Efficacy of Pitolisant on the Treatment of Narcolepsy: A Systematic Review

Stephanie P Fabara 1, Juan Fernando Ortiz 2 3, Anas Anas Sohail 4, Jessica Hidalgo 5, Abbas Altamimi 6, Belen Tama 7, Urvish K Patel 8

Affiliations

07 January 2021

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doi: 10.7759/cureus.16095

Abstract

Narcolepsy is characterized by excessive daytime sleepiness (EDS) and cataplexy. Histamine neurons play an important role in enhancing wakefulness. The objective of our study was to evaluate the efficacy of pitolisant, a histamine 3 (H3)-receptor antagonist/inverse agonist, in patients with a high burden of narcolepsy symptoms. We conducted an advanced PubMed search strategy with inclusion and exclusion criteria. The outcome included the Epworth Sleepiness Scale (ESS) and adverse effects frequency. Our primary outcome included the mean ESS score at the endpoint and showed that pitolisant was superior to the placebo, but not non-inferior to modafinil. Adverse effects were less common and shorter in duration in the pitolisant group compared to the modafinil-treated patients. Pitolisant was efficacious in reducing excessive daytime sleepiness and cataplexy compared with placebo, and it was well-tolerated in patients with severe narcolepsy symptoms as compared with modafinil.

Keywords: clinical trials; efficacy; modafinil; narcolepsy; pitolisant.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1. PRISMA flow chart

Figure 1. PRISMA flow chart

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References

  1.  
    1. The neurobiological basis of narcolepsy. Mahoney CE, Cogswell A, Koralnik IJ, Scammell TE. Nat Rev Neurosci. 2019;20:83–93. - PMC - PubMed
  2.  
    1. Profile of pitolisant in the management of narcolepsy: design, development, and place in therapy. Romigi A, Vitrani G, Lo Giudice T, Centonze D, Franco V. Drug Des Devel Ther. 2018;12:2665–2675. - PMC - PubMed
  3.  
    1. Challenges in the development of therapeutics for narcolepsy. Black SW, Yamanaka A, Kilduff TS. Prog Neurobiol. 2017;152:89–113. - PMC - PubMed
  4.  
    1. Prevalence of narcolepsy symptomatology and diagnosis in the European general population. Ohayon MM, Priest RG, Zulley J, Smirne S, Paiva T. Neurology. 2002;58:1826–1833. - PubMed
  5.  
    1. Epidemiology and pathophysiology of childhood narcolepsy. Dye TJ, Gurbani N, Simakajornboon N. Paediatr Respir Rev. 2018;25:14–18. - PubMed
  6.  
    1. Low cerebrospinal fluid hypocretin (Orexin) and altered energy homeostasis in human narcolepsy. Nishino S, Ripley B, Overeem S, et al. Ann Neurol. 2001;50:381–388. - PubMed
  7.  
    1. Narcolepsy - clinical spectrum, aetiopathophysiology, diagnosis and treatment. Bassetti CLA, Adamantidis A, Burdakov D, et al. Nat Rev Neurol. 2019;15:519–539. - PubMed
  8.  
    1. The European Narcolepsy Network (EU-NN) database. Khatami R, Luca G, Baumann CR, et al. J Sleep Res. 2016;25:356–364. - PubMed
  9.  
    1. The clinical spectrum of narcolepsy with cataplexy: a reappraisal. Sturzenegger C, Bassetti CL. J Sleep Res. 2004;13:395–406. - PubMed
  10.  
    1. Psychotic symptoms in narcolepsy: phenomenology and a comparison with schizophrenia. Fortuyn HA, Lappenschaar GA, Nienhuis FJ, et al. Gen Hosp Psychiatry. 2009;31:146–154. - PubMed
  11.  
    1. Comparing treatment effect measurements in narcolepsy: the sustained attention to response task, Epworth sleepiness scale and maintenance of wakefulness test. van der Heide A, van Schie MK, Lammers GJ, et al. Sleep. 2015;38:1051–1058. - PMC - PubMed
  12.  
    1. Mechanisms of modafinil: a review of current research. Gerrard P, Malcolm R. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654794/ Neuropsychiatr Dis Treat. 2007;3:349–364. - PMC - PubMed
  13.  
    1. Characterization of the neurochemical and behavioral effects of solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake inhibitor. Baladi MG, Forster MJ, Gatch MB, Mailman RB, Hyman DL, Carter LP, Janowsky A. https://pubmed.ncbi.nlm.nih.gov/29891587/. J Pharmacol Exp Ther. 2018;366:367–376. - PubMed
  14.  
    1. Mechanism of action of methylphenidate: insights from PET imaging studies. Volkow ND, Fowler JS, Wang G, Ding Y, Gatley SJ. J Atten Disord. 2002;6:0–43. - PubMed
  15.  
    1. Amphetamine paradoxically augments exocytotic dopamine release and phasic dopamine signals. [May;2021 ];Daberkow DP, Brown HD, Bunner KD, et al. https://pubmed.ncbi.nlm.nih.gov/23303926/. J Neurosci. 2013 33:452–463. - PMC - PubMed
  16.  
    1. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. Sterne JA, Hernán MA, Reeves BC, et al. BMJ. 2016;355:0. - PMC - PubMed
  17.  
    1. RoB 2: a revised tool for assessing risk of bias in randomised trials. Sterne JAC, Savović J, Page MJ, et al. BMJ. 2019;366:0. - PubMed
  18.  
    1. Efficacy of pitolisant in patients with high burden of narcolepsy symptoms: pooled analysis of short-term, placebo-controlled studies. Davis CW, Kallweit U, Schwartz JC, Krahn LE, Vaughn B, Thorpy MJ. Sleep Med. 2021;81:210–217. - PubMed
  19.  
    1. Pitolisant versus placebo or modafinil in patients with narcolepsy: a double-blind, randomised trial. Dauvilliers Y, Bassetti C, Lammers GJ, et al. Lancet Neurol. 2013;12:1068–1075. - PubMed
  20.  
    1. Evaluation of the abuse potential of pitolisant, a selective H3-receptor antagonist/inverse agonist, for the treatment of adult patients with narcolepsy with or without cataplexy. Setnik B, McDonnell M, Mills C, Scart-Grès C, Robert P, Dayno JM, Schwartz JC. Sleep. 2020;43:0. - PMC - PubMed
  21.  
    1. An inverse agonist of the histamine H(3) receptor improves wakefulness in narcolepsy: studies in orexin-/- mice and patients. Lin JS, Dauvilliers Y, Arnulf I, et al. Neurobiol Dis. 2008;30:74–83. - PubMed
  22.  
    1. Pitolisant, an inverse agonist of the histamine H3 receptor: an alternative stimulant for narcolepsy-cataplexy in teenagers with refractory sleepiness. Inocente C, Arnulf I, Bastuji H, et al. https://pubmed.ncbi.nlm.nih.gov/22356925/. Clin Neuropharmacol. 2012;35:55–60. - PubMed
  23.  
    1. Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial. Szakacs Z, Dauvilliers Y, Mikhaylov V, et al. Lancet Neurol. 2017;16:200–207. - PubMed
  24.  
    1. Solriamfetol for the treatment of excessive daytime sleepiness associated with narcolepsy. Yang J, Gao J. Expert Rev Clin Pharmacol. 2019;12:723–728. - PubMed
  25.  
    1. Recently approved and upcoming treatments for narcolepsy. Thorpy MJ. CNS Drugs. 2020;34:9–27. - PMC - PubMed

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