Advertisement

Pharmacy World and Science

, Volume 17, Issue 3, pp 67–75 | Cite as

Pharmacotherapy of insomnia: Practice and prospects

  • Jasper Dingemanse
Pharmacotherapy Evaluations

Abstract

Insomnia is a complex complaint which is often multifactorial in origin. Pharmacotherapy can only be an adjunct in the treatment of insomnia and hypnotics should be given on an intermittent basis for short periods of time. An overview is presented of the currently available hypnotics, of which benzodiazepines are still the most widely prescribed. New drugs which bind to specific receptor subtypes or which are partial benzodiazepine receptor agonists might overcome the disadvantages associated with chronic benzodiazepine use, but more longterm investigations are needed.

Keywords

Adverse effects Aged Clinical trials Drug interactions Hypnotics Insomnia Pharmacodynamics Pharmacokinetics 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    APA (American Psychiatric Association). Diagnostic and statistical manual of mental disorders. 3rd ed, revised. Washington DC: American Psychiatric Press, 1987.Google Scholar
  2. 2.
    Diagnostic Classification Steering Committee. The international classification of sleep disorders: diagnostic and coding manual. Rochester: American Sleep Disorders Association, 1990.Google Scholar
  3. 3.
    Wheatley D. Prescribing short-acting hypnosedatives. Current recommendations from a safety perspective. Drug Safety 1992;7(2):106–15.Google Scholar
  4. 4.
    Johnson LC, Chernik DA. Sedative-hypnotics and human performance. Psychopharmacology 1982;76:101–13.Google Scholar
  5. 5.
    Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders. JAMA 1989;262(11):1479–84.Google Scholar
  6. 6.
    Mendels J. Criteria for selection of appropriate benzodiazepine hypnotic therapy. J Clin Psychiatry 1991;52 Suppl 9:42–6.Google Scholar
  7. 7.
    Sloan EP, Hauri P, Bootzin R, Morin C, Stevenson M, Shapiro CM. The nuts and bolts of behavioral therapy for insomnia. J Psychosom Res 1993;37 Suppl 1:19–38.Google Scholar
  8. 8.
    Morin CM, Culbert JP, Schwartz SM. Nonpharmacological interventions for insomnia: a meta-analysis of treatment efficacy. Am J Psychiatry 1994;151(8):1172–80.Google Scholar
  9. 9.
    Declerck AC. Is ‘poor sleep’ too vague a concept for rational treatment? J Int Med Res 1994;22(1):1–16.Google Scholar
  10. 10.
    Czeisler CA, Richardson GS. Detection and assessment of insomnia. Clin Ther 1991;13(6):663–79.Google Scholar
  11. 11.
    Wincor MZ. The pharmacist's role in the recognition and management of insomnia. J Clin Psychiatry 1992;53 Suppl 12:80–3.Google Scholar
  12. 12.
    Nicholson AN. Hypnotics — their place in therapeutics. Drugs 1986;31:164–76.Google Scholar
  13. 13.
    Dement WC. The proper use of sleeping pills in the primary care setting. J Clin Psychiatry 1992;53:50–6.Google Scholar
  14. 14.
    Benoit O. Benefits and risks of hypnotics. Neurophysiol Clin 1991;21(4):245–65.Google Scholar
  15. 15.
    Dingemanse J, Danhof M, Breimer DD. Pharmacokinetic-pharmacodynamic modelling of CNS drug effects. An overview. Pharmacol Ther 1988;38:1–52.Google Scholar
  16. 16.
    Johnson LC, Chernik DA, Sateia MJ. Sleep, performance, and plasma levels in chronic insomniacs during 14-day use of flurazepam and midazolam: an introduction. J Clin Psychopharmacol 1990;10(4 Suppl):5S-9S.Google Scholar
  17. 17.
    Picone DA, D'Mello DA, Foote ML, Msibi B. A review of the utilization of sedative-hypnotic drugs in a general hospital. Gen Hosp Psychiatry 1993;15(1):51–4.Google Scholar
  18. 18.
