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Effects of single doses of alprazolam and diazepam, alone and in combination with ethanol, on psychomotor and cognitive performance and on autonomic nervous system reactivity in healthy volunteers

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Summary

Effects of alprazolam, alone and in combination with ethanol, on psychomotor and cognitive performance were studied in healthy male volunteers and compared to effects of diazepam.

Alprazolam 2 mg produced relatively long-lasting impairments on tests of tracking, verbal and nonverbal information processing, and memory, and decreased blood pressure without a change in heart rate or plasma norepinephrine levels.

Although ethanol consumption was demonstrated to produce additive decrements in performance on certain tasks, there was little evidence to support a synergistic effect. Alprazolam 2 mg was accompanied by increased selfreports of side effects, especially drowsiness.

Low dose alprazolam, diazepam, and ethanol produced significantly fewer side effects than 2 mg alprazolam, but significantly more than placebo.

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References

  1. Hollister LE (1982) Second-generation antidepressants. Ration DrugTher 16:1–5

    Google Scholar 

  2. Abernethy DR, Greenblatt DJ, Divoll M, Shader RI (1983) Pharmacokinetics of alprazolam. J Clin Psychiatry 44:45–47

    PubMed  CAS  Google Scholar 

  3. Eberts FS Jr, Philopoulos Y, Reineke LM, Vliek RW (1980) Dis- position of 14C-alprazolam, a new anxiolytic-antidepressant, in man. Pharmacologist 22:279

    Google Scholar 

  4. Greenblatt DJ, Divoll M, Abernethy DR, Ochs HR, Shader RI (1983) Clinical pharmacokinetics of the newer benzodiazepines. Clin Pharmacokinet 8:233–252

    PubMed  CAS  Google Scholar 

  5. Dawson GW, Jue SG, Brogden RN (1984) Alprazolam: A review of its pharmacodynamic properties and efficacy in the treatment of anxiety and depression. Drugs 27:132–147

    PubMed  CAS  Google Scholar 

  6. Fawcett JA, Kravitz HM (1982) Alprazolam: Pharmacokinetics, clinical efficacy, and mechanisms of action. Pharmacotherapy 2: 243–254

    PubMed  CAS  Google Scholar 

  7. Van Voigtlander PF, Straw RN (1985) Alprazolam: A review of pharmacological, pharmacokinetic and clinical data. Drug De- velop Res 6:1–12

    Article  Google Scholar 

  8. Aden GC, Thein SG Jr (1980) Alprazolam compared to diaze- pam and placebo in the treatment of anxiety. J Clin Psychiatry 41: 245–248

    PubMed  CAS  Google Scholar 

  9. Cohn JB (1981) Multicenter double-blind efficacy and safety study comparing alprazolan, diazepam and placebo in clinically anxious patients. J Clin Psychiatry 42:347–351

    PubMed  CAS  Google Scholar 

  10. Fabre LF, McLendon DM (1979) A double-blind study compar- ing the efficacy and safety of alprazolam with diazepam and placebo in anxious out-patients. Curr Ther Res 25:519–526

    Google Scholar 

  11. Charney DS, Woods SW, Goodman WK, Rifkin B, Kinch M, Aiken B, Quadrino LM, Heninger GR (1986) Drug treatment of panic disorder: The comparative efficacy of imipramine, alprazolam, and trazodone. J Clin Psychiatry 47: 580–586

    PubMed  CAS  Google Scholar 

  12. Chouinard G, Annable L, Fontaine R, Solyom L (1982) Alprazo- lain in the treatment of generalized anxiety and panic disorders: A double-blind placebo-controlled study. Psychopharmacology 77:229–233

    Article  PubMed  CAS  Google Scholar 

  13. Johnson DAW(1985) The use of benzodiazepines in depression. Br J Clin Pharmaco1 19:31S-35S

    Google Scholar 

  14. Schatzberg AF, Cole JO (1978) Benzodiazepines in depressive disorders. Arch Gen Psychiatry 35:1359–1365

    PubMed  CAS  Google Scholar 

  15. Fabre LF, McLendon D (1980) A double-blind study comparing the efficacy and safety of alprazolam with imipramine and place- bo in primary depression. Curr Ther Res 27:474–482

