Summary
Sixteen depressed elderly patients in hospital (mean age 81 years) received a single oral dose of nortriptyline prior to commencing treatment with this drug. Plasma nortriptyline measurements after the single dose were used to calculate the plasma drug clearance and to predict the daily dose required for each patient to achieve a steady-state concentration within the suggested therapeutic range of 50–150 µg·l−1. Using these dosage regimes, the mean observed steady-state concentration showed a significant correlation with the predicted values (r=0.71, p<0.002). All patients had steady-state concentrations within or very close to this suggested range (mean 106, range 38–157 µg·l−1). Use of the prediction test can prevent the development of toxic plasma concentrations and enhance the possibility of therapeutic success. Our findings suggest that a safe starting dose of nortriptyline for the elderly is 30 mg per day.
Similar content being viewed by others
References
Åsberg M (1970) Correlation of subjective side effects with plasma concentrations of nortriptyline. Br Med J 4: 18–21
Learoyd BM (1972) Psychotropic drugs and the elderly patient. Med J Aust 1: 1131–1133
Åsberg M (1974) Plasma nortriptyline levels — relationship to clinical effects. Clin Pharmacol Ther 16: 215–229
Burrows GD, Vohra J, Hunt D, Sloman JG, Scoggins BA, Davies B (1976) Cardiac effects of different tricyclic antidepressant drugs. Br J Psychiatry 129: 335–341
Dawling S, Braithwaite R (1978) Simplified method for monitoring tricyclic antidepressant therapy using gas-liquid chromatography with nitrogen detection. J. Chromatogr 146: 449–456
Åsberg M, Cronholm B, Sjöqvist F, Tuck R (1971) Relationship between plasma level and therapeutic effect of nortriptyline. Br Med J 3: 331–334
Kragh-Sørensen P, Eggert-Hansen G, Baastrup PC, Hvidberg EF (1976) Self inhibiting action of nortriptylin's antidepressive effect at high plasma levels. Psychopharmacologia 45: 305–312
Ziegler VE, Clayton PJ, Taylor JR, Co BT, Biggs JT (1976) Nortriptyline plasma levels and therapeutic response. Clin Pharmacol Ther 20: 458–463
Montgomery S, Braithwaite R, Dawling S, McAuley R (1978) High plasma nortriptyline levels in the treatment of depression. Clin Pharmacol Ther 23: 309–314
Åsberg M (1978) Treatment of depression with tricyclic drugs — Pharmacokinetic and pharmacodynamic aspects. Pharmakopsychiatr Neuro-Psychopharmakol 9: 18–26
Alexanderson B (1972) Pharmacokinetics of nortriptyline in man after single and multiple oral doses: The predictability of steady-state plasma concentrations from single-dose plasma-level data. Eur J Clin Pharmacol 4: 82–91
Alexanderson B (1973) Prediction of steady-state plasma levels of nortriptyline from single oral dose kinetics: A study in twins. Eur J Clin Pharmacol 6: 44–53
Braithwaite R, Montgomery S, Dawling S (1978) Nortriptyline in depressed patients with high plasma levels. Clin Pharmacol Ther 23: 303–308
Wilkinson GR, Shand DG (1975) A physiological approach to hepatic drug clearance. Clin Pharmacol Ther 18: 377–390
Dettli L, Spring P, Ryter S (1971) Multiple dose kinetics and drug dosage in patients with kidney disease. Acta Pharmacol Toxicol 29 (Suppl 3): 211–224
Gram LF, Fredericson Overø K (1975) First pass metabolism of nortriptyline in man. Clin Pharmacol Ther 18: 305–314
Nies A, Robinson DS, Friedman MJ, Green R, Cooper, TB, Revaris C, Ives JO (1977) Relationship between age and tricyclic antidepressant plasma levels. Am J Psychiatry 134: 790–793
Carr AC, Hobson RP (1977) High serum concentrations of antidepressants in elderly patients. Br Med J 2: 1151
Johnson DAW (1974) A study of the use of antidepressant medication in general practice. Br J Psychiatry 125: 186–192
Tyrer P (1978) Drug treatment of psychiatric patients in general practice. Br Med J 2: 1008–1010
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dawling, S., Crome, P., Braithwaite, R.A. et al. Nortriptyline therapy in elderly patients: Dosage prediction after single dose pharmacokinetic study. Eur J Clin Pharmacol 18, 147–150 (1980). https://doi.org/10.1007/BF00561582
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00561582