Abstract
The differential sensitivity of young and elderly healthy adults to the impairment effects of benzodiazepines was assessed by tasks with several levels of difficulty. Using a double-blind procedure, single doses of placebo, alprazolam (0.75 and 1.5 mg) and triazolam (0.25 and 0.5 mg) were ingested orally by 10 young men, 9 young women, 7 elderly men, and 10 elderly women. Order of drug administration was determined by a random Latin square design. Different versions of the subcritical tracking and digit symbol substitution tasks were characterized by three difficulty levels. Assessments of task performance were conducted at varying intervals for 7 h after drug administration. Both drugs induced a rapid initial onset of impairment in the two age groups. Evidence of increased drug sensitivity in the elderly was provided by the more prolonged duration of the pharmacologic effect in the older than young subjects, especially for the harder versions of the SCT and DSS tasks. In summary, the data provide support for the hypothesis of an age-related decline in the adaptive capacity to inhibit adverse drug effects.
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References
Balter MB, Levine J, Manheimer D (1974) Cross-national study of the extent of anti-anxiety sedative drug use. N Engl J Med 290:766–774
Boston Collaborative Drug Surveillance Program (1973) Clinical depression of the central nervous system due to diazepam and chlordiazepoxide in relation to cigarette smoking and age. N Engl J Med 288:277–280
Braestrup C, Nielsen M (1983) Benzodiazepine receptors. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology: biochemical studies of CNS receptors, vol 17. Plenum Press, New York, pp 285–383
Castleden CM, George CF, Marcer D, Hallett C (1977) Increased sensitivity to nitrazepam in old age. Br Med J 1:10–12
Cook PJ, Flanagan R, James IM (1984) Diazepam tolerance: effect of age, regular sedation, and alcohol. Br Med J 289:351–353
Ellinwood EH Jr, Nikaido AM (1987) Perceptual-neuromotor pharmacodynamics of psychotropic drugs. In: Meltzer HY (ed) Pharmacology: the third generation of progress. Raven Press, New York, pp 1457–1466
Ellinwood EH Jr, Linnoila M, Easler ME, Molter DW (1983) Profile of acute tolerance to three sedative-anxiolytics. Psychopharmacology 79:137–141
Evans SH, Anastasio EJ (1968) Misuse of analysis of covariance when treatment effect and covariate are confounded. Psychol Bull 69:225–234
Giles HG, MacLeod SM, Wright JR, Sellers EM (1978) Influence of age and previous use on diazepam dosage required for endoscopy. Can Med Assoc J 118:513–514
Gilmore G, Royer FL, Gruhn JJ (1983) Age differences in symboldigit substitution. J Clin Psychol 39:114–124
Greenblatt DJ, Divoll M, Abernethy DR, Moschitto LJ, Smith RB, Shader RI (1983a) Alprazolam kinetics in the elderly: relation to antipyrine disposition. Arch Gen Psychiatry 40:287–290
Greenblatt DJ, Divoll M, Abernethy DR, Moschitto LJ, Smith RB, Shader RI (1983b) Reduced clearance of triazolam in old age: relation to antipyrine oxidizing capacity. Br J Clin Pharmacol 15:303–309
Kaplan SA, Jack ML (1983) Metabolism of the benzodiazepines: pharmacokinetic and pharmacodynamic considerations. In: Costa E (ed) Benzodiazepines: from molecular biology to clinical practice. Raven Press, New York, pp 173–199
Keppel G (1982) Design and analysis: a researcher's handbook, 2nd ed. Prentice Hall, Englewood Cliffs
Lader M (1979) Correlation of plasma concentrations of benzodiazepines with clinical effects. In: Priest RG, Pletscher A, Ward J (eds) Sleep research. University Park Press, Baltimore, pp 99–108
MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM (1977) Diazepam actions and plasma concentrations following ethanol ingestion. Eur J Clin Pharmacol 11:345–349
Nikaido AM, Ellinwood EH Jr, Heatherly DG, Dubow D (1987) Differential CNS effects of diazepam in elderly adults. Pharmacol Biochem Behav 27:273–281
Pomara N, Stanley B, Block R, Guido J, Russ D, Berchou R, Stanley M, Greenblatt DJ, Newton RE, Gershon S (1984) Adverse effects of single therapeutic doses of diazepam on performance in normal geriatric subjects: relationship to plasma concentrations. Psychopharmacology 84:342–346
Pomara N, Stanley B, Block R, Berchou RC, Stanley M, Greenblatt DJ, Newton RE, Gershon S (1985) Increased sensitivity of the elderly to the central depressant effects of diazepam. J Clin Psychiatry 46:185–187
Reidenberg MM, Levy M, Warner H, Coutinho CB, Schwartz MA, Yu G, Cheripko J (1978) Relationship between diazepam dose, plasma level, age and central nervous system depression. Clin Pharmacol Ther 23:371–374
Royer FL, Gilmore GC, Gruhn JJ (1981) Normative data for the symbol digit substitution task. J Clin Psychol 37:608–614
Salthouse TA (1978) The role of memory in the age decline in digit-symbol substitution performance. J Gerontol 33:232–238
Salthouse TA (1982) Adult cognition. Springer, New York Berlin Heidelberg
SAS Institute (1982) SAS user's guide: Statistics. SAS Institute, Cary, NC
Stephens RC, Haney CA, Underwood S (1982) Drug taking among the elderly. In: National Institute on Drug Abuse treatment research report and monograph series, DHHS Publication No. ADM 83-1229. U.S. Government Printing Office, Washington, DC, pp 7–25
Storandt M, Hudson W (1975) Misuse of analysis of covariance in aging research and some partial solutions. Exp Aging Res 1:121–125
Swift CG, Stevenson IH (1983) Benzodiazepines in the elderly. In: Costa E (ed) The benzodiazepines: from molecular biology to clinical practice. Raven Press, New York, pp 225–236
Wechsler D (1981) Wechsler Adult Intelligence Scale-revised manual. The Psychological Corporation, Cleveland
Ziegler G, Ludwig L, Klotz U (1983) Relationships between plasma levels and psychological effects of benzodiazepines. Pharmacopsychiatry 16:71–76
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Nikaido, A.M., Ellinwood, E.H., Heatherly, D.G. et al. Age-related increase in CNS sensitivity to benzodiazepines as assessed by task difficulty. Psychopharmacology 100, 90–97 (1990). https://doi.org/10.1007/BF02245796
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DOI: https://doi.org/10.1007/BF02245796