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The Strange Story of Clozapine

Published online by Cambridge University Press:  03 January 2018

P. J. McKenna*
Affiliation:
Fulbourn Hospital, Cambridge CB1 5EF
P. E. Bailey
Affiliation:
Clinical Research, Sandoz Pharma Ltd, CH-4002 Basel, now Boehringer Ingelheim Deutschland GmbH, Klinische Forschung Ingelheim, Bingerstrasse 173, D-6507 Ingelheim am Rhein, Germany
*
Correspondence

Extract

A feature of the recent history of medicine has been the introduction of treatments whose costs are orders of magnitude higher than doctors are used to justifying. Having previously been left almost untouched by these developments, psychiatrists are beginning to find themselves in the position previously occupied by renal physicians, transplant surgeons, and oncologists – having to face uncomfortable decisions about costs versus benefits and the rationing of medical care. To a considerable extent this is a consequence of the launch of the new, ‘atypical’, and ‘superior’ neuroleptic, clozapine.

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Copyright © The Royal College of Psychiatrists 

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References

Bablenis, E., Weber, S. S. & Wagner, R. L. (1989) Clozapine: a novel antipsychotic agent. Drug Intelligence and Clinical Pharmacology, 23, 109115.Google ScholarPubMed
Baldessarini, R. J., Cohen, B. M. & Teicher, M. H. (1988) Significance of neuroleptic dose and plasma levels in the pharmacological management of the psychoses. Archives of General Psychiatry, 45, 7991.CrossRefGoogle Scholar
Baldessarini, R. J. & Frankenburg, F. R. (1991) Clozapine: a novel antipsychotic agent. New England Journal of Medicine, 324, 746754.Google ScholarPubMed
Breier, A., Wolkowitz, O. M., Doran, A. R., et al (1987) Neuroleptic responsivity of negative and positive symptoms. American Journal of Psychiatry, 144, 15491555.Google ScholarPubMed
Brucke, T., Roth, J., Podreka, I., et al (1992) Striatal D2 receptor blockade by typical and atypical neuroleptics. Lancet, i, 497.Google Scholar
Coward, D. M. (1992) General pharmacology of clozapine. British Journal of Psychiatry, 160 (suppl. 17): 512.Google Scholar
Creese, I., Burt, D. R. & Snyder, S. H. (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science, 192, 481483.CrossRefGoogle ScholarPubMed
Davis, J. M. (1985) Organic therapies. In Comprehensive Textbook of Psychiatry (eds Kaplan, H. I. & Sadock, B. J.). Baltimore: Williams & Wilkins.Google Scholar
Ekblom, B. & Haggstrom, J. E. (1974) Clozapine compared with chlorpromazine: a double-blind evaluation of pharmacological and clinical properties. Current Therapeutic Research, 16, 945957.Google ScholarPubMed
Farde, L., Wiesel, F.-A., Hall, H., et al (1987) No D2 receptor increase in PET study of schizophrenia. Archives of General Psychiatry, 44, 671672.CrossRefGoogle ScholarPubMed
Farde, L., Wiesel, F.-A., Nordstrom, A.-L., et al (1989) D,- and D2-dopamine receptor occupancy during treatment with conventional and atypical neuroleptics. Psychopharmacology, 99 (suppl.), S28S31.CrossRefGoogle ScholarPubMed
Farde, L., Wiesel, F.-A., Stone-Elander, S., et al (1990) D2 dopamine receptors in neuroleptic-naive schizophrenic patients. Archives of General Psychiatry, 47, 213219.Google Scholar
Farde, L. & Nordstrom, A.-L. (1992) PET analysis indicates atypical central dopamine receptor occupancy in clozapine-treated patients. British Journal of Psychiatry, 160 (suppl. 17): 3033.Google Scholar
Fischer-Cornelssen, K. A. & Ferner, U. J. (1976) An example of European multi-center trials: multispectral analysis of clozapine. Psychopharmacology Bulletin, 12, 3439.Google Scholar
Fitton, A. & Heel, R. C. (1990) Clozapine: a review of its pharmacological properties and therapeutic use in schizophrenia. Drugs, 40, 722747.Google Scholar
