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Drug Safety

, Volume 26, Issue 4, pp 261–282 | Cite as

New Drugs for Insomnia

Comparative Tolerability of Zopiclone, Zolpidem and Zaleplon
  • Mario Giovanni Terzano
  • Mariano Rossi
  • Vincenzo Palomba
  • Arianna Smerieri
  • Liborio Parrino
Review Article

Abstract

Insomnia affects 30–35% of people living in developed countries. The impact of insomnia on daytime functioning and its relationship with medical and psychiatric illnesses necessitate early treatment to prevent insomnia becoming persistent and to avoid the development of complications. However, pharmacological strategies must achieve a balance between sedative and adverse effects.

In the last 30 years, benzodiazepines have been the preferred drugs for the treatment of insomnia. Benzodiazepines act nonselectively at two central receptor sites, named ω1 and ω2, which are located in different areas of the CNS. The sedative action of benzodiazepines is related to ω1 receptors, whereas ω2 receptors are responsible for their effects on memory and cognitive functioning. According to their pharmacokinetic profile, benzodiazepines can be classified into three groups: short half-life (<3 hours), medium half-life (8–24 hours) and long half-life (>24 hours).

The newer non-benzodiazepine agents zopiclone, zolpidem and zaleplon have a hypnosedative action comparable with that of benzodiazepines, but they display specific pharmacokinetic and pharmacodynamic properties. These three ‘Z’ agents all share a short plasma half-life and limited duration of action. In addition, these agents are selective compounds that interact preferentially with ω1 receptors (sedative effect), whereas benzodiazepines also interact with ω2 receptors (adverse effects on cognitive performance and memory). Zaleplon is characterised by an ultrashort half-life (approximately 1 hour). Zolpidem and zopiclone have longer half-lives (approximately 2.4 and 5 hours, respectively). These properties, together with the low risk of residual effect, may explain the limited negative influences of these agents on daytime performance. Psychomotor tasks and memory capacities appear to be better preserved by non-benzodiazepine agents than by benzodiazepines. When present, cognitive deficits almost exclusively coincide with the peak plasma concentration. In particular, impairment can emerge in the first hours after drug administration, whereas psychomotor and memory tests carried out 7–8 hours later (i.e. in the morning) generally show no relevant alterations.

As with benzodiazepines, the three ‘Z’ non-benzodiazepine agents should be used for a limited period, even in chronic relapsing conditions. Further evaluation is needed of the safety of hypnosedative medications in the long-term management of insomnia.

Keywords

Zolpidem Triazolam Zopiclone Flunitrazepam Zaleplon 
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

Acknowledgments

No sources of funding were used to assist in the preparation of this manuscript. The authors have no potential conflicts of interest that are directly relevant to the contents of this manuscript.

