Advertisement

Drugs & Aging

, Volume 20, Issue 5, pp 361–376 | Cite as

Narcolepsy in the Older Adult

Epidemiology, Diagnosis and Management
  • Sangeeta S. Chakravorty
  • David B. Rye
Therapy in Practice

Abstract

Narcolepsy is a disorder of impaired expression of wakefulness and rapid-eye-movement (REM) sleep. This manifests as excessive daytime sleepiness and expression of individual physiological correlates of REM sleep that include cataplexy and sleep paralysis (REM sleep atonia intruding into wakefulness), impaired maintenance of REM sleep atonia (e.g. REM sleep behaviour disorder [RBD]), and dream imagery intruding into wakefulness (e.g. hypnagogic and hypnopompic hallucinations).

Excessive sleepiness typically begins in the second or third decade followed by expression of auxiliary symptoms. Only cataplexy exhibits a high specificity for diagnosis of narcolepsy. While the natural history is poorly defined, narcolepsy appears to be lifelong but not progressive. Mild disease severity, misdiagnoses or long delays in cataplexy expression often cause long intervals between symptom onset, presentation and diagnosis. Only 15–30% of narcoleptic individuals are ever diagnosed or treated, and nearly half first present for diagnosis after the age of 40 years.

Attention to periodic leg movements (PLM), sleep apnoea and RBD is particularly important in the management of the older narcoleptic patient, in whom these conditions are more likely to occur. Diagnosis requires nocturnal polysomnography (NPSG) followed by multiple sleep latency testing (MSLT). The NPSG of a narcoleptic patient may be totally normal, or demonstrate the patient has a short nocturnal REM sleep latency, exhibits unexplained arousals or PLM. The MSLT diagnostic criteria for narcolepsy include short sleep latencies (<8 minutes) and at least two naps with sleep-onset REM sleep.

Treatment includes counselling as to the chronic nature of narcolepsy, the potential for developing further symptoms reflective of REM sleep dyscontrol, and the hazards associated with driving and operating machinery. Elderly narcoleptic patients, despite age-related decrements in sleep quality, are generally less sleepy and less likely to evidence REM sleep dyscontrol.

Nonpharmacological management also includes maintenance of a strict wake-sleep schedule, good sleep hygiene, the benefits of afternoon naps and a programme of regular exercise. Thereafter, treatment is highly individualised, depending on the severity of daytime sleepiness, cataplexy and sleep disruption.

Wake-promoting agents include the traditional psychostimulants. More recently, treatment with the ‘activating’ antidepressants and the novel wake-promoting agent modafinil has been advocated. Cataplexy is especially responsive to antidepressants which enhance synaptic levels of noradrenaline (norepinephrine) and/or serotonin. Obstructive sleep apnoea and PLMs are more common in narcolepsy and should be suspected when previously well controlled older narcolepsy patients exhibit a worsening of symptoms. The discovery that narcolepsy/cataplexy results from the absence of neuroexcitatory properties of the hypothalamic hypocretin-peptidergic system will significantly advance understanding and treatment of the symptom complex in the future.

Keywords

Modafinil Obstructive Sleep Apnoea Narcolepsy Sodium Oxybate Multiple Sleep Latency Testing 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors express their thanks to members of the Emory Sleep Disorders Laboratory: Dr D. L. Bliwise, Lois Fussell, Monique Williams and Gregory Richardson, without whom this work would not have been possible. This work was supported by USPHS grants NS35345 and NS36697. Dr Rye is a member of Cephalon Inc. Speakers Bureau.

