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Overview of Management of Narcolepsy

  • Chapter
Narcolepsy

Abstract

Narcolepsy is a chronic sleep disorder that is characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. Since these symptoms are often disabling, most patients need lifelong treatments. Non-pharmacological treatments (i.e., behavioral modification) are often helpful for the clinical management of narcoleptic patients. However, over 90 % of diagnosed narcoleptic patients are reported to take medications to control their symptoms. Traditionally, the amphetamine-like CNS stimulants have been used for clinical management to improve EDS and tricyclic antidepressants as anticataplectics, but the treatment has evolved recently with new and better tolerated compounds such as modafinil (and its R-enantiomer, armodafinil) for EDS and adrenergic/serotonergic selective reuptake inhibitors as anticataplectics. Nighttime administration of a short-acting sedative, gamma-hydroxybutyrate (sodium oxybate in the USA) has also been used for the treatment for EDS and cataplexy. Since a large majority of human narcolepsy patients are hypocretin peptide deficient, hypocretin replacement therapy may also be a new therapeutic option, but this is still not available for human patients. If hypocretin replacement is effective in hypocretin-deficient narcolepsy, cell transplantation and/or gene therapy may be developed in the near future. In this review, we first describe clinical symptoms of narcolepsy and then the state-of-the-art knowledge about both pharmacological and non-pharmacological treatments of narcolepsy.

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References

  1. Hublin C et al. The prevalence of narcolepsy: an epidemiological study of the Finnish twin cohort. Ann Neurol. 1994;35:709–16.

    Article  PubMed  CAS  Google Scholar 

  2. Mignot E. Genetic and familial aspects of narcolepsy. Neurology. 1998;50 Suppl 1:S16–22.

    Article  PubMed  CAS  Google Scholar 

  3. ICSD-3, International classification of sleep disorders. 3rd ed. Rochester, MN: American Academy of Sleep Medicine; 2014.

    Google Scholar 

  4. Beusterien KM et al. Health-related quality of life effects of modafinil for treatment of narcolepsy. Sleep. 1999;22(6):757–65.

    PubMed  CAS  Google Scholar 

  5. Mignot E et al. The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol. 2002;59(10):1553–62.

    Article  PubMed  Google Scholar 

  6. Nishino S, Kanbayashi T. Symptomatic narcolepsy, cataplexy and hypersomnia, and their implications in the hypothalamic hypocretin/orexin system. Sleep Med Rev. 2005;9(4):269–310.

    Article  PubMed  Google Scholar 

  7. Nishino S, Mignot E. Pharmacological aspects of human and canine narcolepsy. Prog Neurobiol. 1997;52(1):27–78.

    Article  PubMed  CAS  Google Scholar 

  8. Honda Y. Clinical features of narcolepsy: Japanese experience. In: Honda Y, Juji T, editors. HLA in Narcolepsy. New York: Springer; 1988. p. 24–57.

    Chapter  Google Scholar 

  9. Gelb M et al. Stability of cataplexy over several months-information for the design of therapeutic trials. Sleep. 1994;17:265–73.

    PubMed  CAS  Google Scholar 

  10. Serra L et al. Cataplexy features in childhood narcolepsy. Mov Disord. 2008;23(6):858–65.

    Article  PubMed  Google Scholar 

  11. Rogers AE. Problems and coping strategies identified by narcoleptic patients. J Neurosurg Nurs. 1984;16(6):326–34.

    Article  PubMed  CAS  Google Scholar 

  12. Roehrs T et al. Alerting effects of naps in patients with narcolepsy. Sleep. 1986;9(1):194–9.

    PubMed  CAS  Google Scholar 

  13. Garma L, Marchand F. Non-pharmacological approaches to the treatment of narcolepsy. Sleep. 1994;17:S97–102.

    PubMed  CAS  Google Scholar 

  14. American Narcolepsy Association. Stimulant medication survey. In: The eye opener. 1992. p. 1–3.

    Google Scholar 

  15. Kuczenski R et al. Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine. J Neurosci. 1995;15(2):1308–17.

    PubMed  CAS  Google Scholar 

  16. Taylor KM, Snyder SH. Amphetamine: differentiation by d and l isomers of behavior involving brain norepinephrine or dopamine. Science. 1970;168(938):1487–9.

