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Treating Narcolepsy and Idiopathic Hypersomnia

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Fatigue Management

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Abstract

According to the 2005 International Classification of Sleep Disorders (ICSD-2), narcolepsy and idiopathic hypersomnia are considered hypersomnias of central origin (American Academy of Sleep Medicine. International Classification of Sleep Disorders. Diagnostic and coding manual. 2nd ed. Westchester: American Academy of Sleep Medicine; 2005). In this chapter we will review the treatment of these two conditions. The pathophysiology of idiopathic hypersomnia remains unclear. Large systematic studies are lacking due to the rare prevalence of idiopathic hypersomnia. Treatment is mostly focused on excessive daytime sleepiness (EDS). We will discuss presently available and emerging treatment options for narcolepsy. Symptomatic treatment options for narcolepsy are used for EDS in patients with idiopathic hypersomnia.

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References

  1. American Academy of Sleep Medicine. International classification of sleep disorders. Diagnostic and coding manual. 2nd ed. Westchester: American Academy of Sleep Medicine; 2005.

    Google Scholar 

  2. Westphal C. Eigenthümliche mit Einschläfen verbundene Anfälle. Arch Psychiatr. 1677;7:631–5.

    Google Scholar 

  3. Fisher F. Epileptoide schlafzustände. Arch Psychiatr. 1878;8:200–3.

    Article  Google Scholar 

  4. Mignot E, Hayduk R, Black J, et al. HLA-DQB1*0602 is associated with narcolepsy in 509 narcoleptic patients. Sleep. 1997;20:1012–20.

    PubMed  CAS  Google Scholar 

  5. Zeman A, Britton T, Douglas N, et al. Narcolepsy and excessive daytime sleepiness. BMJ. 2004;329:724–8.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Lin L, Faraco R, Li R, et al. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell. 1999;98:365–76.

    Article  CAS  PubMed  Google Scholar 

  7. Dauviliers Y, Arnulf I, Mignot E. Narcolepsy with cataplexy. Lancet. 2007;369:499–511.

    Article  Google Scholar 

  8. Mignot E, Lammers GJ, Ripley B, et al. The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol. 2002;59:1553–62.

    Article  PubMed  Google Scholar 

  9. Roth B. In: Roth B, editor. Narkolepsie und hypersomnie. Berlin: VEB Verlag; 1962.

    Google Scholar 

  10. Bassetti C, Pelayo R, Guilleminault C. Idiopathic hypersomnia. In: Kryger MH, Roth T, Dement WC, editors. Principle and practice of sleep medicine. 4th ed; 2005. p. 791–800.

    Chapter  Google Scholar 

  11. Bassetti C, Aldrich MS. Idiopathic hypersomnia. A series of 42 patients. Brain. 1997;120(Pt 8):1423–35.

    Article  PubMed  Google Scholar 

  12. Billiard M, Dauvilliers Y. Idiopathic hypersomnia. Sleep Med Rev. 2001;5(5):351–60.

    Google Scholar 

  13. Kanbayashi T, Kodama T, Kondo H, et al. CSF histamine contents in narcolepsy, idiopathic hypersomnia and obstructive sleep apnea syndrome. Sleep. 2009;32(2):175–80.

    Article  Google Scholar 

  14. Snead OC 3rd, Liu CC. Gamma-hydroxybutyric acid binding sites in rat and human brain synaptosomal membranes. Biochem Pharmacol. 1984;33:2587–90.

    Article  CAS  PubMed  Google Scholar 

  15. Mamelak M, Escriu JM, Stokan O. The effects of gamma hydroxybutyrate on sleep. Biol Psychiatry. 1977;12:273–88.

    PubMed  CAS  Google Scholar 

  16. Broughton R, Mamelak M. The treatment of narcolepsy-cataplexy with nocturnal gamma-hydroxybutyrate. Can J Neurol Sci. 1979;6:1–6.

    Article  CAS  PubMed  Google Scholar 

  17. Broughton R, Mamelak M. Effects of nocturnal gamma hydroxybutyrate on sleep/waking patterns in narcolepsy-cataplexy. Can J Neurol Sci. 1980;7:23–31.

    PubMed  CAS  Google Scholar 

  18. Scrima L, Hartman PG, Johnson FH Jr, Hiller FC. Efficacy of gamma-hydroxybutyrate versus placebo in treating narcolepsy cataplexy: double-blind subjective measures. Biol Psychiatry. 1989;26:331–43.