Freeman, H. (1978) Pharmacological treatment and management. In Schizophrenia: Towards a New Synthesis (ed. Wing, J. K.). London: Academic Press.Google Scholar
Gerlach, J., Jorgensen, E. O. & Peacock, L. (1989) Long-term experience with clozapine in Denmark: research and clinical practice. Psychopharmacology, 99 (suppl.), S92S96.Google Scholar
Goldberg, S. C., Klerman, G. L. & Cole, J. O. (1965) Changes in schizophrenic psychopathology and ward behaviour as a function of phenothiazine treatment. British Journal of Psychiatry, 111, 120133.CrossRefGoogle ScholarPubMed
Griffith, R. W. & Saameli, K. (1975) Clozapine and agranulocytosis. Lancet, 2, 657.Google Scholar
Gross, H. & Langner, E. (1966) Das Wirkungsprofil eines chemisch neuartigen Breitband-Neuroleptikums der Dibenzodiazepingruppe. Wiener Medizinische Wochenschrift, 116, 814816.Google Scholar
Hippius, H. (1989) The history of clozapine. Psychopharmacology, 99 (suppl.) S3S5.CrossRefGoogle ScholarPubMed
Johnstone, E. C., Crow, T. J., Frith, C. D., et al (1978) Mechanism of the antipsychotic effect in the treatment of acute schizophrenia. Lancet, i, 848851.Google Scholar
Kane, J. M., Honigfeld, G., Singer, J., et al (1988) Clozapine for the treatment resistant schizophrenic. Archives of General Psychiatry, 45, 789796.CrossRefGoogle ScholarPubMed
Lader, M. (1989) Expert report on the clinical documentation of clozapine. (Sandoz Document 701/165, unpublished).Google Scholar
Letemendia, F. J. J. & Harris, A. D. (1967) Chlorpromazine and the untreated chronic schizophrenic. British Journal of Psychiatry, 113, 950958.CrossRefGoogle ScholarPubMed
Lieberman, J. A., Kane, J. M. & Johns, C. A. (1989) Clozapine: guidelines for clinical management. Journal of Clinical Psychiatry, 50, 329338.Google Scholar
Marder, S. R. & van Putten, T. (1988) Who should receive clozapine? Archives of General Psychiatry, 45, 865867.Google Scholar
Meltzer, H. Y. (1992) Dimensions of outcome with clozapine. British Journal of Psychiatry, 160 (suppl. 17): 4653.Google Scholar
Meltzer, H. Y., Daniels, S. & Fang, V. S. (1975) Clozapine increases rat serum prolactin levels. Life Science, 17, 339342.CrossRefGoogle ScholarPubMed
Pilowsky, L. S., Costa, D. C., Ell, P. J., et al (1992) Clozapine, single photon emission tomography, and the D2 dopamine receptor blockade hypothesis of schizophrenia. Lancet, 2, 199202.CrossRefGoogle Scholar
Seeman, P., Lee, T., Chau-Wong, M., et al (1976) Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature, 261, 717719.CrossRefGoogle ScholarPubMed
Sokoloff, P., Giros, B., Martres, M. P., et al (1990) Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature, 347, 146151.Google Scholar
Stille, G. & Hippius, H. (1971) Kritische Stellungsnahme zum Begriff der Neuroleptika (und von pharmakologischen und klinischen Befunden mit Clozapin). Pharmakopsychiatrie und Neuropsychopharmakologie, 4, 182191.CrossRefGoogle Scholar
Stille, G. & Fischer-Cornelssen, K. (1988) Die Entwicklung von Clozapin (Leponex) – ein Mysterium? In Pharmakopsychiatrie im Wandel der Zeit: Erlebnisse und Ergebnisse (Ed. Linde, O. K.). Germany: Tilia-Verlag Klingenmunster.Google Scholar
Sunahara, R. K., Guan, H.-C., O'Dowd, B. F., et al (1991) Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D,. Nature, 350, 614619.Google Scholar
Tune, L. E., Wong, D. F. & Pearlson, G. D. (1992) Elevated dopamine D2 receptor density in 23 schizophrenic patients: a positron emission tomography study with [11C]N-methylspiperone. Schizophrenia Research, 6, 147.Google Scholar
Van Tol, H. H. M., Bunzow, J. R., Guan, H.-C., et al (1991) Cloning of the gene for a human dopamine D4 receptor with high affinity for the neuroleptic clozapine. Nature, 350, 610614.CrossRefGoogle Scholar
Wong, D. F., Wagner, H. N., Tune, L. E., et al (1986) Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science, 234, 15581563.Google Scholar
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