References

  1. 1.
    Gallup Organization. Sleep in America. Princeton (NJ): The Gallup Organization, 1991Google Scholar
  2. 2.
    Mellinger GD, Baiter MB, Uhlenhuth EH. Insomnia and its treatment: prevalence and correlates. Arch Gen Psychiatr 1985; 42: 225–32PubMedCrossRefGoogle Scholar
  3. 3.
    Sweetwood H, Grant I, Kfipke DF, et al. Sleep disorder over time: psychiatric correlates among males. Br J Psychiatr 1980; 136: 456–62CrossRefGoogle Scholar
  4. 4.
    Karacan I, Thornby JI, Anch M, et al. Prevalence of sleep disturbances in a primarily urban Florida county. Soc Sci Med 1976; 10: 239–44PubMedCrossRefGoogle Scholar
  5. 5.
    Kales JD, Kales A, Bixler EO, et al. Biopsychobehavioral correlates of insomnia, V: clinical characteristics and behavioral correlates. Am J Psychiatr 1984; 141: 1371–6PubMedGoogle Scholar
  6. 6.
    Zammit GK, Weiner J, Damato N, et al. Quality of life in people with insomnia. Sleep 1999; 22Suppl. 2: 379–85Google Scholar
  7. 7.
    American Sleep Disorders Association. The international classification of sleep disorders: diagnostic and coding manual. Lawrence (KS): Allen Press, 1990Google Scholar
  8. 8.
    Walsh JK, Fillingim JM. Role of hypnotic drugs in general practice. Am J Med 1990; 88: 345–85CrossRefGoogle Scholar
  9. 9.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed. Washington DC: American Psychiatric Association, 1994Google Scholar
  10. 10.
    Vaughn McCall W. A psychiatric perspective on insomnia. J Clin Psychiatr 2001; 62Suppl. 10: 27–32Google Scholar
  11. 11.
    Wiggs L, France K. Behavioural treatments for sleep problems in children and adolescents with physical illness, psychological problems or intellectual disabilities. Sleep Med Rev 2000: 314Google Scholar
  12. 12.
    Chouinard G, Lefko-Singh K, Teboul E. Metabolism of anxiolytics and hypnotics: benzodiazepines, buspirone, zopiclone, and zolpidem. Cell Mol Neurobiol 1999; 19(4): 532–52CrossRefGoogle Scholar
  13. 13.
    Ponciano E, Freitas F, Camara J, et al. A comparison of efficacy, tolerance and residual effects of zopiclone, flurazepam and placebo in insomniac out-patients. Int Clin Psychopharmacol 1990; 5Suppl. 2: 69–77PubMedGoogle Scholar
  14. 14.
    Billiard M, Besset A, de Lustrac C, et al. Effects of zopiclone on sleep, daytime somnolence and nocturnal and daytime performance in healthy volunteers [in French]. Neurophysiol Clin 1989; 19: 131–43PubMedCrossRefGoogle Scholar
  15. 15.
    Holbrook AM, Crowther R, Lotter A, et al. Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ 2000 Jan 25; 162(2): 225–33PubMedGoogle Scholar
  16. 16.
    Vermeeren A, Danjou PE, O’Hanlon JF. Residual effects of evening and middle-of-the-night administration of zaleplon 10mg and 20mg on memory and actual driving performance. Hum Psychopharmacol Clin Exp 1998; 13: 98–107CrossRefGoogle Scholar
  17. 17.
    Nicholson AN, Stone BM. Efficacy of zopiclone in middle age. Sleep 1997; 10(l): 35–9Google Scholar
  18. 18.
    Broadhurst A, Cushanaghan C. Residual effects of zopiclone. Sleep 1987; 10-l: 48–53Google Scholar
  19. 19.
    Billiard M, Besset A, De Lustrac C, et al. Dose response effects of zopiclone on night sleep and on nighttimes and daytime functioning. Sleep 1987; 10(l): 27–34PubMedGoogle Scholar
  20. 20.
    Tamminen T, Hansen P. Chronic administration of zopiclone and nitrazepam in the treatment of insomnia. Sleep 1987; 10Suppl l: 63–72PubMedGoogle Scholar
  21. 21.