    Whitehead C, Sanders L, Appadurai I, Power I, Rosen M, Robinson J. Zopiclone as a preoperative night hypnotic: a double-blind comparison with temazepam and placebo. Br J Anaesth 1994;72(4):443–6.Google Scholar
  19. 19.
    Quera Salva MA, Orluc A, Goldenberg F, Guilleminault C. Insomnia and use of hypnotics: study of a French population. Sleep 1991;14(5):386–91.Google Scholar
  20. 20.
    Allgulander C, Nasman P. Regular hypnotic drug treatment in a sample of 32,679 Swedes: associations with somatic and mental health, inpatient psychiatric diagnoses and suicide, derived with automated record-linkage. Psychosom Med 1991;53(1):101–8.Google Scholar
  21. 21.
    Rawson NS, D'Arcy C. Sedative-hypnotic drug use in Canada. Health Rep 1991;3(1):33–57.Google Scholar
  22. 22.
    Seppala M, Rajala T, Sourander L. Subjective evaluation of sleep and the use of hypnotics in nursing homes. Aging 1993;5(3):199–205.Google Scholar
  23. 23.
    Carey DL, Day RO, Cairns DR, Pearce GA, Wodak AD, Lauchlan RL. An attempt to influence hypnotic and sedative drug use. Med J Aust 1992;156(6):389–92.Google Scholar
  24. 24.
    Maczaj M. Pharmacological treatment of insomnia. Drugs 1993;45(1):44–55.Google Scholar
  25. 25.
    Ankier SI, Goa KL. Quazepam — a preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in insomnia. Drugs 1988;35:42–62.Google Scholar
  26. 26.
    Langtry HD, Benfield P. Zolpidem. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential. Drugs 1990;40(2):291–313.Google Scholar
  27. 27.
    Morgan K. Hypnotics in the elderly. What cause for concern? Drugs 1990;40(5):688–96.Google Scholar
  28. 28.
    Mendelson WB, Roehrs TA, Roth T. Replacement of benzodiazepines with ‘old-fashioned’ hypnotics. A cause for concern? Drug Safety 1993;9(3):149–50.Google Scholar
  29. 29.
    Shader RI, Greenblatt DJ, Balter MB. Appropriate use and regulatory control of benzodiazepines. J Clin Pharmacol 1991;31:781–4.Google Scholar
  30. 30.
    Haefely W. Benzodiazepine receptor and ligands: structural and functional differences. In: Hindmarch I, Beaumont G, Brandon S, Leonard BE, editors. Benzodiazepines: Current concepts. Chichester: John Wiley & Sons, 1990:1–18.Google Scholar
  31. 31.
    Jochemsen R, van Boxtel CJ, Hermans J, Breimer DD. Pharmacokinetics of five benzodiazepine hypnotics in the same panel of healthy subjects. Clin Pharmacol Ther 1983; 43(1):42–7.Google Scholar
  32. 32.
    Ashton H. Guidelines for the rational use of benzodiazepines — when and what to use. Drugs 1994;48(1):25–40.Google Scholar
  33. 33.
    Walsh JK, Engelhardt CL. Trends in the pharmacologic treatment of insomnia. J Clin Psychiatry 1992;53 Suppl:10–17.Google Scholar
  34. 34.
    Schoch P, Moreau JL, Martin JR, Haefely WE. Aspects of benzodiazepine receptor structure and function with relevance to drug tolerance and dependence. Biochem Soc Symp 1993;59:121–34.Google Scholar
  35. 35.
    Klepner CA, Lippa AS, Benson DI, Sano MC, Beer B. Resolution of two biochemically and pharmacologically distinct benzodiazepine receptors. Pharmacol Biochem Behav 1979;11:457–62.Google Scholar
  36. 36.
    Langer SZ, Arbilla S. Imidazopyridines as a tool for the characterization of benzodiazepine receptors: a proposal for a pharmacological classification as omega receptor subtypes. Pharmacol Biochem Behav 1988;29:763–6.Google Scholar
  37. 37.
    Langer SZ, Arbilla S, Tan S, Lloyd KG, George P, Allen J, Wick AE. Selectivity for omega-receptor subtypes as a strategy for the development of anxiolytic drugs. Pharmacopsychiatry 1990;23:103–7.Google Scholar
  38. 38.
