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

Abstract

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. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

• Authors: Alberto J Espay, Michael T Guskey, James C Norton, Bruce Coate, Joaquin A Vizcarra, Clive Ballard, Stewart A Factor, Joseph H Friedman, Anthony E Lang, Niccole J Larsen, Candace Andersson, Doral Fredericks, Daniel Weintraub
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 33 Issue 11 Pg. 1769-1776 (11 2018) ISSN: 1531-8257 [Electronic] United States
• PMID: 30387904 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Chemical References

• Antipsychotic Agents
• Nootropic Agents
• Piperidines
• Urea
• pimavanserin

Topics

• Aged
• Aged, 80 and over
• Antipsychotic Agents (therapeutic use)
• Cognition Disorders (drug therapy, etiology)
• Double-Blind Method
• Female
• Humans
• Male
• Mental Status Schedule
• Middle Aged
• Nootropic Agents (therapeutic use)
• Parkinson Disease (complications)
• Piperidines (therapeutic use)
• Psychotic Disorders (drug therapy, etiology)
• Treatment Outcome
• Urea (analogs & derivatives, therapeutic use)