Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-23T20:27:38.590Z Has data issue: false hasContentIssue false
  • English
  • Français

Current Evaluation and Management of Excessive Daytime Sleepiness

Published online by Cambridge University Press:  02 December 2014

M. I. Boulos  and
B. J. Murray
M. I. Boulos
Affiliation:
Division of Neurology, Department of Medicine, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
B. J. Murray*
Affiliation:
Division of Neurology, Department of Medicine, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
*
Division of Neurology, Department of Medicine, University of Toronto, Sunnybrook Health Sciences Centre, 2075 Bayview Ave - Room M1-600, Toronto, Ontario, M4N 3M5, Canada.
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Excessive daytime sleepiness has significant impact on neurological function, and has societal implications. Sleepiness is a common feature of many neurological conditions. A careful history will often reveal one of many common causes of excessive daytime sleepiness and suggest appropriate treatment. Neurophysiological testing can provide objective assessment. Behavioural management is an important first step in management. Treatment of common concurrent sleep disorders is also essential. Currently available medications can further symptomatically improve function in many individuals. The strongest evidence base is for the treatment of narcolepsy - a prototype disorder of excessive daytime sleepiness. Currently used medications include modafinil, stimulants, and sodium oxybate amongst others. This review discusses important features in the diagnosis of daytime sleepiness in adults, and outlines a treatment approach. Further evidence-based information about the management of this common problem is essential.

Type
Review Article
Information
Canadian Journal of Neurological Sciences , Volume 37 , Issue 2 , March 2010 , pp. 167 - 176
Copyright
Copyright © The Canadian Journal of Neurological 2010

References

1. American Academy of Sleep Medicine. The international classification of sleep disorders: diagnostic and coding manual. 2nd ed. Westchester, Ill.: American Academy of Sleep Medicine; 2005.Google Scholar
2. Young, TB. Epidemiology of daytime sleepiness: definitions, symptomatology, and prevalence. J Clin Psychiatry. 2004;65 Suppl 16:12–6.Google Scholar
3. Gibson, ES, Powles, AC, Thabane, L, O’Brien, S, Molnar, DS, Trajanovic, N, et al. “Sleepiness” is serious in adolescence: two surveys of 3235 Canadian students. BMC Public Health. 2006;6:116.CrossRefGoogle ScholarPubMed
4. Masa, JF, Rubio, M, Findley, LJ. Habitually sleepy drivers have a high frequency of automobile crashes associated with respiratory disorders during sleep. Am J Respir Crit Care Med. 2000 Oct; 162(4 Pt 1):1407–12.Google Scholar
5. Howard, ME, Desai, AV, Grunstein, RR, Hukins, C, Armstrong, JG, Joffe, D, et al. Sleepiness, sleep-disordered breathing, and accident risk factors in commercial vehicle drivers. Am J Respir Crit Care Med. 2004 Nov 1;170(9):1014–21.CrossRefGoogle ScholarPubMed
6. Leger, D. The cost of sleep-related accidents: a report for the National Commission on Sleep Disorders Research. Sleep. 1994 Feb;17(1):84–93.Google Scholar
7. Webb, WB. The cost of sleep-related accidents: a reanalysis. Sleep. 1995 May;18(4):276–80.Google Scholar
8. Lyznicki, JM, Doege, TC, Davis, RM, Williams, MA. Sleepiness, driving, and motor vehicle crashes. Council on ScientificAffairs, American Medical Association. JAMA. 1998 Jun 17;279(23): 1908–13.CrossRefGoogle Scholar
9. George, CF. Sleep apnea, alertness, and motor vehicle crashes. Am J Respir Crit Care Med. 2007 Nov 15;176(10):954–6.Google Scholar
