, Volume 101, Issue 2, pp 160–167 | Cite as

Benzodiazepines and caffeine: effect on daytime sleepiness, performance, and mood

  • L. C. Johnson
  • C. L. Spinweber
  • S. A. Gomez
Original Investigations


In a double-blind parallel group design, 80 young adult males were divided into eight treatment groups. Subjects received 15 or 30 mg flurazepam, 0.25 or 0.50 mg triazolam, or placebo at bedtime, and 250 mg caffeine or placebo in the morning for 2 treatment days. Two objective (Multiple Sleep Latency Test and lapses) and two subjective (Stanford Sleepiness Scale and Visual Analog Scale) measures of sleepiness, five performance tests, and two mood measures (Profile of Mood Scale and Visual Analog Mood Scale) were administered repeatedly on both days. Significant treatment effects were found for sleepiness but not for performance or mood. Early morning caffeine significantly antagonized next day hypnotic-induced drowsiness and enhanced alertness in the subjects who received bed-time placebo. Flurazepam, 30 mg, subjects were more sleepy than all other groups. Although not significantly different, the flurazepam, 30 mg, group demonstrated a trend toward poorer performance and a more negative mood than all other groups. Caffeine most improved performance of this group. In all groups, sleepiness was greatest and performance and mood poorest in early morning trials and caffeine was most effective at this time.

