CNS Drugs

, Volume 18, Issue 5, pp 297–328 | Cite as

Residual Effects of Hypnotics

Epidemiology and Clinical Implications
  • Annemiek VermeerenEmail author
Review Article


The risk of ‘hangover’ effects, e.g. residual daytime sleepiness and impairment of psychomotor and cognitive functioning the day after bedtime administration, is one of the main problems associated with the use of hypnotics. However, the severity and duration of these effects varies considerably between hypnotics and is strongly dependent on the dose administered.

This article reviews epidemiological evidence on the effect of hypnotics on patients’ risk for accidents such as traffic accidents, falls and hip fractures (i.e. end-points for residual effects). Information on the duration and severity of residual effects of 11 hypnotics (flunitrazepam, flurazepam, loprazolam, lormetazepam, midazolam, nitrazepam, temazepam, triazolam, zaleplon, zolpidem and zopiclone) was derived from expert ratings, a meta-analysis and actual driving studies. Epidemiological studies show that the risks of an accident increase with increasing half-life of the hypnotic, but that the use of hypnotics with a short half-life, such as triazolam, zopiclone and zolpidem, can also be associated with increased risks. A summary of results from experimental studies should enable prescribing clinicians to compare residual effects of the various hypnotics at different doses and select the one considered most favourable in this respect for the individual patient. This information should also enable them to inform patients more adequately about the likelihood and duration of residual effects of a specific hypnotic dose.


Zolpidem Residual Effect Triazolam Zopiclone Oxazepam 
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.



The author has provided no information on sources of funding or on conflicts of interest directly relevant to the content of this review.


  1. 1.
    Barbone F, McMahon AD, Davey PG, et al. Association of road-traffic accidents with benzodiazepine use. Lancet 1998; 352(9137): 1331–6PubMedCrossRefGoogle Scholar
  2. 2.
    Neutel CI. Risk of traffic accident injury after a prescription for a benzodiazepine. Ann Epidemiol 1995; 5(3): 239–44PubMedCrossRefGoogle Scholar
  3. 3.
    Neutel I. Benzodiazepine-related traffic accidents in young and elderly drivers. Hum Psychopharmacol 1998; 13Suppl. 2: S115–23CrossRefGoogle Scholar
  4. 4.
    Cumming RG, Klineberg RJ. Psychotropics, thiazide diuretics and hip fractures in the elderly. Med J Aust 1993; 158: 414–7PubMedGoogle Scholar
  5. 5.
    Herings RMC, Stricker BH, De Boer A, et al. Benzodiazepines and the risk of falling leading to femur fractures: dosage more mportant than half-life. Arch Intern Med 1995; 155: 1801–7PubMedCrossRefGoogle Scholar
  6. 6.
    Lichtenstein MJ, Griffin MR, Cornell JE, et al. Risk factors for hip fractures occurring in the hospital. Am J Epidemiol 1994; 140(9): 830–8PubMedGoogle Scholar
  7. 7.
    Neutel CI, Downey W, Senet D. Medical events after a prescription for a benzodiazepine. Pharmacoepidemiol Drug Saf 1995; 4: 63–73CrossRefGoogle Scholar
  8. 8.
    Maxwell CJ, Neutel CI, Hirdes JP. A prospective study of falls after benzodiazepine use: a comparison between new and repeat use. Pharmacoepidemiol Drug Saf 1997; 6: 27–35PubMedCrossRefGoogle Scholar
  9. 9.
    Ray WA, Griffin MR, Schaffner W, et al. Psychotropic drug use and the risk of hip fracture. N Engl J Med 1987; 316(7): 363–9PubMedCrossRefGoogle Scholar
  10. 10.
    Ray WA, Griffin MR, Downey W. Benzodiazepines of long and short elimination half-life and the risk of hip fracture. JAMA 1989; 262(23): 3303–7PubMedCrossRefGoogle Scholar
  11. 11.
    ICADTS. Guidelines on experimental studies undertaken to determine a medicinal drug’s effect on driving or skills related to driving. Koeln: Bundes Anstalt fuer Strassenwesen (BASt), 1999 JunGoogle Scholar
  12. 12.
    Vermeeren A, De Gier JJ, O’Hanlon JF. Methodological guidelines for experimental research on medicinal drugs affecting riving performance: an international expert survey. Maastricht: Institute for Human Psychopharmacology, 1993. Report No.: IHP 93-127Google Scholar
  13. 13.
    Wolschrijn H, De Gier JJ, De Smet PAGM. Drugs and driving new categorization system for medicinal drugs. Maastricht: Institute for Drugs, Safety and Behavior, 1991. Report No.: IGVG 91-124Google Scholar
  14. 14.
