Clinical Implications of the Pharmacokinetics of Tricyclic Antidepressants

  • J. C. Nelson
  • C. Mazure
  • P. I. Jatlow
Part of the Psychopharmacology Series book series (PSYCHOPHARM, volume 7)


Knowledge gained during the past 20 years about the pharmacokinetics of tricyclic antidepressant drugs has helped to refine clinical practice. This discussion will focus on kinetic features of tricyclic antidepressants which appear to have important implications for clinical practice.


Antidepressant Activity Healthy sUbjects Hydroxy Metabolite Nonlinear Change Elderly Depressed Patient 
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.


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  1. Amsterdam JD, Brunswick DJ, Potter L et al. (1985) Desipramine and 2-hydroxy-desipramine plasma levels in endogenous depressed patients: lack of correlation with therapeutic response. Arch Gen Psychiatry 42: 361–364PubMedGoogle Scholar
  2. APA Task Force on the Use of Laboratory Tests in Psychiatry (1985) Tricyclic antidepressants - blood level measurements and clinical outcome: an APA task force report. Am J Psychiatry 142: 155–162Google Scholar
  3. Asberg M, Chronholm B, Sjoqvist F et al. (1970) Correlation of subjective side effects with plasma concentration of nortriptyline. Br Med J 4: 18–21PubMedCrossRefGoogle Scholar
  4. Bertilsson L, Mellstrom B, Sjoqvist F (1979) Pronounced inhibition of noradrenaline uptake by 10-hydroxy-metabolites of nortriptyline. Life Sci 25: 1285–1292PubMedCrossRefGoogle Scholar
  5. Bjerre M, Gram LF, Kragh-Sorensen P et al. (1981) Dose-dependent kinetics of imipramine in elderly patients. Psychopharmacology (Berlin) 75: 354–357CrossRefGoogle Scholar
  6. Bock JL, Giller E, Gray S et al. (1982) Steady-state plasma concentrations of cis and trans-lO-OH amitriptyline metabolites. Clin Pharmacol Ther 31: 609–616PubMedCrossRefGoogle Scholar
  7. Bock JL, Nelson JC, Gray S et al. (1983) Desipramine hydroxylation: variability and effect of antipsychotic drags. Clin Pharmacol Ther 33: 190–197CrossRefGoogle Scholar
  8. Breyer-Pfaff U, Gaertner HJ, Kreuter F et al. (1982) Antidepressive effect and pharmacokinetics of amitriptyline with consideration of unbound drag and 10- hydroxynortriptyline plasma levels. Psychopharmacology (Berlin) 76: 240–244CrossRefGoogle Scholar
  9. Brosen K, Gram LF, Klysner R, Bech P (1986) Steady-state levels of imipramine and its metabolites: significance of dose-dependent kinetics. Eur J Clin Pharmacol 30: 43–49PubMedCrossRefGoogle Scholar
  10. Cooke RG, Warsh J J, Stancer HC et al. (1984) The nonlinear kinetics of desipramine and 2-hydroxydesipramine in plasma. Clin Pharmacol Ther 36: 343–349PubMedCrossRefGoogle Scholar
  11. Dawling S, Ford S, Rangedara DC, Lewis RR (1984) Amitriptyline dosage prediction in elderly patients from plasma concentration at 24 hours after a single 100 mg dose. Clin Pharmacokinet 9: 261–266PubMedCrossRefGoogle Scholar
  12. Gram LF, Overo KF (1972) Drag interaction: inhibitory effect of neuroleptics on metabolism of tricyclic antidepressants in man. Br Med J 1: 463–465PubMedCrossRefGoogle Scholar
  13. Javaid JI, Matuzas W, Davis JM, Fawcett J (1985) Plasma protein binding of tricyclic antidepressants in young and elderly. Presented at the American College of Neuro-psychopharmacology, Annual Meeting, December 1985Google Scholar
  14. Kitanaka I, Ross RJ, Cutler NR et al. (1982) Altered hydroxydesipramine concentrations in elderly depressed patients. Clin Pharmacol Ther 31: 51–55PubMedCrossRefGoogle Scholar
  15. Kutcher SP, Reid K, Dubbin JD et al. (1986a) Electrocardiogram changes and therapeutic desipramine and 2-hydroxy-desipramine concentrations in elderly depressives. Br J Psychiatry 148: 676–679CrossRefGoogle Scholar
  16. Kutcher SP, Shulman KI, Reed K (1986 b) Desipramine plasma concentration and therapeutic response in elderly depressives: a naturalistic pilot study. Can J Psychiatry 31: 752–754Google Scholar
  17. Livingston RL, Zucker DK, Isenberg K, Wetzel RD (1983) Tricyclic antidepressants and delirium. J Clin Psychiatry 44: 173–176PubMedGoogle Scholar
  18. Madakasira S, Khazanie PG (1985) Reliability of amitriptyline dose prediction based on single-dose plasma levels. Clin Pharmacol Ther 37: 145–149PubMedCrossRefGoogle Scholar
