Abstract
In a group of elderly depressed patients treated with imipramine (50–200 mg/day), six patients had the dose changed after 1–3 weeks of treatment. In all cases an increased dose resulted in a considerably disproportional rise in the plasma level of the active metabolite desipramine. In a group of elderly depressed patients treated with nortriptyline (40–100 mg/day) the dose/plasma level ratio could be examined in 6 patients, and there was no tendency towards a disproportional rise in plasma level, when the dose was raised. Dose changes, thus, may result in unpredictable changes in plasma levels during imipramine treatment and therapy control by plasma level monitoring may be difficult in these patients. Additional treatment with perphenazine (8–16 mg/day) to patients on imipramine (N=3) or nortriptyline (N=2) caused a marked rise in drug levels for imipramine in particular affecting the desipramine levels.
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References
von Bahr C (1971) Spectral studies on the interaction of imipramine and some of its oxidized metabolites with rat liver microsomes. Xenobiotica 2:69–78
Bech P, Gram LF, Reisby N, Rafaelsen OJ (1980) The WHO depression scale: Relationship to the Newcastle scales. Acta Psychiatr Scand 62:140–143
Brunswick DJ, Amsterdam JD, Mendels J, Stern SL (1979) Prediction of steady-state imipramine and desmethylimipramine plasma singledose data. Clin Pharmacol Ther 25:605–610
Fenimore DC, Meyer CJ, Davis CM (1977) High performance thin-layer chromatographic determination of psychopharmacologic agents in blood serum. J Chromatogr 142:399–409
Glassman A, Perel JM, Shostak M, Kantor SJ, Fleiss JL (1977) Clinical implications of imipramine plasma levels for depressive illness. Arch Gen Psychiatry 34:197–204
Gram LF (1977a) Factors influencing the metabolism of tricyclic antidepressants. Dan Med Bull 24:81–89
Gram LF (1977b) Plasma level monitoring of tricyclic antidepressants. Clin Pharmacokinet 2:237–251
Gram LF, Christiansen J, Fredricson Overø K (1974) Pharmacolinetic interaction between neuroleptics and tricyclic antidepressants in rats. Acta Pharmacol 35:223–232
Gram LF, Fredricson Overø K (1972) Drug interaction: Inhibitory effect of neuroleptics on metabolism of tricyclic antidepressants in man. Br Med J 1:463–465
Gram LF, Søndergaard I, Christiansen J, Odden Petersen G, Bech P, Reisby N, Ibsen I, Ortmann J, Nagy A, Dencker SJ, Jacobsen O, Krautwald O (1977) Steady-state kinetics of imipramine in patients. Psychopharmacology 54:255–261
Gurney C, Roth M, Garside RF, Kerr TA, Schapira K (1972) Studies on the classification of affective disorder. Br J Psychiatry 121:162–166
Hamilton M (1967) Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 6:278–296
Kragh-Sørensen P, Brogå O, Garle M, Bolvig-Hansen L, Hansen CE, Hvidberg EF, Larsen N-E, Sjöqvist F (1977) Effects of simultaneous treatment with low doses of perphenazine and plasma and urine concentrations of nortriptyline and 10-hydroxynortriptyline. Eur J Clin Pharmacol 11:479–483
Kragh-Sørensen P, Hansen CE, Åsberg M (1973) Plasma levels of nortriptyline in the treatment of endogenous depression. Acta Psychiatr Scand 49:444–456
Kragh-Sørensen P, Hansen CE, Baastrup PC, Hvidberg EF (1976) Selfinhibiting action of nortriptyline antidepressive effect at high plasma levels. Psychopharmacologia 45:305–316
Kragh-Sørensen P, Larsen NE (1980) Factors influencing the steadystate kinetics of nortriptyline in patients. Clin Pharmacol Ther 28:796–803
Nagy A, Johansson R (1977) The demethylation of imipramine and clomipramine as apparent from their plasma kinetics. Psychopharmacology 54:125–131
Nagy A, Treiber L (1973) Quantitative determination of imipramine and desipramine in human blood by direct densitometry of thin-layer chromatograms. J Pharm Pharmacol 25:599–603
Nies A, Robinson DS, Friedman MJ, Green R, Cooper TB, Ravaris CL, Ives JO (1977) Relationship between age and tricyclic antidepressant plasma levels. Am J Psychiatry 134:790–793
Reisby N, Gram LF, Bech P, Nagy A, Petersen GO, Ortmann J, Ibsen I Dencker SJ, Jacobsen O, Krautwald O, Søndergaard I, Christiansen J (1977) Imipramine: Clinical effects and pharmacokinetic variability. Psychopharmacology 54:263–272
Thayssen P, Bjerre M, Kragh-Sørensen P, Møller M, Pedersen DL, Kristensen CB, Gram LF (1981) Cardiovascular effects of imipramine and nortriptyline in elderly patients. Psychopharmacology 74:360–364
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Bjerre, M., Gram, L.F., Kragh-Sørensen, P. et al. Dose-dependent kinetics of imipramine in elderly patients. Psychopharmacology 75, 354–357 (1981). https://doi.org/10.1007/BF00435852
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DOI: https://doi.org/10.1007/BF00435852