References

  1. 1.
    Gelineau J. De la narcolepsie. Gaz Hop (Paris) 1880; 53: 626–8Google Scholar
  2. 2.
    Henneberg R. Uber genuine Narkolpesie. Neurol Centralbl 1916; 35: 282–90Google Scholar
  3. 3.
    Vogel G. Studies in psychophysiology of dreams: III. the dream of narcolepsy. Arch Gen Psychiatry 1960; 3: 421–8PubMedCrossRefGoogle Scholar
  4. 4.
    Rechtschaffen A, Wolpert E, Dement W. Nocturnal sleep of narcoleptics. Electroencephalogr Clin Neurophysiol 1963; 15: 599–609PubMedCrossRefGoogle Scholar
  5. 5.
    Dement W, Rechtschaffen A, Gulevich G. The nature of the narcoleptic sleep attack. Neurology 1966; 16: 18–33PubMedCrossRefGoogle Scholar
  6. 6.
    Dantz B, Edgar DM, Dement WC. Circadian rhythms in narcolepsy: studies on a 90 minute day. Electroencephalogr Clin Neurophysiol 1994; 90(1): 24–35PubMedCrossRefGoogle Scholar
  7. 7.
    Moscovitch A, Partinen M, Guilleminault C. The positive diagnosis of narcolepsy and narcolepsy’s borderland. Neurology 1993; 43: 55–60PubMedCrossRefGoogle Scholar
  8. 8.
    Daniels L. Narcolepsy. Medicine 1934; 13: 1–122Google Scholar
  9. 9.
    Yoss R, Daly D. Criteria for the diagnosis of the narcoleptic syndrome. Proc Staff Meet Mayo Clin 1957; 32: 320–8PubMedGoogle Scholar
  10. 10.
    Yoss R, Daly D. Narcolepsy. Med Clin North Am 1960; 44: 953–68PubMedGoogle Scholar
  11. 11.
    Rye D, Dihenia B, Weissman J, et al. Presentation of narcolepsy after forty. Neurology 1998; 50: 459–65PubMedCrossRefGoogle Scholar
  12. 12.
    Hublin C, Kaprio J, Partinen M, et al. The prevalence of narcolepsy: an epidemiological study of the Finnish twin cohort. Ann Neurol 1994; 35: 709–16PubMedCrossRefGoogle Scholar
  13. 13.
    Mignot E. Genetic and familial aspects of narcolepsy. Neurology 1998; 50Suppl. 1: S16–22PubMedCrossRefGoogle Scholar
  14. 14.
    Ohayon M, Priest R, Zulley J, et al. Prevalence of narcolepsy symptomatology and diagnosis in the European general population. Neurology 2002; 58: 1826–3PubMedCrossRefGoogle Scholar
  15. 15.
    Lavie P, Peled R. Narcolepsy is a rare disease in Israel. Sleep 1987; 10: 608–9PubMedGoogle Scholar
  16. 16.
    Honda Y. Census of narcolepsy, cataplexy and sleep life among teenagers in Fujisawa city [abstract]. Sleep Res 1979; 8: 191Google Scholar
  17. 17.
    Hublin C, Partinen M, Kaprio J, et al. Epidemiology of narcolepsy. Sleep 1994; 17: S7–S12PubMedGoogle Scholar
  18. 18.
    Silber MH, Rye DB. Solving the mysteries of narcolepsy. Neurology 2001; 56: 1616–8PubMedCrossRefGoogle Scholar
  19. 19.
    Kilduff T, Peyron C. The hypocretin/orexin ligand-receptor system: implications for sleep and sleep disorders. Trends Neurosci 2000; 23(8): 359–65PubMedCrossRefGoogle Scholar
  20. 20.
    Bourgin P, Huitron-Resendiz S, Spier AD, et al. Hypocretin-1 modulates rapid eye movement sleep through activation of locus coeruleus neurons. J Neurosci 2000; 20: 7760–5PubMedGoogle Scholar
  21. 21.
    Ivanov A, Aston-Jones G. Hypocretin/orexin depolarizes and decreases potassium conductance in locus coeruleus neurons. Neuroreport 2000; 11: 1755–8PubMedCrossRefGoogle Scholar
  22. 22.
    Peyron C, Faraco J, Rogers W, et al. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med 2000; 6(9): 991–7PubMedCrossRefGoogle Scholar
  23. 23.
    Thannickal T, Moore R, Nienhuis R, et al. Reduced number of hypocretin neurons in human narcolepsy. Neuron 2000; 27(3): 469–74PubMedCrossRefGoogle Scholar
  24. 24.
    Mignot E, Lin X, Arrigoni J, et al. DQB1-0602 and DQA1-0102 (DQ1) are better markers than DR2 for narcolepsy in Caucasian and Black Americans. Sleep 1994; 17(8): S60–7PubMedGoogle Scholar
  25. 25.
    Lin L, Faraco J, Li R, et al. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 1999; 98(3): 365–76PubMedCrossRefGoogle Scholar
  26. 26.
    Kisamuki Y, Chemelli R, Sinton C, et al. The role of orexin receptor type-1 (OX1R) in the regulation of sleep [abstract]. Sleep 2000; 23Suppl. 2: A91Google Scholar
