, Volume 64, Issue 13, pp 1385–1399 | Cite as

Pharmacotherapies for Obstructive Sleep Apnoea

Where Are We Now?
  • Ian E. Smith
  • Timothy G. Quinnell
Leading Article


Obstructive sleep apnoea (OSA) is common, causes considerable morbidity and probably contributes to mortality particularly through associated cardiovascular disease. The physical therapy of continuous positive airway pressure (CPAP) is extremely effective in the majority of patients but most patients would prefer an alternative. Intuitively, OSA should be amenable to pharmacotherapy. The upper airway of affected individuals can be narrowed but is patent during wakefulness. Collapse of the airway during sleep occurs when negative intra-luminal pressure generated by inspiratory effort exceeds the tone of the upper airway dilators. This mismatch may be in part due to respiratory drive instability but the state-dependent fall in drive to the airway dilator muscles is the biggest factor in most patients.

Various drugs have been investigated as treatment for OSA. Acetazolamide, theophylline, nicotine, opioid antagonists and medroxyprogesterone have been used to increase respiratory drive. Clonidine has been tested with the aim of reducing rapid eye movement sleep when OSA is often most severe. Variousantidepressants have been used to suppress rapid eye movement sleep and to preferentially activate the upper airway dilators. The drug trials have often been of poor design and none has included more than a few patients. Most of the drugs have been found to be ineffective and those that have worked for some patients (acetazolamide and protriptyline) have produced intolerable adverse effects.

There have been recent advances in the understanding of the neurotransmitters involved in the control of sleep and the upper airway motor neurones, offering the possibility of novel approaches to the drug treatment of OSA for those patients who cannot tolerate or do not benefit from CPAP. It seems likely that a better understanding of the mechanisms of OSA in individual patients and tailoring of drug therapy will be the way forward.


Continuous Positive Airway Pressure Modafinil Obstructive Sleep Apnoea Continuous Positive Airway Pressure Therapy Continuous Positive Airway Pressure Treatment 
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.



Dr Smith has received travel funds and honoraria for speaking at meetings sponsored by Cephalon UK.


  1. 1.
    Diagnostic Classification Steering Committee, Thorpy MJ. International classification of sleep disorders: diagnostic and coding manual. Rochester (MN): American Sleep Disorders Association, 1990Google Scholar
  2. 2.
    Davies RJ, Ali NJ, Stradling JR. Neck circumference and other clinical features in the diagnosis of the obstructive sleep apnoea syndrome. Thorax 1992; 47: 101–5PubMedCrossRefGoogle Scholar
  3. 3.
    Flemons WW, Whitelaw WA, Brant R, et al. Likelihood ratios for a sleep apnoea clinical prediction rule. Am J Respir Crit Care Med 1994; 150: 1279–85PubMedGoogle Scholar
  4. 4.
    Remmers JE, Degroot WJ, Sauerland EK, et al. Pathogenesis of upper airway occlusion during sleep. J Appl Physiol 1978; 11: 931–8Google Scholar
  5. 5.
    Younes M, Ostrowski M, Thompson W, et al. Chemical control stability in patients with obstructive sleep apnea. Am J Respir Crit Care Med 2001; 163: 829–39PubMedGoogle Scholar
  6. 6.
    Younes M. Contributions of upper airway mechanics and control mechanisms to severity of obstructive sleep apnea. Am J Respir Crit Care Med 2003; 168: 645–58PubMedCrossRefGoogle Scholar
  7. 7.
    Friberg D. Heavy snorers' disease: a progressive local neuropathy. Acta Otolaryngol 1999; 119: 925–33PubMedCrossRefGoogle Scholar
  8. 8.
    Issa FG, Sullivan CE. Alcohol, snoring and sleep apnea. J Neurol Neurosurg Psychiatry 1982; 45: 353–9PubMedCrossRefGoogle Scholar
  9. 9.
    Young T, Palta M, Dempsey J, et al. The occurrence of sleep disordered breathing in middle aged adults. N Engl J Med 1993; 328: 1230–5PubMedCrossRefGoogle Scholar
  10. 10.