    Berghaus G. Arzneimittel und Fahrtuechtigkeit: Metaanalyse experimenteller Studien. Bergisch Gladbach: Bundesanstalt fuer Strassenwesen, 1998. Report No.: FP 2.9108Google Scholar
  15. 15.
    O’Hanlon JF, Haak TW, Blaauw GJ, et al. Diazepam impairs lateral position control in highway driving. Science 1982; 217(4554): 79–81PubMedCrossRefGoogle Scholar
  16. 16.
    O’Hanlon JF. Driving performance under the influence of drugs: rationale for, and application of, a new test. Br J Clin Pharmacol 1984; 18Suppl. 1: 121s–9PubMedCrossRefGoogle Scholar
  17. 17.
    Patat A, Paty I, Hindmarch I. Pharmacodynamic profile of zaleplon, a new non-benzodiazepine hypnotic agent. Hum Psychopharmacol 2001; 16(5): 369–92PubMedCrossRefGoogle Scholar
  18. 18.
    Goa KL, Heel RC. Zopiclone: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy as a hypnotic [update of 1986]. Drugs 1991; 32: 48–65CrossRefGoogle Scholar
  19. 19.
    O’Hanlon JF. Zopiclone’s residual effects on psychomotor and information processing skills involved in complex tasks such as car driving: a critical review. Eur Psychiatry 1995; 10Suppl. 3: 137s–43PubMedCrossRefGoogle Scholar
  20. 20.
    Nicholson AN. Residual sequelae of zopiclone. Rev Contemp Pharmacother 1998; 9(2): 123–9Google Scholar
  21. 21.
    Noble S, Langtry HD, Lamb HM. Zopiclone: an update of its pharmacology, clinical efficacy and tolerability in the treatment of insomnia. Drugs 1998; 55(2): 277–302PubMedCrossRefGoogle Scholar
  22. 22.
    Langtry HD, Benfield P. Zolpidem: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential. Drugs 1990; 40(2): 291–313PubMedCrossRefGoogle Scholar
  23. 23.
    Rush CR. Behavioral pharmacology of zolpidem relative to benzodiazepines: a review. Pharmacol Biochem Behav 1998; 61(3): 253–69PubMedCrossRefGoogle Scholar
  24. 24.
    Johnson LC, Chernik DA. Sedative-hypnotics and human performance. Psychopharmacology 1982; 76: 101–13PubMedCrossRefGoogle Scholar
  25. 25.
    Roth T, Roehrs T. Determinants of residual effects of hypnotics. Accid Anal Prev 1985; 17(4): 291–6PubMedCrossRefGoogle Scholar
  26. 26.
    Roth T, Roehrs TA. A review of the safety profiles of benzodiazepinehypnotics. J Clin Psychiatry 1991; 52 Suppl.: 38–41PubMedGoogle Scholar
  27. 27.
    Roth T, Roehrs TA, Stepanski EJ, et al. Hypnotics and behavior.Am J Med 1990; 88(3a): 43s–6PubMedCrossRefGoogle Scholar
  28. 28.
    Van Laar MW, Volkerts ER. Driving and benzodiazepine use:evidence that they do not mix. CNS Drugs 1998; 10(5):383–96CrossRefGoogle Scholar
  29. 29.
    Leger D, Guilleminault C, Dreyfus JP, et al. Prevalence ofnsomnia in a survey of 12,778 adults in France. J Sleep Res 2000; 9(1): 35–42PubMedCrossRefGoogle Scholar
  30. 30.
    Baiter MB, Manheimer DI, Mellinger GD, et al. A cross-nationalcomparison of anti-anxiety/sedative drug use. Curr Med Res Opin 1984; 8 Suppl. 4: 5–20Google Scholar
  31. 31.
    Mellinger GD, Balter MB, Uhlenhuth EH. Insomnia and itstreatment: prevalence and correlates. Arch Gen Psychiatry 1985; 42(3): 225–32PubMedCrossRefGoogle Scholar
  32. 32.
    Pallesen S, Nordhus IH, Nielsen GH, et al. Prevalence ofinsomnia in the adult Norwegian population. Sleep 2001; 24(7): 771–9PubMedGoogle Scholar
  33. 33.
    Simon GE, VonKorff M. Prevalence, burden, and treatment ofinsomnia in primary care. Am J Psychiatry 1997; 154(10):1417–23PubMedGoogle Scholar
  34. 34.
