Pitolisant 4.5mg tablets

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.

Abstract licence: CC BY-NC 3.0

There remains an unmet need for a targeted treatment to address residual excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA) after primary treatment. This network meta-analysis evaluated the efficacy and safety of wake-promoting agents (WPAs), namely solriamfetol, pitolisant, modafinil, and armodafinil, for treating residual EDS in patients with OSA. We conducted a comprehensive search which ultimately included 18 studies in the final analysis. All 4 WPAs demonstrated significant therapeutic benefits for the Epworth sleepiness scale (ESS) and maintenance of wakefulness test (MWT). Based on the surface under the cumulative ranking curve (SUCRA) score, solriamfetol, pitolisant, modafinil and armodafinil were ranked from highest to lowest for the ESS. A similar ranking was observed for MWT, where pitolisant was not included in the analysis. The subgroup analysis also evaluated the efficacy of WPAs in the primary treatment adherent and nonadherent subgroups. Regarding adverse reactions, solriamfetol demonstrated the lowest risk of all-cause discontinuation, whereas pitolisant exhibited minimal risks of adverse events leading to treatment discontinuation and treatment-emergent adverse events. Our analysis comprehensively compared the effects and adverse reactions of different WPAs in treating residual EDS in treated patients with OSA. This has significant implications for the practical clinical use of WPAs and future research.

Abstract licence: CC BY-NC-ND

Narcolepsy is a neurological disease characterized by a core symptom of excessive daytime sleepiness (EDS). Although effective pharmacological interventions for narcolepsy have been developed, a lack of comparative evidence supporting the relative efficacy among these medications leads to clinical treatment challenge. Therefore, we performed a network meta-analysis to overcome this lack of head-to-head comparisons. Databases were searched systematically for randomized controlled trials that compared pharmacological interventions for narcolepsy. The primary outcomes were changes in the Epworth Sleepiness Scale (ESS) and the Maintenance of Wakefulness Test (MWT). A random-effects frequentist network meta-analysis was conducted. A total of 19 RCTs involving 2504 patients were included. Solriamfetol achieved the highest ranking based on the P-scores, and was superior to pitolisant (MD -2.88, 95% CI -4.89--0.88) and sodium oxybate (MD -2.56, 95% CI -4.62--0.51) for ESS change. Consistently, solriamfetol achieved the highest ranking according to MWT change, and was superior to pitolisant (SMD 0.45, 95% CI 0.02-0.88) and modafinil (SMD 0.42, 95% CI 0.05-0.79). Although solriamfetol demonstrated superior efficacy in EDS improvement, evidence from the clustered ranking plot supported that efficacy-safety profiles of pitolisant, sodium oxybate, and modafinil are more balanced than solriamfetol. Therefore, the choice of medication for EDS in narcolepsy should be made on an individual basis.

Abstract licence: CC BY