    Article  CAS  PubMed  Google Scholar 

  19. Lammers GJ, Arends J, Declerck AC, et al. Gamma hydroxybutyrate and narcolepsy: a double-blind placebo-controlled study. Sleep. 1993;16:216–20.

    Article  CAS  PubMed  Google Scholar 

  20. A randomized, double blind, placebo-controlled multicenter trial comparing the effects of three doses of orally administered sodium oxybate with placebo for the treatment of narcolepsy. Sleep. 2002;25: 42–9.

    Google Scholar 

  21. U.S. Xyrem Multicenter Study Group. Sodium oxybate demonstrates long-term efficacy for the treatment of cataplexy in patients with narcolepsy. Sleep Med. 2004;5:119–23.

    Article  Google Scholar 

  22. Mamelak M, Black J, Montplaisir J, Ristanovic R. A pilot study on the effects of sodium oxybate on sleep architecture and daytime alertness in narcolepsy. Sleep. 2004;27:1327–34.

    Article  PubMed  Google Scholar 

  23. Borgen LA, Okerholm RA, Lai A, et al. The pharmacokinetics of sodium oxybate oral solution following acute and chronic administration to narcoleptic patients. J Clin Pharmacol. 2004;44:253–7.

    Article  CAS  PubMed  Google Scholar 

  24. Scharf MB. Assessment of sodium oxybate for the long-term treatment of narcolepsy. Sleep. 2001;23(Abstract Suppl):A234.

    Google Scholar 

  25. Hornfeltdt C, Pertile T. Lack of withdrawal symptoms following abrupt cessation of therapeutically administered sodium oxybate. Sleep. 2001;24(Abstract Suppl):A236.

    Google Scholar 

  26. Black J, Ristanovic R, Mamelak M, et al. Dose response effects of sodium oxybate on polysomnographic (PSG) measures in narcolepsy patients; preliminary findings. Sleep. 2001;24(Abstract Suppl):A321.

    Google Scholar 

  27. Ristanovic RA, Black J, Mamelak M, et al. Effect of increasing doses of sodium oxybate on nocturnal respiratory disturbances. Sleep. 2002;25(Abstract Suppl):A473–4.

    Google Scholar 

  28. Black J, Ristanovic RA, Mamelak M, et al. Effect of increasing doses of sodium oxybate on nocturnal oxygen saturation: preliminary findings. Sleep. 2002;25(Abstract Suppl):A474–5.

    Google Scholar 

  29. Hishikawa Y, Ida H, Nakai K, et al. Treatment of narcolepsy with imipramine (tofranil) and desmethylimipramine (pertofran). J Neurol Sci. 1965;3:453–61.

    Article  Google Scholar 

  30. Nishino S, Mao J, Sampathkumaran R, et al. Increased dopaminergic transmission mediates the wake-promoting effects of CNS stimulants. Sleep Res Online. 1998;1(1):49–61.

    PubMed  CAS  Google Scholar 

  31. Minzenberg MJ, Carter CS. Modafinil: a review of neurochemical actiosn and effects on cognition. Neuropsychopharmacology. 2008;33(7):1477–502.

    Article  CAS  PubMed  Google Scholar 

  32. De Saint-Hilaire Z, Orosco M, Rouch C, et al. Variations in extra-cellular monoamines in the prefrontal cortex and median hypothalamus after modafinil administration: a microdialysis study in rats. Neuroreport. 2001;12(16):3533–7.

    Article  PubMed  Google Scholar 

  33. Wisor JP, Nishino S, Sora I, et al. Dopaminergic role in stimulant-induced wakefulness. J Neurosci. 2001;21(5):1787–94.

    Article  CAS  PubMed  Google Scholar 

  34. Murillo-Rodriguez E, Haro R, Palomero-Rivero M, et al. Modafinil enhances extracellular levels of dopamine in the nucleus accumbens and increases wakefulness in rats. Behav Brain Res. 2007;176(2):353–7.

    Article  CAS  PubMed  Google Scholar 

  35. Parkes JD, Dahlitz M. Amphetamine prescription. Sleep. 1993;16(3):201–3.

    Article  CAS  PubMed  Google Scholar 

  36. Anderson KN, Pilsworth S, Sharpless LD, et al. Idiopathic hypersomnia: a study of 77 cases. Sleep. 2007;30(10):1274–81.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Ali M, Auger RR, Slocumb NL, et al. Idiopathic hypersomnia: clinical features and response to treatment. J Clin Sleep Med. 2009;5(6):562–8.

