Abstract
In a double-blind phenelzine controlled clinical trial, 49 depressed outpatients were treated with a fixed dose of amitriptyline (AMI) 150 mg/day for 6 weeks. No significant relationships were found between steady-state plasma levels of AMI and its metabolite, nortriptyline, at 4 weeks and therapeutic response at 6 weeks or side effects. In the patient subgroup with more severe endogenous symptoms, there was a general trend for a weak positive association between AMI plasma levels and clinical improvement. Plasma tricyclic determinations appear to have little if any predictive value for antidepressant effect in outpatients treated with AMI.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alexanderson, B., Price Evans, D. A., Sjoquist, F.: Steady state levels of nortriptyline in twins: Influence of genetic factors and drug therapy. Br. Med. J. 1969 I, 764–768
Biggs, J. T., Holland, W. H., Chang, S., Hipps, P. P., Sherman, W. R.: Electron beam ionization mass fragmentographic analysis of tricyclic antidepressants in human plasma. J. Pharm. Sci. 65, 261–268 (1976)
Borga, O., Plafsky, K. M., Nilsen, O. G.: Plasma protein binding of basic drugs. I. Selective displacement from α1-acid glycoprotein by tris (2-butoxyethyl) phosphate. Clin. Pharmacol. Ther. 22, 539–544 (1977)
Braithwaite, R. A., Goulding, R., Theano, G., Bailey, J., Coppen, A.: Plasma concentration of amitriptyline and clinical response. Lancet 1972 I, 1297–1299
Brunswick, D. J., Mendels, J.: Reduced levels of tricyclic antidepressants in plasma from Vacutainers. Comm. in Psychopharmacology 1, 131–134 (1977)
Brunswick, D. J., Needleman, B., Mendels, J.: Radioimmunoassay of imipramine and desmethylimipramine. Life Sci. 22, 137–146 (1978)
Brunswick, D. J., Needleman, B., Mendels, J.: Radioimmunoassay of amitriptyline and nortriptyline. Br. J. Clin. Pharmacol. (in press, 1979)
Burrows, G. D., Davies, B., Scoggins, B. A.: Plasma concentrations of nortriptyline and clinical response in depressive illness. Lancet 1972 II, 619–623
Burrows, G., Scoggins, B. A., Turecek, L. R., Davies, b.: Plasma nortriptyline and clinical response. Clin. Pharmacol. Ther. 16, 639–644 (1974)
Cooper, T. B., Allen, D., Simpson, G. M.: A sensitive method for the determination of amitriptyline and nortriptyline in human plasma. Psychopharmacol. Comm. 2, 105–116 (1976)
Cooper, T. B., Simpson, G. M.: Prediction of individual dosage of nortriptyline. Am. J. Psychiatry 135, 333–335 (1978)
Coppen, A., Ghose, K., Montgomery, S., Rama Raa, V. A., Bailey, J., Christiansen, S. J., Mikkleson, P. L., van Praag, H. M., van de Poel, F., Minsker, E. J., Kozulja, V. J., Matussek, N., Kungkunz, G., Jorgensen, A.: Amitriptyline plasma-concentration and clinical effect. Lancet 1978 I, 63–66
Cotham, R. H., Shand, D.: Spuriously low plasma propranolol concentrations resulting from blood collection methods. Clin. Pharmacol. Ther. 18, 535–538 (1975)
Derogatis, L. P., Lipman, R. S., Covi, L., Rickels, K.: Factorial invariance of symptom dimensions in anxious and depressive neuroses. Arch. Gen. Psychiatry 131, 168–171 (1972)
Downing, R. S., Rickels, K.: Predictors of response to amitriptyline and placebo in three outpatient treatment settings. J. Nerv. Ment. Dis. 156, 109–129 (1973)
Fremstad, D., Bergerud, K.: Plasma protein binding of drugs as influenced by blood collection methods. Acta Pharmacol. Toxicol. 39, 570–572 (1976)
Gram, L. F.: Plasma level monitoring of tricyclic antidepressant therapy. Clin. Pharmacokinetics 2, 237–251 (1977)
Gram, L. F., Fredricson Overo, K.: Drug interaction: Inhibitory effect of neuroleptics on metabolism of tricyclic antidepressants in man. Br. Med. J. 1972 I, 463–465
Hamilton, M.: A rating scale for depression. J. Neurol. Neurosurg. Psychiatry 23, 56–62 (1960)
Hammer, W. M., Brodie, B. B.: Application of isotope derivative technique to assay of secondary amines: estimation of desipramine by acetylation with H3-acetic. anhydride. J. Pharmacol. Exp. Ther. 157, 503–508 (1967)
Kaul, P., Whitfield, L. R.: Demonstration of amitriptyline in blood levels following a single oral dose in humans. Proc. West. Pharmacol. Soc. 18, 251–255 (1976)
Khosla, T., Lowe, C. R.: Indices of obesity derived from body weight and height. Br. J. Prev. Soc. Med. 21, 122–128 (1967)