    Google Scholar 

  16. Rickels K, Hack RC, Csanalosi IB, Hurowitz AM, London J, Wiseman K, Kaplan M, Amsterdam JD (1985) Alprazolam, diazepam, imipramine, and placebo in outpatients with major depression. Arch Gen Psychiatry 44:862–866

    Google Scholar 

  17. Kolin IS, Linet OI (1981) Double-blind comparison of alprazo- lam and diazepam for subchronic withdrawal from alcohol. J Clin Psychiatry 42:169–174

    PubMed  CAS  Google Scholar 

  18. McLendon DM, Fabre LF (1979) A double-blind comparison of the anxiolytic efficacy of alprazolam and chlordiazepoxide hy- drochloride in the chronic withdrawal period from alcohol. Curr Ther Res 26: 430–439

    Google Scholar 

  19. Fernandez F, Adams F, Holms VF (1987) Analgesic effect of al- prazolam in patients with chronic, organic pain of malignant origin. J Clin Psychopharmacol 7:167–169

    Article  PubMed  CAS  Google Scholar 

  20. Islas J-A, Yarahnan N (1988) The effect of alprazolam on chronic pain. Curr Ther Res 43:384–390

    Google Scholar 

  21. Othmer SC, Othmer E, Varanka TM, Strong DM (1985) Refrac- tory migraine headache controlled with alprazolam: Case report. J Clin Psychiatry 46: 494–495

    PubMed  CAS  Google Scholar 

  22. Itil TM, Saletu B, Marasa J, Mucciardi AN (1971) Digital computer analyzed awake and sleep EEG (sleep prints) in prediciing the effects of a triazolobenzodiazepine (U-31, 889). Pharmakopsychiatrie Neuro-Psychopharmakologie 5: 225–240

    Google Scholar 

  23. Kramer M (1982) Dose-response effects of alprazolam on sleep architecture in normal subjects. Curr Ther Res 31: 960–968

    CAS  Google Scholar 

  24. Lysaght R, Roth T, Kramer M, Lutz T, Zovick F (1977) A dose- response study of the acute effects of diazepam and alprazolam on human sleep. Sleep Res 6:78

    Google Scholar 

  25. Arana GW, Pearlman C, Shader RI (1985) Alprazolam-induced mania: Two clinical cases. Am J Psychiatry 142:368–369

    PubMed  CAS  Google Scholar 

  26. France RD, Krishnan KRR (1984) Alprazolam-induced manic reaction. Am J Psychiatry 141:1127–1128

    PubMed  CAS  Google Scholar 

  27. Noyes R Jr, DuPont RL, Pecknold JC, Rifkin A, Rubin RT, Swin- son RE Batlenger JC, Burrows GD (1988) Alprazolam in panic disorder and agoraphobia: Results from a mutticenter trial. II. Patient acceptance, side effects, and safety. Arch Gen Psy- chiatry 45:423–428

    Google Scholar 

  28. Lydiard RB, Howell EE Laraia MT, Ballenger JC (1987) Sexual side effects of alprazotam. Am J Psychiatry 144:254–255

    PubMed  CAS  Google Scholar 

  29. Breier A, Charney DS, Nelson JC (1984) Seizures induced by ab- rupt discontinuation of alprazolam. Am J Psychiatry 141: 1606–1607

    PubMed  CAS  Google Scholar 

  30. Browne JL, Hauge KJ (1986) A review of alprazoIam withdra- wal. Drug Intell Clin Pharm 20:837–841

    PubMed  CAS  Google Scholar 

  31. Aranko K, Mattila MJ, Bordignon D (1985) Psychomotor effects of alprazolam and diazepam during acute and subacute treat- ment, and during the followup phase. Acta Pharmacol Toxicol 56:364–372

    Article  CAS  Google Scholar 

  32. Block RI, Berchou R (1984) Alprazolam and lorazepam effects on memory acquisition and retrieval processes. Pharmacol Biochem Behav 20:233–241

    Article  PubMed  CAS  Google Scholar 

  33. Danjou P, Warot D, Puech AJ (1988) Effets de l’alprazolam sur la vigilance, la memoire et le stress induit chez le volontaire sain. Therapie 43:93–96

    PubMed  CAS  Google Scholar 

  34. Ellinwood EHJr, Heatherly DG, Nikaido AM, Bjornsson TD, Kilts C (1985) Comparative pharmacokinetics and pharmacody- namics of lorazepam, alprazolam and diazepam. Pschopharm 86: 392–399