    Article  PubMed  CAS  Google Scholar 

  17. Mitler MM et al. Narcolepsy and its treatment with stimulants. ASDA standards of practice. Sleep. 1994;17(4):352–71.

    PubMed  CAS  Google Scholar 

  18. Morgenthaler TI et al. Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin. Sleep. 2007;30(12):1705–11.

    PubMed  PubMed Central  Google Scholar 

  19. Mitler MM, Hajdukovic R. Relative efficacy of drugs for the treatment of sleepiness in narcolepsy. Sleep. 1991;14(3):218–20.

    PubMed  CAS  PubMed Central  Google Scholar 

  20. Simpson LL. Blood pressure and heart rate responses produced by d-amphetamine: correlation with blood levels of drug. J Pharmacol Exp Ther. 1978;205:366–73.

    PubMed  CAS  Google Scholar 

  21. Akimoto H, Honda Y, Takahashi Y. Pharmacotherapy in narcolepsy. Dis Nerv Syst. 1960;21:704–6.

    PubMed  CAS  Google Scholar 

  22. Parkes JD et al. Natural history, symptoms and treatment of the narcoleptic syndrome. Acta Neurol Scand. 1975;52:337–53.

    Article  PubMed  CAS  Google Scholar 

  23. Guilleminault C, Carskadon M, Dement WC. On the treatment of rapid eye movement narcolepsy. Arch Neurol. 1974;30:90–3.

    Article  PubMed  CAS  Google Scholar 

  24. Passouant P, Billiard M. The evolution of narcolepsy with age. In: Guilleminault C, Dement WC, Passouant P, editors. Narcolepsy. New York: Spectrum publication; 1976. p. 179–86.

    Google Scholar 

  25. Rogers AE et al. Compliance with stimulant medications in patients with narcolepsy. Sleep. 1997;20(1):28–33.

    PubMed  CAS  Google Scholar 

  26. Prinzmetal M, Bloomberg W. The use of benzedrine for the treatment of narcolepsy. J Am Med Assoc. 1935;105:2051–4.

    Article  CAS  Google Scholar 

  27. Alles GA. The comparative physiological actions of d 1-beta-phenylisopropylamines: pressor effects and toxicity. J Pharmacol Exp Ther. 1933;47:339–54.

    CAS  Google Scholar 

  28. Parkes JD, Fenton GW. Levo(−) amphetamine and dextro (+) amphetamine in the treatment of narcolepsy. J Neurol Neurosurg Psychiatry. 1973;36:1076–81.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. Parkes JD. Amphetamines and other drugs, in Sleep and its disorders. London: W.B. Saunders Company; 1985. p. 459–82.

    Google Scholar 

  30. Parkes JD. Amphetamines and alertness. In: Guilleminault C, Dement WC, Passouant P, editors. Narcolepsy. New York: Spectrum publication; 1976. p. 643–58.

    Google Scholar 

  31. Williams RT, Caldwell RJ, Dreng LG. Comparative metabolism of some amphetamine in various species. In: Schneider SH, Esdin E, editors. Frontiers of Catecholamine Research. Oxford: Pergamon; 1973. p. 927–32.

    Chapter  Google Scholar 

  32. Beckett AH, Rowland M, Turner P. Influence of urinary pH on excretion of amphetamine. Lancet. 1965;1:303.

    Article  PubMed  CAS  Google Scholar 

  33. Yoss RE, Daly D. Treatment of narcolepsy with ritalin. Neurology. 1959;9(3):171–3.

    Article  PubMed  CAS  Google Scholar 

  34. Pawluk LK et al. Psychiatric morbidity in narcoleptics on chronic high dose methylphenidate therapy. J Nerv Ment Dis. 1995;183(1):45–8.