10. Philip, P, Vervialle, F, Le Breton, P, Taillard, J, Horne, JA. Fatigue, alcohol, and serious road crashes in France: factorial study of national data. BMJ. 2001 Apr 7;322(7290):829–30.Google Scholar
11. Connor, J, Norton, R, Ameratunga, S, Robinson, E, Civil, I, Dunn, R, et al. Driver sleepiness and risk of serious injury to car occupants: population based case control study. BMJ. 2002 May 11;324(7346):1125.Google Scholar
12. Young, T, Blustein, J, Finn, L, Palta, M. Sleep-disordered breathing and motor vehicle accidents in a population-based sample of employed adults. Sleep. 1997 Aug;20(8):608–13.Google Scholar
13. Krieger, J, Meslier, N, Lebrun, T, Levy, P, Phillip-Joet, F, Sailly, JC, et al. Accidents in obstructive sleep apnea patients treated with nasal continuous positive airway pressure: a prospective study. The Working Group ANTADIR, Paris and CRESGE, Lille, France. Association Nationale de Traitement a Domicile des Insuffisants Respiratoires. Chest. 1997 Dec;112(6):1561–6.Google Scholar
14. Dawson, D, Reid, K. Fatigue, alcohol and performance impairment. Nature. 1997 Jul 17;388(6639):235.Google Scholar
15. Arnedt, JT, Owens, J, Crouch, M, Stahl, J, Carskadon, MA. Neurobehavioral performance of residents after heavy night call vs after alcohol ingestion. JAMA. 2005 Sep 7;294(9):1025–33.Google Scholar
16. Suzuki, K, Ohida, T, Kaneita, Y, Yokoyama, E, Uchiyama, M. Daytime sleepiness, sleep habits and occupational accidents among hospital nurses. J Adv Nurs. 2005 Nov;52(4):445–53.CrossRefGoogle ScholarPubMed
17. Landrigan, CP, Rothschild, JM, Cronin, JW, Kaushal, R, Burdick, E, Katz, JT, et al. Effect of reducing interns’ work hours on serious medical errors in intensive care units. N Engl J Med. 2004 Oct 28;351(18):1838–48.Google Scholar
18. Mulgrew, AT, Ryan, CF, Fleetham, JA, Cheema, R, Fox, N, Koehoorn, M, et al. The impact of obstructive sleep apnea and daytime sleepiness on work limitation. Sleep Med. 2007 Dec;9(1):42–53.Google Scholar
19. Reilly, JJ, Armstrong, J, Dorosty, AR, Emmett, PM, Ness, A, Rogers, I, et al. Early life risk factors for obesity in childhood: cohort study. BMJ. 2005 Jun 11;330(7504):1357.Google Scholar
20. Morgenthaler, TI, Kapur, VK, Brown, T, Swick, TJ, Alessi, C, Aurora, RN, et al. Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin. Sleep. 2007 Dec 1;30(12):1705–11.Google Scholar
21. Wise, MS, Arand, DL, Auger, RR, Brooks, SN, Watson, NF. Treatment of narcolepsy and other hypersomnias of central origin. Sleep. 2007 Dec 1;30(12):1712–27.Google Scholar
22. Peppard, PE, Young, T, Palta, M, Skatrud, J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000 May 11;342(19):1378–84.Google Scholar
23. Yaggi, HK, Concato, J, Kernan, WN, Lichtman, JH, Brass, LM, Mohsenin, V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005 Nov 10;353(19):2034–41.CrossRefGoogle ScholarPubMed
24. Marin, JM, Carrizo, SJ, Vicente, E, Agusti, AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoeahypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005 Mar 19-25;365(9464):1046–53.Google Scholar
25. Scammell, TE. The neurobiology, diagnosis, and treatment of narcolepsy. Ann Neurol. 2003 Feb;53(2):154–66.Google Scholar
26. Mignot, E, Lin, X, Arrigoni, J, Macaubas, C, Olive, F, Hallmayer, J, et al. DQB1*0602 and DQA1*0102 (DQ1) are better markers than DR2 for narcolepsy in Caucasian and black Americans. Sleep. 1994 Dec;17 Suppl 8:S60–7.Google Scholar
27. Chemelli, RM, Willie, JT, Sinton, CM, Elmquist, JK, Scammell, T, Lee, C, et al. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell. 1999 Aug 20;98(4):437–51.Google Scholar