    Article  Google Scholar 

  35. Ellinwood EH Jr, Nikaido AM, Heatherly DG, Bjornsson TD (1987) Benzodiazepine pharmacodynamics: Evidence for bio- phase rate limiting mechanisms. Psychopharm 91:168–174

    CAS  Google Scholar 

  36. Frei A, Mollenkopf W, Gaertner HJ (1988) Sedative action of al- prazolam and diazepam as measured by EWL and two different flicker fusion methods. Psychopharm 96 [Suppl]: 355

    Google Scholar 

  37. Greenblatt DJ, Harmatz JS, Dorsey C, Shader RI (1988) Comparative single-dose kinetics and dynamics of lorazepam, alprazolam, prazepam, and placebo. Clin Pharmacol Ther 44: 326–334

    Article  PubMed  CAS  Google Scholar 

  38. Hindmarch I (1983) Measuring the side-effects of psychoactive drugs: a pharmacodynamic profile of alprazolam. Alcohol Alco-holism 18:361–364

    Google Scholar 

  39. Kroboth PD, Smith RB, Erb RJ (1988) Tolerance to alprazolam after intravenous bolus and continuous infusion: Psychomotor and EEG effects. Clin Pharmacol Ther 43:270–277

    Article  PubMed  CAS  Google Scholar 

  40. Kumar R, Mac DS, Gabrielli WF, Goodwin DW (1987) Anxioly- tics and memory: A comparison of lorazepam and alprazolam. J Clin Psychiatry 48:158–160

    PubMed  CAS  Google Scholar 

  41. Smith RB, Kroboth PD (1987) Influence of dosing regimen on al- prazolam and metabolite serum concentrations and tolerance to sedative and psychomotor effects. Psychopharmacology 93: 105–112

    Article  PubMed  CAS  Google Scholar 

  42. Smith RB, Kroboth PD, Vanderlugt JT, Phillips JR Juhl RP (1984) Pharmacokinetics and pharmacodynamics of alprazolam after oral and IV administration. Psychopharmacology 84: 452–456

    Article  PubMed  CAS  Google Scholar 

  43. Subhan Z, Harrison C, Hindmarch I (1986) Alprazolam and lorazepam, single and multiple-dose effects on psychomotor skills and sleep. Eur J Clin Pharmaco1 29:709–712

    Article  CAS  Google Scholar 

  44. Milner G (1969) Drinking and driving in 753 general practice and psychiatric patients. Br J Psychiatry 115: 99–100

    Article  PubMed  CAS  Google Scholar 

  45. DHEW (1979) Weight and height of adults 18–74 years of age. Hyattsville MD: DHEW, PHS 79-159

  46. Spielberger CD, Gorsuch RL, Lushere RE (1968) Manual for the State/Trait Anxiety Inventory. Florida State University Press, Gainesville

    Google Scholar 

  47. Derogatis LR, Lipman RS, Covi L (1973) The SCL-90: an out- patient psychiatric rating scale. Psychopharm Bull 9:13–28

    CAS  Google Scholar 

  48. Linnoila M, Erwin CW, Cleveland WR Logue P, Gentry D (1978) Effects of alcohol on psychomotor performance of men and women. J Stud Alcohol 39:745–748

    PubMed  CAS  Google Scholar 

  49. Weingartner H, Rudorfer MV, Buchsbaum MS, Linnoila M (1983) Effects of serotonin on memory impairments produced by ethanol. Science 221:471–474

    Google Scholar 

  50. Adams WJ, Bombardt PA, Brewer JE (1984) Normal-phase liquid chromatographic determination of alprazolam in human serum. Anal Chemistry 56:1590–1594

    Article  CAS  Google Scholar 

  51. Rao SN, Dhar AK, Kutt H, Okamoto M (1982) Determination of diazepam and its pharmacologically active metabolites in blood by bond elut column extraction and reversed-phase high-performance liquid chromatography. J Chromatogr 231: 341–348

    Article  PubMed  CAS  Google Scholar 

  52. Mefford IN, Ota M, Stipetic M, Singleton W (1987) Application of a novel cation-exchange reagent, igepon T-77 (N-methyl oleoyl taurate), to microbore separations of alumina extracts of catecholamines from cerebrospinal fluid, plasma, urine and brain tissue with amperometric detection. J Chromatogr 420: 241–251