    Article  PubMed  CAS  Google Scholar 

  35. Goenechea S, Wagner GM. Quantitative determination of pemoline in serum and urine after ingestion of therapeutic doses (author’s transl). Arzneimittelforschung. 1977;27(8):1604–5.

    PubMed  CAS  Google Scholar 

  36. Berkovitch M et al. Pemoline-associated fulminant liver failure: testing the evidence for causation. Clin Pharmacol Ther. 1995;57(6):696–8.

    Article  PubMed  CAS  Google Scholar 

  37. Shevell M, Schreiber R. Pemoline-associated hepatic failure: a critical analysis of the literature. Pediatr Neurol. 1997;16(1):14–6.

    Article  PubMed  CAS  Google Scholar 

  38. Bastuji H, Jouvet M. Successful treatment of idiopathic hypersomnia and narcolepsy with modafinil. Prog Neuropsychopharmacol Biol Psychiatry. 1988;12:695–700.

    Article  PubMed  CAS  Google Scholar 

  39. Besset A et al. The effects of modafinil (300 mg) on sleep, sleepiness and arousal in narcoleptic patients. Neurophysiol Clin. 1993;23(1):47–60.

    Article  PubMed  CAS  Google Scholar 

  40. Boivin DB et al. Effects of modafinil on symptomatology of human narcolepsy. Clin Neuropharmacol. 1993;16(1):46–53.

    Article  PubMed  CAS  Google Scholar 

  41. Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy: US Modafinil in Narcolepsy Multicenter Study Group. Neurology. 2000; 54(5): 1166–75.

    Google Scholar 

  42. Broughton RJ et al. Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy. Neurology. 1997;49(2):444–51.

    Article  PubMed  CAS  Google Scholar 

  43. Golicki D et al. Modafinil for narcolepsy: systematic review and meta-analysis. Med Sci Monit. 2010;16(8):RA177–86.

    PubMed  Google Scholar 

  44. Agency EM. Questions and answers on the review of medicines containing modafinil. 2011. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Modafinil_31/WC500099177.pdf

  45. Wong YN et al. Single-dose pharmacokinetics of modafinil and methylphenidate given alone or in combination in healthy male volunteers. J Clin Pharmacol. 1998;38:276–82.

    Article  PubMed  CAS  Google Scholar 

  46. Robertson Jr P, Hellriegel ET. Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123–37.

    Article  PubMed  CAS  Google Scholar 

  47. Nishino S, Okuro M. Armodafinil for excessive daytime sleepiness. Drugs Today (Barc). 2008;44(6):395–414.

    Article  CAS  Google Scholar 

  48. Hermant JF, Rambert FA, Deuteil J. Lack of cardiovascular effects after administration of modafinil in conscious monkeys. In French Association des Pharmacologistes Tours. Fundam Clin Pharmacol. 1991;5:825.

    Google Scholar 

  49. Gold LH, Balster RL. Evaluation of the cocaine-like discriminative stimulus effects and reinforcing effects of modafinil. Psychopharmacology (Berl). 1996;126(4):286–92.

    Article  CAS  Google Scholar 

  50. Edgar DM et al. Modafinil promotes EEG wake without intensifying motor activity in the rat. Can J Physiol Pharmacol. 1994;72(S1):362.

    Google Scholar 

  51. Darwish M et al. Armodafinil and modafinil have substantially different pharmacokinetic profiles despite having the same terminal half-lives: analysis of data from three randomized, single-dose, pharmacokinetic studies. Clin Drug Investig. 2009;29(9):613–23.