28. Lin, L, Faraco, J, Li, R, Kadotani, H, Rogers, W, Lin, X, et al. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell. 1999 Aug 6;98(3):365–76.Google Scholar
29. Nishino, S. Clinical and neurobiological aspects of narcolepsy. Sleep Med. 2007 Jun;8(4):373–99.CrossRefGoogle ScholarPubMed
30. Thannickal, TC, Moore, RY, Nienhuis, R, Ramanathan, L, Gulyani, S, Aldrich, M, et al. Reduced number of hypocretin neurons in human narcolepsy. Neuron. 2000 Sep;27(3):469–74.CrossRefGoogle ScholarPubMed
31. Anderson, KN, Pilsworth, S, Sharples, LD, Smith, IE, Shneerson, JM. Idiopathic hypersomnia: a study of 77 cases. Sleep. 2007 Oct 1;30(10):1274–81.Google Scholar
32. Arnulf, I, Lin, L, Gadoth, N, File, J, Lecendreux, M, Franco, P, et al. Kleine-Levin syndrome: a systematic study of 108 patients. Ann Neurol. 2008 Apr;63(4):482–93.Google Scholar
33. Morgenthaler, TI, Lee-Chiong, T, Alessi, C, Friedman, L, Aurora, RN, Boehlecke, B, et al. Practice parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders. An American Academy of Sleep Medicine report. Sleep. 2007 Nov 1;30(11):1445–59.Google Scholar
34. Sack, RL, Brandes, RW, Kendall, AR, Lewy, AJ. Entrainment of free-running circadian rhythms by melatonin in blind people. N Engl J Med. 2000 Oct 12;343(15):1070–7.CrossRefGoogle ScholarPubMed
35. Winkelman, JW, Sethi, KD, Kushida, CA, Becker, PM, Koester, J, Cappola, JJ, et al. Efficacy and safety of pramipexole in restless legs syndrome. Neurology. 2006 Sep 26;67(6):1034–9.CrossRefGoogle ScholarPubMed
36. Quilici, S, Abrams, KR, Nicolas, A, Martin, M, Petit, C, Lleu, PL, et al. Meta-analysis of the efficacy and tolerability of pramipexole versus ropinirole in the treatment of restless legs syndrome. Sleep Med. 2008 Oct;9(7):715–26.Google Scholar
37. Trenkwalder, C, Hening, WA, Montagna, P, Oertel, WH, Allen, RP, Walters, AS, et al. Treatment of restless legs syndrome: an evidence-based review and implications for clinical practice. Mov Disord. 2008 Dec 15;23(16):2267–302.CrossRefGoogle ScholarPubMed
38. Paus, S, Brecht, HM, Koster, J, Seeger, G, Klockgether, T, Wullner, U. Sleep attacks, daytime sleepiness, and dopamine agonists in Parkinson’s disease. Mov Disord. 2003 Jun;18(6):659–67.CrossRefGoogle ScholarPubMed
39. Schenck, CH, Mahowald, MW. REM sleep behavior disorder: clinical, developmental, and neuroscience perspectives 16 years after its formal identification in SLEEP. Sleep. 2002 Mar 15;25 (2):120–38.Google Scholar
40. Thannickal, TC, Lai, YY, Siegel, JM. Hypocretin (orexin) cell loss in Parkinson’s disease. Brain. 2007 Jun;130(Pt 6):1586–95.Google Scholar
41. Hobson, DE, Lang, AE, Martin, WR, Razmy, A, Rivest, J, Fleming, J. Excessive daytime sleepiness and sudden-onset sleep in Parkinson disease: a survey by the Canadian Movement Disorders Group. JAMA. 2002 Jan 23-30;287(4):455–63.Google Scholar
42. Comella, CL. Sleep disturbances and excessive daytime sleepiness in Parkinson disease: an overview. J Neural Transm Suppl. 2006 (70):349–55.Google Scholar
43. Bhatt, MH, Podder, N, Chokroverty, S. Sleep and neurodegenerative diseases. Semin Neurol. 2005 Mar;25(1):39–51.Google Scholar
44. McCurry, SM, Ancoli-Israel, S. Sleep dysfunction in Alzheimer’s disease and other dementias. Curr Treat Options Neurol. 2003 May;5(3):261–72.CrossRefGoogle ScholarPubMed
45. Auger, C, Montplaisir, J, Duquette, P. Increased frequency of restless legs syndrome in a French-Canadian population with multiple sclerosis. Neurology. 2005 Nov 22;65(10):1652–3.Google Scholar
46. Bassetti, CL. Sleep and stroke. Semin Neurol. 2005 Mar;25(1):19–32.Google Scholar
