Pimavanserin for Parkinson's Disease psychosis: Effects stratified by baseline cognition and use of cognitive-enhancing medications

• Type of Material: Article
• Authors: Alberto J. Espay, University of Cincinnati; Michael T. Guskey, ACADIA Pharmaceuticals Inc.; James C. Norton, ACADIA Pharmaceuticals Inc.; Bruce Coate, ACADIA Pharmaceuticals Inc.; Joaquin A. Vizcarra, University of Cincinnati; Clive Ballard, University of Exeter; Stewart Factor, Emory University; Joseph H. Friedman, Brown University; Anthony E. Lang, University of Toronto; Niccole J. Larsen, ACADIA Pharmaceuticals Inc.; Candace Andersson, ACADIA Pharmaceuticals Inc.; Doral Fredericks, ACADIA Pharmaceuticals Inc.; Daniel Weintraub, University of Pennsylvania
• Language: English
• Date: 2018-11-01
• Publisher: Wiley
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/mds.27488
• Title of Journal or Parent Work: Movement Disorders
• ISSN: 0885-3185
• Volume: 33
• Issue: 11
• Start Page: 1769
• End Page: 1776
• Grant/Funding Information: The study for this post‐hoc analyses was funded by ACADIA Pharmaceuticals Inc.
• Keywords: Life Sciences & Biomedicine; cholinesterase inhibitors; CLOZAPINE; IMPAIRMENT; Clinical Neurology; NEUROPSYCHIATRIC SYMPTOMS; MANAGEMENT; SEVERE ALZHEIMERS-DISEASE; Parkinson's disease psychosis; MEMANTINE; MOTOR FUNCTION; memantine; cognitive impairment; DEMENTIA; Neurosciences & Neurology; pimavanserin; PERFORMANCE; cognitive-enhancing medications; HALLUCINATIONS; Science & Technology
• Research Categories: Health Sciences, Pathology; Biology, Neuroscience

Abstract

Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. Background: PD psychosis is often associated with cognitive impairment, including dementia, and involves dopaminergic, serotonergic, and cholinergic mechanisms. Objective: To evaluate the differential effect of the antipsychotic pimavanserin, a selective serotonin 2A receptor inverse agonist, in PD psychosis patients with versus without cognitive impairment and in those receiving versus not receiving cognitive-enhancing medications. Methods: Data from the pivotal randomized clinical trial of pimavanserin for PD psychosis were stratified by (1) screening MMSE score as cognitively impaired (21-24) versus unimpaired (≥25) and (2) concomitant use versus nonuse of cognitive-enhancing medications. The primary outcome measure was change in the PD-adapted Scale for the Assessment of Positive Symptoms. Results: Mean (pimavanserin vs. placebo) change from baseline was larger in the cognitively impaired (n = 50; –6.62 vs. –0.91; P = 0.002) versus the cognitively unimpaired (n = 135; –5.50 vs. –3.23; p = 0.046) group. The comparable change was –6.04 versus –2.18 (P = 0.012) and –5.66 versus –3.15 (P = 0.041) in patients treated (n = 69) and not treated (n = 116) with concomitant cognitive-enhancing medication. Pimavanserin was similarly tolerated across all cognitive groups with no additional safety concerns identified. Overall adverse event rates were comparable across the concomitant cognitive-enhancing medication groups; however, rates of serious adverse events and discontinuations attributed to adverse events were increased in patients taking cholinesterase inhibitors. Conclusions: The antipsychotic effect of pimavanserin is robust in PD patients with cognitive impairment and may be enhanced by concomitant cognitive-enhancing medication use. Future prospective studies are needed to confirm these preliminary findings.