  27. 27.
    Chemelli R, Willie J, Sinton C, et al. olepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 1999; 98(4): 437–51PubMedCrossRefGoogle Scholar
  28. 28.
    Olafsdottir B, Rye D, Matheson J, et al. Polymorphisms in hypocretin (orexin) pathway genes and narcolepsy. Neurology 2001; 57: 1896–9PubMedCrossRefGoogle Scholar
  29. 29.
    Arii J, Kanbayashi T, Tanabe Y, et al. A hypersomnolent girl with decreased CSF hypocretin level after removal of a hypothalamic tumor. Neurology 2001; 56(12): 1775–6PubMedCrossRefGoogle Scholar
  30. 30.
    Scammell T, Nishino S, Mignot E, et al. Narcolepsy and low CSF orexin (hypocretin) concentration after a diencephalic stroke. Neurology 2001; 56: 1616–8CrossRefGoogle Scholar
  31. 31.
    Aldrich MS, Naylor MW. Narcolepsy associated with lesions of the diencephalon. Neurology 1989; 39: 1505–8PubMedCrossRefGoogle Scholar
  32. 32.
    Honda Y, Juji T, Matsuki K, et al. HLA-DR2 and Dw2 in narcolepsy and in other disorders of excessive somnolence without cataplexy. Sleep 1986; 9: 133–42PubMedGoogle Scholar
  33. 33.
    Neely S, Rosenberg R, Spire J-P, et al. HLA antigens in narcolepsy. Neurology 1987; 37: 1858–60PubMedCrossRefGoogle Scholar
  34. 34.
    Mignot E, Tafti M, Dement W, et al. Narcolepsy and immunity. Adv Neuroimmunol 1995; 5: 23–37PubMedCrossRefGoogle Scholar
  35. 35.
    Rogers A, Meehan J, Guilleminault C, et al. HLA DR15 (DR2) and DQBl*0602 typing studies in 188 narcoleptic patients with cataplexy. Neurology 1997; 48: 1550–6PubMedCrossRefGoogle Scholar
  36. 36.
    Mignot E, Hayduck R, Black J, et al. HLA DQB1*0602 is associated with cataplexy in 509 narcoleptic patients. Sleep 1997; 20: 1012–20PubMedGoogle Scholar
  37. 37.
    Nishino S, Ripley B, Overeem S, et al. Hypocretin (orexin) deficiency in human narcolepsy [letter]. Lancet 2000; 355(9197): 39–40PubMedCrossRefGoogle Scholar
  38. 38.
    Dalai M, Schuld A, Haack M, et al. Normal plasma levels of orexin A in narcoleptic patients. Neurology 2001; 56: 1749–51CrossRefGoogle Scholar
  39. 39.
    Kanbayashi T, Inoue Y, Chiba S, et al. CSF hypocretin-1 (orexin-A) concentrations in narcolepsy with and without cataplexy and idiopathic hypersomnia. J Sleep Res 2002; 11: 91–3PubMedCrossRefGoogle Scholar
  40. 40.
    Mignot E, Lammers G, Ripley B, et al. The role of CSF hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol 2002; 59: 1553–62PubMedCrossRefGoogle Scholar
  41. 41.
    Anic-Labat S, Guilleminault C, Kraemer HC, et al. Validation of a cataplexy questionnaire in 983 sleep-disorders patients. Sleep 1999; 22(1): 77–87PubMedGoogle Scholar
  42. 42.
    Hussain A, Qadiri M, Rees P, et al. An unusual cause of falls in an elderly patient. Int J Clin Pract 1999; 53(5): 399–400PubMedGoogle Scholar
  43. 43.
    International Classification of Sleep Disorders. Diagnostic and Coding Manual, Revised. Rochester (MN): American Sleep Disorders Association, 1997Google Scholar
  44. 44.
    Aldrich M. Narcolepsy. Neurology 1992; 42 (7 Suppl. 6): 34–43PubMedGoogle Scholar
  45. 45.
    Aldrich MS. The clinical spectrum of narcolepsy and idiopathic hypersomnia. Neurology 1996; 46: 393–401PubMedCrossRefGoogle Scholar
  46. 46.
    Ohayon M, Zulley J, Guilleminault C, et al. Prevalence and pathologic associations of sleep paralysis in the general population. Neurology 1999; 52: 1194–200PubMedCrossRefGoogle Scholar
  47. 47.
    Douglass A, Hays P, Pazderka E, et al. Florid refractory schizophrenia that turns out to be treatable variants of HLA-associated narcolepsy. J Nerv Ment Dis 1991; 179: 12–7PubMedCrossRefGoogle Scholar
  48. 48.
    Jackson C, Bachman D. Narcolepsy-related psychosis misinterpreted as schizophrenia. Neuropsychiatry Neuropsychol Behav Neurol 1996; 9(2): 139–40Google Scholar
  49. 49.