    Article  PubMed  CAS  Google Scholar 

  52. Harsh JR et al. The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy. Curr Med Res Opin. 2006;22(4):761–74.

    Article  PubMed  CAS  Google Scholar 

  53. Iijima S et al. Therapeutic effects of mazindol on narcolepsy. Sleep. 1986;9(1):265–8.

    PubMed  CAS  Google Scholar 

  54. Nishino S 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 

  55. Hadler AJ. Mazindol, a new non-amphetamine anorexigenic agent. J Clin Pharmacol. 1972;12(11):453–8.

    CAS  Google Scholar 

  56. Kanbayashi T et al. Increased dopaminergic transmission mediates wake-promoting effects of amphetamine isomers. Soc Neurosci Abstr. 1998;23:954.

    Google Scholar 

  57. Rye DB, Dihenia B, Bliwise DL. Reversal of atypical depression, sleepiness, and REM-sleep propensity in narcolepsy with bupropion. Depress Anxiety. 1998;7(2):92–5.

    Article  PubMed  CAS  Google Scholar 

  58. Sicard BA et al. The effects of 600 mg of slow release caffeine on mood and alertness. Aviat Space Environ Med. 1996;67(9):859–62.

    PubMed  CAS  Google Scholar 

  59. Rall TR. Central nervous system stimulants. In: Gilman AG et al., editors. The Pharmacological Basis of Therapeutics. 7th ed. New York: Pergamon Press; 1985. p. 345–82.

    Google Scholar 

  60. Sulfonylamino-acetic derivatives and their use as orexin receptor antagonists. Patent publication No. WO 2004033418 A3. 2004.

    Google Scholar 

  61. Okuro M et al. Effects of paraxanthine and caffeine on sleep, locomotor activity, and body temperature in orexin/ataxin-3 transgenic narcoleptic mice. Sleep. 2010;33(7):930–42.

    PubMed  PubMed Central  Google Scholar 

  62. Thorpy MJ et al. Short-term triazolam use improves nocturnal sleep of narcoleptics. Sleep. 1992;15(3):212–6.

    PubMed  CAS  Google Scholar 

  63. Scrima L et al. The effects of gamma-hydroxybutyrate (GHB) on multiple sleep latency test (MSLT) in narcolepsy patients; a long term study. Sleep Res. 1990;19:288.

    Google Scholar 

  64. Scrima L et al. Efficacy of gamma-hydroxybutyrate versus placebo in treating narcolepsy-cataplexy: double-blind subjective measures. Biol Psychiatry. 1989;26(4):331–43.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  66. Broughton R, Mamelak M. Gamma-hydroxybutyrate in the treatment of compound narcolepsy: a preliminary report. In: Guilleminault C, Dement WC, Passouant P, editors. Narcolepsy. New York: Spectrum; 1976. p. 59–67.

    Google Scholar 

  67. Chin MY, Kreutzer RA, Dyer JE. Acute poisoning from gamma-hydroxybutyrate in California. West J Med. 1992;156(4):380–4.

    PubMed  CAS  PubMed Central  Google Scholar 

  68. Mack RB. Love potion number 8 1/2. Gamma-Hydroxybutyrate poisoning. N C Med J. 1993;54(5):232–3.

    PubMed  CAS  Google Scholar 

  69. Wong CG, Gibson KM, Snead 3rd OC. From the street to the brain: neurobiology of the recreational drug gamma-hydroxybutyric acid. Trends Pharmacol Sci. 2004;25(1):29–34.

    Article  PubMed  CAS  Google Scholar 

  70. Nicholson KL, Balster RL. GHB: a new and novel drug of abuse. Drug Alcohol Depend. 2001;63(1):1–22.

    Article  PubMed  CAS  Google Scholar 

  71. Group U.X.M.S. Sodium oxybate demonstrates long-term efficacy for the treatment of cataplexy in patients with narcolepsy. Sleep Med. 2004;5(2):119–23.

    Article  Google Scholar 

  72. Group U.X.M.S. A 12-month, open-label, multicenter extension trial of orally administered sodium oxybate for the treatment of narcolepsy. Sleep. 2003;26(1):31–5.