    Elie R, Lavoie G, Bourgouin J, et al. Zopiclone versus flurazepam in insomnia: prolonged administration and withdrawal. Int Clin Psychopharmacol 1990; 5: 279–86PubMedCrossRefGoogle Scholar
  22. 22.
    Bocca ML, Le Doze F, Etard O, et al. Residual effect of zolpidem 10mg and zopiclone 7.5mg versus flunitrazepam 1mg and placebo on driving performance and ocular saccades. Psychopharmacology 1999; 143(4): 373–9PubMedCrossRefGoogle Scholar
  23. 23.
    Hajak G, Clarenbach P, Fisher W, et al. Zopiclone improves sleep quality and daytime well-being in insomniac patients: comparison with triazolam, flunitrazepam and placebo. Int Clin Psychopharmacol 1994; 9: 251–61PubMedCrossRefGoogle Scholar
  24. 24.
    Dietrich B, Emilien G, Salinas E, et al. Zaleplon does not produce residual sedation in a phase-advance model of transient insomnia [abstract]. J Sleep Res 1998; 7Suppl. 2: 67Google Scholar
  25. 25.
    Disayavanish C, Srisurapanont M, Disayavanish P, et al. Zopiclone in the treatment of insomnia: an open clinical test. J Med Assoc Thai 1998 Jun; 81-6: 393–6Google Scholar
  26. 26.
    Anderson A. Zopiclone and nitrazepam: a multicenter placebo controlled comparative study of efficacy and tolerance in 27-34 insomniac patients in general practice. Sleep 1987; 10(1): 54–62PubMedGoogle Scholar
  27. 27.
    Bianchi M, Mush B. Zopiclone discontinuation: a review of 25 studies assessing withdrawal and rebound phenomena. Int Clin Psychopharmacol 1990; 5(2): 45Google Scholar
  28. 28.
    Inman W, Kubota K, Pearl G, et al. PEM reporter number 10: zopiclone. Pharmacoepidemiol Drug Saf 1993; 2: 499–521CrossRefGoogle Scholar
  29. 29.
    Tiberge M, Calvet U, Khayi N, et al. Comparaison des effects de la zopiclone et du triazolam sur le sommeil du sujet sain. L’Encefale 1988; XIV: 319–24Google Scholar
  30. 30.
    Nakajiama T, Sasaki T, Nakagome K, et al. Comparison of the effects of zolpidem and zopiclone on nocturnal sleep and sleep latency in the morning: a cross-over study in healthy volunteers. Life Sci 2000; 67: 81–90CrossRefGoogle Scholar
  31. 31.
    Jones IR, Sullivan G. Physical dependence on zopiclone: case report. BMJ 1998; 316: 317Google Scholar
  32. 32.
    Anyonrinde O, Sampson E. Physical dependence on zopiclone: risk of dependence may be greater in those with dependent personalities. BMJ 1998; 317: 146Google Scholar
  33. 33.
    Beaumont G, Holland RL. A multicenter open study in general practice to evaluate the efficacy and acceptability of zopiclone 7.5mg nocte in patients requiring the prescription of an hypnotic. Int Clin Psychopharmacol 1990; 5(l): 11–20PubMedGoogle Scholar
  34. 34.
    Allain H, Delahaye Ch, Lecoz F, et al. Postmarketing surveillance of zopiclone in insomnia: analysis of 20,513 cases. Sleep 1991; 14(5): 408–13PubMedGoogle Scholar
  35. 35.
    Eligulashvili TS. The effects of Imovane on sleep structure and respiratory index during sleep in insomniacs patients [abstract]. Am Vein Zh Nevropatol Psikhiat Im S S Korsakova 1997; 97(4): 50–2Google Scholar
  36. 36.
    Salvà P, Costa J. Clinical pharmacokinetics and pharmacodynamics of zolpidem: therapeutic implications. Clin Pharmacokinet 1995; 29(3): 142–53PubMedCrossRefGoogle Scholar
  37. 37.
    Greenblatt DJ, Harmatz JS, von Moltke LL, et al. Comparative kinetics and dynamics of zaleplon, zolpidem, and placebo. Clin Pharmacol Ther 1998; 64(5): 553–61PubMedCrossRefGoogle Scholar
  38. 38.
    Rush CR. Behavioral pharmacology of zolpidem relative to benzodiazepines: a review. Pharmacol Biochem Behav 1998; 61(3): 253–69PubMedCrossRefGoogle Scholar
