Narcolepsy is a neurological disease that affects 1 in 2,000 individuals and is 
characterized by excessive daytime sleepiness (EDS). In 60-70% of individuals 
with narcolepsy, it is also characterized by cataplexy or a sudden loss of 
muscle tone that is triggered by positive or negative emotions. Narcolepsy 
decreases the quality of life of the afflicted individuals. Currently used drugs 
treat EDS alone (modafinil/armodafinil, methylphenidate, and amphetamine), 
cataplexy alone ("off-label" use of antidepressants), or both EDS and cataplexy 
(sodium oxybate). These drugs have abuse, tolerability, and adherence issues. A 
greater diversity of drug options is needed to treat narcolepsy. The small 
molecule drug, pitolisant, acts as an inverse agonist/antagonist at the H3 
receptor, thus increasing histaminergic tone in the wake promoting system of the 
brain. Pitolisant has been studied in animal models of narcolepsy and used in 
clinical trials as a treatment for narcolepsy. A comprehensive search of online 
databases (eg, Medline, PubMed, EMBASE, the Cochrane Library Database, Ovid 
MEDLINE, Europe PubMed Central, EBSCOhost CINAHL, ProQuest Research Library, 
Google Scholar, and ClinicalTrials.gov) was performed. Nonrandomized and 
randomized studies were included. This review focuses on the outcomes of four 
clinical trials of pitolisant to treat narcolepsy. These four trials show that 
pitolisant is an effective drug to treat EDS and cataplexy in narcolepsy.