Abstract
Sixty-six hospitalized depressed patients were treated for 4 weeks with imipramine (Tofranil®) 225 mg/day. Blood samples were drawn twice weekly 15 h after the last drug intake, and IP and DMI concentrations in plasma were assayed by quantitative in situ thin-layer chromatography. Clinical rating was carried out once weekly by Hamilton's Rating Scale (HRS), Beck's Depression Inventory, WHO Depression Scale (Quantitative Part), and a side-effect scale. The patients were classified on the basis of the WHO Depression Scale (Qualitative Part) as ‘endogenous’ (N=37) or ‘non-endogenous’ depressions (N=29). Antidepressive effect was evaluated on the basis of the posttreatment rating scores.
In patients classified as ‘endogenous’ depressions all 12 responding patients (HRS≦7) had plasma levels of IP>45 μg/l and DMI>75 μg/l, whereas 11 out of 14 nonresponding patients (HRS≧16) had plasma levels of one or both compounds below these limits. Ten out of 12 responders had levels of IP+DMI above 240 μg/l, and all nonresponders had levels of IP+DMI below this limit. Patients with partial response (HRS: 8–15) formed an overlapping group. There was no sign of an upper plasma level limit for the antidepressive effect of imipramine.
The plasma level/effect relationship was less clear in patients with ‘non-endogenous’ depressions, since several of them responded at low plasma levels.
Some relationship between effect on blood pressure (orthostatic effect) and high plasma levels of IP and DMI was found.
Using a plasma level limit of IP≷45 μg/l and DMI≷75 μg/l, it was possible to predict the response of the ‘endogenous’ depression group for 10 out of 12 responders and 10 out of 14 nonresponders on the basis of plasma level measurements obtained after 1 week of treatment.
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Åsberg, M., Cronholm, B., Sjöqvist, F., Tuck, D.: Relationship between plasma level and therapeutic effect of nortriptyline. Br. Med. J. 1971III, 331–334
Bech, P., Gram, L. F., Dein, E., Jacobsen, O., Vitger, J., Bolwig, T. G.: Quantitative rating of depressive states. Acta Psychiatr. Scand. 51, 161–170 (1975)
Beck, A. T., Ward, C. H., Mendelsohn, M., Moch, J., Erbaugh, J.: An inventory for measuring depression. Arch. Gen. Psychiatry 4, 561–571 (1961)
Benett, J. F.: Is there a superior antidepressant? In: Antidepressant drugs, S. Garattini and M. N. G. Duker, eds. Excepta Medica ICS 122, 375–393 (1967)
Carney, M. W. P., Roth, M., Garside, R. F.: The diagnosis of depressive syndromes and the prediction of ECT response. Br. J. Psychiatry 111, 659–674 (1965)
Carney, M. W. P., Sheffield, B. F.: Depression and the Newcastle scales. Br. J. Psychiatry 121, 35–40 (1972)
Gessner, P. K.: The isobolographic method applied to drug interaction. In: Drug interactions, P. L. Morselli, S. Garattini, and S. N. Cohen, eds., pp. 349–362. New York: Raven Press 1974
Glassman, A. H., Hurwic, M. J., Perel, J. M.: Plasma binding of imipramine and clinical outcome. Am. J. Psychiatry 130, 1367–1369 (1973)
Glassman, A. H., Kantor, S. J., Shostak, M.: Depression, delusions, and drug response. Am. J. Psychiatry 132, 716–719 (1975a)
Glassman, A. H., Shostak, M., Kantor, S. J., Perel, J. M.: Plasma levels of imipramine and clinical outcome. Psychopharmacol. Bull. 11, 27–28 (1975b)
Gram, L. F.: Requirements for controlled clinical trials with antidepressants. In: Neuropsychopharmacology, Proc. IX Congr. Coll. Int. Neuropsychopharm., Paris, 1974, J. R. Boissier, H. Hippius, and P. Pichot, eds., pp. 817–821. ICS 359 Amsterdam 1975
Gram, L. F.: Clinical significance of measuring plasma levels of antidepressants. In: Proc. Xth Congr. Coll. Int. Neuropsychopharm., Quebec, 1976, P. Deniker, C. Radouco-Thomas, and A. Villeneuve, eds. Oxford and New York: Pergamon Press (1977)
Gram, L. F., Fredricson Overø, K., Kirk, L.: Influence of neuroleptics and benzodiazepines on metabolism of tricyclic antidepressants in man. Am. J. Psychiatry 131, 863–866 (1974)
Gram, L. F., Reisby, N., Ibsen, I., Nagy, A., Dencker, S.-J., Bech, P., Odden Petersen, G., Christiansen, J.: Plasma levels and antidepressive effect of imipramine. Clin. Pharmacol. Ther. 19, 318–324 (1976)
Gram, L. F., Søndergaard, I., Christiansen, J., Odden Petersen, G., Bech, P., Reisby, N., Ibsen, I., Ortmann, J., Nagy, A., Dencker, S.-J., Jacobsen, O., Krautwald, O.: Steady-state kinetics of imipramine in patients. Psychopharmacology 54, 255–261 (1977)
Gurney, C., Roth, M., Garside, R. F., Kerr, T. A., Schapira, K.: Studies in the classification of affective disorders. The relationship between anxiety state and depressive illness. Br. J. Psychiatry 121, 162–166 (1972)
Hamilton, M.: A rating scale for depression. Neurol. Neurosurg. Psychiatry 23, 56–62 (1960)
Hamilton, M.: Psychotropic drugs: general considerations. Int. Encyclop. Pharmacol. Ther. 6, 181–201 (1966)
Kerr, T. A., Roth, M., Schapira, K., Gurney, C.: The assessment and prediction of outcome in affective disorders. Br. J. Psychiatry 121, 167–174 (1972)
Kragh-Sørensen, P., Hansen, C. E., Åsberg, M.: Plasma-nortriptyline levels in endogenous depressions. Lancet 1973 I, 113–115
Kragh-Sørensen, P., Hansen, C. E., Baastrup, P. C., Hvidberg, E. F.: Self-inhibiting action of nortriptyline's antidepressive effect at high plasma levels. Psychopharmacologia (Berl.) 45, 305–312 (1976)
Nagy, A., Treiber, L.: Quantitative determination of imipramine and desipramine in human blood by direct densitometry of thin layer chromatography. J. Pharm. Pharmacol. 25, 599–603 (1973)
Perris, C.: The course of depressive psychoses. Acta Psychiatr. Scand. 44, 238–248 (1968)
Sartorius, N.: Description and classification of depressive disorders. Pharmakopsychiatr. Neuropsychopharmakol. 7, 76–79 (1974)
Silvermann, G., Braithwaite, R. A.: Benzodiazepines and tricyclic antidepressant plasma levels. Br. Med. J. 1973 III, 18–20
Whyte, S. F., MacDonald, A. J., Naylor, G. J., Moody, J. P.: Plasma concentrations of protriptyline and clinical effects in depressive women. Br. J. Psychiatry 128, 384–390 (1976)
Ziegler, V. E., Clayton, P. J., Taylor, J. R., Co, B. T., Biggs, J. T.: Nortriptyline plasma levels and therapeutic response. Clin. Pharmacol. Ther. 20, 458–463 (1976a)
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 (1976b)
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Reisby, N., Gram, L.F., Bech, P. et al. Imipramine: Clinical effects and pharmacokinetic variability. Psychopharmacology 54, 263–272 (1977). https://doi.org/10.1007/BF00426574
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DOI: https://doi.org/10.1007/BF00426574