  39. 39.
    Isawa S, Suzuki M, Uchiiumi M, et al. The effects of zolpidem and zopiclone on memory. Nihon Shinkei Seishin Yakurigaku Zasshi 2000 May; 20(2): 61–9PubMedGoogle Scholar
  40. 40.
    Troy SM, Lucki I, Unruh MA, et al. Comparison of the effects of zaleplon, zolpidem, and triazolam on memory, learning, and psychomotor performance. J Clin Psychopharmacol 2000; 20(3): 328–37PubMedCrossRefGoogle Scholar
  41. 41.
    Danjou P, Paty I, Fruncillo R, et al. A comparison of the residual effects of zaleplon and zolpidem following administration 5 to 2h before awakening. J Clin Pharmacol 1999; 48: 367–74Google Scholar
  42. 42.
    Wesensten NJ, Blankin TJ, Belenky GL, et al. Reversal of triazolam and zolpidem-induced memory impairment by flumazenil. Psychopharmacology 1995; 121: 242–9PubMedCrossRefGoogle Scholar
  43. 43.
    Wesenten NJ, Blakin TJ, Belenky GL. Effects of daytime administration of zolpidem versus triazolam on memory. Eur J Clin Pharmacol 1995; 48: 115–22Google Scholar
  44. 44.
    Rush CR, Griffiths RR. Zolpidem, triazolam, and temazepam: behavioral and subject-rated effects in normal volunteers. J Clin Psychopharmacol 1996; 16: 145–57CrossRefGoogle Scholar
  45. 45.
    Giesche R, Cluydts RJ, Dingemanse J, et al. Effects of bretazenil vs zolpidem and placebo on experimentally induced sleep disturbance in healthy volunteers. Meth Find Clin Pharmacol 1994; 16(9): 667–75Google Scholar
  46. 46.
    Dujardin K, Guieu JD, Lenconte-Lambert C, et al. Comparison of the effects of zolpidem and flunitrazepam on sleep structure and daytime cognitive functions. Pharmacopsychiatry 1998; 31: 14–8PubMedCrossRefGoogle Scholar
  47. 47.
    Mintzer MZ, Frey JM, Yingling JE, et al. Triazolam and zolpidem: a comparison of their psychomotor, cognitive, and subjective effects in healthy volunteers. Behav Pharmacol 1997 Nov; 8(6-7): 561–74PubMedCrossRefGoogle Scholar
  48. 48.
    Mintzer MZ, Griffiths RR. Triazolam and zolpidem: effects on human memory and attentional processes. Psychopharmacology 1999; 144(1): 8–19PubMedCrossRefGoogle Scholar
  49. 49.
    Mintzer MZ, Griffiths RR. Selective effects of zolpidem on human memory function. J Psychopharmacol 1999; 13(1): 18–31PubMedCrossRefGoogle Scholar
  50. 50.
    Berlin I, Warot D, Hergurta T, et al. Comparison of the effects of zolpidem and triazolam on memory function, psychomotor performances, and postural sway in healthy subjects. J Clin Psychopharmacol 1993; 13: 100–6PubMedCrossRefGoogle Scholar
  51. 51.
    Wesensten NJ, Blankin TJ, Belenky GL. Effects of daytime administration of zolpidem and triazolam on performance. Aviat Space Environ Med 1996 Feb; 67(2): 115–20PubMedGoogle Scholar
  52. 52.
    Vermeeren A, O’Hanlon JF. Acute effects of zolpidem and flunitrazepam on sleep, memory and driving performance, compared to those of partial sleep deprivation and placebo. Acta Ther 1995; 21: 47–64Google Scholar
  53. 53.
    Hindmarch I, Stanley N, Paty I, et al. Comparison of the residual effects of zaleplon and zolpidem after administration during the night [abstract]. Eur Neuropsychopharmacol 2000; 10Suppl. 3: 394CrossRefGoogle Scholar
  54. 54.
    Sicard BA, Trocherie S, Moreau J, et al. Evaluation of zolpidem on alertness and psychomotor abilities among aviation ground personnel pilot. A viat. Space Environ Med 1993; 64: 371–5Google Scholar
  55. 55.
    Fleming J, Moldofsky H, Walsh JK, et al. Comparison of the residual effects and efficacy of short term zolpidem, flurazepam and placebo in patients with chronic insomnia. Clin Drug Invest 1995; 9(6): 303–13CrossRefGoogle Scholar