47. Kaneko, Y, Hajek, VE, Zivanovic, V, Raboud, J, Bradley, TD. Relationship of sleep apnea to functional capacity and length of hospitalization following stroke. Sleep. 2003 May 1;26(3): 293–7.Google Scholar
48. Mendez, M, Radtke, RA. Interactions between sleep and epilepsy. J Clin Neurophysiol. 2001 Mar;18(2):106–27.Google Scholar
49. Malow, BA, Levy, K, Maturen, K, Bowes, R. Obstructive sleep apnea is common in medically refractory epilepsy patients. Neurology. 2000 Oct 10;55(7):1002–7.Google Scholar
50. Guilleminault, C, Shergill, RP. Sleep-disordered breathing in neuromuscular disease. Curr Treat Options Neurol. 2002 Mar;4 (2):107–12.Google Scholar
51. Laberge, L, Begin, P, Dauvilliers, Y, Beaudry, M, Laforte, M, Jean, S, et al. A polysomnographic study of daytime sleepiness in myotonic dystrophy type 1. J Neurol Neurosurg Psychiatry. 2009 Jun;80(6)642-6.Google Scholar
52. Cochen, V, Arnulf, I, Demeret, S, Neulat, ML, Gourlet, V, Drouot, X, et al. Vivid dreams, hallucinations, psychosis and REM sleep in Guillain-Barre syndrome. Brain. 2005 Nov;128(Pt 11):2535–45.CrossRefGoogle ScholarPubMed
53. Kleopa, KA, Sherman, M, Neal, B, Romano, GJ, Heiman-Patterson, T. Bipap improves survival and rate of pulmonary function decline in patients with ALS. J Neurol Sci. 1999 Mar 15;164(1):82–8.Google Scholar
54. Saper, CB, Chou, TC, Scammell, TE. The sleep switch: hypothalamic control of sleep and wakefulness. Trends Neurosci. 2001 Dec;24(12):726–31.Google Scholar
55. Baumann, CR, Stocker, R, Imhof, HG, Trentz, O, Hersberger, M, Mignot, E, et al. Hypocretin-1 (orexin A) deficiency in acute traumatic brain injury. Neurology. 2005 Jul 12;65(1):147–9.Google Scholar
56. Benz, RL, Pressman, MR, Hovick, ET, Peterson, DD. Potential novel predictors of mortality in end-stage renal disease patients with sleep disorders. Am J Kidney Dis. 2000 Jun;35(6):1052–60.Google Scholar
57. Doghramji, K, editor. The sleep-psychiatry interface. Philadelphia: Elsevier; 2006.Google Scholar
58. American Psychiatric Association. Task Force on DSM-IV. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. 4th ed. Washington, DC: American Psychiatric Association; 2000.Google Scholar
59. Rapoport, MJ, Lanctot, KL, Streiner, DL, Bedard, M, Vingilis, E, Murray, B, et al. Benzodiazepine use and driving: a meta-analysis. J Clin Psychiatry. 2009 May;70(5):663–73.Google Scholar
60. Roth, T, Roehrs, TA. Etiologies and sequelae of excessive daytime sleepiness. Clin Ther. 1996 Jul-Aug;18(4):562–76; discussion 1.Google Scholar
61. Vermeeren, A. Residual effects of hypnotics: epidemiology and clinical implications. CNS Drugs. 2004;18(5):297–328.Google Scholar
62. Buysse, DJ, Reynolds, CF 3rd, Monk, TH, Berman, SR, Kupfer, DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193–213.Google Scholar
63. Douglass, AB, Bornstein, R, Nino-Murcia, G, Keenan, S, Miles, L, Zarcone, VP Jr., et al. The Sleep Disorders Questionnaire. I: Creation and multivariate structure of SDQ. Sleep. 1994 Mar;17(2):160–7.Google Scholar
64. Weatherwax, KJ, Lin, X, Marzec, ML, Malow, BA. Obstructive sleep apnea in epilepsy patients: the Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ) is a useful screening instrument for obstructive sleep apnea in a disease-specific population. Sleep Med. 2003 Nov;4(6):517–21.Google Scholar
65. Hattan, E, Chalk, C, Postuma, RB. Is there a higher risk of restless legs syndrome in peripheral neuropathy? Neurology. 2009 Mar 17;72(11):955–60.Google Scholar
66. Johns, MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991 Dec;14(6):540–5.Google Scholar
67. Miletin, MS, Hanly, PJ. Measurement properties of the Epworth sleepiness scale. Sleep Med. 2003 May;4(3):195–9.Google Scholar