    Lamphere J, Young D, Roehrs T, et al. Fragmented sleep, daytime somnolence and age in narcolepsy. Clin Electroencephalogr 1989; 20: 49–54PubMedGoogle Scholar
  50. 50.
    Gosselin A, Montplaisir J, Lesperance P, et al. The effect of age on the MSLT in 137 patients with narcolepsy [abstract]. Sleep Res 1997; 26: 368Google Scholar
  51. 51.
    Young D, Zorick F, Lamphere J, et al. Fragmented sleep, daytime somnolence and age in narcolepsy [abstract]. Sleep Res 1986; 15: 186Google Scholar
  52. 52.
    Sangal R, Mitler M, Sangal J. MSLT, MWT, and ESS: indices of sleepiness in 522 drug-free patients with narcolepsy [abstract]. Sleep Res 1997; 26: 492Google Scholar
  53. 53.
    Guilleminault C, Mignot E, Aldrich M. Prazosin contraindicated in patients with narcolepsy [letter]. Lancet 1988; II: 511CrossRefGoogle Scholar
  54. 54.
    Aldrich M, Rogers A. Exacerbation of human cataplexy by prazosin. Sleep 1989; 12(3): 254–6PubMedGoogle Scholar
  55. 55.
    Nishino S, Arrigoni J, Valtier D, et al. Dopamine D2 mechanisms in canine narcolepsy. J Neurosci 1991; 11: 2666–71PubMedGoogle Scholar
  56. 56.
    Baker T, Guilleminault C, Nino-Murcia G, et al. Comparative polysomnographic study of narcolepsy and idiopathic central nervous system hypersomnia. Sleep 1986; 9(1): 232–42PubMedGoogle Scholar
  57. 57.
    Montplaisir J, Godbout R. Nocturnal sleep of narcoleptic patients: revisited. Sleep 1986; 9: 159–61PubMedGoogle Scholar
  58. 58.
    Iranzo A, Santamaria J. Hyperkalemic periodic paralysis associated with multiple sleep onset REM periods. Sleep 1999; 22(8): 1123–4PubMedGoogle Scholar
  59. 59.
    Moriguchi T, Sakurai T, Sambu T, et al. Neurons containing orexin in the lateral hypothalamic area of the adult rat brain are activated by insulin-induced acute hypoglycemia. Neuroscience Letters 1999; 264: 101–4PubMedCrossRefGoogle Scholar
  60. 60.
    Chokroverty S. Sleep apnea in narcolepsy. Sleep 1986; 9(1): 250–3PubMedGoogle Scholar
  61. 61.
    Guilleminault C, Philip P. Tiredness and somnolence despite initial treatment of obstructive sleep apnea syndrome (what to do when an OSAS patient stays hypersomnolent despite treatment). Sleep 1996; 19(9): S117–22PubMedGoogle Scholar
  62. 62.
    Johns M. A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep 1991; 14(6): 540–5PubMedGoogle Scholar
  63. 63.
    Carskadon M. Guidelines for the multiple sleep latency test (MSLT): a standard measure of sleepiness. Sleep 1986; 9: 519–24PubMedGoogle Scholar
  64. 64.
    Mitler MM, Carskadon MA, Hirshkowitz M. Evaluating sleepiness. In: Kryger M, Roth T, Dement W, editors. Principles and practice of sleep medicine. 32nd ed. Philadelphia (PA): WB Saunders, 2000: 1251–57Google Scholar
  65. 65.
    Aldrich M, Chervin R. Predictive value of MSLT REM periods for the diagnosis of narcolepsy [abstract]. Sleep Res 1995; 24: 186Google Scholar
  66. 66.
    Mitler M, Walsleben J, Sangal R, et al. Sleep latency on the maintenance of wakefulness test (MWT) for 530 patients with narcolepsy while free of psychoactive drugs. Electroencephalogr Clin Neurophysiol 1998; 107: 33–8PubMedCrossRefGoogle Scholar
  67. 67.
    Pollmächer T, Mullington J, Lauer C. REM sleep disinhibition at sleep onset: A comparison between narcolepsy and depression. Biol Psychiatry 1997; 42: 713–20PubMedCrossRefGoogle Scholar
  68. 68.
    Walsh J, Smitson S, Kramer M. Sleep-onset REM sleep: comparison of narcoleptic and obstructive sleep apnea patients. Clin Electroencephalogr 1982; 13: 57–60PubMedGoogle Scholar
  69. 69.
    Kales A, Cadieux RJ, Soldatos CR, et al. Narcolepsy-cataplexy I. Clinical and electrophysiological characteristics. Arch Neurology 1982; 39: 164–8CrossRefGoogle Scholar
  70. 70.
    Schenck C, Mahowald M. Motor dyscontrol in narcolepsy: Rapid-eye-movement (REM) sleep without atonia and REM sleep behavior disorder. Ann Neurol 1992; 32: 3–10PubMedCrossRefGoogle Scholar
