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

Jay T Guevarra, Robert Hiensch, Andrew W Varga, David M Rapoport Division of Pulmonary, Critical Care, and Sleep Medicine, Mount Sinai Integrative Sleep Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USACorrespondence: Jay T GuevarraDivision of Pulmonary, Critical Care, and Sleep Medicine, Mount Sinai Integrative Sleep Center, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USATel +1 646 339-3862Fax +1 212 876 5519Email jay.guevarra@mountsinai.orgAbstract: 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