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Clinical Efficacy of Clozapine in Treatment-Refractory Schizophrenia: An Overview

Published online by Cambridge University Press:  06 August 2018

John M. Kane
John M. Kane*
Affiliation:
Department of Psychiatry, Hillside Hospital, Division of Long Island Jewish Medical Center, Glen Oaks, New York, Albert Einstein College of Medicine, Bronx, New York
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Abstract

The treatment of patients with schizophrenia who fail to respond to antipsychotic medications remains a challenge. Despite numerous attempts to establish effective somatic treatment approaches for this population, clozapine appears to be the only well established alternative. Depending upon trial duration and response criteria, between 30% and 60% of previously unresponsive patients appear to derive clinically significant benefit from clozapine. Clozapine also has important advantages in terms of its reduced propensity to produce extrapyramidal side-effects. Agranulocytosis remains an important risk, so strategies to improve the benefit-to-risk ratio should be explored. Issues such as trial duration, dosage, blood levels and predictors of response require additional study.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 160 , Issue S17: Clozapine - The Atypical Antipsychotic , May 1992 , pp. 41 - 45
Copyright
Copyright © The Royal College of Psychiatrists 

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References

Ackenheil, V. M., Brau, H., Burkhart, A., et al (1976) Antipsychotic efficacy in relation to plasma levels of clozapine. Arzneimittel Forschung Drug Research, 26, 1156–1158.Google Scholar
American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised) (DSM-III-R). Washington, DC: APA.Google Scholar
Baldessarini, R. J. & Frankenburg, F. R. (1991) Clozapine: a novel antipsychotic agent. New England Journal of Medicine, 324, 746–754.Google ScholarPubMed
Brau, H., Burkhart, A., Pacha, W., et al (1978) Relationships between effects and plasma levels of clozapine. Arzneimittel Forschung Drug Research, 28, 1300.Google Scholar
Cheng, Y. F., Lundberg, T., Bondesson, U., et al (1988) Clinical pharmacokinetics of clozapine in chronic schizophrenic patients. European Journal of Clinical Pharmacology, 34, 445–449.CrossRefGoogle ScholarPubMed
Christisen, G. W., Kirch, D. G. & Wyatt, R. J. (1991) When symptoms persist: choosing among alternative somatic treatments for schizophrenia. Schizophrenia Bulletin, 17, 217–245.Google Scholar
Ereshefsky, L., Watanabe, M. D. & Tran-Johnson, T. K. (1989) Clozapine: an atypical antipsychotic agent. Clinical Pharmacology, 8, 691–709.Google ScholarPubMed
Fitton, A. & Heel, R. C. (1990) Clozapine: a review of its pharmacological properties and therapeutic use in schizophrenia. Drugs, 40, 722–747.CrossRefGoogle ScholarPubMed
Friedman, L., Bastani, B., Ramirez, L. F., et al (1991) Pre-frontal sulcal prominence is inversely related to treatment response to clozapine in schizophrenia. Schizophrenia Research, 4, 317.Google Scholar
Guy, W. (1976) ECDEU Assessment Manual for Psychopharmacology, pp. 218–222. Rockville, MD: US Dept of Health and Human Services Publication (ADM) 76–338.Google Scholar
Haring, C., Fleischhacker, W. W., Schett, P., et al (1990) Influence of patient-related variables on clozapine plasma levels. American Journal of Psychiatry, 147, 1471–1475.Google ScholarPubMed
Honigfeld, G., Gillis, R. D. & Klelt, C. J. (1966) NOSIE-30: a treatment-sensitive ward behaviour scale. Psychological Reports, 19, 180–182.Google Scholar
Honigfeld, G. & Patin, J. (1989) Predictors of response to clozapine therapy. Psychopharmacology, 99, S64–S67.Google Scholar
Kane, J., Honigfeld, G., Singer, J., et al (1988) Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlorpromazine. Archives of General Psychiatry, 45, 789–796.Google Scholar
Kuha, S. & Miettinen, E. (1986) Long-term effect of clozapine in schizophrenia: A retrospective study of 108 chronic schizophrenics treated with clozapine for up to 7 years. Nordisk Psykiatrisk Tidsskrift, 40, 225–230.CrossRefGoogle Scholar