    Stradling JR, Barbour C, Glennon J, et al. Prevalence of sleepiness and its relation to autonomic arousal and increased inspiratory effort in a community based population of men and women. J Sleep Res 2000; 9: 381–8PubMedCrossRefGoogle Scholar
  11. 11.
    Olson LG, King MT, Hensley MJ, et al. A community study of snoring and sleep disordered breathing prevalence. Am J Respir Crit Care Med 1995; 152: 711–6PubMedGoogle Scholar
  12. 12.
    Bixler E, Vgontzas A, Ten Have T, et al. Prevalence of sleep disordered breathing in women. Am J Respir Crit Care Med 2001; 163: 608–13PubMedGoogle Scholar
  13. 13.
    Lacasse Y, Godbout C, Series F. Health-related quality of life in obstructive sleep apnoea. Eur Respir J 2002; 19: 499–503PubMedCrossRefGoogle Scholar
  14. 14.
    Smith IE, Shneerson JM. Is the SF 36 sensitive to sleep disruption? A study in subjects with sleep apnoea. J Sleep Res 1995; 4: 183–8PubMedCrossRefGoogle Scholar
  15. 15.
    Shahar E, Whitney CW, Redline S, et al. Sleep disordered breathing and cardiovascular disease. Am J Respir Crit Care Med 2001; 163: 19–25PubMedGoogle Scholar
  16. 16.
    Brooks D, Horner RL, Kozar LF, et al. Obstructive sleep apnea as a cause of systemic hypertension: evidence from a canine model. J Cin Invest 1997; 99: 106–9CrossRefGoogle Scholar
  17. 17.
    Nieto FJ, Young TB, Lind BK, et al. Association of sleep disordered breathing, sleep apnea and hypertension in a large community based study: Sleep Heart Health Study. JAMA 2000; 283: 1829–36PubMedCrossRefGoogle Scholar
  18. 18.
    Lavie P, Heret P, Hoffstein V. Obstructive sleep apnoea syndrome as a risk factor for hypertension: population study. BMJ 2000; 320: 479–82PubMedCrossRefGoogle Scholar
  19. 19.
    Peppard PE, Young T, Palta M, et al. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000; 342: 1378–84PubMedCrossRefGoogle Scholar
  20. 20.
    Juniper M, Hack MA, George CF, et al. Steering simulation performance in patients with obstructive sleep apnoea and matched control subjects. Eur Respir J 2000; 15: 590–5PubMedCrossRefGoogle Scholar
  21. 21.
    George CFP. Reduction in motor vehicle collisions following treatment of sleep apnoea with nasal CPAP. Thorax 2001; 56: 508–12PubMedCrossRefGoogle Scholar
  22. 22.
    Piper AJ, Sullivan CE. Effects of short-term NIPPV in the treatment of patients with severe obstructive sleep apnea and hypercapnia. Chest 1994; 105: 434–40PubMedCrossRefGoogle Scholar
  23. 23.
    Smith I, Lasserson T, Wright J. Drug treatments for obstructive sleep apnoea (Cochrane Review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 2. Oxford: Update Software, 2003Google Scholar
  24. 24.
    Sullivan CE, Issa FG, Berthon-Jones M. Reversal of obstructive sleep apnoea by continuous positive airway pressure applied through the nares. Lancet 1981; I: 862–5CrossRefGoogle Scholar
  25. 25.
    Jenkinson C, Davies RJO, Mullins R, et al. Comparison of therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised prospective parallel trial. Lancet 1999; 353: 2100–5PubMedCrossRefGoogle Scholar
  26. 26.
    McFadyen TA, Espie CA, McArdle N, et al. Controlled prospective trial of psychosocial function before and after continuous positive airway pressure therapy. Eur Respir J 2001; 18: 996–1002PubMedCrossRefGoogle Scholar
  27. 27.
    Pepperell JC, Mullins B, Dow SR, et al. Ambulatory blood pressure following therapeutic and sub-therapeutic nasal continuous positive airway pressure for moderate to severe obstructive sleep apnoea: a randomised prospective parallel trial. Lancet 2002; 359: 204–10PubMedCrossRefGoogle Scholar
  28. 28.