    Google Scholar 

  73. Group U.S.X.M.S. 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(1):42–9.

    Google Scholar 

  74. Group U.X.M.S. A double-blind, placebo-controlled study demonstrates sodium oxybate is effective for the treatment of excessive daytime sleepiness in narcolepsy. J Clin Sleep Med. 2005;1(4):391–7.

    Google Scholar 

  75. Black J, Houghton WC. Sodium oxybate improves excessive daytime sleepiness in narcolepsy. Sleep. 2006;29(7):939–46.

    PubMed  Google Scholar 

  76. Robinson DM, Keating GM. Sodium oxybate: a review of its use in the management of narcolepsy. CNS Drugs. 2007;21(4):337–54.

    Article  PubMed  CAS  Google Scholar 

  77. Bedard MA et al. Nocturnal gamma-hydroxybutyrate. Effect on periodic leg movements and sleep organization of narcoleptic patients. Clin Neuropharmacol. 1989;12(1):29–36.

    Article  PubMed  CAS  Google Scholar 

  78. Palatini P et al. Dose-dependent absorption and elimination of gamma-hydroxybutyric acid in healthy volunteers. Eur J Clin Pharmacol. 1993;45(4):353–6.

    Article  PubMed  CAS  Google Scholar 

  79. Vickers MD. Gammahydroxybutyric acid. Int Anesthesiol Clin. 1969;7(1):75–89.

    Article  PubMed  CAS  Google Scholar 

  80. Lavie P, Peled R. Narcolepsy is a rare disease in Israel. Sleep. 1987;10(6):608–9.

    PubMed  CAS  Google Scholar 

  81. Li J, Stokes SA, Woeckener A. A tale of novel intoxication: seven cases of gamma-hydroxybutyric acid overdose. Ann Emerg Med. 1998;31(6):723–8.

    Article  PubMed  CAS  Google Scholar 

  82. Group U.X.M.S. The abrupt cessation of therapeutically administered sodium oxybate (GHB) does not cause withdrawal symptoms. J Toxicol Clin Toxicol. 2003;41(2):131–5.

    Article  CAS  Google Scholar 

  83. Dyer JE, Roth B, Hyma BA. Gamma-hydroxybutyrate withdrawal syndrome. Ann Emerg Med. 2001;37(2):147–53.

    Article  PubMed  CAS  Google Scholar 

  84. Perez E, Chu J, Bania T. Seven days of gamma-hydroxybutyrate (GHB) use produces severe withdrawal. Ann Emerg Med. 2006;48(2):219–20.

    Article  PubMed  Google Scholar 

  85. Henry GK et al. Effects of protriptyline on vigilance and information processing in narcolepsy. Psychopharmacology. 1988;95:109–12.

    Article  PubMed  CAS  Google Scholar 

  86. Raynal D. Polygraphic aspects of narcolepsy. In: Passouant P, WC D, Guilemminault C, editors. Narcolepsy. New York: Spectrum publications Inc.; 1976. p. 669–84.

    Google Scholar 

  87. Thorpy MJ, Goswami M. Treatment of narcolepsy. In: Thorpy MJ, editor. Handbook of Sleep Disorders. New York: Marcel Dekker, Inc.; 1990. p. 235–58.

    Google Scholar 

  88. Baldessarini RJ. How do antidepressants work? In: Davis JM, Mass JW, editors. The Affective Disorders. Wachington, DC: American Psychiatric Press; 1983. p. 243–60.

    Google Scholar 

  89. Langdon N et al. Fluoxetine in the treatment of cataplexy. Sleep. 1986;9:371–3.

    PubMed  CAS  Google Scholar 

  90. Montplaisir J, Godbout R. Serotoninergic reuptake mechanisms in the control of cataplexy. Sleep. 1986;9(1 Pt 2):280–4.

    PubMed  CAS  Google Scholar 

  91. Schrader H et al. The treatment of accessory symptoms in narcolepsy: a double-blind cross-over study of a selective serotonin re-uptake inhibitor (femoxetine) versus placebo. Acta Neurol Scand. 1986;74(4):297–303.