  71. 71.
    van den Hoed J, Kraemer H, Guilleminault C, et al. Disorders of excessive daytime sleepiness: polygraphic and clinical data for 100 patients. Sleep 1981; 4: 23–37PubMedGoogle Scholar
  72. 72.
    Nykamp K, Rosenthal L, Helmus T, et al. Repeated nocturnal sleep latencies in narcoleptic, sleepy and alert subjects. Clin Neurophysiol 1999; 110: 1531–4PubMedCrossRefGoogle Scholar
  73. 73.
    Aldrich M. Diagnostic aspects of narcolepsy. Neurology 1988: 50Suppl. 1: S2–7Google Scholar
  74. 74.
    Mullington J, Broughton R. Scheduled naps in the management of daytime sleepiness in narcolepsy-cataplexy. Sleep 1993; 16: 444–56PubMedGoogle Scholar
  75. 75.
    Helmus T, Rosenthal L, Bishop C, et al. The alerting effects of short and long naps in narcoleptic, sleep deprived, and alert individuals. Sleep 1997; 20: 251–7PubMedGoogle Scholar
  76. 76.
    Browman Cp, Gujavarty KS, Mitler MM. Tobacco use by narcoleptics and daytime sleep tendency. Drug Alcohol Depend 1984; 14: 23–6PubMedCrossRefGoogle Scholar
  77. 77.
    Broughton RJ, Guberman A, Roberts J. Comparison of the psychosocial effects of epilepsy and narcolepsy/cataplexy: a controlled study. Epilepsia 1984; 25(4): 423–33PubMedCrossRefGoogle Scholar
  78. 78.
    Kales A, Soldatos C, Bixler E, et al. Narcolepsy-cataplexy: II. psychosocial consequences and associated psychopathology. Arch Neurol 1982; 39: 169–71PubMedCrossRefGoogle Scholar
  79. 79.
    Reynolds CF, Christiansen CL, Taska LS, et al. Sleep in narcolepsy and depression: does it all look alike? J Nerv Ment Dis 1983; 171(5): 290–5PubMedCrossRefGoogle Scholar
  80. 80.
    Rye D, Dihenia B, Bliwise D. Reversal of atypical depression, sleepiness, and REM-sleep propensity in narcolepsy with bupropion. Depress Anxiety 1998; 7: 92–5PubMedCrossRefGoogle Scholar
  81. 81.
    American Sleep Disorders Association. Standards of Practice: practice parameters for the use of stimulants in the treatment of narcolepsy. Sleep 1994; 17(4): 348–51Google Scholar
  82. 82.
    Littner M, Johnson S, McCall W, et al. Practice parameters for the treatment of narcolepsy: an update for 2000. Sleep 2001: 24: 451–66PubMedGoogle Scholar
  83. 83.
    Koob GF. Stimulants: basic mechanisms and pharmacology. In: Kryger M, Roth T, Dement WC, editors. Principles and practice of sleep medicine. 3rd ed. Philadelphia (PA): WB Saunders, 2000: 419–28Google Scholar
  84. 84.
    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): 49–61PubMedGoogle Scholar
  85. 85.
    Berridge C, O’Neil J, Wifler K. Amphetamine acts within the medial basal forebrain to initiate and maintain alert waking. Neuroscience 1999; 93: 885–96PubMedCrossRefGoogle Scholar
  86. 86.
    Wisor J, Nishino S, Sora I, et al. Dopaminergic role in stimulant-induced wakefulness. J Neurosci 2001; 21(5): 1787–94PubMedGoogle Scholar
  87. 87.
    Kanbayashi T, Honda K, Kodama T, et al. Implication of dopaminergic mechanisms in the wake-promoting effects of amphetamine: a study of D- and L-derivatives in canine narcolepsy. Neuroscience 2000; 99(4): 651–9PubMedCrossRefGoogle Scholar
  88. 88.
    Guilleminault C. Controversies in sleep physiology and sleep medicine: amphetamines and narcolepsy 1. amphetamines and narcolepsy: use of the Stanford database. Sleep 1993; 16(3): 199–201PubMedGoogle Scholar
  89. 89.
    Parkes J, Dahlitz M. Controversies in sleep physiology and sleep medicine: amphetamines and narcolepsy 2. amphetamine prescription. Sleep 1993; 16(3): 201–3PubMedGoogle Scholar
  90. 90.
    Mitler M, Erman M, Hajdukovic R. Controversies in sleep physiology and sleep medicine: amphetamines and narcolepsy 3. the treatment of excessive somnolence with stimulant drugs. Sleep 1993; 16(3): 203–6PubMedGoogle Scholar
  91. 91.