Key words

Humans Benzodiazepines Caffeine Sleepiness Performance Mood 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adam K, Oswald I (1989) Can a rapidly-eliminated hypnotic cause daytime anxiety? Pharmacopsychiatry 22:115–119Google Scholar
  2. Bixler EO, Scharf MD, Soldatos CR, Miisky DJ, Kales A (1979) Effects of hypnotic drugs on memory. Life Sci 25:1379–1388Google Scholar
  3. Bixler EO, Kales A, Brubaker BH, Kakes JD (1987) Adverse reactions to benzodiazepine hypnotics: spontaneous reporting system. Pharmacology 35:286–300Google Scholar
  4. Bond AJ, Lader MH (1973) The residual effects of flurazepam. Psychopharmacology 32:223–235Google Scholar
  5. Bonnett MH, Webb WB, Barnard G (1979) Effects of flurazepam, pentobarbital, and caffeine on arousal threshold. Sleep 1:271–279Google Scholar
  6. Borbély AA, Loepfe M, Maitmann P, Tobler I (1983) Midazolam and triazolam hypnotic action and residual effects after a single bedtime dose. Arzneimittelforschung 33:1500–1502Google Scholar
  7. Brezinova V (1974) Effects of caffeine on sleep: EEG study in the late middle-age people. Br J Clin Pharmacol 1:203–208Google Scholar
  8. Broughton R (1982) Performance and evoked potential measures of various states of daytime sleepiness. Sleep 5:S135-S136Google Scholar
  9. Carskadon MA (1986) Guidelines for the multiple sleep latency test (MSLT). A standard measure of sleepiness. Sleep 9:519–524Google Scholar
  10. Carskadon MA, Dement WC (1982) The multiple sleep latency test: what does it measure? Sleep 5:S67-S72Google Scholar
  11. Carskadon MA, Seidel WF, Greenblatt DJ, Dement WC, et al. (1982) Daytime carry over of triazolam and flurazepam in elderly insomniacs. Sleep 5:364–371Google Scholar
  12. Church MW, Johnson LC (1979) Mood and performance of poor sleepers during repeated use of flurazepam. Psychopharmacology 61:309–316Google Scholar
  13. Clodore M, Foret J, Benoit O (1986) Diurnal variation in subjective and objective measures of sleepiness: the effects of sleep reduction and circadian type. Chronobiol Int 3:225–203Google Scholar
  14. Dement WC, Carskadon MA, Richardson G (1978) Excessive daytime sleepiness in the sleep apnea syndrome. In: Guilleminault C, Dement WC (eds) Sleep apnea syndromes. Liss, New York, pp 23–46Google Scholar
  15. Dows PB (1982) Caffeine. Annu Rev Nutr 2:323–341Google Scholar
  16. File SE, Bond AJ, Lister RG (1982) Interaction between effects of caffeine and lorazepam in performance testing and self-ratings. J Clin Psychopharmacol 2:102–106Google Scholar
  17. Gillin JC, Spinweber CL, Johnson LC (1989) Rebound insomnia: a critical review. J Clin Psychopharmacol 9:161–172Google Scholar
  18. Ghoneim MM, Hinrichs JV, Chiang CK, Loke WH (1986) Pharmacokinetics and pharmacodynamics interactions between caffeine and diazepam. J Clin Psychopharmacol 6:75–80Google Scholar
  19. Goldstein A, Warren R, Kaizer S (1965) Psychomotor effects of caffeine in man: I. individual difference in sensitivity to caffeine induced wakefulness. J Pharmacol Exp Ther 149:156–159Google Scholar
  20. Goodman A, Goodman LS, Rall TW, Coots A (1985) Goodman and Gilman's The pharmacological basis of therapeutics, 7th edn. McMillan, New YorkGoogle Scholar
  21. Gorenstein C, Gentil V (1983) Residual and acute effects of flurazepam and triazolam in normal subjects. Psychopharmacology 80:376–379Google Scholar
  22. Greenblatt DJ, Shader RI, Divoll M, Harmatz JS (1984) Adverse reactions to triazolam, flurazepam, and placebo in controlled clinical trials. J Clin Psychiatry 45:152–155Google Scholar
  23. Hoddes E, Zarcone V, Smythe H, Phillips R, Dement WC (1973) Quantification of sleepiness: a new approach. Psychophysiology 10:431–436Google Scholar
  24. Johnson LC, Chernik DA (1982) Sedative-hypnotics and human performance. Psychopharmacology 76:101–113Google Scholar
  25. Johnson LC, Spinweber CL, Gomez SA, Matteson LT (1989) Daytime sleepiness, performance, mood, nocturnal sleep: the effect of benzodiazepine and caffeine on their relationship. Sleep (in press)Google Scholar
  26. Johnson LC, Freeman CR, Spinweber CL, Gomez SA (1988) The subjective and objective measures of sleepiness: effect of benzodizepine and caffeine on their relationship. Psychophysiology (in press)Google Scholar
  27. Kales A, Soldatos CR, Bixler EO, Kales JD (1983) Early morning insomnia with rapidly eliminated benzodiazepines. Science 220:95–97Google Scholar