    Hoy CJ, Vennelle M, Kingshott RN, et al. Can intensive support improve continuous positive airway pressure use in patients with the sleep apnea/hypopnea syndrome? Am J Respir Crit Care Med 1999; 159: 1096–100PubMedGoogle Scholar
  29. 29.
    Loube-DI. Technologic advances in the treatment of obstructive sleep apnea syndrome. Chest 1999 Nov; 116: 1426–33PubMedCrossRefGoogle Scholar
  30. 30.
    Wright J, White J. Continuous positive airways pressure for obstructive sleep apnoea (Cochrane Review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 3. Oxford: Update Software, 1999Google Scholar
  31. 31.
    Guilleminault C, Philip P. Tiredness and somnolence despite initial treatment of obstructive sleep apnea syndrome (what to do when an OSAS patients stays hypersomnolent despite treatment). Sleep 1996; 19 Suppl. 9: S117–22PubMedGoogle Scholar
  32. 32.
    Stradling J. Handbook of sleep-related breathing disorders. Oxford: Oxford University Press, 1993Google Scholar
  33. 33.
    Cistuli P, Barnes D, Grunstein R, et al. Effect of short term hormone replacement in the treatment of obstructive sleep apnoea in post-menopausal women. Thorax 1994; 49: 699–702CrossRefGoogle Scholar
  34. 34.
    St John WM, Bartlett D, Knuth KV, et al. Differential depression of hypoglossal nerve activity by alcohol: protection by pre-treatment with medroxyprogesterone acetate. Am Rev Respir Dis 1986; 133: 46–8Google Scholar
  35. 35.
    Block AJ, Wynne JW, Boysen PG, et al. Menopause, medroxyprogesterone and breathing during sleep. Am J Med 1981; 70: 506–10PubMedCrossRefGoogle Scholar
  36. 36.
    Cook WR, Benich JJ, Wooten SA. Indices of severity of obstructive sleep apnea syndrome do not change during medroxyprogesterone acetate therapy. Chest 1989; 96: 262–6PubMedCrossRefGoogle Scholar
  37. 37.
    Dexter DD, Dovre EJ. Obstructive sleep apnea due to endogenous testosterone production in a woman. Mayo Clin Proc 1998; 73: 246–8PubMedCrossRefGoogle Scholar
  38. 38.
    Yee B, Liu PY, Yang Q, et al. A double blind, placebo controlled randomised crossover study of intramuscular testosterone esters onsleep in men over 60 years of age [abstract]. J Sleep Res 2002; 11 Suppl. 1: 254Google Scholar
  39. 39.
    Sandblom RE, Matsumoto AM, Schoene RB, et al. Obstructive sleep apnea syndrome induced by testosterone administration. N Engl J Med 1983; 308: 508–10PubMedCrossRefGoogle Scholar
  40. 40.
    Luboshitzky R, Aviv A, Hefetz A, et al. Decreased pituitarygonadal secretion in men with obstructive sleep apnea. J Clin Endocrinol Metab 2002; 87: 3394–8PubMedCrossRefGoogle Scholar
  41. 41.
    White DP, Zwillich CW, Pickett CK, et al. Central sleep apnoea: improvement with acetazolamide therapy. Arch Intern Med 1982; 142: 1816–9PubMedCrossRefGoogle Scholar
  42. 42.
    Tojima H, Kunitomo F, Kimura H, et al. Effects of acetazolamide in patients with sleep apnoea syndrome. Thorax 1988; 43: 113–9PubMedCrossRefGoogle Scholar
  43. 43.
    Whyte K, Gould G, Airlie A, et al. Role of protriptyline and acetazolamide in the sleep apnoea/hypopnoea syndrome. Sleep 1988; 11: 463–72PubMedGoogle Scholar
  44. 44.
    Brownell LGP, West P, Sweatman P, et al. Protriptyline in obstructive sleep apnea: a double blind trial. N Engl J Med 1982; 307: 1037–42PubMedCrossRefGoogle Scholar
  45. 45.
    Stepanski E, Conway W, Young D, et al. A double blind trial of protriptyline in the treatment of sleep apnea syndrome. Henry Ford Hosp Med J 1988; 36: 5–8PubMedGoogle Scholar
  46. 46.