    Nishino S, Mao J, Sampathkumaran R, et al. Adrenergic, but not dopaminergic, uptake inhibition reduces REM sleep and cataplexy concomitantly [abstract]. Sleep Res 1997; 26: 445Google Scholar
  92. 92.
    Nishino S, Mignot E. Pharmacological aspects of human and canine narcolepsy. Prog Neurobiol 1997; 52(1): 27–78PubMedCrossRefGoogle Scholar
  93. 93.
    Wu MF, Gulyani SA, Yau E, et al. Locus coeruleus neurons: cessation of activity during cataplexy. Neuroscience 1999; 91(4): 1389–99PubMedCrossRefGoogle Scholar
  94. 94.
    Mitler M, Aldrich M, Koob G, et al. ASDA standards of practice: narcolepsy and its treatment with stimulants. Sleep 1994; 17(4): 352–71PubMedGoogle Scholar
  95. 95.
    Mitler M, Hajdukovic R, Erman M. Treatment of narcolepsy with methamphetamine. Sleep 1993; 16(4): 306–17PubMedGoogle Scholar
  96. 96.
    Honda Y, Hishikawa Y, Takahashi Y. Long-term treatment of narcolepsy with methylphenidate (Ritalin). Curr Ther Res 1979; 25: 288–98Google Scholar
  97. 97.
    Mitler M, Shafor R, Hajdukovich R, et al. Treatment of narcolepsy: objective studies on methylphenidate, pemoline, and protriptyline. Sleep 1986; 9(1): 260–4PubMedGoogle Scholar
  98. 98.
    Mignot E. Pathophysiology of narcolepsy. In: Kryger M, Roth T, Dement WC, editors. Principles and practice of sleep medicine. 3rd ed. Philadelphia (PA): WB Saunders, 2000: 663–75Google Scholar
  99. 99.
    Honda Y, Hishikawa Y. A long-term treatment of narcolepsy and excessive daytime sleepiness with pemoline (Betanamin). Curr Therap Res 1980; 27: 429–41Google Scholar
  100. 100.
    Safer DJ, Zito JM, Gardner JE. Pemoline hepatotoxicity and postmarketing surveillance. J Am Acad Child Adolesc Psychiatry 2001; 40: 622–9PubMedCrossRefGoogle Scholar
  101. 101.
    Shevell M, Schreiber R. Pemoline-associated hepatic failure: a critical analysis of the literature. Pediatric Neurology 1997; 16: 14–6PubMedCrossRefGoogle Scholar
  102. 102.
    Edgar DM, Seidel WF. Modafinil induces wakefulness without intensifying motor activity or subsequent rebound hyper-somnolence in the rat. J Pharmacol Exp Ther 1997; 283(2): 757–69PubMedGoogle Scholar
  103. 103.
    Ferraro L, Antonelli T, O’Connor W, et al. Modafinil: an antinarcoleptic drug with differential neurochemical profile to d-amphetamine and dopamine reuptake blockers. Biol Psychiatry 1997; 42: 1181–3PubMedCrossRefGoogle Scholar
  104. 104.
    Mignot E, Nishino S, Guilleminault C, et al. Modafinil binds to the dopamine uptake carrier site with low affinity. Sleep 1994: 17(5): 436–7PubMedGoogle Scholar
  105. 105.
    Scammell T, Estabrooke I, McCarthy M, et al. Hypothalamic arousal regions are activated during modafinil-induced wakefulness. J Neurosci 2000; 20(22): 8620–8PubMedGoogle Scholar
  106. 106.
    Saletu B, Grunberger J, Linzmayer L, et al. Pharmaco-EEG, psychometric and plasma level studies with two novel alpha-adrenergic stimulants CRL 40476 and 40028 (Adranifil) in elderlies. New Trend Exp Clin Psychiat 1986; II(1): 5–31Google Scholar
  107. 107.
    Saletu B, Frey R, Krupka M, et al. Differential effects of the new central adrenergic agonist modafinil and d-amphetamine on sleep and early morning behaviour in elderlies. Arzneimittelforschung 1989; 39(II): 1268–73PubMedGoogle Scholar
  108. 108.
    Billiard M, Besset A, Montplaisir J, et al. Modafinil: a double-blind multicentric study. Sleep 1994; 17: S107–12PubMedGoogle Scholar
  109. 109.
    Bastuji H, Jouvet M. Successful treatment of idiopathic hypersomnia and narcolepsy with modafinil. Prog Neuropsychopharmacol Biol Psychiatry 1988; 12: 695–700PubMedCrossRefGoogle Scholar
  110. 110.
    Laffont F, Mayer G, Minz M. Modafinil in diurnal sleepiness: a study of 123 patients. Sleep 1994; 17: S113–5PubMedGoogle Scholar
  111. 111.
    Besset A, Tafti M, Villemin E, et al. The effects of modafinil (300mg) on sleep, sleepiness and arousal in narcoleptic patients. Neurophysiol Clin 1993; 23: 47–60PubMedCrossRefGoogle Scholar