    Article  PubMed  CAS  Google Scholar 

  92. Mignot E et al. Canine cataplexy is preferentially controlled by adrenergic mechanisms: evidence using monoamine selective uptake inhibitors and release enhancers. Psychopharmacology. 1993;113(1):76–82.

    Article  PubMed  CAS  Google Scholar 

  93. Nishino S et al. Desmethyl metabolites of serotonergic uptake inhibitors are more potent for suppressing canine cataplexy than their parent compounds. Sleep. 1993;16(8):706–12.

    PubMed  CAS  Google Scholar 

  94. Martinez-Rodriguez J et al. Status cataplecticus induced by abrupt withdrawal of clomipramine. Neurologia. 2002;17(2):113–6.

    PubMed  CAS  Google Scholar 

  95. Poryazova R et al. Unusually prolonged rebound cataplexy after withdrawal of fluoxetine. Neurology. 2005;65(6):967–8.

    Article  PubMed  Google Scholar 

  96. Izzi F et al. Effective treatment of narcolepsy-cataplexy with duloxetine: a report of three cases. Sleep Med. 2009;10(1):153–4.

    Article  PubMed  CAS  Google Scholar 

  97. Takahashi S. The action of tricyclics (alone or in combination with methylphenidate) upon several symptoms of narcolepsy. In: Guilleminault C, Dement WC, Passouant P, editors. Narcolepsy. New York: Spectrum Publication; 1976. p. 625–38.

    Google Scholar 

  98. Koran LM, Raghavan S. Fluoxetine for isolated sleep paralysis. Psychosomatics. 1993;34(2):184–7.

    Article  PubMed  CAS  Google Scholar 

  99. Mamelak M, Scharf MB, Woods M. Treatment of narcolepsy with gamma-hydroxybutyrate. A review of clinical and sleep laboratory findings. Sleep. 1986;9(1 Pt 2):285–9.

    PubMed  CAS  Google Scholar 

  100. Fujiki N et al. Effects of IV and ICV hypocretin-1 (orexin A) in hypocretin receptor-2 gene mutated narcoleptic dogs and IV hypocretin-1 replacement therapy in a hypocretin-ligand-deficient narcoleptic dog. Sleep. 2003;26(8):953–9.

    PubMed  Google Scholar 

  101. Schatzberg SJ et al. Case study: effect of hypocretin replacement therapy in a 3-year-old Weimaraner with narcolepsy. J Vet Intern Med. 2004;18(4):586–8.

    Article  PubMed  Google Scholar 

  102. Mieda M 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(13):4649–54.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  103. Kantor S et al. Orexin neurons are necessary for the circadian control of REM sleep. Sleep. 2009;32(9):1127–34.

    PubMed  PubMed Central  Google Scholar 

  104. Deadwyler SA et al. Systemic and nasal delivery of orexin-A (Hypocretin-1) reduces the effects of sleep deprivation on cognitive performance in nonhuman primates. J Neurosci. 2007;27(52):14239–47.

    Article  PubMed  CAS  Google Scholar 

  105. Baier PC et al. Effects of intranasal hypocretin-1 (orexin A) on sleep in narcolepsy with cataplexy. Sleep Med. 2011;12(10):941–6.

    Article  PubMed  CAS  Google Scholar 

  106. Mishima K et al. Hypocretin receptor expression in canine and murine narcolepsy models and in hypocretin-ligand deficient human narcolepsy. Sleep. 2008;31(8):1119–26.

    PubMed  PubMed Central  Google Scholar 

  107. Ripley B et al. Hypocretin levels in sporadic and familial cases of canine narcolepsy. Neurobiol Dis. 2001;8(3):525–34.

    Article  PubMed  CAS  Google Scholar 

  108. Huang ZL et al. Arousal effect of orexin A depends on activation of the histaminergic system. Proc Natl Acad Sci U S A. 2001;98(17):9965–70.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  109. Nishino S et al. CSF histamine content is decreased in hypocretin-deficient human narcolepsy. Sleep. 2002;25(suppl):A476.