    Ohayon MM, Roth T. What are the contributing factors forinsomnia in the general population? J Psychosom Res 2001; 51(6): 745–55PubMedCrossRefGoogle Scholar
  35. 35.
    Ancoli-Israel S, Roth T. Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. I. Sleep 1999; 22Suppl. 2: S347–53PubMedGoogle Scholar
  36. 36.
    Christer GM, Hublin CGM, Partinen MM. The extent andimpact of insomnia as a public health problem. Primary Care Companion J Clin Psychiatry 2002; 4 Suppl. 1: 8–12Google Scholar
  37. 37.
    Reite MD. Treatment of insomnia. In: Schatzberg AF, Nemeroff CB, editors. Textbook of psychopharmacology. 2nd ed. Washington,DC: American Psychiatric Press Inc., 1998: 997–1014Google Scholar
  38. 38.
    Benca RM. Consequences of insomnia and its therapies. J Clin Psychiatry 2001; 62 Suppl. 10: 33–8Google Scholar
  39. 39.
    Bond AJ, Lader MH. Residual effects of hypnotics. Psychopharmacology 1972; 25(2): 117–32CrossRefGoogle Scholar
  40. 40.
    Bond AJ, Lader MH. The residual effects of flurazepam.Psychopharmacology 1973; 32(3): 223–35CrossRefGoogle Scholar
  41. 41.
    Bond AJ, Lader MH. Residual effects of flunitrazepam. Br J Clin Pharmacol 1975; 2(2): 143–50PubMedCrossRefGoogle Scholar
  42. 42.
    Borland RG, Nicholson AN. Comparison of the residual effects of two benzodiazepines (nitrazepam and flurazepam hydrochloride) and pentobarbitone sodium on human performance. Br J Clin Pharmacol 1975; 2(1): 9–17PubMedGoogle Scholar
  43. 43.
    Hindmarch I. A repeated dose comparison of three benzodiazepine derivative (nitrazepam, flurazepam and flunitrazepam) on subjective appraisals of sleep and measures of psychomotor performance the morning following night-time medication.Acta Psychiatr Scand 1977; 56(5): 373–81PubMedCrossRefGoogle Scholar
  44. 44.
    Hindmarch I. Effects of hypnotic and sleep-inducing drugs on objective assessments of human psychomotor performanceand subjective appraisals of sleep and early morning behaviour.Br J Clin Pharmacol 1979; 8(1): 43s–6sPubMedCrossRefGoogle Scholar
  45. 45.
    Hindmarch I, Clyde CA. The effects of triazolam and nitrazepamon sleep quality, morning vigilance and psychomotorperformance. Arzneimittel Forschung 1980; 30(7): 1163–6PubMedGoogle Scholar
  46. 46.
    Aranko K, Mattila MJ, Seppala T. Development of toleranceand cross-tolerance to the psychomotor actions of lorazepamand diazepam in man. Br J Clin Pharmacol 1983; 15(5):545–52PubMedCrossRefGoogle Scholar
  47. 47.
    Gillin JC, Spinweber CL, Johnson LC. Rebound insomnia: acritical review. J Clin Psychopharmacol 1989; 9(3): 161–72PubMedCrossRefGoogle Scholar
  48. 48.
    Kales A, Soldatos CR, Bixler EO, et al. Rebound insomnia andrebound anxiety: a review. Pharmacology 1983; 26(3): 121–37PubMedCrossRefGoogle Scholar
  49. 49.
    Hurst M, Noble S. Zaleplon. CNS Drugs 1999; 11(5): 387–92CrossRefGoogle Scholar
  50. 50.
    Lapeyre-Mestre M, Chastan E, Louis A, et al. Drug consumptionin workers in France: a comparative study at a 10-yearinterval (1996 versus 1986). J Clin Epidemiol 1999; 52(5):471–8PubMedCrossRefGoogle Scholar
  51. 51.
    Walsh JK, Schweitzer PK. Ten-year trends in the pharmacologicaltreatment of insomnia. Sleep 1999; 22(3): 371–5PubMedGoogle Scholar
  52. 52.
    Doghramji K. The need for flexibility in dosing of hypnoticagents. Sleep 2000; 23Suppl. 1: s16–20PubMedGoogle Scholar
  53. 53.
    Kirkwood CK. Management of insomnia. J Am Pharm Assoc 1999; 39(5): 688–96Google Scholar
  54. 54.
    Ohayon MM, Caulet M. Insomnia and psychotropic drug consumption.Prog Neuropsychopharmacol Biol Psychiatry 1995;19(3): 421–31PubMedCrossRefGoogle Scholar
  55. 55.
