Pitolisant (Wakix®), an orally available, first-in-class antagonist/inverse 
agonist of the histamine 3 receptor, is approved in the EU (as of March 2016) 
for the treatment of narcolepsy with or without cataplexy in adults and in the 
USA (as of August 2019) for the treatment of excessive daytime sleepiness (EDS) 
in adults with narcolepsy. Pitolisant was demonstrated to have minimal risk of 
abuse in preclinical and clinical studies, and is the only anti-narcoleptic drug 
not scheduled as a controlled substance in the USA. The totality of evidence 
from pivotal and supportive phase III trials suggests that pitolisant 
administered at up to the recommended maximum dose of 36 mg once daily reduces 
EDS and cataplexy in adults with narcolepsy relative to placebo. Noninferiority 
of pitolisant to modafinil in the management of EDS was not demonstrated. 
Pitolisant was generally well tolerated in clinical trials. Consistent with its 
mechanism of action, the most common treatment-emergent adverse events included 
headache, insomnia and anxiety. With minimal abuse potential and offering the 
convenience of oral, once-daily administration, pitolisant extends the range of 
approved treatment options available to adult patients with narcolepsy with or 
without cataplexy.