    PubMed  PubMed Central  Google Scholar 

  38. Lavault S, Dauvilliers Y, Drouot X, et al. Benefit and risk of modafinil in idiopathic hypersomnia vs. narcolepsy with cataplexy. Sleep Med. 2011;12(6):550–6.

    Article  PubMed  Google Scholar 

  39. Hedner J, Zou D. Pharmacological management of sleep-disordered breathing. In: McNicholas WT, Bonsignore MR, editors. Sleep apnoea, vol. 50. Sheffield: European Respiratory Society; 2010. p. 321–39.

    Chapter  Google Scholar 

  40. Billiard M. Narcolepsy: current treatment options and future approaches. Neuropsychiatr Dis Treat. 2008;4:557–66.

    PubMed  PubMed Central  CAS  Google Scholar 

  41. Lankford DA. Armodafinil: a new treatment for excessive sleepiness. Expert Opin Investig Drugs. 2008;17:565–73.

    Article  CAS  PubMed  Google Scholar 

  42. Harsh JR, Hayduk R, Rosenberg R, et al. The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy. Curr Med Res Opin. 2006;22:761–74.

    Article  CAS  PubMed  Google Scholar 

  43. Seiden LS, Sabol KE, Ricaurte GA. Amphetamine: effects on catecholamine systems and behavior. Annu Rev Pharmacol Toxicol. 1993;33:639–77.

    Article  CAS  PubMed  Google Scholar 

  44. Mitler M, Erman M, Hajdukovic R. The treatment of excessive somnolence with stimulant drugs. Sleep. 1993;16:203–6.

    Article  CAS  PubMed  Google Scholar 

  45. Guilleminault C, Carskadon MA, Dement WC. On the treatment of rapid eye movement narcolepsy. Arch Neurol. 1974;30(1):90–3.

    Article  CAS  PubMed  Google Scholar 

  46. Roth T. Narcolepsy: treatment issues. J Clin Psychiatry. 2007;68(Suppl. 13):16–9.

    PubMed  CAS  Google Scholar 

  47. Akimoto H, Honda Y, Takahashi Y. Pharmacotherapy in narcolepsy. Dis Nerv Syst. 1960;21:1–3.

    Google Scholar 

  48. Schmidt HS, Clark RW, Hyman PR. Protriptyline: an effective agent in the treatment of the narcolepsy-cataplexy syndrome and hypersomnia. Am J Psychiatry. 1977;134:183–5.

    Article  CAS  PubMed  Google Scholar 

  49. Billiard M, Bassetti C, Dauvilliers Y, EFNS Task Force, et al. EFNS guidelines on management of narcolepsy. Eur J Neurol. 2006;13(10):1035–48.

    Article  CAS  PubMed  Google Scholar 

  50. Parkes D. Introduction to the mechanism of action of different treatments of narcolepsy. Sleep. 1994;17:S93–6.

    Article  CAS  PubMed  Google Scholar 

  51. Lammers GJ. In: Barkoukis T, Matheson J, Ferber R, Doghramji K, editors. Therapy in sleep medicine. 1st ed. Philadelphia: Elsevier; 2011. p. 293.

    Google Scholar 

  52. Langdon N, Bandak S, Shindler J, et al. Fluoxetine in the treatment of cataplexy. Sleep. 1986;9:371–2.

    Article  CAS  PubMed  Google Scholar 

  53. Mignot E, Nishino S. Emerging therapies in narcolepsy-cataplexy. Sleep. 2005;28(6):754–63.

    Article  PubMed  Google Scholar 

  54. Nishino S, ripley B, Overeem S, et al. Hypocretin (orexin) deficiency in human narcolepsy. Lancet. 2000;355:39–40.

    Article  CAS  PubMed  Google Scholar 

  55. John J, Wu MF, Siegel JM. Systemic administration of hypocretin-1 reduces cataplexy and normalizes sleep and waking durations in narcoleptic dogs. Sleep Res Online. 2000;3:23–8.

    PubMed  CAS  Google Scholar 

  56. Hanson LR, Martinez PM, Taheri M, et al. Intranasal administration of hypocretin 1 (orexin A) bypasses the blood-brain barrier and target the brain: a new strategy for the treatment of narcolepsy. Drug Deliv Technol. 2004;4:1–10.

    Google Scholar 

  57. Baier PC, Hallschmid M, Seeck-Hirschner M, et al. Sleep Med. 2011;12(10):941–6.

    Article  CAS  PubMed  Google Scholar 

  58. Zeitzer JM, Buckmaster CL, parker KJ, et al. Circadian and homeostatic regulation of hypocretin in a primate model: implications for the consolidation of wakefulness. J Neurosci. 2003;23:3555–60.