    Ohayon MM, Caulet M, Guilleminault C. How a general populationperceives its sleep and how this relates to the complaintof insomnia. Sleep 1997; 20(9): 715–23PubMedGoogle Scholar
  56. 56.
    Ohayon MM, Caulet M, Priest RG, et al. Psychotropic medicationconsumption patterns in the UK general population. J Clin Epidemiol 1998; 51(3): 273–83PubMedCrossRefGoogle Scholar
  57. 57.
    Ohayon MM, Vecchierini MF. Daytime sleepiness and cognitiveimpairment in the elderly population. Arch Intern Med 2002; 162(2): 201–8PubMedCrossRefGoogle Scholar
  58. 58.
    Roehrs T, Hollebeek E, Drake C, et al. Substance use forinsomnia in Metropolitan Detroit. J Psychosom Res 2002; 53(1): 571–6PubMedCrossRefGoogle Scholar
  59. 59.
    Weyerer S, Dilling H. Prevalence and treatment of insomnia in the community: results from the Upper Bavarian Field Study.Sleep 1991; 14(5): 392–8PubMedGoogle Scholar
  60. 60.
    Bader G, Ohayon MM. Insomnia in the general population ofSweden. J Sleep Res 2002; 11 Suppl. 1: 10–1Google Scholar
  61. 61.
    Ohayon MM, Lader MH. Use of psychotropic medication in thegeneral population of France, Germany, Italy, and the United Kingdom. J Clin Psychiatry 2002; 63(9): 817–25PubMedCrossRefGoogle Scholar
  62. 62.
    Nowell PD, Buysse DJ, Reynolds 3rd CF, et al. Clinical factorscontributing to the differential diagnosis of primary insomniaand insomnia related to mental disorders. Am J Psychiatry 1997; 154(10): 1412–6PubMedGoogle Scholar
  63. 63.
    Doble A. New insights into the mechanism of action of hypnotics.J Psychopharmacol 1999; 13(4 Suppl. 1): S11–20PubMedGoogle Scholar
  64. 64.
    Landolt H-P, Gillin JC. GABA-A1a receptors: involvement insleep regulation and potential of selective agonists in thetreatment of insomnia. CNS Drugs 2000; 13(3): 185–99CrossRefGoogle Scholar
  65. 65.
    Moehler H, Fritschy JM, Rudolph U. A new benzodiazepinepharmacology. J Pharmacol Exp Ther 2002; 300(1): 2–8CrossRefGoogle Scholar
  66. 66.
    McKernan RM, Rosahl TW, Reynolds DS, et al. Sedative butnot anxiolytic properties of benzodiazepines are mediated bythe GABA (A) receptor alphal subtype. Nat Neurosci 2000; 3(6): 587–92PubMedCrossRefGoogle Scholar
  67. 67.
    Hardman JG, Limbird LE, Gilman A. Goodman and Gillman’s:the pharmacological basis of therapeutics. 10th ed. New York: MacMillan, 2001Google Scholar
  68. 68.
    Neutel CI, Hirdes JP, Maxwell CJ. New evidence on benzodiazepineuse and falls: the time factor. Age Ageing 1996; 25: 273–8PubMedCrossRefGoogle Scholar
  69. 69.
    Herings RMC. Geneesmiddelen als determinant van ongevallen.Utrecht: Universiteit Utrecht, Faculteit Farmacie, 1994Google Scholar
  70. 70.
    Passaro A, Volpato S, Romagnoni F, et al. Benzodiazepineswith different half-life and falling in a hospitalized population:The GIFA study. Gruppo Italiano di Farmacovigilanza nell’Anziano.J Clin Epidemiol 2000; 53(12): 1222–9Google Scholar
  71. 71.
    Pierfitte C, Macouillard G, Thicoipe M, et al. Benzodiazepinesand hip fractures in elderly people: case-control study. BMJ 2001; 322(7288): 704–8PubMedCrossRefGoogle Scholar
  72. 72.
    Ray WA, Fought RL, Decker MD. Psychoactive drugs and therisk of injurious motor vehicle crashes in elderly drivers. Am JEpidemiol 1992; 136: 873–83CrossRefGoogle Scholar
  73. 73.
    Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in olderpeople: a systematic review and meta-analysis: I. psychotropicdrugs. J Am Geriatr Soc 1999; 47(1): 30–9Google Scholar
  74. 74.
    Neutel CI, Perry S, Maxwell C. Medication use and risk of falls.Pharmacoepidemiol Drug Saf 2002; 11(2): 97–104PubMedCrossRefGoogle Scholar
  75. 75.
