Narcolepsy is a rare
sleep disorder characterized by
excessive daytime sleepiness and rapid eye movement sleep dysregulation, manifesting as
cataplexy and
sleep paralysis, as well as hypnagogic and hypnopompic
hallucinations. Disease onset may occur at any age, although adolescents and young adults are mainly affected. Currently, the diagnosis delay ranges from 8 to 10 years and
drug therapy may only attenuate symptoms.
Pitolisant is a first-in-class new drug currently authorized by the European Medicines Agency to treat
narcolepsy with or without
cataplexy in adults and with an expanded evaluation for the treatment of neurologic diseases such as
Parkinson's disease and
epilepsy. This article reviews the pharmacokinetic and pharmacodynamic profile of
pitolisant, highlighting its effectiveness and safety in patients with
narcolepsy. We performed a systematic review of the literature using PubMed, Embase, and Google Scholar. We report on the efficacy and safety data of
pitolisant in narcoleptic patients regarding
cataplexy episodes and subjective and objective
daytime sleepiness. The development program of
pitolisant was characterized by eight Phase II/III studies. One proof-of-concept study followed by two pivotal studies, three randomized controlled trials, and two open studies were evaluated. Our review confirmed the effectiveness of
pitolisant in treating major clinically relevant
narcolepsy symptoms, including
cataplexy, as compared to placebo. In addition,
pitolisant revealed a safe profile when compared with placebo and active comparators.
Headache,
insomnia, and
nausea were the prominent side effects. Further long-term randomized controlled trials comparing the efficacy of
pitolisant with active comparators (ie,
modafinil and
sodium oxybate) may clarify its real place in
therapy and its possible use as a first-line agent on the basis of its safety and tolerability.