No significant differences in safety endpoints were found. The Epworth Sleepiness Scale (ESS) and Oxford Sleep Resistance (OSleR) tests were co-primary endpoints.ResultsA total of 512 patients, including 384 treated with pitolisant and 128 with placebo, were included in the analysis.Ĭompared with placebo, pitolisant reduced mean ESS by − 3.1 (95% CI p < 0.001) and improved OSleR by 1.18 (1.02 1.35, p = 0.022) 30% more patients had reduced fatigue (risk ratio = 1.3, ), p = 0.001) and 46% more patients had improved Clinical Global Impression (CGI) (RR = 1.46, p = 0.005).

This article assesses the efficacy and safety of pitolisant 20 mg in patients with OSA, based on existing randomised controlled studies.MethodsĪn individual patient data (IPD) meta-analytical two-level (study-patient) hierarchical model was used assuming a random treatment effect. Pitolisant is an orally active selective histamine H3 receptor (H3R) antagonist/inverse agonist, which enhances histaminergic transmissions in the brain and thereby elicits strong wake-promoting effects. Since hypothalamic dysfunction seems to partially influence metabolic, respiratory and sleep/wake characteristics of this syndrome, additional studies are required in this framework.īackground and objectiveExcessive daytime sleepiness (EDS) and fatigue are major complaints in patients with obstructive sleep apnoea (OSA) syndrome. Sleep disorders in humans with PWS are multifaceted and are often the result of different mechanisms. Moreover, we performed a meta-analysis of cerebrospinal fluid orexin levels in patients with PWS significantly lower levels of orexin were detected in PWS with respect to control subjects (although significantly higher than the ones of narcoleptic patients). We reviewed the genetic features of the syndrome and the possible relationship with sleep alterations in animal models, and we described sleep phenotypes, diagnostic tools and therapeutic approaches in humans. The aim of the review is to highlight the pathophysiology and the clinical features of sleep disorders in PWS, providing the basis for early diagnosis and management. Sleep alterations and sleep disorders such as Sleep-disordered breathing and Central disorders of hypersomnolence are frequently recognized (either isolated or in comorbidity). Prader-Willi Syndrome (PWS) is a complex genetic disorder with multiple cognitive, behavioral and endocrine dysfunctions. 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. Consistent with its mechanism of action, the most common treatment-emergent adverse events included headache, insomnia and anxiety. Pitolisant was generally well tolerated in clinical trials. Noninferiority of pitolisant to modafinil in the management of EDS was not demonstrated. 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. 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. 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.

Mild narcolepsy without cataplexy