    De Gier JJ. Review of investigations of prevalence of illicitdrugs in road traffic in diffrent European countries. In: Group P, editor. Road traffic and drugs; 1999. Strasbourg: Council ofEurope, 1999: 13–60Google Scholar
  76. 76.
    Longo MC, Hunter CE, Lokan RJ, et al. The prevalence ofalcohol, cannabinoids, benzodiazepines and stimulantsamongst injured drivers and their role in driver culpability: parti: the prevalence of drug use in drive the drug-positive group.Accid Anal Prev 2000; 32(5): 613–22PubMedCrossRefGoogle Scholar
  77. 77.
    Longo MC, Hunter CE, Lokan RJ, et al. The prevalence ofalcohol, cannabinoids, benzodiazepines and stimulantsamongst injured drivers and their role in driver culpability: partII: the relationship between drug prevalence and drug concentration,and driver culpability. Accid Anal Prev 2000; 32(5):623–32PubMedCrossRefGoogle Scholar
  78. 78.
    Honkanen R, Ertama L, Linnoila M, et al. Role of drugs intraffic accidents. BMJ 1980; 281: 1309–12PubMedCrossRefGoogle Scholar
  79. 79.
    Skegg DCG, Richards SM, Doll R. Minor tranquilisers and roadaccidents. BMJ 1979; 1(6168): 917–9PubMedCrossRefGoogle Scholar
  80. 80.
    Hemmelgarn B, Suissa S, Huang A, et al. Benzodiazepine useand the risk of motor vehicle crash in the elderly. JAMA 1997;278(1): 27–31PubMedCrossRefGoogle Scholar
  81. 81.
    Leveille SG, Buchner DM, Koepsell TD, et al. Psychoactivemedications and injurious motor vehicle collisions involvingolder drivers. Epidemiology 1994; 5(6): 591–8PubMedCrossRefGoogle Scholar
  82. 82.
    Vermeeren A, Danjou PE, O’Hanlon JF. Residual effects ofevening and middle-of-the-night administration of zaleplon 10and 20mg on memory and actual driving performance. Hum Psychopharmacol 1998; 13 Suppl. 2: S98–107CrossRefGoogle Scholar
  83. 83.
    Vermeeren A, Riedel WJ, Van Boxtel CJ, et al. Differentialresidual effects of zaleplon and zopiclone on actual driving: acomparison with a low dose of alcohol. Sleep 2002; 25(2):224–31PubMedGoogle Scholar
  84. 84.
    Volkerts ER, O’Hanlon JF. Residu effecten op de actuele rijprestatie:zopiclone versus flunitrazepam en nitrazepam (Residualeffects on real car driving performance: zopiclone versus flunitrazepamand nitrazepam; Dutch with English summary andlegends). J Drug Ther Res 1988; 13: 111–4Google Scholar
  85. 85.
    Bramness JG, Skurtveit S, Morland J. Zopiklonfunn hos mangebilforere-tegn pa feilbruk og misbruk. Tidsskr Nor Laegeforen 1999; 119(19): 2820–1PubMedGoogle Scholar
  86. 86.
    Cumming RG, Le Couteur DG. Benzodiazepines and risk of hipfractures in older people: a review of the evidence. CNS Drugs 2003; 17: 825–37PubMedCrossRefGoogle Scholar
  87. 87.
    Tromp AM, Pluijm SM, Smit JH, et al. Fall-risk screening test:a prospective study on predictors for falls in community-dwellingelderly. J Clin Epidemiol 2001; 54(8): 837–44PubMedCrossRefGoogle Scholar
  88. 88.
    Ray WA, Thapa PB, Gideon P. Benzodiazepines and the risk offalls in nursing home residents. J Am Geriatr Soc 2000; 48(6):682–5PubMedGoogle Scholar
  89. 89.
    Ray WA, Thapa PB, Gideon P. Misclassification of currentbenzodiazepine exposure by use of single baseline measurementand its effects upon studies of injuries.Pharmacoepidemiol Drug Saf 2002; 11(11): 1–7Google Scholar
  90. 90.
    Mendelson WB. The use of sedative/hypnotic medication andits correlation with falling down in the hospital. Sleep 1996; 19(9): 698–701PubMedGoogle Scholar
  91. 91.
    Lord SR, Anstey KJ, Williams P, et al. Psychoactive medicationuse, sensori-motor function and falls in older women.Br J Clin Pharmacol 1995; 39(3): 227–34PubMedCrossRefGoogle Scholar
  92. 92.
    Cumming RG, Miller JP, Kelsey JL, et al. Medications andmultiple falls in elderly people: the St Louis OASIS Study.Age Ageing 1991; 20: 455–61PubMedCrossRefGoogle Scholar
  93. 93.