  56. 56.
    Richens A, Mercer AJ, Jones DM, et al. Effects of zolpidem on saccadic eye movements and psychomotor performance: a double-blind, placebo controlled study in healthy volunteers. Br J Clin Pharmacol 1993; 36: 61–5PubMedCrossRefGoogle Scholar
  57. 57.
    Hajak G, Bandelow B. Safety and tolerance of zolpidem in the treatment of disturbed sleep: a post-marketing surveillance of 16944 cases. Int Clin Psychopharmacol 1998; 13: 157–67PubMedCrossRefGoogle Scholar
  58. 58.
    Ganzoni E, Santoni J, Chevillard V, et al. Zolpidem in insomnia: a 3-year post-marketing surveillance study in Switzerland. J Int Med Res 1995; 23: 61–73PubMedGoogle Scholar
  59. 59.
    Walsh JK, Roth T, Randazzo A, et al. Eight weeks of non-nightly use of zolpidem for primary insomnia. Sleep 2000; 23(8): 1087–96PubMedGoogle Scholar
  60. 60.
    Volkerts ER, Verster JC, Van Heuckelum JHG, et al. The impact on car-driving performance of zaleplon or zolpidem administration during the night [abstract]. Eur Neuropsychopharmacol 2000; 10Suppl. 3: 395CrossRefGoogle Scholar
  61. 61.
    Sakkas P, Psarros C, Masdrakis V, et al. Dependence on zolpidem: a case report. Eur Psychiatry 1999; 14(6): 358–9PubMedCrossRefGoogle Scholar
  62. 62.
    Courtet P, Pignay V, Castelnau D, et al. Abuse and dependence on zolpidem: a report of seven cases. Encephale 1999; 25(6): 652–7PubMedGoogle Scholar
  63. 63.
    Vartzopoulos D, Bozikas V, Phocas C, et al. Dependence on zolpidem in high dose. Int Clin Psychopharmacol 2000; 15(3): 181–2PubMedCrossRefGoogle Scholar
  64. 64.
    Soyka M, Bottlender R, Moller HJ. Epidemiological evidence for a low abuse potential of zolpidem. Pharmacopsychiatry 2000; 33(4): 138–41PubMedCrossRefGoogle Scholar
  65. 65.
    Soldatos CR, Dikeos DG, Whitehead A. Tolerance and rebound insomnia with rapidly eliminated hypnotics: a meta-analysis of sleep laboratory studies. Int Clin Psychopharmacol 1999; 14: 287–303PubMedGoogle Scholar
  66. 66.
    Sanchez LGB, Sanchez JM, Moreno JLL. Dependence and tolerance with zolpidem. Am J Health-Syst Pharm 1996; 53(1): 2638PubMedGoogle Scholar
  67. 67.
    Aragona M. Abuse, dependence, and epileptic seizures after zolpidem withdrawal: review and case report. Clin Neuropharmacol 2000; 23(5): 281–3PubMedCrossRefGoogle Scholar
  68. 68.
    Monti JM, Monti D, Estevez F, et al. Sleep in patients with chronic primary insomnia during long-term zolpidem administration and after its withdrawal. Int Clin Psychopharmacol 1996; 11: 255–63PubMedCrossRefGoogle Scholar
  69. 69.
    Poirrier R, Franck G, Scheldewaert R, et al. The effects of long-term zolpidem treatment on nocturnal polysomnography and daytime vigilance in patients with psychophysiological insomnia. Acta Ther 1994; 20: 77–84Google Scholar
  70. 70.
    Scharf MB, Roth T, Vogel GW, et al. A multicenter, placebo-controlled study evaluating zolpidem in the treatment of chronic insomnia. J Clin Psychiatry 1994; 55: 192–9PubMedGoogle Scholar
  71. 71.
    Monti JM, Attali P, Monti D, et al. Zolpidem and rebound insomnia: a double-blind, controlled polysomnographic study in chronic insomniac patients. Pharmacopsychiatry 1994; 27: 166–75PubMedCrossRefGoogle Scholar
  72. 72.
    Herrmann WM, Kubiscki ST, Boden S, et al. Pilot controlled double-blind study of the hypnotic effects of zolpidem in patients with chronic learned insomnia: psychometric and polysomnographic evaluation. J Int Med Res 1993; 21: 306–22PubMedGoogle Scholar