  28. Karacan I, Thornby JI, Anch AM, Booth GH, Williams RL, Solis PJ (1976) Sleep related disturbances induced by coffee and caffeine. Clin Pharmacol Ther 20:682–689Google Scholar
  29. Karacan I, Orr W, Roth T, Kramer M, Thornby J, Bingham S, Kay D (1981) Dose-related effects of flurazepam on human sleep-waking patterns. Psychopharmacology 73:332–339Google Scholar
  30. Leibowitz M, Sunchine A (1978) Long-term hypnotic efficacy and safety of triazolam and flurazepam. J Clin Pharmacol 18:302–309Google Scholar
  31. Levine B, Roehrs T, Zorick F, Roth T (1988) Daytime sleepiness in young adults. Sleep 11:39–46Google Scholar
  32. Lieberman HR, Wurtman RJ, Emde GG, Roberts C, Coviella ILG (1987) The effects of low doses of caffeine on human performance and mood. Psychopharmacology 92:308–312Google Scholar
  33. Lipschutz L, Roehrs T, Spielman A, Zwyghuizen H, Lamphere J, Roth T (1988) Caffeine's alerting effects in sleepy normals. Sleep Res 17:49Google Scholar
  34. Loke WH, Hinrichs JV, Ghoneim MM (1985) Caffeine and diazepam: separate and combined effects on mood, memory, and psychomotor performance. Psychopharmacology 87:344–350Google Scholar
  35. Lumley M, Roehrs T, Asker D, Zorick F, Roth T (1987) Ethanol and caffeine effects on daytime sleepiness/alertness. Sleep 10:306–312Google Scholar
  36. Matilla MJ, Palva E, Savolainen K (1982) Caffeine antagonizes diazepam effects in man. Med Biol 60:121–123Google Scholar
  37. Mitler MM, Seidel WF, VanDerHoed J, Greenblatt DJ, Dement WC (1984) Comparative hypnotic affects of flurazepam, triazolam, and psychopharmacology placebo: a long term simultaneous nighttime and day time study. J Clin Psychopharmacol 4:2–13Google Scholar
  38. Monk TH, Fookson JE, Kream J, Moline ML, Pollak CP, Weitzman MB (1985) Circadian factors during sustained performance: background and methodology. Behav Res Methods Instr Comput 17:19–26Google Scholar
  39. Morgan K, Oswald I (1982) Anxiety caused by a short-life hypnotic. Br Med J 284:942Google Scholar
  40. National Institute of Health Consensus Conference Report (1984) Drugs and insomnia. JAMA 251:2410–2414Google Scholar
  41. Nicholson AN, Stone BM (1981) Stimulants and sleep in man. Agressologie 22:73–78Google Scholar
  42. Ogura C, Nakazawa K, Majima K, Nakamura K, Ueda H, Umezawa Y, Wardell WM (1980) Residual effects of hypnotics: triazolam, flurazepam, and nitrazepam. Psychopharmacology 68:61–65Google Scholar
  43. Pressman MR, Fry JM (1989) Relationship of autonomic nervous system activity to daytime sleepiness and prior sleep. Sleep 12:239–245Google Scholar
  44. Richardson GS, Carskadon MA, Flagg W, Van den Hoed J, Dement WC, Mitler MM (1978) Excessive daytime sleepiness in man: multiple sleep latency measurement in narcoleptic and control subjects. Electroencephalogr Clin Neurophysiol 45:621–627Google Scholar
  45. Roehrs T, Zorick FJ, Sicklesteel JM, Wittig RM, Hartse KM, Roth T (1983) Effects of hypnotics on memory. J Clin Psychopharmacol 3:310–313Google Scholar
  46. Roehrs T, Zwyghuizen-Doorenbos A, Smith D, Zorick F, Roth T (1988) Reversal by caffeine of triazolam-induced impairment of waking function. In: Hindermach I, Ott H (eds) Benzodiazepine receptor ligands, memory and information processing. Psychopharmacology Series 6, Springer, Berlin Heidelberg New York, pp 194–202Google Scholar
  47. Roth T, Kramer M, Lutz T (1977) The effects of hypnotics on sleep performance and subjective state. Drug Exp Res 1:279–286Google Scholar
  48. Roth T, Hartse KM, Saab PG, Piccione PM, Kramer MH (1980) The effects of flurazepam, lorazepam and triazolam on sleep and memory. Psychopharmacology 70:231–237Google Scholar
  49. Seidel WF, Ball S, Cohen S, Patterson N, Yost D, Dement WC (1984) Daytime alertness in relation to mood, performance, and nocturnal sleep in chronic insomniacs and noncomplaining sleepers. Sleep 7:230–238Google Scholar
  50. Shader RI, Greenblatt DJ (1983) Triazolam and anterograde amnesia: all is not well in the Z-zone (editorial). J Clin Psychopharmacol 3:272Google Scholar
  51. Spinweber CL, Johnson LC (1982) Effects of triazolam (0.5 mg) on sleep, performance, memory, and arousal threshold. Psychopharmacology 76:5–12Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • L. C. Johnson
    • 1
  • C. L. Spinweber
    • 2
  • S. A. Gomez
    • 1
  1. 1.Naval Health Research CenterSan DiegoUSA
  2. 2.University of California at San DiegoSan DiegoUSA

Personalised recommendations