    Campbell AJ, Borrie MJ, Spears GF. Risk factors for falls in acommunity-based prospective study of people 70 years andolder. J Gerontol A Biol Sci Med Sci 1989; 44(4): 112–7Google Scholar
  94. 94.
    Granek E, Baker SP, Abbey H, et al. Medications and diagnosesin relation to falls in a long-term care facility. J Am Geriatr Soc 1987; 35(6): 503–11PubMedGoogle Scholar
  95. 95.
    Wang PS, Bohn RL, Glynn RJ, et al. Zolpidem use and hipfractures in older people. J Am Geriatr Soc 2001; 49(12):1685–90PubMedCrossRefGoogle Scholar
  96. 96.
    Sgadari A, Lapane KL, Mor V, et al. Oxidative and nonoxidative benzodiazepines and the risk of femur fracture: the Systematic Assessment of Geriatric Drug Use Via Epidemiology Study Group. J Clin Psychopharmacol 2000; 20(2): 234–9PubMedCrossRefGoogle Scholar
  97. 97.
    Blake AJ, Morgan K, Bendall MJ, et al. Falls by elderly peopleat home: prevalence and associated factors. Age Ageing 1988;17(6): 365–72PubMedCrossRefGoogle Scholar
  98. 98.
    Riedel WJ, Vermeeren A, Van Boxtel MPJ, et al. Mechanismsof drug-induced driving impairment: a dimensional approach.Hum Psychopharmacol 1998; 13Suppl. 2: S49–63CrossRefGoogle Scholar
  99. 99.
    O’Hanlon JF, Ramaekers JG. Antihistamine effects on actualdriving performance in a standard test: a summary of Dutchexperience, 1989–94. Allergy 1995; 50(3): 234–42PubMedCrossRefGoogle Scholar
  100. 100.
    O’Hanlon JF, Vermeeren A, Uiterwijk MM, et al. Anxiolytics’effects on the actual driving performance of patients andhealthy volunteers in a standardized test: an integration ofthree studies. Neuropsychobiol 1995; 31(2): 81–8CrossRefGoogle Scholar
  101. 101.
    Louwerens JW, Gloerich ABM, De Vries G, et al. The relationshipbetween drivers’ blood alcohol concentration (BAC) andactual driving performance during high speed travel. In:Noordzij PC, Roszbach R, editors. International congress onalcohol, drugs and traffic safety, T86; 1987. Amsterdam: ExerptaMedica, 1987: 183–6Google Scholar
  102. 102.
    Borkenstein RF. The role of the drinking driver in traffic accidents,the Grand Rapids study. 2nd ed. Blutalcohol 1974; 11Suppl. 1: 1–131Google Scholar
  103. 103.
    Vermeeren A, O’Hanlon JF, Declerck AC, et al. Acute effectsof zolpidem and flunitrazepam on sleep, memory and drivingperformance, compared to those of partial sleep deprivationand placebo. Acta Ther 1995; 21: 47–64Google Scholar
  104. 104.
    Verster JC, Volkerts ER, Schreuder AH, et al. Residual effectsof middle-of-the-night administration of zaleplon and zolpidemon driving ability, memory functions, and psychomotorperformance. J Clin Psychopharmacol 2002; 22: 576–83PubMedCrossRefGoogle Scholar
  105. 105.
    O’Hanlon JF, Volkerts ER. Hypnotics and actual driving performance.Acta Psychiatr Scand Suppl 1986; 332: 95–104PubMedCrossRefGoogle Scholar
  106. 106.
    Volkerts ER, Van Laar MW, Van Willigenburg AP, et al. Acomparative study of on-the-road and simulated driving performanceafter nocturnal treatment with lormetazepam 1mgand oxazepam 50mg. Hum Psychopharmacol 1992; 7(5):297–309CrossRefGoogle Scholar
  107. 107.
    Brookhuis KA, Volkerts ER, O’Hanlon JF. Repeated dose effectsof lormetazepam and flurazepam upon driving performance.Eur J Clin Pharmacol 1990; 39(1): 83–7PubMedCrossRefGoogle Scholar
  108. 108.
    Volkerts ER, O’Hanlon JF. Hypnotics’ residual effects on drivingperformance. In: O’Hanlon JF, De Gier JJ, editors. Drugsand driving. London: Taylor Francis, 1986Google Scholar
  109. 109.
    O’Hanlon JF. Alcohol and hypnotic hangovers as an influenceon driving performance. Trav Traf Med Int 1983; 1(3): 147–52Google Scholar
  110. 110.