    Wadworth AN, McTavish D. Zopiclone. A review of its pharmacological properties and therapeutic efficacy as an hypnotic. Drugs Aging 1993;3:441–59.Google Scholar
  39. 39.
    Berlin I, Warot D, Hergueta T, Molinier P, Bagot C, Puech AJ. Comparison of the effects of zolpidem and triazolam on memory functions, psychomotor performances, and postural sway in healthy subjects. J Clin Psychopharmacol 1993;13(2):100–6.Google Scholar
  40. 40.
    Roehrs T, Merlotti L, Zorick F, Roth T. Sedative, memory, and performance effects of hypnotics. Psychopharmacology 1994;116:130–4.Google Scholar
  41. 41.
    Dorian P, Sellers EM, Kaplan M, Hamilton C. Evaluation of zopiclone physical dependence liability in normal volunteers. Pharmacology 1983;27 Suppl 2:228–34.Google Scholar
  42. 42.
    Beer B, Ieni JR, Wu W-H, Clody D, Amorusi P, Rose J, et al. A placebo-controlled evaluation of single, escalating doses of CL 284,846, a non-benzodiazepine hypnotic. J Clin Pharmacol 1994;34:335–44.Google Scholar
  43. 43.
    Vanover KE, Barrett JE. Evaluation of the discriminative stimulus effects of the novel sedative-hypnotic CL 284,846. Psychopharmacology 1994;115:289–96.Google Scholar
  44. 44.
    Martin JR, Moreau J-L, Jenck F, Widmer U. Pharmacological profile of several quinolizinones acting as partial agonists at the benzodiazepine receptor. Neuropsychopharmacology 1994;10(3S pt 2):170S.Google Scholar
  45. 45.
    Dingemanse J, Bury M, Roncari G, Zell M, Gieschke R, Gaillard AWK, et al. Pharmacokinetics and pharmacodynamics of Ro 41-3696, a novel non-benzodiazepine hypnotic. J Clin Pharmacol. In press.Google Scholar
  46. 46.
    Dingemanse J, Bury M, Bock J, Odink J, Gaillard AWK. Comparative pharmacodynamics of zolpidem and Ro 41-3696, a new hypnotic, after night time administration to healthy volunteers. Pharm Res 1994;11:S357.Google Scholar
  47. 47.
    Kammerer E. Phytogenic sedative-hypnotics — does a combination of valerian and hops have a value in the modern drug repertoire? Z Arztl Fortbild 1993;87(5):401–6.Google Scholar
  48. 48.
    Schulz H, Stolz C, Müller J. The effect of valerian extract on sleep polygraphy in poor sleepers: a pilot study. Pharmacopsychiatry 1994;27:147–51.Google Scholar
  49. 49.
    Folkard S, Arendt J, Aldhous M, Kennett H. Melatonin stabilises sleep onset time in blind man without entrainment of cortisol or temperature rhythms. Neurosci Lett 1990;113:193–8.Google Scholar
  50. 50.
    Silvestri R, Mento G, Raffaele M, De Luca G, Buttini G, Casella C, et al. Indole-3-pyruvic acid as a possible hypnotic agent in insomniac subjects. J Int Med Res 1991;19(5):403–9.Google Scholar
  51. 51.
    Borbély AA, Tobler I. Endogenous sleep-promoting substances and sleep regulation. Physiol Rev 1989;69:605–70.Google Scholar
  52. 52.
    American Sleep Disorders Association. The clinical use of the multiple sleep latency test. Sleep 1992;15(3):268–76.Google Scholar
  53. 53.
    Volkerts ER, O'Hanlon JF. Hypnotics' residual effects on driving performance. In: O'Hanlon JF, de Gier JJ, editors. Drugs and driving. London: Taylor and Francis, 1986:123–37.Google Scholar
  54. 54.
    Ray WA, Fought RL, Decker MD. Psychoactive drugs and the risk of injurious motor vehicle crashes in elderly drivers. Am J Epidemiol 1992;136:873–83.Google Scholar
  55. 55.
    ‘Benzodiazepine/Driving’ Collaborative Group. Are benzodiazepines a risk factor for road accidents? Drug Alcohol Depend 1993;33:19–22.Google Scholar
  56. 56.
    Lader M. Benzodiazepines — a risk-benefit profile. CNS Drugs 1994;1(5):377–87.Google Scholar
  57. 57.
    King DJ. Benzodiazepines, amnesia and sedation: theoretical and clinical issues and controversies. Hum Psychopharmacol 1992;7:79–87.Google Scholar