  112. 112.
    Besset A, Chetrit M, Carlander B, et al. Use of modafinil in the treatment of narcolepsy: a long term follow-up study. Neurophysiol Clin 1996; 26: 60–6PubMedCrossRefGoogle Scholar
  113. 113.
    Broughton R, Fleming J, George C, et al. Randomized, doubleblind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy. Neurology 1997; 49(2): 444–51PubMedCrossRefGoogle Scholar
  114. 114.
    Group UMiNMS. Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy. Ann Neurol 1998; 43: 88–97CrossRefGoogle Scholar
  115. 115.
    Fry J. Treatment modalities for narcolepsy. Neurology 1998; 50Suppl. 1: S43–8PubMedCrossRefGoogle Scholar
  116. 116.
    Moachon G, Kanmacher I, Clenet M, et al. Pharmacokinetic profile of modafinil. Drugs Today 1996; 32: 327–37Google Scholar
  117. 117.
    Wong Y, King S, Simcoe D, et al. Open-label, single-dose pharmacokinetic study of modafinil tablets: influence of age and gender in normal subjects. J Clin Pharmacol 1999; 39: 281–8PubMedGoogle Scholar
  118. 118.
    Gillin J, Post R, Wyatt R, et al. REM inhibitory effect of L-dopa infusion during human sleep. Electroencephalogr Clin Neurophysiol 1973; 35: 181–6PubMedCrossRefGoogle Scholar
  119. 119.
    Gunne LM, Lidvall H, Widen L. Preliminary clinical trial with L-dopa in narcolepsy. Psychopharmacologia 1971; 19: 204–6PubMedCrossRefGoogle Scholar
  120. 120.
    Boivin D, Montplaisir J. The effects of L-dopa on excessive daytime sleepiness in narcolepsy. Neurology 1991; 41: 1267–9PubMedCrossRefGoogle Scholar
  121. 121.
    Mayer G, Meier K, Hephata K. Selegeline hydrochloride treatment in narcolepsy: a double-blind placebo-controlled study. Clin Neuropharmacol 1995; 18(4): 306–19PubMedCrossRefGoogle Scholar
  122. 122.
    Hublin C, Partinen M, Heinonen E, et al. Selegiline in the treatment of narcolepsy. Neurology 1994; 44: 2095–101PubMedCrossRefGoogle Scholar
  123. 123.
    Reynolds G, Elsworth J, Blau K, et al. Deprenyl is metabolized to methamphetamine and amphetamine in man. Br J Clin Pharmacol 1978; 6: 542–4PubMedCrossRefGoogle Scholar
  124. 124.
    Gillin JC, Horwitz D, Wyatt RJ. Pharmacologic studies of narcolepsy involving serotonin, acetylcholine and monoamine oxidase. In: Guilleminault C, Dement WC, Passouant P, editors. Narcolepsy: Proceedings of the First International Symposium on Narcolepsy, July 1975, Montpellier, France. West Sussex (UK): Johns Wiley & Sons, 1976: 585–604Google Scholar
  125. 125.
    Knoll J. The possible mechanisms of action of (-) deprenyl in Parkinson’s disease. J Neural Transm 1978; 43: 177–98PubMedCrossRefGoogle Scholar
  126. 126.
    Ascher J, Cole J, Colin J-N, et al. Bupropion: a review of its mechanism of antidepressant activity. J Clin Psychiatry 1995: 56(9): 395–401PubMedGoogle Scholar
  127. 127.
    Schmidt H, Clark R, Hyman R. Protriptyline: an effective agent in the treatment of the narcolepsy-cataplexy syndrome and hypersomnia. Am J Psychiatry 1977; 134: 183–5PubMedGoogle Scholar
  128. 128.
    Henry G, Hart H, Kwentus J, et al. Effects of protriptyline on vigilance and information processing in narcolepsy. Psychopharmacol 1988; 95: 109–12Google Scholar
  129. 129.
    Mitler M, Hajdukovic R. Relative efficacy of drugs for the treatment of sleepiness in narcolepsy. Sleep 1991; 14(3): 218–20PubMedGoogle Scholar
  130. 130.
    Fry J, Pressman M, DiPhillipo M, et al. Treatment of narcolepsy with codeine. Sleep 1986; 9(1): 269–74PubMedGoogle Scholar
  131. 131.
    Mignot E, Renaud A, Nishino S, et al. Canine cataplexy is preferentially controlled by adrenergic mechanisms: evidence using monoamine selective uptake inhibitors and release enhancers. Psychopharmacology 1993; 113: 76–82PubMedCrossRefGoogle Scholar
  132. 132.
    Larrosa O, de la Llave Y, Bario S, et al. Stimulant and anticataplectic effects of reboxetine in patients with narcolepsy: a pilot study. Sleep 2001; 24: 282–5PubMedGoogle Scholar