Kiloh, L. G., Ball, J. R. B., Garside, R. F.: Prognostic factors in treatment of depressive states with imipramine. Br. Med. J. 1962 I, 1225–1227
Klein, D. F., Davis, J. M.: Diagnosis and drug treatment of psychiatric disorders. Baltimore: Williams and Wilkins 1969
Kupfer, D. J., Hanin, L., Spiker, D. G., Grau, G., Koble, P.: Amitriptyline plasma levels and clinical response in primary depression. Clin. Pharmacol. Ther. 22, 902–911 (1977)
Liisberg, P., Mose, H., Amdisen, A., Jorgensen, A., Hopfner Petersen, H. E.: A clinical trial comparing sustained release amitriptyline (Saroten® Retard) and conventional amitriptyline tablets (Saroten®) in endogenously depressed patients with simultaneous determination of serum levels of amitriptyline and nortriptyline. Acta Psychiatr. Scand. 57, 426–435 (1978)
Nies, A., Robinson, D. S., Friedman, J. M., Green, R., Cooper, T. B., Ravaris, C. L., Ives, J. O.: Relationship between age and tricyclic antidepressant plasma levels. Am. J. Psychiatry 134, 790–793 (1977)
Nies, A., Robinson, D. S., Lamborn, K. R., Ravaris, C. L., Ives, J. O.: The efficacy of the MAO inhibitor, phenelzine: dose effects and prediction of response. In: Neuropsychopharmacology, J. R. Boissier, H. Hippius, P. Pichot, eds., pp. 765–770. Amsterdam: Excerpta Medica 1975
Oliver-Martin, R., Marzin, D., Buschenschutz, E., Pichot, P., Boissier, J.: Concentration plasmatiques de l'imipramine et de la desmethylimipramine et effect antidepresseur au cours d'un traitement controle. Psychopharmacologia 41, 187–195 (1975)
Perel, J., Shostak, M., Gann, E., Kantor, S. J., Glassman, A. H.: Pharmacodynamics of imipramine and clinical outcome in depressed patients. In: Pharmacokinetics of psychoactive drugs: blood levels and clinical response, L. S. Gottschalk and S. Merlis, eds., pp. 229–241. New York: Spectrum 1976
Raskin, A., Schulterbrandt, J. G., Reatig, N., McKeon, J. J.: Differential response to chlorpromazine, imipramine and placebo. Arch. Gen. Psychiatry 23, 164–173 (1970)
Ravaris, C. L., Robinson, D. S., Ives, J. O., Nies, A., Bartlett, D.: A comparison of phenelzine and amitriptyline in the treatment of depression. (in preparation)
Reisby, N., Gram, L. F., Bech, P., Nagy, A., Petersen, G. O., Ortmann, J., Ibsen, I., Dencker, S. J., Jacobsen, O., Krautwald, O., Sondergaard, I., Christiansen, J.: Imipramine: clinical effects and pharmacokinetic variability. Psychopharmacology 54, 263–272 (1977)
Robinson, D. S., Lovenberg, W., Keiser, H., Sjoerdsma, A.: The effects of drugs on human blood platelet and plasma amine oxidase activity in vitro and in vivo. Biochem. Pharmacol. 17, 109–119 (1968)
Robinson, D. S., Nies, A., Ravaris, C. L.: The monoamine oxidase inhibitor, phenelzine, in the treatment of depressive-anxiety states. Arch. Gen. Psychiatry 29, 407–413 (1973)
Robinson, D. S., Nies, A., Ravaris, C. L., Ives, J. O., Bartlett, D.: Clinical psychopharmacology of phenelzine: MAO activity and clinical response. In: Psychopharmacology: a generation of progress, M. A. Lipton, A. Di-Mascio and K. F. Killam, eds., pp. 961–973. New York: Raven 1977
Robinson, D. S., Nies, A., Ravaris, C. L., Ives, J. O., Bartlett, D.: Clinical pharmacology of phenelzine. Arch. Gen. Psychiatry 35, 629–635 (1978)
Turner, W. J., Turano, P., Badzinski, S.: An attempt to establish quality control in determination of plasma chlorpromazine by a multilaboratory collaboration. In: Pharmacokinetics of psychoactive drugs: blood levels and clinical response, L. A. Gottschalk and S. M. Merlis, eds., pp. 33–42. New York: Spectrum 1976
Ziegler, V. E., Co, B. T., Taylor, J. R., Clayton, P. J., Biggs, J. T.: Amitriptyline plasma levels and therapeutic response. Clin. Pharmacol. Ther. 19, 795–801 (1976)
Ziegler, V. E., Meyer, D. A., Rosen, S. H., Knesevich, J. W., Biggs, J. T.: Amitriptyline dosage schedule, sampling time and tricyclic plasma levels. Br. J. Psychiatry 131, 168–171 (1977)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Robinson, D.S., Cooper, T.B., Ravaris, C.L. et al. Plasma tricyclic drug levels in amitriptyline-treated depressed patients. Psychopharmacology 63, 223–231 (1979). https://doi.org/10.1007/BF00433554
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00433554