  58. 58.
    Scharf MB, Fletcher K, Graham JP. Comparative amnestic effects of benzodiazepine hypnotic agents. J Clin Psychiatry 1988;49:134–7.Google Scholar
  59. 59.
    Kales A, Kales J. Sleep laboratory studies of hypnotic drugs: efficacy and withdrawal effects. J Clin Psychopharmacol 1983;3:140–50.Google Scholar
  60. 60.
    Lader M. Rebound insomnia and newer hypnotics. Psychopharmacology 1992;108(3):248–55.Google Scholar
  61. 61.
    Kales A, Soldatos CR, Bixler EO, Kales JD. Rebound insomnia and rebound anxiety: a review. Pharmacology 1983;26:121–37.Google Scholar
  62. 62.
    Scharf MB. Feasibility of an every-other-night regimen in insomniac patients: subjective hypnotic effectiveness of quazepam, triazolam, and placebo. J Clin Psychiatry 1993;54(1):33–8.Google Scholar
  63. 63.
    Nutt D. Benzodiazepine dependence in the clinic: reason for anxiety? Trends Pharmacol Sci 1986;7:457–60.Google Scholar
  64. 64.
    Kales A, Manfredi RL, Vgontzas AN, Bixler EO, Vela-Bueno A, Fee EC. Rebound insomnia after only brief and intermittent use of rapidly eliminated benzodiazepines. Clin Pharmacol Ther 1991;49:468–76.Google Scholar
  65. 65.
    Monti JM, Attali P, Monti D, Zipfel A, de la Giclais B, Morselli PL. Zolpidem and rebound insomnia — a double-blind, controlled polysomnographic study in chronic insomniac patients. Pharmacopsychiatry 1994;27:166–75.Google Scholar
  66. 66.
    Greenblatt DJ, Harmatz JS, Zinny MA, Shader RI. Effect of gradual withdrawal on the rebound sleep disorder after discontinuation of triazolam. N Engl J Med 1987;317:722–8.Google Scholar
  67. 67.
    Shapiro CM, MacFarlane JG, MacLean AW. Alleviating sleep-related discontinuance symptoms associated with benzodiazepine withdrawal: a new approach. J Psychosom Res 1993;37(1):55–7.Google Scholar
  68. 68.
    Clift A. Dependence on hypnotics. In: Hallström C, editor. Benzodiazepine dependence, Oxford: Oxford University Press, 1993:203–20.Google Scholar
  69. 69.
    Busto U, Sellers EM, Naranjo CA, Cappell HD, Sanchez-Craig M, Simpkins J. Patterns of benzodiazepine abuse and dependence. Br J Addict 1986;81:87–94.Google Scholar
  70. 70.
    Evans SM, Critchfield TS, Griffiths RR. Abuse liability assessment of anxiolytics/hypnotics: rationale and laboratory lore. Br J Addict 1991;86(12):1625–32.Google Scholar
  71. 71.
    Cavallaro R, Regazzetti MG, Covelli G, Smeraldi E. Tolerance and withdrawal with zolpidem. Lancet 1993;342:374–5.Google Scholar
  72. 72.
    Rosholm J-U, Hallas J, Gram LF. Concurrent use of more than one major psychotropic drug (polypsychopharmacy) in outpatients — a prescription database study. Br J Clin Pharmacol 1994;37:533–8.Google Scholar
  73. 73.
    Nolen WA, Haffmans PM, Bouvy PF, Duivenvoorden HJ. Hypnotics as concurrent medication in depression. A placebo-controlled, double-blind comparison of flunitrazepam and lormetazepam in patients with major depression, treated with a (tri)cyclic antidepressant. J Affect Disord 1993;28(3):179–88.Google Scholar
  74. 74.
    Sellers EM, Busto U. Benzodiazepines and ethanol: assessment of the effects and consequences of psychotropic drug interactions. J Clin Psychopharmacol 1982;2:249–62.Google Scholar
  75. 75.
    Kuitunen T, Mattila MJ, Seppala T. Actions and interactions of hypnotics on human performance: single doses of zopiclone, triazolam and alcohol. Int Clin Psychopharmacol 1990;5 Suppl 2:115–30.Google Scholar
  76. 76.
    Wysowski DK, Baum C. Outpatient use of prescription sedative-hypnotic drugs in the United States, 1970 through 1989. Arch Intern Med 1991;151(9):1779–83.Google Scholar
