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Randomized Controlled Trial
. 2024 Feb:119:105951.
doi: 10.1016/j.parkreldis.2023.105951. Epub 2023 Dec 12.

Pimavanserin for psychosis in Parkinson's disease dementia: Subgroup analysis of the HARMONY Trial

Daniel Weintraub  1 , Alberto J Espay  2 , Vibhash D Sharma  3 , Pierre N Tariot  4 , Victor Abler  5 , Sanjeev Pathak  6 , Srdjan Stankovic  7
Affiliations
Free article
Randomized Controlled Trial

Pimavanserin for psychosis in Parkinson's disease dementia: Subgroup analysis of the HARMONY Trial

Daniel Weintraub et al. Parkinsonism Relat Disord. 2024 Feb.
Free article

Abstract

Introduction: Pimavanserin is FDA-approved to treat Parkinson's disease (PD) psychosis. We analyzed the effect of pimavanserin on psychosis in the PD dementia (PDD) subgroup from the phase 3 HARMONY trial.

Methods: This subgroup analysis included PDD patients enrolled in an international, multicenter, randomized discontinuation study of pimavanserin for dementia-related psychosis. PDD patients with moderate-to-severe psychosis, age 50-90 years, received pimavanserin 34 mg/day for 12 weeks (open-label period). Those with a sustained psychosis response to pimavanserin at weeks 8 and 12 were randomized during the double-blind period to continue pimavanserin or receive placebo. Primary efficacy endpoint was time to psychosis relapse as measured by the SAPS-H + D and CGI-I. Safety was assessed, as were effects on motor symptoms and cognitive abilities using the ESRS-A and MMSE.

Results: 392 patients were enrolled in HARMONY (mean age: 72.6 years; 38.8 % female): 59 had PDD; 49/59 remained on pimavanserin during the open-label period (safety analysis set), and 36/49 were randomized to pimavanserin (n = 16) or placebo (n = 20) in the double-blind phase (intent-to-treat analysis set). Risk of psychosis relapse was lower with pimavanserin 34 mg compared with placebo in the double-blind phase (HR = 0.052; 95 % CI 0.016-0.166; 1-sided nominal p < 0.001). During the open-label period, 46.9 % experienced a treatment-emergent adverse event; event incidence was similar across arms in the double-blind period. Pimavanserin did not adversely affect motor or cognitive function in either treatment phase.

Conclusions: Pimavanserin significantly reduced risk of psychosis relapse in patients with PDD, was well tolerated, and did not worsen motor or cognitive function.

Keywords: Delusions; Hallucinations; Parkinson's disease; Pimavanserin.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DW received research funding or support from the Michael J. Fox Foundation for Parkinson's Research, Alzheimer's Therapeutic Research Initiative, Alzheimer's Disease Cooperative Study, the International Parkinson and Movement Disorder Society, and the National Institute on Aging; honoraria for consultancy from Acadia, CHDI Foundation, Clintrex LLC (Aptinyx, Avanir, and Otsuka), Eisai, Janssen, Sage, Signant Health, and Sunovion; and license fee payments from the University of Pennsylvania for the QUIP and QUIP-RS. AJE has received grant support from the National Institutes of Health and the Michael J. Fox Foundation; personal compensation as a consultant/scientific advisory board member for AbbVie, Neuroderm, Neurocrine, Amneal, Acadia, Acorda, Bexion, Kyowa Kirin, Sunovion, Supernus (formerly, USWorldMeds), Avion Pharmaceuticals, and Herantis Pharma; and publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer. He cofounded REGAIN Therapeutics, as an owner of a patent application that covers synthetic soluble nonaggregating peptide analogs as a replacement treatment in proteinopathies. He serves on the editorial boards of the Journal of Parkinson's Disease, Journal of Alzheimer's Disease, European Journal of Neurology, Movement Disorders Clinical Practice, and JAMA Neurology. VDS has received grant support from the International Essential Tremor Foundation and served as a consultant for Abbott. PNT reports consulting fees from Acadia, AC Immune, Avanir, Axsome, BioXcel, Eisai, Otsuka/Astex, and Syneos; reports consulting fees and research support from AbbVie, Biogen, Cortexyme, Genentech, Lilly, Merck & Co., and Roche; reports research support only from Novartis; and owns stock in Adamas Pharmaceuticals. VA, SP, and SS are employees of Acadia Pharmaceuticals Inc. and may hold stock/stock options.

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