bureau: ACADIA Pharmaceuticals Inc.; Allergan; Avanir Pharmaceuticals Inc.
Learning Objective Utilize a team approach engaging psychiatry, neurology, and caregivers to optimize treatment for Parkinson s disease psychosis.
Long-Term, Progressive Course of Parkinson s Disease Psychosis (PDP) Year Psychosis + Prevalence Baseline 41/230 18% Year 4 51/142 36% Year 8 45/88 51% Year 12 12/25 48% Cumulative 137/230 60% Particular attention should be given to patients who Develop PD at an older age Are in need of high doses of dopaminergic medication Present with clinical symptoms of REM sleep behavior disorder Forsaa EB et al. Arch Neurol. 2010;67(8):996-1001.
PDP a Source of Increasing Morbidity, Mortality, and Caregiver Burden Increased risk of hospitalization and nursing home placement 1,2 24% of hospitalizations in patients with Parkinson s disease (PD) 29% of prolonged hospital stay and repeat admissions PD patients with hallucinations 2.5x more likely to be admitted to a nursing home Caregiver burden increases as PDP progresses 3,4 Psychosis symptoms a strong predictor of caregiver burden More than 40% of caregivers report a decline in health 66% report that their close relationships suffer Nearly 50% have increased depression scores 1 Klein C, et al. J Neural Transm (Vienna). 2009;116:1509-1512. 2 Aarsland D, et al. J Am Geriatr Soc.. 2000;48:938-942 2 Marsh L, et al, Neurology. 2004;63:293-300. 3 Schrag A, et al. Parkinsonism Relat Disord.2006;12:35-41.
Patients and Caregivers Not Always Forthcoming with Disclosure of Symptoms of PDP Despite the having greater impact on quality of life than motor symptoms in PD, patients and/or caregivers often do not disclose symptoms 1 In a survey of 242 PD patients 2 41.5% reported that they did not disclose hallucinations 65.2% did not disclose delusions Proposed reasons for nondisclosure included Embarrassment Did not realize they were related to PD Forgot 1 Bernal-Pacheco O, et al. Neurologist. 2012;18:1-16. 2 Chaudhuri KR, et al. Mov Disord. 2010;25:704-709.
Parkinson s Disease Psychosis (PDP) has a Clinical Profile Distinct from Other Psychotic Conditions with Severity Increasing Over Time Visual Both Complex and Minor 16%-72% Auditory 0%-22% Olfactory 11% Symptoms of PDP Delusions 1-14% Gustatory 3% Tactile 12% Somatic 1% Goldman JG, et al. Expert Opin Pharmacother. 2011;12:2009-2024.; Voss T, et al. Parkinsonism Relat Disord. 2013;19:295-299.; Fenelon G, Alves G. J Neurol Sci. 2010;289:12-17
2007 Provisional NINDS-NIMH Diagnostic Criteria for PDP Requires the presence of at least 1 of the following symptoms Hallucinations Delusions Illusion False sense of presence Must occur in patients with prior diagnosed Parkinson s disease Must be recurrent or continuous for at least 1 month Other causes excluded Delirium, schizophrenia, Alzheimer s disease psychosis, major depression with psychosis, and other psychiatric disorders May occur with or without Insight, dementia, or Parkinson s disease treatment Ravina B, et al. Mov Disord. 2007;22:1061-1068.
Prescribing of Antipsychotics for PDP 50% of PD patients with psychosis in a VA population of 2,547 were prescribed an antipsychotic for psychosis Quetiapine prescribed most frequently in 66% of patients 30% receive high potency typical and atypical antipsychotics Clozapine prescribed < 2% Weintraub D, et al. Arch Neurol. 2011;68(7):899-904.
Treatment Options for PDP: Clozapine* Requires monitoring for neutropenia Adverse effects: Serotonergic and anticholinergic Black box warning 1 Severe neutropenia (.38%) Increased mortality in elderly patients with dementia-related psychosis Change in Score, Mean 14 12 10 8 6 4 2 0 Clozapine Placebo CGI SAPS CGI PANSS Parkinson s Study Group 2 French Clozapine Parkinson s Study Group 3 SAPS = Scale for positive symptoms; CGI: Clinical global impression scale *Not approved by the FDA for the treatment of PDP 1 Package insert available at Drugs@FDA.com.; 2[No authors listed] N Engl J Med. 1999;340(10):757-763.; 3 Pollack P, et al. J Neurol Neurosurg Psychiatry. 2004;75:689-695.
Treatment Options: Quetapine* Safety and efficacy studied in 4 randomized trials 1-4 Did not demonstrate improvement in BPRS Did not worsen motor symptoms Black box warning 5 Increased mortality in elderly patients with dementia-related psychosis BPRS = Brief psychiatric rating scale *Not approved by the FDA for the treatment of PDP 1 Kurlan R, et al. Neurology. 2007; 68:1356-1363.; 2 Rabey JM, et al. Mov Disord. 2007;15:113-118.; 4 Ondo WG, et al. Mov Disord. 2005;20:958-963.; 5 Package insert available at Drugs@FDA.com.
Treatment Options: Pimavanserin Pimavanserin resulted in a significant 37% improvement in SAPS-PD vs 14% for placebo (p = 0.006) No change in motoric function by UPDRS (parts 2 + 3) UPDRS = Unified Parkinson s Disease Rating Scale Cummings J, et al. Lancet. 2014;383:533-540. 12
Pimavanserin: CGI Change from Baseline Significant improvements were observed in CGI-S and CGI-I scores CGI-S CGI-I Cummings J, et al. Lancet. 2014;383:533-540. 13
Adverse Events Occurring in 5% in Either Treatment Group Event Placebo (n = 94) Pimavanserin (n = 104) Nausea 6% 6% Peripheral edema 3% 7% Urinary tract infection 12% 13% Fall 9% 11% Confusional state 3% 6% Headache 5% 1% Hallucination 4% 7% Cummings J et al. Lancet. 2014;383:533-540. 14
Call to Action Recognize that psychosis is very common in patients with Parkinson s disease Patient/caregivers may not volunteer information. Ask patients/caregivers about hallucinations Address potential impact of medication and other medical conditions on symptoms of psychosis
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