  77. 77.
    Jonas JM. Idiosyncratic side effects of short half-life benzodiazepine hypnotics: fact or fancy? Hum Psychopharmacol 1992;7:205–16.Google Scholar
  78. 78.
    Jonas JM, Coleman BS, Sheridan AQ, Kalinske RW. Comparative clinical profiles of triazolam versus other shorter-acting hypnotics. J Clin Psychiatry 1992;53 Suppl:19–31.Google Scholar
  79. 79.
    Kales A. Benzodiazepine hypnotics and insomnia. Hosp Pract 1990;25 Suppl 3:7–23.Google Scholar
  80. 80.
    Martin VL. Appropriately treating insomnia with triazolam. J Psychoact Drugs 1990;22(1):35–43.Google Scholar
  81. 81.
    Guidelines for the clinical evaluation of hypnotic drugs, US Department of Health, Education and Welfare Publication No. (FDA) 78-3051. Washington DC: US Government Printing Office, 1977.Google Scholar
  82. 82.
    ECSC-EEC-EAEC. Guidelines on psychotropic drugs for the EC. Eur Neuropsychopharmacol 1994;4:61–77.Google Scholar
  83. 83.
    Angst J, Borbely A, Engel RR, Ferner U, Gaszner P, Hippius H, et al. Report on the sixth consensus conference on the methodology of clinical trials with hypnotic drugs. Pharmacopsychiatry. 1995;28:2–7.Google Scholar
  84. 84.
    Borbély AA, Akerstedt T, Benoit O, Holsboer F, Oswald I. Hypnotics and sleep physiology: a consensus report. Eur Arch Psychiatry Clin Neurosci 1991;241(1):13–21.Google Scholar
  85. 85.
    Kales A, Scharf MB, Soldatos CR, Bixler EO. Clinical evaluation of hypnotic drugs: Contributions from sleep laboratory studies. J Clin Pharmacol 1979;19:329–36.Google Scholar
  86. 86.
    Hohagen F, Berger M. Testing the efficacy of new hypnotic drugs. In: Benkert O, Maier W, Rickels K, editors. Methodology of the evaluation of psychotropic drugs. (Psychopharmacology Series 8). Berlin: Springer-Verlag, 1990:56–69.Google Scholar
  87. 87.
    Kryger MH, Steljes D, Pouliot Z, Neufeld H, Odynski T. Subjective versus objective evaluation of hypnotic efficacy: experience with zolpidem. Sleep 1991;14(5):399–407.Google Scholar
  88. 88.
    Fischer W, Haase W, Ruther E, Clarenbach P, Hajak G. Problems in performing a double-blind multicenter study using a hypnotic in private practice. Int J Clin Pharmacol Ther Toxicol 1992;30(11):474.Google Scholar
  89. 89.
    Walsh JK, Schweitzer PK, Sugerman JL, Muehlbach MJ. Transient insomnia associated with a 3-hour phase advance of sleep time and treatment with zolpidem. J Clin Psychopharmacol 1990;10(3):184–9.Google Scholar
  90. 90.
    Balter MB, Uhlenhuth EH. New epidemiologic findings about insomnia and its treatment. J Clin Psychiatry 1992;53 Suppl 12:34–42.Google Scholar
  91. 91.
    Horne J. Human slow wave sleep: a review and appraisal of recent findings, with implications for sleep functions, and psychiatric illness. Experientia 1992;48(10):941–54.Google Scholar
  92. 92.
    Lavoisy J, Zivkovic B, Benavides J, Perrault GH, Robert P. Contribution of zolpidem in the management of sleep disorders. Encephale 1992;18(4):379–92.Google Scholar
  93. 93.
    Brunner DP, Dijk D-J, Münch M, Borbély AA. Effect of zolpidem on sleep and sleep EEG spectra in healthy young men. Psychopharmacology 1991;104:1–5.Google Scholar
  94. 94.
    Schwilden H, Schüttler J, Stoeckel H. Quantitation of the EEG and pharmacodynamic modelling of hypnotic drugs: etomidate as an example. Eur J Anaesthesiol 1985;2:121–31.Google Scholar
  95. 95.
    Bührer M, Maitre PO, Crevoisier C, Stanski DR. Electroencephalographic effects of benzodiazepines. II. Pharmacodynamic modelling of the electroencephalographic effects of midazolam and diazepam. Clin Pharmacol Ther 1990;48(5):555–67.Google Scholar