68. Chervin, RD. Epworth sleepiness scale? Sleep Med. 2003 May;4(3):175–6.Google Scholar
69. Chervin, RD, Aldrich, MS. The Epworth Sleepiness Scale may not reflect objective measures of sleepiness or sleep apnea. Neurology. 1999 Jan 1;52(1):125–31.Google Scholar
70. Hoddes, E, Zarcone, V, Smythe, H, Phillips, R, Dement, WC. Quantification of sleepiness: a new approach. Psychophysiology. 1973 Jul;10(4):431–6.Google Scholar
71. Iber, C, American Academy of Sleep Medicine. The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications. Westchester, IL: American Academy of Sleep Medicine; 2007.Google Scholar
72. Carskadon, MA, Dement, WC, Mitler, MM, Roth, T, Westbrook, PR, Keenan, S. Guidelines for the multiple sleep latency test (MSLT): a standard measure of sleepiness. Sleep. 1986 Dec;9(4):519–24.Google Scholar
73. Littner, MR, Kushida, C, Wise, M, Davila, DG, Morgenthaler, T, Lee-Chiong, T, et al. Practice parameters for clinical use of the multiple sleep latency test and the maintenance of wakefulness test. Sleep. 2005 Jan 1;28(1):113–21.Google Scholar
74. Wise, MS. Objective measures of sleepiness and wakefulness: application to the real world? J Clin Neurophysiol. 2006 Feb;23(1):39–49.Google Scholar
75. Lim, J, Dinges, DF. Sleep deprivation and vigilant attention. Ann N Y Acad Sci. 2008;1129:305–22.Google Scholar
76. Doran, SM, Van Dongen, HP, Dinges, DF. Sustained attention performance during sleep deprivation: evidence of state instability. Arch Ital Biol. 2001 Apr;139(3):253–67.Google Scholar
77. Baillargeon, L, Landreville, P, Verreault, R, Beauchemin, JP, Gregoire, JP, Morin, CM. Discontinuation of benzodiazepines among older insomniac adults treated with cognitive-behavioural therapy combined with gradual tapering: a randomized trial. CMAJ. 2003 Nov 11;169(10):1015–20.Google Scholar
78. Rogers, AE, Aldrich, MS, Lin, X. A comparison of three different sleep schedules for reducing daytime sleepiness in narcolepsy. Sleep. 2001 Jun 15;24(4):385–91.Google Scholar
79. Won, CH, Li, KK, Guilleminault, C. Surgical treatment of obstructive sleep apnea: upper airway and maxillomandibular surgery. Proc Am Thorac Soc. 2008 Feb 15;5(2):193–9.CrossRefGoogle ScholarPubMed
80. US Modafinil in Narcolepsy Multicenter Study Group. Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy. Ann Neurol. 1998 Jan;43(1):88–97.Google Scholar
81. US Modafinil in Narcolepsy Multicenter Study Group. Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy: Neurology. 2000 Mar 14;54(5):1166–75.Google Scholar
82. Schwartz, JR, Feldman, NT, Bogan, RK, Nelson, MT, Hughes, RJ. Dosing regimen effects of modafinil for improving daytime wakefulness in patients with narcolepsy. Clin Neuropharmacol. 2003 Sep-Oct;26(5):252–7.Google Scholar
83. Schwartz, JR, Nelson, MT, Schwartz, ER, Hughes, RJ. Effects of modafinil on wakefulness and executive function in patients with narcolepsy experiencing late-day sleepiness. Clin Neuropharmacol. 2004 Mar-Apr;27(2):74–9.Google Scholar
84. Schwartz, JR, Feldman, NT, Bogan, RK. Dose effects of modafinil in sustaining wakefulness in narcolepsy patients with residual evening sleepiness. J Neuropsychiatry Clin Neurosci. 2005 Summer;17(3):405–12.Google Scholar
85. Ivanenko, A, Tauman, R, Gozal, D. Modafinil in the treatment of excessive daytime sleepiness in children. Sleep Med. 2003 Nov;4(6):579–82.Google Scholar
86. Bastuji, H, Jouvet, M. Successful treatment of idiopathic hypersomnia and narcolepsy with modafinil. Prog Neuropsychopharmacol Biol Psychiatry. 1988;12(5):695–700.Google Scholar