    Google Scholar 

  110. Kanbayashi T et al. CSF histamine and noradrenaline contents in narcolepsy and other sleep disorders. Sleep. 2004;27(Abstarct Suppliment):A236.

    Google Scholar 

  111. Lin JS et al. Involvement of histaminergic neurons in arousal mechanisms demonstrated with H3-receptor ligands in the cat. Brain Res. 1990;523(2):325–30.

    Article  PubMed  CAS  Google Scholar 

  112. Shiba T et al. Wake promoting effects of thioperamide, a histamine H3 antagonist in orexin/ataxin-3 narcoleptic mice. Sleep. 2004;27(suppl):A241–2.

    Google Scholar 

  113. Parmentier R et al. The brain H3-receptor as a novel therapeutic target for vigilance and sleep-wake disorders. Biochem Pharmacol. 2007;73(8):1157–71.

    Article  PubMed  CAS  Google Scholar 

  114. Lin JS 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(1):74–83.

    Article  PubMed  CAS  Google Scholar 

  115. Dauvilliers Y et al. Pitolisant versus placebo or modafinil in patients with narcolepsy: a double-blind, randomised trial. Lancet Neurol. 2013;12(11):1068–75.

    Article  PubMed  CAS  Google Scholar 

  116. Sharif NA, To ZP, Whiting RL. Analogs of thyrotropin-releasing hormone (TRH): receptor affinities in brain, spinal cords, and pituitaries of different species. Neurochem Res. 1991;16:95–103.

    Article  PubMed  CAS  Google Scholar 

  117. Riehl J et al. Chronic oral administration of CG-3703, a thyrotropin releasing hormone analog, increases wake and decreases cataplexy in canine narcolepsy. Neuropsychopharmacology. 2000;23(1):34–45.

    Article  PubMed  CAS  Google Scholar 

  118. Nishino S et al. Effects of thyrotropin-releasing hormone and its analogs on daytime sleepiness and cataplexy in canine narcolepsy. J Neurosci. 1997;17(16):6401–8.

    PubMed  CAS  Google Scholar 

  119. Nicoll RA. Excitatory action of TRH on spinal motoneurons. Nature. 1977;265:242–3.

    Article  PubMed  CAS  Google Scholar 

  120. Sharp T, Bennett GW, Marsden CA. Thyrotropin-releasing hormone analogues increase dopamine release from slices of rat brain. J Neurochem. 1982;39:1763–6.

    Article  PubMed  CAS  Google Scholar 

  121. Keller HH, Bartholini G, Pletscher A. Enhancement of cerebral noradrenaline turnover by thyrotropin-releasing hormone. Nature. 1974;248:528–9.

    Article  PubMed  CAS  Google Scholar 

  122. Heuer H et al. Expression of thyrotropin-releasing hormone receptor 2 (TRH-R2) in the central nervous system of rats. J Comp Neurol. 2000;428(2):319–36.

    Article  PubMed  CAS  Google Scholar 

  123. Broberger C. Neurotransmitters switching the thalamus between sleep and arousal: functional effects and cellular mechanism. In Showa University International Symposium for Life Science. 1st Annual Meeting New Frontiers in Neuroscience Research, August 31, 2004. 2004. Showa University Kamijo Hall (Tokyo).

    Google Scholar 

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

    PubMed  Google Scholar 

  125. Okura M et al. Sulpiride, a D2/D3 blocker, reduces cataplexy but not REM sleep in canine narcolepsy. Neuropsychopharmacology. 2000;23(5):528–38.

    Article  PubMed  CAS  Google Scholar 

  126. Hallmayer J et al. Narcolepsy is strongly associated with the T-cell receptor alpha locus. Nat Genet. 2009;41(6):708–11.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  127. Kawashima M et al. Anti-Tribbles homolog 2 (TRIB2) autoantibodies in narcolepsy are associated with recent onset of cataplexy. Sleep. 2010;33(7):869–74.