  96. 96.
    Mandema JW, Tuk B, van Steveninck AL, Breimer DD, Cohen AF, Danhof M. Pharmacokinetic-pharmacodynamic modelling of the central nervous system effects of midazolam and its main metabolite α-hydroxymidazolam in healthy volunteers. Clin Pharmacol Ther 1992;51:715–28.Google Scholar
  97. 97.
    Caccia S, Garattini S. Formation of active metabolites of psychotropic drugs. An updated review of their significance. Clin Pharmacokin 1990;18:434–59.Google Scholar
  98. 98.
    Schlich D, L-Heritier C, Coquelin JP, Attali P. Long-term treatment of insomnia with zolpidem: a multicentre general practitioner study of 107 patients. J Int Med Res 1991; 19(3):271–9.Google Scholar
  99. 99.
    Matalon A, Yinnon AM, Hurwitz A. Chronic use of hypnotics in a family practice — patients' reluctance to stop treatment. Fam Pract 1990;7(4):258–60.Google Scholar
  100. 100.
    Mullan E, Katona C, Bellew M. Patterns of sleep disorders and sedative hypnotic use in seniors. Drugs Aging 1994;5(1):49–58.Google Scholar
  101. 101.
    Greenblatt DJ, Harmatz JS, Shader RI. Clinical pharmacokinetics of anxiolytics and hypnotics in the elderly. Therapeutic considerations (Part I). Clin Pharmacokin 1991;21(3):165–77.Google Scholar
  102. 102.
    Greenblatt DJ, Harmatz JS, Shader RI. Clinical pharmacokinetics of anxiolytics and hypnotics in the elderly. Therapeutic considerations (Part II). Clin Pharmacokin 1991;21(4):262–73.Google Scholar
  103. 103.
    Salzman C. Geriatric psychopharmacology. Annu Rev Med 1985;36:217–28.Google Scholar
  104. 104.
    Greenblatt DJ, Harmatz JS, Shapiro L, Engelhardt N, Gouthro TA, Shader RI. Sensitivity to triazolam in the elderly. N Engl J Med 1991;324(24):1691–98.Google Scholar
  105. 105.
    Sorock GS, Shimkin EE. Benzodiazepine sedatives and the risk of falling in a community-dwelling elderly cohort. Ann Int Med 1988;148:2441–4.Google Scholar
  106. 106.
    Shorr RI, Bauwens SF, Landefeld CS. Failure to limit quantities of benzodiazepine hypnotic drugs for outpatients: placing the elderly at risk. Am J Med 1990;89(6):725–32.Google Scholar
  107. 107.
    Weintraub M, Handy BM. Benzodiazepines and hip fracture: the New York State experience. Clin Pharmacol Ther 1993;54(3):252–6.Google Scholar
  108. 108.
    Rumble R, Morgan K. Hypnotics, sleep, and mortality in elderly people. J Am Geriatr Soc 1992;40(8):787–91.Google Scholar
  109. 109.
    Shorr RI, Robin DW. Rational use of benzodiazepines in the elderly. Drugs Aging 1994;4(1):9–20.Google Scholar
  110. 110.
    Yonkers KA, Kando JC, Cole JO, Blumenthal S. Gender differences in pharmacokinetics and pharmacodynamics of psychotropic medication. Am J Psychiatry 1992;149(5): 587–95.Google Scholar
  111. 111.
    Cohen LS, Heller VL, Rosenbaum JF. Treatment guidelines for psychotropic drug use in pregnancy. Psychosomatics 1989;30:25–33.Google Scholar
  112. 112.
    Cohn MA. Hypnotics and the control of breathing: a review. Br J Clin Pharmacol 1983;16:245S-250S.Google Scholar
  113. 113.
    Hanly P, Powles P. Hypnotics should never be used in patients with sleep apnoea. J Psychosom Res 1993;37 Suppl 1:59–65.Google Scholar
  114. 114.
    Steens RD, Pouliot Z, Millar TW, Kryger MH, George CF. Effects of zolpidem and triazolam on sleep and respiration in mild to moderate chronic obstructive pulmonary disease. Sleep 1993;16(4):318–26.Google Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1995

Authors and Affiliations

  • Jasper Dingemanse
    • 1
  1. 1.Department of Clinical PharmacologyF. Hoffmann-La Roche LtdBaselSwitzerland

Personalised recommendations