  73. 73.
    Biondi F, Casadei GL. Results of a multicenter trial with the hypnotic zolpidem in 1152 insomniac patients. Curr Ther Res 1994 Mar; 55(3): 262–74CrossRefGoogle Scholar
  74. 74.
    Elko CJ, Burgess JL, Robertson WO. Zolpidem-associated hallucinations and serotonin reuptake inhibitor: a possible interaction. J Toxicol Clin Toxicol 1998; 36(3): 195–203PubMedCrossRefGoogle Scholar
  75. 75.
    Lahmeyer H, Wilcox CS, Kann J, et al. Subjective efficacy of zolpidem in outpatients with chronic insomnia. Clin Drug Invest 1997; 13(3): 134–44CrossRefGoogle Scholar
  76. 76.
    Shaw SH, Curson H, Coquelin JP. A double-blind, comparative study of zolpidem and placebo in the treatment of insomnia in elderly psychiatric in-patients. J Int Med Res 1992; 20: 150–61PubMedGoogle Scholar
  77. 77.
    Kummer J, Guendel L, Linden J, et al. Long term polysomnographic study of the efficacy and safety of zolpidem in elderly psychiatric in-patients with insomnia. J Int Med Res 1993; 21: 171–84PubMedGoogle Scholar
  78. 78.
    Maarek L, Cramer P, Attali P, et al. The safety and efficacy of zolpidem in insomniac patients: a long-term open study in general practice. J Int Med Res 1992; 20: 162–70PubMedGoogle Scholar
  79. 79.
    Terzano MG, Parrino L, Boselli M, et al. Sensitivity of cyclic alternating pattern to prolonged pharmacotherapy: a 5-week study evaluating zolpidem in insomniac patients. Clin Neuropharmacol 1997; 20(5): 447–54PubMedCrossRefGoogle Scholar
  80. 80.
    Cluydts R, Peeters K, de Bouyalsky I, et al. Comparison of continuous versus intermittent administration of zolpidem in chronic insomniacs: a double-blind, randomized pilot study. J Int Med Res 1998; 26: 13–24PubMedGoogle Scholar
  81. 81.
    Silvestri R, Ferrillo F, Murri L, et al. Rebound insomnia after abrupt discontinuation of hypnotic treatment: double-blind randomized comparison of zolpidem versus triazolam. Hum Psychopharmacol 1996; 11: 225–33CrossRefGoogle Scholar
  82. 82.
    Elie R, Ruther E, Farr J, et al. Zaleplon Clinical Study Group. Sleep latency is shortened during 4 weeks of treatment with zaleplon, a novel nonbenzodiazepine hypnotic. J Clin Psychiatry 1999; 60: 536–44PubMedCrossRefGoogle Scholar
  83. 83.
    Peeters K, Boucau M, De Bouyalsky I. Efficacy and safety of one-month treatment with zolpidem in a middle-aged and elderly insomniacs. Acta Ther 1997; 23: 5–19Google Scholar
  84. 84.
    Cluydts RJ, Roeck DJM. Three week multicentre general practitioner study of zolpidem in 651 patients with insomnia. Acta Ther 1993; 19: 73–90Google Scholar
  85. 85.
    Ahrens J. Treatment of sleep disorders with zolpidem: efficacy without potential dependency [in German]. Ther Schweiz 1993; 9: 660–2Google Scholar
  86. 86.
    Walsh JK, Erman M, Erwin CW, et al. Subjective hypnotic efficacy of trazodone and zolpidem in DSMIII-R primary insomnia. Hum Psychopharmacol Clin Exp 1998; 13: 191–8CrossRefGoogle Scholar
  87. 87.
    Allard S, Sainati SM, Roth-Schechter BF, et al. Coadministration of short-term zolpidem with sertraline in healthy women. J Clin Pharmacol 1998; 39: 184–91Google Scholar
  88. 88.
    Piergies AA, Sweet J, Johnson M, et al. The effects of co-administration of zolpidem with fluoxetine: pharmacokinetics and pharmacodynamics. Int J Pharmacol Ther 1996; 34(4): 178–83Google Scholar
  89. 89.
    Markowitz JS, Pharm D, Brewerton TD. Zolpidem-induced psychosis. Ann Clin Psychiatry 1996; 8(2): 89–91PubMedCrossRefGoogle Scholar
  90. 90.