87. Hogl, B, Saletu, M, Brandauer, E, Glatzl, S, Frauscher, B, Seppi, K, et al. Modafinil for the treatment of daytime sleepiness in Parkinson’s disease: a double-blind, randomized, crossover, placebo-controlled polygraphic trial. Sleep. 2002 Dec;25(8): 905–9.Google Scholar
88. Nieves, AV, Lang, AE. Treatment of excessive daytime sleepiness in patients with Parkinson’s disease with modafinil. Clin Neuropharmacol. 2002 Mar-Apr;25(2):111–4.CrossRefGoogle ScholarPubMed
89. Ondo, WG, Fayle, R, Atassi, F, Jankovic, J. Modafinil for daytime somnolence in Parkinson’s disease: double blind, placebo controlled parallel trial. J Neurol Neurosurg Psychiatry. 2005 Dec;76(12):1636–9.Google Scholar
90. Talbot, K, Stradling, J, Crosby, J, Hilton-Jones, D. Reduction in excess daytime sleepiness by modafinil in patients with myotonic dystrophy. Neuromuscul Disord. 2003 Jun;13(5): 357–64.Google Scholar
91. Rammohan, KW, Rosenberg, JH, Lynn, DJ, Blumenfeld, AM, Pollak, CP, Nagaraja, HN. Efficacy and safety of modafinil (Provigil) for the treatment of fatigue in multiple sclerosis: a two centre phase 2 study. J Neurol Neurosurg Psychiatry. 2002 Feb;72(2):179–83.Google Scholar
92. Zifko, UA, Rupp, M, Schwarz, S, Zipko, HT, Maida, EM. Modafinil in treatment of fatigue in multiple sclerosis. Results of an openlabel study. J Neurol. 2002 Aug;249(8):983–7.Google Scholar
93. Pack, AI, Black, JE, Schwartz, JR, Matheson, JK. Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea. Am J Respir Crit Care Med. 2001 Nov 1;164(9):1675–81.Google Scholar
94. Czeisler, CA, Walsh, JK, Roth, T, Hughes, RJ, Wright, KP, Kingsbury, L, et al. Modafinil for excessive sleepiness associated with shiftwork sleep disorder. N Engl J Med. 2005 Aug 4;353(5):476–86.Google Scholar
95. Harsh, JR, Hayduk, R, Rosenberg, R, Wesnes, KA, Walsh, JK, Arora, S, et al. The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy. Curr Med Res Opin. 2006 Apr;22(4):761–74.Google Scholar
96. U. S. Xyrem Multicenter Study Group. 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 Feb 1;25(1):42–9.Google Scholar
97. U. S. Xyrem Multicenter Study Group. Sodium oxybate demonstrates long-term efficacy for the treatment of cataplexy in patients with narcolepsy. Sleep Med. 2004 Mar;5(2):119–23.Google Scholar
98. Xyrem International Study Group. Further evidence supporting the use of sodium oxybate for the treatment of cataplexy: a double-blind, placebo-controlled study in 228 patients. Sleep Med. 2005 Sep;6(5):415–21.Google Scholar
99. Black, J, Houghton, WC. Sodium oxybate improves excessive daytime sleepiness in narcolepsy. Sleep. 2006 Jul 1;29(7):939–46.Google Scholar
100. Xyrem International Study Group. 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 Oct 15;1(4):391–7.Google Scholar
101. 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 Nov 1;27(7):1327–34.Google Scholar
102. U. S. Xyrem Multicenter Study Group. A 12-month, open-label, multicenter extension trial of orally administered sodium oxybate for the treatment of narcolepsy. Sleep. 2003 Feb 1;26(1):31–5.Google Scholar
103. van der Meche, FG, Bogaard, JM, van der Sluys, JC, Schimsheimer, RJ, Ververs, CC, Busch, HF. Daytime sleep in myotonic dystrophy is not caused by sleep apnoea. J Neurol Neurosurg Psychiatry. 1994 May;57(5):626–8.Google Scholar
104. Poppe, M, Friebel, D, Reuner, U, Todt, H, Koch, R, Heubner, G. The Kleine-Levin syndrome - effects of treatment with lithium. Neuropediatrics. 2003 Jun;34(3):113–9.Google Scholar
105. Deadwyler, SA, Porrino, L, Siegel, JM, Hampson, RE. Systemic and nasal delivery of orexin-A (Hypocretin-1) reduces the effects of sleep deprivation on cognitive performance in nonhuman primates. J Neurosci. 2007 Dec 26;27(52):14239–47.Google Scholar