Pitolisant to Treat Excessive Daytime Sleepiness and Cataplexy in Adults with Narcolepsy: Rationale and Clinical Utility

Abstract

Narcolepsy is a sleep disorder marked by chronic, debilitating excessive daytime sleepiness and can be associated with cataplexy, sleep paralysis and sleep-related hallucinations. Pharmacological therapy for narcolepsy primarily aims to increase wakefulness and reduce cataplexy attacks. Pitolisant is a first-in-class agent utilizing histamine to improve wakefulness by acting as an antagonist/inverse agonist of the presynaptic histamine 3 receptor. This review summarizes the clinical efficacy, safety and tolerability of pitolisant in treating the symptoms of narcolepsy. Randomized and observational studies demonstrate pitolisant to be effective in treating both hypersomnolence and cataplexy while generally being well tolerated at prescribed doses. The most common adverse reactions include headache, insomnia and nausea.

Keywords:

• narcolepsy
• pitolisant
• histamine 3 receptor
• excessive daytime sleepiness
• cataplexy

Disclosure

Dr. Jay T. Guevarra and Dr. Robert Hiensch have no disclosures. Dr. Andrew W. Varga has previously served as a consultant for Merck and Eisai Pharmaceuticals and reports grants, personal fees, and non-financial support from Merck, and personal fees from Eisai, outside the submitted work. He is supported by: NIH/NIA R01AG056682, R01AG066870, R21AG059179, the Alzheimer’s Association, the McClung Foundation, and the Merck Investigators Studies Program. Dr. David M. Rapoport receives patent royalties from Fisher & Paykel Healthcare Limited and Sefam Medical, Ltd for CPAP modifications; consulting fees and grant support from Fisher & Paykel Healthcare Limited; and consulting fees from BioMarin Pharmaceutical Inc, Morphy, Inc, and Jazz Pharmaceuticals plc. The authors report no other potential conflicts of interest for this work.