    Hoyler CL, Tekell JL, Silva JA. Zolpidem-induced agitation and disorganization. Gen Hosp Psychiatry 1996; 18: 452–3PubMedCrossRefGoogle Scholar
  91. 91.
    Toner LC, Tsambiras BM, Catalano G, et al. Central nervous system side effects associated with zolpidem treatment. Clin Neuropharmacol 1999; 23(1): 54–8CrossRefGoogle Scholar
  92. 92.
    Girault C, Mihaltan MF, Borderies P, et al. Effects of repeated administration of zolpidem on sleep, diurnal and nocturnal respiratory function, vigilance, and physical performance in patients with COPD. Chest 1996 Nov; 110(5): 1203–11PubMedCrossRefGoogle Scholar
  93. 93.
    Pagot R, Cramer P, L’Heritier C, et al. Comparison of the efficacy and tolerability of zolpidem 20mg and triazolam 0.5mg in anxious or depressed insomniac patients. Curr Ther Res 1993; 53(1): 88–97CrossRefGoogle Scholar
  94. 94.
    Cohn MA. Effects of zolpidem, codeine phosphate and placebo on respiration. Drug Saf 1993; 9(4): 312–9PubMedCrossRefGoogle Scholar
  95. 95.
    Cirignotta F, Mondini S, Zucconi M, et al. Zolpidem-polysomnographic study of new hypnotic drug in sleep apnea syndrome. Pharmacol Biochem Behav 1988; 29: 807–9PubMedCrossRefGoogle Scholar
  96. 96.
    Karsenti D, Blanc P, Bacq Y, et al. Hepatotoxicity associated with zolpidem treatment. BMJ 1999; 318(7192): 1179PubMedCrossRefGoogle Scholar
  97. 97.
    Clarck A. Worsening hepatic encephalopathy secondary to zolpidem. J Pharm Technol 1999; 15: 139–41Google Scholar
  98. 98.
    Langer S, Mendelson W, Richardson G. Symptomatic treatment of insomnia. Sleep 1999; 22Suppl. 3: 437–45Google Scholar
  99. 99.
    Hajak G, Cluydts R, Declerk A, et al. Continuous versus non-nightly use of zolpidem in chronic insomnia: results of a large-scale, double-blind, randomized, outpatient study. Int Clin Psychopharmacol 2002; 17: 9–17PubMedCrossRefGoogle Scholar
  100. 100.
    Allain H, Arbus L, Schuck S, et al. Efficacy and safety of zolpidem administered ‘as needed’ in primary insomnia: results of a double-blind, placebo-controlled study. Clin Drug Invest 2001; 21 (6): 391–400Google Scholar
  101. 101.
    Krystal AD, Perlis ML, McCall WV, et al. Three-month non-nightly use of zolpidem for the treatment of primary insomnia [abstract]. Sleep 2002; 25Suppl. 2: A68Google Scholar
  102. 102.
    Cluydts R, Heyde K, De Volder F. Efficacy and safety of discontinuous zolpidem treatment - an exploratory polysomnographic study [abstract]. Sleep 2001 Apr; 24: A332Google Scholar
  103. 103.
    Weitzel KW, Wickman JM, Augustin SG, et al. Zaleplon: a pyrazolopyrimidine sedative-hypnotic agent for the treatment of insomnia. Clin Ther 2000; 22(11): 1254–67PubMedCrossRefGoogle Scholar
  104. 104.
    Cada DJ, Baker DE, Levien T. Zaleplon. Hosp Pharm 2000; 35(1): 77–86Google Scholar
  105. 105.
    Beer B, Ieni JR, Wu WH, et al. A placebo-controlled evaluation of single, escalating doses of CL 284,846, a non benzodiazepine hypnotic. J Clin Pharmacol 1994; 34(4): 335–44PubMedGoogle Scholar
  106. 106.
    Walsh JK, Fry J, Erwin CW, et al. Efficacy and tolerability of 14-day administration of zaleplon 5mg and 10mg for the treatment of primary insomnia. Clin Drug Invest 1998; 16: 347–54CrossRefGoogle Scholar
  107. 107.
    Allen D, Curran HV, Lader M. The effects of single doses of CL 284,846, lorazepam, and placebo on psychomotor and memory function in normal male volunteers. Eur J Clin Pharmacol 1993; 45: 313–20PubMedCrossRefGoogle Scholar
  108. 108.