    Article  PubMed  CAS  Google Scholar 

  53. Linnoila M, Johnson J, Dubyoski T, Ross R, Buchsbaum M, Pot- ter WZ, Weingartner H (1983) Effects of amitriptyline, desi- pramine and zimelidine, alone and in combination with ethanol, on information processing and memory in healthy volunteers. Acta Psychiatry Scand [Suppt 308] 68:175–181

    Google Scholar 

  54. Linnoila M, Johnson J, Dubyoski K, Buchsbaum MS, Schneinin M, Kilts C (1984) Effects of antidepressants on skilled perfor- mance. Br J Clin Pharmaco1 18:109S-120S

    Google Scholar 

  55. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM (1977) Diazepam actions and plasma concentrations following ethanol ingestion. Eur J Clin Pharmaco1 11:345–359

    Article  CAS  Google Scholar 

  56. Linnoila M (1978) Psychomotor effects of drugs and alcohol on healthy volunteers and psychiatric patients. In: Olive G (ed) Ad- vances in pharmacology and therapeutics, vol 8: Drug-action modification-comparative pharmacology. Pergamon, Oxford, pp 235–249

    Google Scholar 

  57. Lister RG (1985) The amnesic action of benzodiazepines in man. Neurosci Biobehav Rev 9:87–94

    Article  PubMed  CAS  Google Scholar 

  58. Cote P, Gueret P, Bourassa MG (1974) Systemic and coronary hemodynamic effect of diazepam in patients with normal and diseased coronary arteries. Circulation 50:1210–1216

    PubMed  CAS  Google Scholar 

  59. Marty J, Gauzit R, Lefevre P, Couderc E, Farinotti R, Henzel C, Desmonts JM (1986) Effects of diazepam and midazolam on baroreflex control of heart rate and on sympathetic activity in humans. Anesth Analg 65:113–119

    PubMed  CAS  Google Scholar 

  60. Roy-Byrne PP, Lewis N, Villacres E, Greenblatt DJ, Shader RI, Veith RC (1988) Suppression of norepinephrine appearance rate in plasma by diazepam in humans. Life Sci 43: 1615–1623

    Article  PubMed  CAS  Google Scholar 

  61. Charney DS, Breier A, Jatlow PI, Heninger GR (1986) Behavio- ral, biochemical, and blood pressure responses to atprazolam in healthy subjects. Interactions with yohimbine. Psychopharmaco- logy 88:133–140

    Article  CAS  Google Scholar 

  62. Stratton JR, Halter JB (1985) Effect of a benzodiazepine (alpra- zolam) on plasma epinephrine and norepinephrine levels during exercise stress. Am J Cardio1 56:136–139

    Article  CAS  Google Scholar 

  63. Chan AWK (1984) Effects of combined alcohol and benzo- diazepine: A review. Drug Alcohol Depend 13:315–341

    Article  PubMed  CAS  Google Scholar 

  64. Hoyumpa AM (1984) Alcohol interactions with benzo- diazepines and cocaine. Adv Alcohol Subst Abuse 3:21–34

    PubMed  CAS  Google Scholar 

  65. Sellers EM, Busto U (1982) Benzodiazepines and ethanol: As- sessment of the effects and consequences of psychotropic drug interactions. J Clin Psychopharmacology 2:249–262

    Article  CAS  Google Scholar 

  66. Linnoila M (1983) Benzodiazepines and performance. In: E Costa (ed) From molecular biology to clinical practice. Raven, New York, pp 267–278

    Google Scholar 

  67. Palva ES, Linnoila M, Saario I, Mattila MJ (1979) Acute and sub- acute effects of diazepam on psychomotor skills: Interactions with alcohol. Acta Pharmacol Toxico1 45:257–264

    CAS  Google Scholar 

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Linnoila, M., Stapleton, J.M., Lister, R. et al. Effects of single doses of alprazolam and diazepam, alone and in combination with ethanol, on psychomotor and cognitive performance and on autonomic nervous system reactivity in healthy volunteers . Eur J Clin Pharmacol 39, 21–28 (1990). https://doi.org/10.1007/BF02657051

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