    PubMed  PubMed Central  Google Scholar 

  128. Plazzi G et al. Intravenous high-dose immunoglobulin treatment in recent onset childhood narcolepsy with cataplexy. J Neurol. 2008;255(10):1549–54.

    Article  PubMed  Google Scholar 

  129. Dauvilliers Y et al. Successful management of cataplexy with intravenous immunoglobulins at narcolepsy onset. Ann Neurol. 2004;56(6):905–8.

    Article  PubMed  CAS  Google Scholar 

  130. Dauvilliers Y et al. Normalization of hypocretin-1 in narcolepsy after intravenous immunoglobulin treatment. Neurology. 2009;73(16):1333–4.

    Article  PubMed  CAS  Google Scholar 

  131. Bergstrom DL, Keller C. Narcolepsy: pathogenesis and nursing care. J Neurosci Nurs. 1992;24(3):153–7.

    Article  PubMed  CAS  Google Scholar 

  132. Guilleminault C, Stoohs R, Clerk A. Daytime somnolence: therapeutic approaches. Neurophysiol Clin. 1993;23(1):23–33.

    Article  PubMed  CAS  Google Scholar 

  133. Mullington J, Broughton R. Scheduled naps in the management of daytime sleepiness in narcolepsy-cataplexy. Sleep. 1993;16(5):444–56.

    PubMed  CAS  Google Scholar 

  134. Marín-Agudelo HA et al. Cognitive behavioral treatment for narcolepsy: can it complement pharmacotherapy? Sleep Sci. 2014;7(1):30–42.

    Article  PubMed  PubMed Central  Google Scholar 

  135. Kolko DJ. Behavioral treatment of excessive daytime sleepiness in an elderly woman with multiple medical problems. J Behav Ther Exp Psychiatry. 1984;15(4):341–5.

    Article  PubMed  CAS  Google Scholar 

  136. Brulowski A. The role of lucid dreaming in the treatment of narcolepsy and nightmares: a case study. Sleep Res. 1987;16:319.

    Google Scholar 

  137. Nardi TJ. Treating sleep paralysis with hypnosis. Int J Clin Exp Hypn. 1981;29(4):358–65.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  139. Liu M et al. Orexin (hypocretin) gene transfer diminishes narcoleptic sleep behavior in mice. Eur J Neurosci. 2008;28(7):1382–93.

    Article  PubMed  PubMed Central  Google Scholar 

  140. Arias-Carrion O et al. Transplant of hypocretin neurons into the pontine reticular formation: preliminary results. Sleep. 2004;27:1465–70.

    PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Sleep and Circadian Neurobiology Laboratory & Center for Narcolepsy, Stanford University School of Medicine, 3155 Porter Drive, Rm 2106, Palo Alto, CA, 94304, USA

    Seiji Nishino MD, PhD

  2. Department of Neuropsychiatry, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan

    Nozomu Kotorii MD, PhD

Authors
  1. Seiji Nishino MD, PhD
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  2. Nozomu Kotorii MD, PhD
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Corresponding author

Correspondence to Seiji Nishino MD, PhD .

Editor information

Editors and Affiliations

  1. Montefiore Medical Center Narcolepsy Institute, Bronx, New York, USA

    Meeta Goswami

  2. Montefiore Hospital Sleep-Wake Disorders Center, Bronx, New York, USA

    Michael J. Thorpy

  3. Somnogen Canada Inc, President and Chief Executive Officer, Toronto, Ontario, Canada

    S.R. Pandi-Perumal

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Nishino, S., Kotorii, N. (2016). Overview of Management of Narcolepsy. In: Goswami, M., Thorpy, M., Pandi-Perumal, S. (eds) Narcolepsy. Springer, Cham. https://doi.org/10.1007/978-3-319-23739-8_21

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  • DOI: https://doi.org/10.1007/978-3-319-23739-8_21

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