    Javaheri S, Evers JAM, Teppema LJ. Increase in ventilation caused by aminophylline in the absence of changes in ventral medullary extra cellular fluids, pH and carbon dioxide tension. Thorax 1989; 44: 121–5PubMedCrossRefGoogle Scholar
  47. 47.
    Aubier M, Detroya A, Sampson M, et al. Aminophylline improves diaphragmatic contractility. N Engl J Med 1981; 305: 249–52PubMedCrossRefGoogle Scholar
  48. 48.
    Mulloy E, McNicholas WT. Theophylline in obstructive sleep apnoea: a double blind evaluation. Chest 1992; 101: 753–7PubMedCrossRefGoogle Scholar
  49. 49.
    Espinosa H, Antic R, Thornton AT, et al. The effects of aminophylline on the sleep and sleep-disordered breathing in patients with obstructive sleep apnea syndrome. Am Rev Respir Dis 1987; 136: 80–4CrossRefGoogle Scholar
  50. 50.
    Saletu B, Oberndorfer S, Anderer P, et al. Efficiency of continuous positive airway pressure versus theophylline therapy in sleep apnea: comparative sleep laboratory studies on objective and subjective sleep and awakening quality. Neuropsychobiology 1999; 39: 151–9PubMedCrossRefGoogle Scholar
  51. 51.
    Gislason T, Almqvist M, Boman G, et al. Increased CSF opioid activity in sleep apnea syndrome: regression after successful treatment. Chest 1989; 96: 250–4PubMedCrossRefGoogle Scholar
  52. 52.
    Atkinson RL, Suratt PM, Wilhoit SC. Naloxone improves sleep apnea in obese humans. Int J Obes Relat Metab Disord 1985; 9: 233–9Google Scholar
  53. 53.
    Suratt PM, Wilhoit SC, Brown ED, et al. Effect of doxapram on obstructive sleep apnea. Bull Eur Physiopathol Respir 1986; 22: 127–31PubMedGoogle Scholar
  54. 54.
    Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med 2002; 165: 1217–39PubMedCrossRefGoogle Scholar
  55. 55.
    Shao XM, Feldman JL. Pharmacology of nicotinic receptors in preBötzinger complex that mediate modulation of respiratory pattern. J Neurophysiol 2002; 88: 1851–8PubMedGoogle Scholar
  56. 56.
    Gothe B, Strohl KP, Levin S, et al. Nicotine: a different approach to treatment of obstructive sleep apnea. Chest 1985; 87: 11–7PubMedCrossRefGoogle Scholar
  57. 57.
    Davila DG, Hunt RD, Offord KP, et al. Acute effects of transdermal nicotine on sleep architecture, snoring, and sleepdisordered breathing in nonsmokers. Am J Respir Crit Care Med 1994; 150: 469–74PubMedGoogle Scholar
  58. 58.
    Kraiczi H, Hedner J, Peker Y, et al. Comparison of atenolol, amlodipine, enalapril, hydrochlorothiazide and losartan for antihypertensive treatment in obstructive sleep apnea. Am J Respir Crit Care Med 2000; 161: 1423–8PubMedGoogle Scholar
  59. 59.
    Weichler U, Kerres-Mayer B, Mayer J, et al. Influence of antihypertensive drug therapy on sleep pattern and sleep apnea activity. Cardiology 1991; 78: 124–30PubMedCrossRefGoogle Scholar
  60. 60.
    Mayer J, Peter JH. First experience with cilazapril in the treatment of sleep apnoea-related hypertension. Drugs 1991; 41 Suppl. 1: 37–47CrossRefGoogle Scholar
  61. 61.
    Grote L, Wutkewicz K, Knaack L, et al. Association between blood pressure reduction with antihypertensive treatment and sleep apnea activity. Am J Hypertens 2000; 13: 1280–7PubMedCrossRefGoogle Scholar
  62. 62.
    Planes C, Foucher A, Leroy M, et al. Effect of celiprolol treatment in hypertensive patients with sleep apnea. Sleep 1999; 22: 507–13PubMedGoogle Scholar
  63. 63.
    Kammo O, Clarebarch P. Effects of clonidine and yohimbine on sleep in man: polygraphic study and EEG analysis by normalised slope descriptors. Electroencephalogr Clin Neurophysiol 1985; 60: 478–84CrossRefGoogle Scholar
  64. 64.
