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Clinical Response and Tricyclic Plasma Levels During Treatment with Clomipramine

  • L. Della Corte (a1), A. D. Broadhurst (a2), G. P. Sgaragli (a1), S. Filippini (a3), A. F. Heeley (a4), H. D. James (a5), C. Faravelli (a6) and A. Pazzagli (a3)...


Fifty depressed in-patients at two psychiatric units, one in Italy the other in England, were treated with clomipramine, either orally, or intravenously and orally. A comparison of clinical response with plasma levels of clomipramine and its metabolite, desmethylclomipramine, showed clear relationships especially in the case of desmethylclomipramine. In the intravenously-treated group this was linear, in the orally-treated group it was curvilinear. Plasma levels of desmethylclomipramine and administered clomipramine correlate highly.

These findings, together with the fact that significant clinical improvement was observed in only 55 per cent of the patients, suggest that titration of the administered dose to obtain more effective plasma levels of the metabolite might improve the clinical response to the drug in some patients.



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Ásberg, M., Crönholm, B., Sjöqvist, F. & Tuck, D. (1971) Relationship between plasma level and therapeutic effect of nortriptyline. British Medical Journal, 3, 331–4.
Benett, J. F. (1967) Is there a superior antidepressant? In: Antidepressant Drugs (eds. S. Grattini and M. N. G. Duker). Excerpta Medica ICS, 122, 375–93.
Biggs, J. T. & Ziegler, V. E. (1977) Protriptyline plasma levels and antidepressant response. Clinical Pharmacology and Therapeutics, 22, 269–73.
Braithwaite, R. A., Goulding, R., Theano, G., Bailey, J. & Coppen, A. (1972) Plasma concentration of amitriptyline and clinical response. The Lancet, i, 1297–300.
Broadhurst, A. D., James, H. D., Della Corte, L. & Heeley, A. F. (1977) Clomipramine plasma level and clinical response. Postgraduate Medical Journal, 53 (Suppl. 4), 139–45.
Burrows, G. D., Davies, B. & Scoggins, B. A. (1972) Plasma concentration of nortriptyline and clinical response in depressive illness. The Lancet, ii, 619–23.
Burrows, G., Scoggins, B. A., Turecek, L. R. & Davies, B. (1974) Plasma nortriptyline and clinical response. Clinical Pharmacology and Therapeutics, 16, 639–44.
Coppen, A., Montgomery, S., Ghose, K., Ramarao, V. A., Bailey, J., Christiansen, J., Mikkleson, P. L., van Praag, H. M., van De Poel, F., Minsker, E. J., Kozulja, V. G., Matussek, N., Kungkunz, G. & J⊘rgensen, A. (1978) Amitriptyline plasma concentration and clinical effect. The Lancet, i, 63–6.
Della Corte, L., Heeley, A. F., James, H. D., Broadhurst, A. D., Faravelli, C., Filippini, S. & Sgaragli, G. P. (1976) Pharmacokinetics of clomipramine in man. Evaluation of therapeutic and toxic effects. 1st USSR–ITALIAN Joint Meeting, Modena 23–25 September.
Dencker, H., Dencker, S. J., Green, A. & Nagy, A. (1976) Intestinal absorption, demethylation and entheropatic circulation of imipramine. Clinical Pharmacology and Therapeutics, 19, 584–6.
Feighner, J. P., Robins, E., Guze, S. B., Woodruff, R. A., Winokur, G. & Munoz, R. (1972) Diagnostic criteria for use in psychiatric research. Archives of General Psychiatry, 26, 5763.
Glassman, A. H., Perel, J. M., Shostak, M., Kantor, S. J. & Fless, J. L. (1977) Clinical implications of imipramine plasma levels for depressive illness. Archives of General Psychiatry, 34, 197204.
Gram, L. F., Over⊘, K. F. & Kirk, L. (1974) Influence of neuroleptics and benzodiazepines on metabolism of tricyclic antidepressants in man. American Journal of Psychiatry, 131, 863–6.
Gram, L. F., Reisby, N., Ibsen, I., Nagy, J. A., Dencker, S. J., Bech, P., Petersen, G. O. & Christiansen, J. (1976) Plasma levels and antidepressive effect of imipramine. Clinical Pharmacology and Therapeutics, 19, 318–24.
Hamilton, M. (1960) A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry, 23, 5662.
Kragh-S⊘rensen, P., Åsberg, M. & Eggert-Hansen, C. (1973) Plasma nortriptyline levels in endogenous depression. The Lancet, i, 113–5.
Kupfer, D. J., Hanin, I., Spiker, D. G., Grau, T. & Coble, T. (1977) Amitriptyline plasma levels and clinical response in primary depression. Clinical Pharmacology and Therapeutics, 22, 904–11.
Medical Research Council, Clinical Psychiatry Committee (1965) British Medical Journal, i, 881.
Miller, P., Luscombe, D. K., Jones, R. B., Seldrup, J., Beaumont, G. & John, V. (1977) Relationships between clinical response, plasma levels and side-effects of clomipramine (Anafranil) in general practitioner trials. Journal International Medical Research, 5, Supplement 1, 108–18.
Nagy, A. & Johansson, R. (1977) The demethylation of imipramine and clomipramine as apparent from their plasma kinetics. Psychopharmacology (Berlin), 54, 125–31.
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. (1977) Imipramine: clinical effects and pharmacokinetic variability. Psychopharmacology (Berlin), 54, 263–72.
Silverman, G. & Braithwaite, R. A. (1973) Benzodiazepines and tricyclic antidepressants plasma levels. British Medical Journal, iii, 1820.
Sjöqvist, F. (1975) Assessment of antidepressants— Pharmacokinetic aspects. In Advance Medicine Topics in Therapeutics, vol. 1, 198215. ed A. M. Breckenridge Pitman Medical.
Sulser, F., Vetulani, J. & Mobley, P. L. (1978) Mode of action of antidepressant drugs. Biochemical Pharmacology, 27, 257–61.
Whyte, S. F., McDonald, A. J., Naylor, G. J. & Moody, J. P. (1976) Plasma concentrations of protriptyline and clinical effects in depressed women. British Journal of Psychiatry, 128, 384–90.
Ziegler, V. E., Clayton, P. J., Taylor, J. R., Co, B. T. & Biggs, J. T. (1976) Nortriptyline plasma levels and therapeutic response. Clinical Pharmacology and Therapeutics, 20, 458–63.
Ziegler, V. E., Clayton, P. J. & Biggs, J. T. (1977) A comparison study of amitriptyline and nortriptyline with plasma levels. Archives General Psychiatry, 34, 607–12.


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Clinical Response and Tricyclic Plasma Levels During Treatment with Clomipramine

  • L. Della Corte (a1), A. D. Broadhurst (a2), G. P. Sgaragli (a1), S. Filippini (a3), A. F. Heeley (a4), H. D. James (a5), C. Faravelli (a6) and A. Pazzagli (a3)...
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