  133. 133.
    Langdon N, Shindler J, Parkes J, et al. Fluoxetine in the treatment of cataplexy. Sleep 1986; 9: 371–3PubMedGoogle Scholar
  134. 134.
    Frey J, Darbonne C. Fluoxetine suppresses human cataplexy: a pilot study. Neurology 1994; 44: 707–9PubMedCrossRefGoogle Scholar
  135. 135.
    Nishino S, Arrigoni J, Shelton J, et al. Desmethyl metabolites of serotonergic uptake inhibitors are more potent for suppressing canine cataplexy than their parent compounds. Sleep 1993; 16: 706–12PubMedGoogle Scholar
  136. 136.
    Chen S, Clift S, Dahlitz M, et al. Treatment in the narcoleptic syndrome: self assessment of the action of dexamphetamine and clomipramine. J Sleep Res 1995; 4: 113–8PubMedCrossRefGoogle Scholar
  137. 137.
    Guilleminault C, Raynal D, Takahaski S, et al. Evaluation of short-term and long-term treatment of the narcolepsy syndrome with clomipramine hydrochloride. Acta Neurol Scand 1976; 54: 71–87PubMedCrossRefGoogle Scholar
  138. 138.
    Shapiro W. Treatment of cataplexy with clomipramine. Arch Neurol 1975; 32: 653–6PubMedCrossRefGoogle Scholar
  139. 139.
    Schachter M, Parkes J. Fluvoxamine and clomipramine in the treatment of cataplexy. J Neurol Neurosurg Psychiatry 1980: 43: 171–4PubMedCrossRefGoogle Scholar
  140. 140.
    Bental E, Lavie P, Sharf B. Sever hypermotility during sleep in treatment of cataplexy with clomipramine. Isr J Med Sci 1979: 15: 607–9PubMedGoogle Scholar
  141. 141.
    Niiyama Y, Shimizu T, Abe M, et al. Cortical reactivity in REM sleep with tonic mentalis EMG activity induced by clomipramine: an evaluation by slow vertex response. Electroencephalogr Clin Neurophysiol 1993; 86: 247–51PubMedCrossRefGoogle Scholar
  142. 142.
    Salin-Pascual R, Galicia-Polo L, Drucker-Colin R. Sleep changes after 4 consecutive days of venlafaxine administration in normal volunteers. J Clin Psychiatry 1997; 58(8): 348–50PubMedCrossRefGoogle Scholar
  143. 143.
    Bedard M-A, Montplaisir J, Godbout R, et al. Nocturnal gamma-hydroxybutyrate — effect on periodic leg movements and sleep organization of narcoleptic patients. Clin Neuropharmacol 1989; 12: 29–36PubMedCrossRefGoogle Scholar
  144. 144.
    Mamelak M, Scharf M, Woods M. Treatment of narcolepsy with gammahydroxybutyrate: a review of clinical and sleep lab findings. Sleep 1986; 9: 285–9PubMedGoogle Scholar
  145. 145.
    Scrima L, Hartman P, Johnson F, et al. The effects of gammahydroxybutyrate on the sleep of narcoleptic patients: a double-blind study. Sleep 1990; 13(6): 479–90PubMedGoogle Scholar
  146. 146.
    Scharf M, Brown D, Woods M, et al. The effects and effectiveness of gamma-hydroxybutyrate in patients with narcolepsy. J Clin Psychiatry 1985; 46: 222–5PubMedGoogle Scholar
  147. 147.
    USXMS 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; 25: 42–9Google Scholar
  148. 148.
    Scharf MB, Lai AA, Branigan B, et al. Pharmacokinetics of gammahydroxybutyrate (GHB) in narcoleptic patients. Sleep 1998; 21(5): 507–14PubMedGoogle Scholar
  149. 149.
    Boivin D, Montplaisir J, Poirier G. The effects of L-dopa on periodic leg movements and sleep organization in narcolepsy. Clin Neuropharmacol 1989; 12(4): 339–45PubMedCrossRefGoogle Scholar
  150. 150.
    Boivin D, Lorrain D, Montplaisir J. Effects of bromocriptine on periodic limb movements in human narcolepsy. Neurology 1993; 43: 2134–6PubMedCrossRefGoogle Scholar
  151. 151.
    Mahowald M, Schenck C. REM sleep parasomnias. In: Kryger M, Roth T, Dement W, editors. Principles and practice of sleep medicine. 3rd ed. St Louis: WB Saunders, 2000: 724–43Google Scholar

Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of PittsburghPittsburghPennsylvaniaUSA
  2. 2.Department of NeurologyEmory University School Of Medicine; The Emory Sleep Disorders CenterAtlantaUSA

Personalised recommendations