    Issa F. Effect of clonidine in obstructive sleep apnoea. Am Rev Respir Dis 1992; 145: 465–9Google Scholar
  65. 65.
    Hudgel DW. Pharmacologic treatment of obstructive sleep apnea. J Lab Clin Med 1995; 126: 13–8PubMedGoogle Scholar
  66. 66.
    Bonora M, St John WM, Bledsoe TA. Differential elevation by protriptyline and depression by diazepam of upper airway respiratory motor activity. Am Rev Respir Dis 1985; 131: 41–5PubMedGoogle Scholar
  67. 67.
    Mezzanotte WS, Tangel DJ, White DP, et al. Waking genioglossal electromyogram in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanism). J Clin Invest 1992; 89: 1571–9PubMedCrossRefGoogle Scholar
  68. 68.
    Horner RL. The neuropharmacology of upper airway motor control in the awake and asleep states: implications for obstructive sleep apnoea. Respir Res 2001; 2: 286–94PubMedCrossRefGoogle Scholar
  69. 69.
    Chase MH, Soja PJ, Morales FR. Evidence that glycine mediates the post-synaptic potentials that inhibit lumbar motoneurons during the atonia of active sleep. J Neurosci 1989; 9: 743–51PubMedGoogle Scholar
  70. 70.
    Kubin L, Kimura H, Tojima H, et al. Suppression of hypoglossal motorneurons during the carbachol induced atonia of REM sleep is not caused by fast synaptic inhibition. Brain Res 1993; 611: 300–12PubMedCrossRefGoogle Scholar
  71. 71.
    Kubin L, Tojima H, Davies RO, et al. Serotonergic excitatory drive to hypoglossal motorneurons in the decerabrate cat. Neurosci Lett 1992; 139: 243–8PubMedCrossRefGoogle Scholar
  72. 72.
    Jacobs BL, Azmitia EC. Structure and function of the brain serotonin system. Physiol Rev 1992; 72: 165–229PubMedGoogle Scholar
  73. 73.
    Jelev A, Sood S, Liu H, et al. Microdialysis perfusion of 5-HT into the hypoglossal motor nucleus differentially modulates genioglossus activity across natural sleep-wake states in rats. J Physiol (Lond) 2001; 532: 467–81CrossRefGoogle Scholar
  74. 74.
    Morin D, Monteau R, Hilaire G. Compared effects of serotonin on cervical and hypoglossal activities: an in-vitro study in the newborn rat. J Physiol (Lond) 1992; 451: 605–29Google Scholar
  75. 75.
    Veasey SC, Chachkes J, Fenik P, et al. The effects of ondansetron on sleep-disordered breathing in the English bulldog. Sleep 2001; 24: 155–60PubMedGoogle Scholar
  76. 76.
    Stradling J, Smith D, Radulovacki M, et al. Effect of ondansetron on moderate obstructive sleep apnoea, a single night, placebo-controlled trial. J Sleep Res 2003; 12: 169–70PubMedCrossRefGoogle Scholar
  77. 77.
    Sunderram J, Parisi RA, Strobel RJ. Serotonergic stimulation of the genioglossus and the response to nasal continuous positive airway pressure. Am J Respir Crit Care Med 2000; 162: 925–9PubMedGoogle Scholar
  78. 78.
    Hanzel DA, Proia NG, Hudgel DW. Response of obstructive sleep apnea to fluoxetine and protriptyline. Chest 1991; 100: 416–21PubMedCrossRefGoogle Scholar
  79. 79.
    Kraiczi H, Hedner J, Dahlof P, et al. Effect of serotonin uptake inhibition on breathing during sleep and daytime symptoms in obstructive sleep apnea. Sleep 1999; 22: 61–7PubMedGoogle Scholar
  80. 80.
    Greenstone M. Doxapram for ventilatory failure due to exacerbations of chronic obstructive pulmonary disease. (Cochrane Review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 2. Oxford: Update Software, 2003Google Scholar
  81. 81.
    Bellemare F. Bigland-Ritchie B. Central components of diaphragmatic fatigue assessed by phrenic nerve stimulation. J Appl Physiol 1987; 62: 1307–16Google Scholar
  82. 82.