Leppig, M., Bosch, B., Naber, D., et al (1989) Clozapine in the treatment of 121 outpatients. Psychopharmacology, 9, S77–S79.Google Scholar
Lieberman, J. A., Kane, J. M. & Johns, C. (1989) Clozapine: guidelines for clinical management. Journal of Clinical Psychiatry, 50, 329–338.Google Scholar
Lieberman, J. A., Yunis, J., Egea, E., et al (1990) HLA-B38, DR4, DQW3 and clozapine-induced agranulocytosis in Jewish patients with schizophrenia. Archives of General Psychiatry, 47, 945–948.Google Scholar
Lieberman, J. A., Mayerhoff, D., Loebel, A., et al (1991) Biologie indices of heterogenity in schizophrenia: Relationship to psychopathology and treatment outcome. Schizophrenia Research, 4, 289–290.CrossRefGoogle Scholar
Lindström, L. H. (1988) The effect of long-term treatment of clozapine in schizophrenia: a retrospective study of 96 patients treated with clozapine for up to 13 years. Acta Psychiatrica Scandinavica, 77, 524–529.CrossRefGoogle ScholarPubMed
Mattes, J. A. (1989) Clozapine for refractory schizophrenia: an open study of 14 patients treated up to two years. Journal of Clinical Psychiatry, 50, 389–391.Google Scholar
Meltzer, H. Y., Bastani, B., Youngkwon, K., et al (1989) A prospective study of clozapine in treatment-resistant schizophrenic patients. I. Preliminary report. Psychopharmacology, 99, S68–S72.CrossRefGoogle ScholarPubMed
Meltzer, H. Y., Burnett, S., Bastani, B., et al (1990) Effects of six months of clozapine treatment on the quality of life of schizophrenic patients. Hospital and Community Psychiatry, 41, 892–897.Google Scholar
Naber, D. & Hippius, H. (1990) The European experience with the use of clozapine. Hospital and Community Psychiatry, 41, 886–889.Google ScholarPubMed
Naber, D., Leppig, M., Grohmann, R., et al (1989) Efficacy and adverse effects in the treatment of schizophrenia and tardive dyskinesia - a retrospective study of 387 patients. Psychopharmacology, 99, S73–S76.CrossRefGoogle ScholarPubMed
Overall, J. E. & Gorham, D. R. (1962) The Brief Psychiatric Rating Scale. Psychological Reports, 10, 799–812.CrossRefGoogle Scholar
Owen, R. R., Beake, B. J. & Marby, D. (1989) Response to clozapine in chronic psychotic patients. Psychopharmacology Bulletin, 25, 253–256.Google ScholarPubMed
Perry, P. J., Miller, D. D., Arndt, S. V., et al (1991) Clozapine and norclozapine plasma concentrations and clinical response in treatment-refractory schizophrenics. American Journal of Psychiatry, 148, 231–235.Google Scholar
Povlsen, U. J., Noring, U., Fog, R., et al (1985) Tolerability and therapeutic effect of clozapine: a retrospective investigation of 216 patients treated with clozapine for up to 12 years. Acta Psychiatrica Scandinavica, 71, 176–185.Google Scholar
Revicki, D. A., Luce, B. R., Weschler, J. M., et al (1990) Economic grand rounds: cost-effectiveness of clozapine for treatment-resistant schizophrenic patients. Hospital and Community Psychiatry, 41, 850–862.Google Scholar
Safferman, A., Lieberman, J., Kane, J., et al (1991) Update on the clinical efficacy and side effects of clozapine. Schizophrenia Bulletin, 17, 247–261.CrossRefGoogle ScholarPubMed
Simpson, G. M. & Cooper, T. A. (1978) Clozapine plasma levels and convulsions. American Journal of Psychiatry, 135, 99–100.Google Scholar
Small, J. G., Milstein, V., Marhenke, J. D., et al (1987a) Treatment outcome with clozapine in tardive dyskinesia, neuroleptic sensitivity in treatment-resistant psychosis. Journal of Clinical Psychiatry, 48, 263–267.Google Scholar
Small, J. G., Small, I. F., et al (1987b) Computerized EEG profiles of haloperidol, chlorpromazine, clozapine and placebo in treatment resistant schizophrenia. Clinical Electroencephalography, 18, 124–135.Google ScholarPubMed
Thorup, M. & Fog, R. (1977) Clozapine treatment of schizophrenic patients: plasma concentrations and coagulation factors. Acta Psychiatrica Scandinavica, 55, 123–126.Google Scholar
Zapletálek, M., Hanus, H., Kucera, V., et al (1989) Results of the long-term treatment with clozapine: clinical and electro-encephalographic study. Activitas Nervosa Superior, 31, 36–37.Google Scholar
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