Summary
Seven male inpatients suffering from acute schizophrenia were treated with chlorpromazine elixir 100mg 8-hourly for 9 weeks. Nortriptyline 50mg 8-hourly was added during weeks 4, 5 and 6. Plasma chlorpromazine concentrations, antipyrine plasma half-life, blood pressure, pulse rate, pupil size, salivation, handwriting and clinical state were measured at weekly intervals.
Plasma chlorpromazine concentrations rose when nortriptyline was added, and the antipyrine plasma half-life was prolonged. Blood pressure dropped on institution of chlorpromazine and dropped further with the addition of nortriptyline. The pulse rate rose in a parallel fashion. Pupil size, salivation and handwriting were diminished by chlorpromazine, but hardly affected further by nortriptyline. The addition of nortriptyline dramatically reversed the therapeutic actions of chlorpromazine, mainly through pharmacodynamic interaction.
It is concluded that this combination is potentially deleterious, and must be used with care.
Similar content being viewed by others
References
Brodie, B.B.; Axelrod, J.; Soberman, R. and Levy, B.B.: The estimation of antipyrine in biological materials. Journal of Biological Chemistry 179: 25–29 (1949).
Curry, S.H.: Determination of nanogram quantities of chlorpromazine and some of its metabolites in plasma using gas-liquid chromatography with an electron-capture detector. Analytical Chemistry 40: 1251–1256 (1968).
Curry, S.H.: Antipsychotic agents. Chlorpromazine: pharmacokinetics, plasma levels and clinical response; in Burrows and Norman (Eds) Psychotropic Drugs — Plasma Concentration and Clinical Response, pp.243–286 (Marcel Dekker, New York 1980).
Curry, S.H.; Marshall, J.H.L.; Davis, J.M. and Janowsky, D.S.: Chlorpromazine plasma levels and effects. Archives of General Psychiatry 22: 289–296 (1970).
Goldberg, S.C.; Cole, J.O. and Clyde, D.J.: Factor analyses of ratings of schizophrenic behavior. Psychopharmacology Service Center Bulletin 2: 23–38 (1963).
Gram, L.F. and Øvero, K.F.: Inhibitory effect of neuroleptics on metabolism of tricyclic antidepressants in man. British Medical Journal 1: 463–465 (1972).
Hollister, L.: Clinical Pharmacology of Psychotherapeutic Drugs (Churchill Livingstone, New York 1978).
Johnson, D.A.W.: Studies of depressive symptoms in schizophrenia. British Journal of Psychiatry 139: 89–101 (1981).
Loga, S.; Curry, S. and Lader, M.: Interactions of orphenadrine and phenobarbitone with chlorpromazine: Plasma concentrations and effects in man. British Journal of Clinical Pharmacology 2: 197–208 (1975).
Rivera-Calimlim, L.; Castanéda, L. and Lasagna, L.: Effects of mode of management on plasma chlorpromazine in psychiatric patients. Clinical Pharmacology and Therapeutics 14: 987–988 (1973).
Sakalis, G.; Curry, S.H.; Mould, G.P. and Lader, M.H.: Physiology and clinical effects of chlorpromazine and their relationship to plasma level. Clinical Pharmacology and Therapeutics 13: 931–946 (1972).
van Putten, T.; May, P.R.A. and Jenden, D.J.: Does a plasma level of chlorpromazine help? Psychological Medicine. In press (1981).
Vesell, E.S.; Passananti, T. and Greene, F.E.: Impairment of drug metabolism in man by allopurinol and nortriptyline. New England Journal of Medicine 283: 1484–1488 (1970).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Loga, S., Curry, S. & Lader, M. Interaction of Chlorpromazine and Nortriptyline in Patients with Schizophrenia. Clin Pharmacokinet 6, 454–462 (1981). https://doi.org/10.2165/00003088-198106060-00003
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003088-198106060-00003