  19. Nelson JC, Jatlow P (1980) Neuroleptic effect on desipramine steady state plasma concentrations. Am J Psychiatry 137: 1232–1234PubMedGoogle Scholar
  20. Nelson JC, Jatlow PI (1987) Nonlinear desipramine kinetics: prevalence and importance. Clin Pharmacol Ther 41: 666–670PubMedCrossRefGoogle Scholar
  21. Nelson JC, Jatlow PI, Bock J, Quinlan DM, Bowers MB (1982a) Major adverse reactions during desipramine treatment. Arch Gen Psychiatry 39: 1055–1061PubMedGoogle Scholar
  22. Nelson JC, Jatlow PI, Quinlan DM, Bowers MB (1982 b) Desipramine plasma concentration and antidepressant response. Arch Gen Psychiatry 39: 1419–1422Google Scholar
  23. Nelson JC, Bock J, Jatlow P (1983) The clinical implications of 2-hydroxydesipramine in plasma. Clin Pharmacol Ther 33: 183–189PubMedCrossRefGoogle Scholar
  24. Nelson JC, Jatlow P, Quinlan DM (1984) Subjective side effects during desipramine treatment. Arch Gen Psychiatry 41: 55–59PubMedGoogle Scholar
  25. Nelson JC, Jatlow PI, Mazure C (1987) Rapid desipramine dose adjustment using 24-hour levels. J Clin Psychopharmacol 7: 72–77PubMedGoogle Scholar
  26. Nelson JC, Mazure C, Jatlow PI (1988a) Antidepressant activity of 2-hydroxy-desipramine. Clin Pharmacol Ther 44: 283–288PubMedCrossRefGoogle Scholar
  27. Nelson JC, Atillasoy E, Mazure C, Jatlow PI (1988b) Hydroxydesipramine in the elderly. J Clin Psychopharmacol 8: 428–433PubMedCrossRefGoogle Scholar
  28. Nies A, Robinson DS, Friedman MJ et al. (1977) Relationship between age and tricyclic antidepressant plasma levels. Am J Psychiatry 134: 790–793PubMedGoogle Scholar
  29. Nordin C, Bertilsson L, Siwers B (1985) CSF and plasma levels of nortriptyline and its 10- hydroxy metabolite. Br J Clin Pharmacol 20: 411–413PubMedGoogle Scholar
  30. Nordin C, Bertilsson L, Siwers B (1987a) Clinical and biochemical effects during treatment of depression with nortriptyline — the role of 10-hydroxynortriptyline. Clin Pharmacol Ther 42: 10–19PubMedCrossRefGoogle Scholar
  31. Nordin C, Bertilsson L, Otani K et al. (1987b) Little anticholinergic effect of E-10- hydroxynortriptyline compared with nortriptyline in healthy subjects. Clin Pharmacol Ther 41: 97–102PubMedCrossRefGoogle Scholar
  32. Potter WZ, Calil HM, Sutfin TA et al. (1982) Active metabolites of imipramine and desipramine in man. Clin Pharmacol Ther 31: 393–401PubMedCrossRefGoogle Scholar
  33. Preskorn SH, Simpson S (1982) Tricyclic antidepressant induced delirium and plasma drug concentration. Am J Psychiatry 139: 822–823PubMedGoogle Scholar
  34. Preskorn SH, Dorey RC, Jerkovich GS (1988) Therapeutic drug monitoring of tricyclic antidepressants. Clin Chem 34: 822–828PubMedGoogle Scholar
  35. Quitkin FM et al. (1984) Duration of antidepressant drug treatment. Arch Gen Psychiatry 41: 238–245PubMedGoogle Scholar
  36. Robinson DS, Cooper TB, Howard D et al. (1985) Amitriptyline and hydroxylated metabolite plasma levels in depressed outpatients. J Clin Psychopharmacol 5: 83–88PubMedGoogle Scholar
  37. Spiker DG, Perei JM, Hanin I et al. (1986) The pharmacological treatment of delusional depression: part II. J Clin Psychopharmacol 6: 339–342PubMedCrossRefGoogle Scholar
  38. Steiner E, Dumont E, Spina E, Dahlqvist R (1987) Inhibition of desipramine 2-hydroxylation by quinidine and quinine. Clin Pharmacol Ther 43: 577–581CrossRefGoogle Scholar
  39. Stewart JW, Quitkin F, Fyer A, Rifkin A, McGrath P, Liebowitz M, Rosnick L, Klein D (1980) Efficacy of desipramine in endogenously depressed patients. J Affect Dis 2: 165–176PubMedCrossRefGoogle Scholar
  40. Young RC, Alexopoulos GS, Shamoian CA et al. (1984) Plasma 10-hydroxynortriptyline in elderly depressed patients. Clin Pharmacol Ther 35: 540–544PubMedCrossRefGoogle Scholar
  41. Young RC, Alexopoulos GS, Shamoian CA et al. (1985) Plasma 10-hydroxynortriptyline and ECG changes in elderly depressed patients. Am J Psychiatry 142: 866–868PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • J. C. Nelson
  • C. Mazure
  • P. I. Jatlow
    • 1
    • 2
  1. 1.Department of PsychiatryYale University School of MedicineNew HavenUSA
  2. 2.Yale-New Haven HospitalYale University School of MedicineNew HavenUSA

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