    Vermeeren A, Ramaekers JG, Van Leeuwen CJ, et al. Residualeffects on actual car driving of evening dosing ofchlorpheniramine 8 and 12mg when use with terfenadine 60mgin the morning. Hum Psychopharmacol 1998; 13Suppl. 2:S79–86CrossRefGoogle Scholar
  111. 111.
    Brookhuis KA, Volkerts ER, O’Hanlon JF. Repeated dose effectsof lormetazepam 1 and 2mg (in soft gelatine capsules)and flurazepam 30mg upon driving performance [Report VK86-18]. Haren: Traffic Research Centre, 1986. Report No.: VK86-18Google Scholar
  112. 112.
    Riedel WJ, Quasten R, Hausen C, et al. A study comparing thehypnotic efficacies and residual effects on actual driving performanceof midazolam 15mg, triazolam 0.5mg, temazepam20mg and placebo in shiftworkers on night duty. Technicalreport. Maastricht: Institute for Drugs Safety and Behavior,1988. Report No.: IGVG 88-01Google Scholar
  113. 113.
    Mclnnes GT, Bunting EA, Ings RM, et al. Pharmacokineticsand pharmacodynamics following single and repeated nightlyadministrations of loprazolam, a new benzodiazepine hypnotic.Br J Clin Pharmacol 1985; 19(5): 649–56CrossRefGoogle Scholar
  114. 114.
    Danjou P, Paty I, Fruncillo R, et al. A comparison of theresidual effects of zaleplon and zolpidem following administration5 to 2h before awakening. Br J Clin Pharmacol 1999; 48(3): 367–74PubMedCrossRefGoogle Scholar
  115. 115.
    Hindmarch I, Patat A, Stanley N, et al. Residual effects ofzaleplon and zolpidem following middle of the night administrationfive hours to one hour before awakening. Hum Psychopharmacol 2001; 16: 159–67PubMedCrossRefGoogle Scholar
  116. 116.
    Troy SM, Lucki I, Unruh MA, et al. Comparison of the effectsof zaleplon, zolpidem, and triazolam on memory, learning, andpsychomotor performance. J Clin Psychopharmacol 2000; 20(3): 328–37PubMedCrossRefGoogle Scholar
  117. 117.
    Stone BM, Turner C, Mills SL, et al. Sleep in a noisy environment:hypnotic and residual effects of zaleplon [abstract]. JSleep Res 2000; 9 Suppl. 1: 183Google Scholar
  118. 118.
    O’Hanlon JF. Residual effects on memory and psychomotorperformance of zaleplon and other hypnotic drugs. Prim CareCompanion J Clin Psychiatry 2002; 4 Suppl. 1: 38–44Google Scholar
  119. 119.
    Darcourt G, Pringuey D, Salliere D, et al. The safety andtolerability of zolpidem: an update. J Psychopharmacol 1999;3(1): 81–93CrossRefGoogle Scholar
  120. 120.
    Lader M, Hindmarch I. Memory, psychomotor and cognitivefunctions after treatment with zolpidem. In: Freeman H, Puech AJ, Roth T, editors. Zolpidem: un update of its pharmacologicalproperties and therapeutic place in management of insomnia.Paris: Elsevier, 1996Google Scholar
  121. 121.
    Unden M, Roth Schechter B. Next day effects after nighttimetreatment with zolpidem: a review. Eur Psychiatry 1996; 11Suppl. 1: S21–30CrossRefGoogle Scholar
  122. 122.
    Erman MK, Erwin CW, Gengo FM, et al. Comparative efficacyof zolpidem and temazepam in transient insomnia. Hum Psychopharmacol 2001; 16: 169–76PubMedCrossRefGoogle Scholar
  123. 123.
    Zammit G. Zaleplon vs zolpidem: differences in next-dayresidual sedation after middle-of-the-night administration [abstract].J Sleep Res 2000; 9Suppl. 1: 214Google Scholar
  124. 124.
    Cluydts R, De Roeck J, Schotte C, et al. Comparative study onthe residual daytime effects of flunitrazepam, triazolam, andplacebo in healthy volunteers. Acta Ther 1986; 12: 205–17Google Scholar
  125. 125.
    Lobo BL, Greene WL. Insomnia. N Engl J Med 1997; 336(26):1919–20PubMedCrossRefGoogle Scholar
  126. 126.
    Mintzer MZ, Frey JM, Yingling JE, et al. Triazolam andzolpidem: a comparison of their psychomotor, cognitive, andsubjective effects in healthy volunteers. Behav Pharmacol1997; 8(6–7): 561–74PubMedCrossRefGoogle Scholar
  127. 127.
