pitolisant, a novel histamine-3 receptor competitive antagonist,  and inverse agonist, in the treatment of excessive daytime  sleepiness in adult patients with narcolepsy

Noeen Sarfraz; David Okuampa; Hannah Hansen; Mark Alvarez; Elyse M. Cornett; Juyeon Kakazu; Adam M. Kaye; Alan D. Kaye

doi:10.52965/​001c.34222

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pitolisant, a novel histamine-3 receptor competitive antagonist, and inverse agonist, in the treatment of excessive daytime sleepiness in adult patients with narcolepsy

Noeen Sarfraz¹, David Okuampa², Hannah Hansen², Mark Alvarez², Elyse M. Cornett³, Juyeon Kakazu^4*, Adam M. Kaye⁵, Alan D. Kaye³

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¹ Department of Psychiatry, Louisiana State University Health Shreveport

² College of Medicine, Louisiana State University Health Shreveport

³ Department of Anesthesiology, Louisiana State University Health Shreveport

⁴ Georgetown University School of Medicine, Georgetown University School of Medicine

⁵ Department of Pharmacy Practice, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific

HPR 2022 , 10(2), 1; https://doi.org/10.52965/001c.34222

Submitted: 22 November 2021 | Accepted: 11 January 2022 | Published: 30 May 2022

© 2022 by the Author(s). Licensee Health Psychology Research, USA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/ )

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Abstract

Narcolepsy is a debilitating sleep disorder that presents with excessive daytime sleepiness (EDS) and cataplexy, which is a sudden paralysis of muscle tone triggered by strong emotions such as laughing. It is also associated with many other disorders, including psychiatric disorders, neurologic illnesses, and medication side effects. Common causes of delayed and incorrect diagnoses of these conditions include lack of physician familiarity with narcolepsy symptoms and comorbidities which mask narcolepsy signs and symptoms. Current pharmacologic therapies include Modafinil and Armodafinil for EDS and sodium oxybate for cataplexy. This review discusses the epidemiology, pathophysiology, risk factors, presentation, treatment of narcolepsy, and the role of a novel drug, Pitolisant, in the treatment of EDS in adults with narcolepsy. Pitolisant is a histamine-3 receptor (H3R), competitive antagonist, and inverse agonist, acting through the histamine system to regulate wakefulness. It is a novel drug approved in August 2019 by the FDA, is not classified as a controlled substance, and is approved for use in Europe and the United States to treat EDS and cataplexy in narcolepsy. Recent phase II and III trials have shown that Pitolisant helps reduce the ESS score and cataplexy. In summary, based on comparative studies, recent evidence has shown that Pitolisant is non-inferior to Modafinil in the treatment of EDS but superior to Modafinil in reducing cataplexy.

Keywords

Pitolisant

excessive daytime sleepiness

narcolepsy

NT1

NT2

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Conflict of interest

The authors did not receive any funding or financial support or potential sources of conflict of interests.

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