    Article  CAS  PubMed  Google Scholar 

  59. Mieda M, Willie JT, Hara J, et al. Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice. Proc Natl Acad Sci U S A. 2004;101:4649–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Thannickal TC, Moore RY, Nienhuis R, et al. Reduced number of hypocretin neurons in human narcolepsy. Neuron. 2000;27:469–74.

    Article  CAS  PubMed  Google Scholar 

  61. Thorpy M. Therapeutic advances in narcolepsy. Sleep Med. 2007;8:427–40.

    Article  PubMed  Google Scholar 

  62. Arias-Carrion O, MurilloRodriguez E, Xu M, et al. Transplantation of hypocretin neurons into the pontine reticular formation: preliminary results. Sleep. 2004;27:1465–70.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Boehmer LN, Wu MF, John J, et al. Treatment with immunosuppressive and anti-inflammatory agents delays onset of canine genetic narcolepsy and reduces symptom severity. Exp Neurol. 2004;188:292–9.

    Article  CAS  PubMed  Google Scholar 

  64. Hect M, Lin L, Kushida CA, et al. Report of a case of immunosuppression with prednisone in an 8-year-old boy with an acute onset of hypocretin-deficiency narcolepsy. Sleep. 2003;26:809–10.

    Article  Google Scholar 

  65. Chen W, black J, Call P, et al. Late-onset narcolepsy presenting as rapidly progressing muscle weakness: response to plasmapheresis. Ann Neurol. 2005;58:489–90.

    Article  PubMed  Google Scholar 

  66. Dauvilliers Y, Carlander B, rivier F, et al. Successful management of cataplexy with intravenous immunoglobulins at narcolepsy onset. Ann Neurol. 2004;56:905–8.

    Article  CAS  PubMed  Google Scholar 

  67. Zuberi SM, Mignot E, Ling L, et al. Variable response to intravenous immunoglobulin therapy in childhood narcolepsy. J Sleep Res. 2004;13(Suppl 1):828.

    Google Scholar 

  68. Nishino S, Arrigoni J, Shelton J, et al. Effects of thyrotropin-releasing hormone and its analogs on daytime sleepiness and cataplexy in canine narcolepsy. J Neurosci. 1997;17:6401–8.

    Article  CAS  PubMed  Google Scholar 

  69. Nishino S, Sakurai E, Nevsimalova S, et al. Decreased CSF histamine in narcolepsy with and without low CSF hypocretin-1 in comparison to healthy controls. Sleep. 2009;32:175–80.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Lin JS, Sakai K, Vanni-Mercier G, et al. Involvement of histaminergic neurons in arousal mechanisms demonstrated with H3-receptor ligands in the cat. Brain Res. 1990;523:325–30.

    Article  CAS  PubMed  Google Scholar 

  71. Wijtmans M, Leurs R, de Esch I. Histamine H3 receptor ligands break ground in a remarkable plethora of therapeutic areas. Expert Opin Investig Drugs. 2007;16:967–85.

    Article  CAS  PubMed  Google Scholar 

  72. Lin JS, Dauvilliers Y, Arnulf I, et al. An inverse agonist of the histamine H(3) receptor improves wakefulness in narcolepsy: studies in orexin−/− mice and patients. Neurobiol Dis. 2008;30:74–83.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Stanford University Division of Sleep Medicine, Redwood City, CA, USA

    Tony J. Masri MD, Vikas Jain MD, FAASM, CCSH & Christian Guilleminault MD, D Bio

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  1. Tony J. Masri MD
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  2. Vikas Jain MD, FAASM, CCSH
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  3. Christian Guilleminault MD, D Bio
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Correspondence to Christian Guilleminault MD, D Bio .

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Editors and Affiliations

  1. Department of Medicine, Baylor College of Medicine, Houston, Texas, USA

    Amir Sharafkhaneh

  2. Division of Public Mental Health and Population Sciences, School of Medicine, Stanford University, Stanford, California, USA

    Max Hirshkowitz

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Masri, T.J., Jain, V., Guilleminault, C. (2018). Treating Narcolepsy and Idiopathic Hypersomnia. In: Sharafkhaneh, A., Hirshkowitz, M. (eds) Fatigue Management. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-8607-1_10

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  • DOI: https://doi.org/10.1007/978-1-4939-8607-1_10

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