    Rush CR, Griffiths RR. Zolpidem, triazolam, and temazepam:behavioral and subject-rated effects in normal volunteers. JClin Psychopharmacol 1996; 16(2): 146–57CrossRefGoogle Scholar
  128. 128.
    Moskowitz H, Linnoila M, Roehrs T. Psychomotor performancein chronic insomniacs during 14-day use of flurazepam andmidazolam. J Clin Psychopharmacol 1990; 104Suppl. 4: 44s–55Google Scholar
  129. 129.
    Jackson JL, Louwerens JW, Cnossen F, et al. Testing the effectsof hypnotics on memory via the telephone: fact or fiction? Psychopharmacology 1993; 111(2): 127–33PubMedCrossRefGoogle Scholar
  130. 130.
    Godtlibsen OB, Jerko D, Gordeladze JO, et al. Residual effectof single and repeated doses of midazolam and nitrazepam inrelation to their plasma concentrations. Eur J Clin Pharmacol 1986; 29: 595–600CrossRefGoogle Scholar
  131. 131.
    Borbely AA, Mattmann P, Loepfe M. Hypnotic action andresidual effects of a single bedtime dose of temazepam.Arzneimittel Forschung 1984; 34(1): 101–3PubMedGoogle Scholar
  132. 132.
    Hemmeter U, Muller M, Bischof R, et al. Effect of zopicloneand temazepam on sleep EEG parameters, psychomotor andmemory functions in healthy elderly volunteers. Psychopharmacology 2000; 147(4): 384–96PubMedCrossRefGoogle Scholar
  133. 133.
    Hindmarch I. Hypnotics and residual sequalae. In: Nicholson AN, editor. Hypnotics in clinical practice. Edinburgh: MedicinePublishing Foundation, 1982: 7–16Google Scholar
  134. 134.
    Porcu S, Bellatreccia A, Ferrara M, et al. Performance, abilityto stay awake, and tendency to fall asleep during the night aftera diurnal sleep with temazepam or placebo. Sleep 1997; 20(7):535–41PubMedGoogle Scholar
  135. 135.
    Warburton DM, Wesnes K. A comparison of temazepam andflurazepam in terms of sleep quality and residual changes inactivation and performance. Arzneimittel Forschung 1984; 34(11): 1601–4PubMedGoogle Scholar
  136. 136.
    Volkerts ER, Abbink F. Kater-effecten op de rijvaardigheid naslaapmiddelgebruik? Lormetazepam en oxazepam versus placebo(Hangover effects on driving performance following useof hypnotics?). J Drug Ther Res 1990; 15(1): 22–6Google Scholar
  137. 137.
    Bourin M, Hubert C, Colombel MC, et al. Residual effects oftemazepam versus nitrazepam on memory and vigilance in thenormal subject. Hum Psychopharmacol 1987; 2: 185–9CrossRefGoogle Scholar
  138. 138.
    Laurell H, Tornros J. The carry-over effects of triazolam comparedwith nitrazepam and placebo in acute emergency drivingsituations and in monotonous simulated driving. Acta Pharmacol Toxicol (Copenh) 1986; 58(3): 182–6CrossRefGoogle Scholar
  139. 139.
    Morgan K. Effects of repeated dose nitrazepam andlormetazepam on psychomotor performance in the elderly.Psychopharmacology 1985; 86(1–2): 209–11PubMedCrossRefGoogle Scholar
  140. 140.
    Subhan Z, Hindmarch I. Asessing residual effects of benzodiazepineson short term memory. Pharm Med 1984; 1: 27–32Google Scholar
  141. 141.
    Woods JH, Winger G. Abuse liability of flunitrazepam. J Clin Psychopharmacol 1997; 17(3 Suppl. 2): 1s–57PubMedCrossRefGoogle Scholar
  142. 142.
    Carvey PM. Drug action in the central nervous system. NewYork: Oxford University Press, 1998Google Scholar
  143. 143.
    Roehrs T, Kribbs N, Zorick F, et al. Hypnotic residual effects ofbenzodiazepines with repeated administration. Sleep 1986; 9(2): 309–16PubMedGoogle Scholar
  144. 144.
    Menzin J, Lang KM, Levy P, et al. A general model of theeffects of sleep medications on the risk and cost of motorvehicle accidents and its application to France. Pharmacoeconomics 2001; 19(1): 69–78PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Experimental Psychopharmacology Unit, Brain & Behaviour Institute, Faculty of PsychologyMaastricht UniversityMaastrichtThe Netherlands

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