    Walsh JK, Pollak CP, Scharf MB, et al. Lack of residual sedation following middle-of-the-night zaleplon administration in sleep maintenance insomnia. Clin Neuropharmacol 2000; 23(1): 17–21PubMedCrossRefGoogle Scholar
  109. 109.
    Walsh JK, Vogel GW, Scharf M, et al. A five week polysomnographic assessment of zaleplon 10mg for the treatment of primary insomnia. Sleep Med 2000; 1: 41–9PubMedCrossRefGoogle Scholar
  110. 110.
    Scharf M. The safety of long-term treatment of insomnia with zaleplon [abstract]. Eur Coll Neuropsych 1999; 9Suppl. 5: 360CrossRefGoogle Scholar
  111. 111.
    Elie R, Davignon M, Emilien G. Zaleplon decreases sleep latency in outpatients without producing rebound insomnia after 4 weeks of treatment [abstract]. J Sleep Res 1998; 7Suppl. 2: 76Google Scholar
  112. 112.
    Fry J, Scharf MB, Berkowitz DW, et al. A phase III, 28 day, multicenter, randomized, double-blind, comparator and placebo-controlled, parallel-group safety, tolerability, and efficacy study of 5, 10, and 20mg of zaleplon, compared with 10mg of zolpidem or placebo, in adult outpatients with insomnia [abstract]. Sleep 1998; 21Suppl.: 262Google Scholar
  113. 113.
    Rush CR, Frey JM, Griffiths RR. Zaleplon and triazolam in humans: acute behavioral effects and abuse potential. Psychopharmacology 1999; 145: 39–51PubMedCrossRefGoogle Scholar
  114. 114.
    Zaleplon (Sonata®) [package insert]. Philadelphia (PA); Wyeth Laboratories, 1999Google Scholar
  115. 115.
    Bhatia SC, Arora M, Bhatia SK. Perceptual disturbances with zaleplon. Psychiatr Serv 2001; 52(1): 109–10PubMedCrossRefGoogle Scholar
  116. 116.
    Parrino L, Terzano MG. Polysomnographic effects of hypnotic drugs. Psychopharmacology 1996; 126: 1–16PubMedCrossRefGoogle Scholar
  117. 117.
    Dooley M, Plosker GL. Zaleplon: a review of its use in the treatment of insomnia. Drugs 2000; 60(2): 413–45PubMedCrossRefGoogle Scholar
  118. 118.
    Parrino L, Smerieri A, Spaggiari MC, et al. Modifications of sleep structure in insomniac patients treated with zolpidem and zopiclone [abstract]. Sleep Res Online 1999; 2Suppl. 1: 158Google Scholar
  119. 119.
    Krakow B, Melendrez B, Ferreira E, et al. Prevalence of insomnia symptoms in patients with sleep-disordered breathing. Chest 2001; 120(6): 1923–9PubMedCrossRefGoogle Scholar
  120. 120.
    Terzano MG, Parrino L. Clinical applications of cyclic alternating pattern. Physiol Behav 1993; 54: 807–13PubMedCrossRefGoogle Scholar
  121. 121.
    Terzano MG, Parrino L. Origin and significance of the cyclic alternating pattern. Sleep Med Rev 2000; 4(1): 101–23PubMedCrossRefGoogle Scholar
  122. 122.
    World Psychiatric Association. Report of the task force on sedative hypnotics. Eur Psychiatry 1993; 8: 45–9Google Scholar
  123. 123.
    Stoller MK. Economic effects of insomnia. Clin Ther 1994; 16: 873–96PubMedGoogle Scholar
  124. 124.
    Hatoum HT, Kong SX, Kania CM, et al. Insomnia, health-related quality of life and health-care resource consumption: a study of managed-care organisation enrolees. Pharmacoeconomics 1998; 14: 629–37PubMedCrossRefGoogle Scholar
  125. 125.
    Dement WC, Pelayo R. Public health and treatment of insomnia. Eur Psychiatry 1997; 12Suppl. 1: 31s–9sCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2003

Authors and Affiliations

  • Mario Giovanni Terzano
    • 1
  • Mariano Rossi
    • 1
  • Vincenzo Palomba
    • 1
  • Arianna Smerieri
    • 1
  • Liborio Parrino
    • 1
  1. 1.Sleep Disorders Center, University of Parma, Istituto di Neurologia - UniversitàParmaItaly

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