    Jokic R, Klimaszewski A, Crossley M, et al. Positional treatment vs continuous positive airway pressure in patients with positional obstructive sleep apnoea syndrome. Chest 1999; 115: 771–81PubMedCrossRefGoogle Scholar
  83. 83.
    Rubinstein I, Colapinto N, Rotstein LE, et al. Improvement in upper airway function after weight loss in patients with obstructive sleep apnoea. Am Rev Respir Dis 1988; 138: 1192–5PubMedGoogle Scholar
  84. 84.
    Sampol G, Munoz X, Sagales MT, et al. Long-term efficacy of dietary weight loss in sleep apnoea/hypopnoea syndrome. Eur Respir J 1998; 12: 1156–9PubMedCrossRefGoogle Scholar
  85. 85.
    National Institute for Clinical Excellence. Guidance on the use of orlistat for the treatment of obesity in adults. Technology Appraisal Guidance no. 22, 2001 Mar [online]. Available from URL: [Accessed 2003 Oct 10]
  86. 86.
    National Institute for Clinical Excellence. Guidance on the use of sibutramine for the treatment of obesity in adults. Technology Appraisal Guidance no. 31, 2001 Oct [online]. Available from URL: [Accessed 2003 Oct 10]
  87. 87.
    Bray GA. Drug treatment of obesity. Rev Endocr Metab Disord 2001; 2: 403–18PubMedCrossRefGoogle Scholar
  88. 88.
    Kapur VK, Koepsell TD, deMaine J, et al. Association of hypothyroidism and obstructive sleep apnea. Am J Respir Crit Care Med 1998; 158: 1379–83PubMedGoogle Scholar
  89. 89.
    Lin CC, Tsan KW, Chen PJ. The relationship between sleep apnea syndrome and hypothyroidism. Chest 1992; 102: 1663–7PubMedCrossRefGoogle Scholar
  90. 90.
    Rajagopal KR, Abbrecht PH, Derderian SS, et al. Obstructive sleep apnea in hypothyroidism. Ann Intern Med 1984; 101: 491–4PubMedGoogle Scholar
  91. 91.
    Grunstein RR, Sullivan CE. Sleep apnea and hypothyroidism: mechanisms and management. Am J Med 1988; 85: 775–9PubMedCrossRefGoogle Scholar
  92. 92.
    Skatrud J, Iber C, Ewart R, et al. Disordered breathing during sleep in hypothyroidism. Am Rev Respir Dis 1981; 124: 325–9PubMedGoogle Scholar
  93. 93.
    Mezon BJ, West P, MaClean JP, et al. Sleep apnea in acromegaly. Am J Med 1980; 69: 615–8PubMedCrossRefGoogle Scholar
  94. 94.
    Hart TB, Radow SK, Blackard WG, et al. Sleep apnoea in active acromegaly. Arch Intern Med 1985; 145: 865–6PubMedCrossRefGoogle Scholar
  95. 95.
    Perks WH, Horrocks PM, Cooper RA, et al. Sleep apnoea in acromegaly. BMJ 1980 Mar 29; 280: 894–7PubMedCrossRefGoogle Scholar
  96. 96.
    Pack AI, Black JE, Schwartz JRL, et al. Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnoea. Am J Respir Crit Care Med 2001; 164: 1675–81PubMedGoogle Scholar
  97. 97.
    Black JE, Douglas NJ, Earl CQ, et al. Efficacy and safety of modafinil as adjunctive therapy for excessive sleepiness associated with obstructive sleep apnea [abstract]. Sleep 2002; 25 Suppl. 1: A22Google Scholar
  98. 98.
    Kingshott RN, Vennelle M, Coleman EL, et al. Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of residual excessive daytime sleepiness in the sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med 2001; 163: 918–23PubMedGoogle Scholar
  99. 99.
    Pack AI. Should a pharmaceutical be approved for the broad indication of excessive sleepiness? Am J Respir Crit Care Med 2003; 167: 109–11PubMedCrossRefGoogle Scholar

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© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Respiratory Support and Sleep CentrePapworth Hospital, Papworth EverardCambridgeUK

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