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The Effects of Clozapine on Tardive Dyskinesia

  • Jeffrey A. Lieberman (a1), Bruce L. Saltz (a2), Celeste A. Johns (a3), Simcha Pollack (a4), Michael Borenstein (a3) and John Kane (a5)...

This article reviews eight published studies that describe clozapine's effects on TD and examines the outcome of 30 patients with TD treated with clozapine for up to 36 months. These data indicate that TD response to clozapine is variable but that approximately 43% of cases, particularly those with dystonic features, improved after clozapine treatment. Methodological limitations of the studies described, however, preclude definitive conclusions, which must await appropriately controlled trials.

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Hillside Hospital, Division of Long Island Jewish Medical Center, PO Box 38, Glen Oaks, New York, USA
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Anderson, P. H. & Braestrup, C. (1986) Evidence for different states of the dopamine D1 receptor: clozapine and fluperlapine may preferentially label an adenylate cyclase-coupled state of the D1 receptor. Journal of Neurochemistry, 47, 18221831.
Arnt, J. & Hyttel, J. (1984) Differential inhibition by dopamine D1 and D2 antagonists of circling behavior induced by dopamine agonists in rats with unilateral 6–hydroxy-dopamine lesions. European Journal of Pharmacology, 102, 349359.
Baldessarini, R. J., Cole, J. O., Davis, J. M., et al (1980) Tardive Dyskinesia: Task Force Report. Washington, DC: APA.
Barnes, T. R. E. & Braude, W. M. (1985) Akathisia variants and tardive dyskinesia. Archives of General Psychiatry, 42, 874878.
Burke, R. E., Fahn, S., Jankovic, J., et al (1982) Tardive dystonia: late onset and persistent dystonia caused by antipsychotic drugs. Neurology, 32, 13351346.
Burki, H. R., Sayers, A. C., Ruch, W., et al (1975) Clozapine and the dopamine hypothesis of schizophrenia, a critical appraisal. Pharmacopsychiatry, 8, 115121.
Caine, E. D., Polinsky, R. J., Kartzinel, R., et al (1979) The trial use of clozapine for abnormal involuntary movement disorders. American Journal of Psychiatry, 136, 317320.
Carroll, B. J., Curtiss, C. G. & Kokmen, E. (1977) Paradoxical response to dopamine agonists in tardive dyskinesia. American Journal of Psychiatry, 134, 785790.
Chiodo, L. A. & Bunney, B. S. (1983) Typical and atypical neuroleptics: differential effects of chronic administration on the activity of A9 and A10 midbrain dopaminergic neurons. Journal of Neuroscience, 3, 16071619.
Cole, J. O., Gardos, G., Tarsy, D., et al (1980) Drug trials in persistent dyskinesia. In Tardive Dyskinesia, Research and Treatment (eds W. E. Fann, R. C. Smith, J. M. Davis, et al), pp. 419427. New York: SP Medical and Scientific Books.
Gerbino, L., Shopsin, B. & Collora, M. (1980) Clozapine in the treatment of tardive dyskinesia: an interim report. In Tardive Dyskinesia, Research and Treatment (eds W. E. Fann, R. C. Smith, J. M. Davis, et al), pp. 475489. New York: SP Medical and Scientific Books.
Gerlach, J., Koppelhus, P. & Helweg, E. (1974) Clozapine and haloperidol in a single-blind crossover trial: therapeutic and biochemical aspects in the treatment of schizophrenia. Acta Psychiatrica Scandinavica, 50, 410424.
Jeste, D. V. & Wyatt, R. J. (1982) Therapeutic strategies against tardive dyskinesia: two decades of experience. Archives of General Psychiatry, 39, 803816.
Juul Povisen, U., 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, 176185.
Kane, J. & Smith, J. (1982) Tardive dyskinesia: prevalence and risk factors. Archives of General Psychiatry, 39, 473481.
Kane, J., Woerner, M., Lieberman, J., et al (1986) Tardive dyskinesias and drugs. Drug Development Research, 9, 4151.
Kane, J., Honigfeld, G., Singer, J., et al (1988) Clozapine for the treatment-resistant schizophrenic: a double blind comparison versus chlorpromazine. Archives of General Psychiatry, 45, 789796.
Lieberman, J., Kane, J., Woerner, M., et al (1984) Prevalence of tardive dyskinesia in elderly samples. Psychopharmacology Bulletin, 20, 2226.
Lieberman, J., Kane, J., Johns, C., et al (1986) Clozapine: clinical evidence of novel effects. Clinical Neuropharmacology, 9, 140.
Lieberman, J., Pollack, S., Lesser, M. S., et al (1988) Pharmacologic characterization of tardive dyskinesia. Journal of Clinical Psychopharmacology, 8, 254260.
Lieberman, J., Kane, J. & Johns, C. (1989a) Clozapine: guidelines for clinical management. Journal of Clinical Psychiatry, 50, 329338.
Lieberman, J., Alvir, J., Mukherjee, S., et al (1989b) Treatment of tardive dyskinesia with bromocriptine: a test of the receptor modification strategy. Archives of General Psychiatry, 46, 908913.
Ljungberg, T. & Ungerstedt, U. (1978) Classification of neuroleptic drugs according to their ability to inhibit apomorphine-induced locomotion and gnawing: evidence for two different mechanisms of action. Psychopharmacology, 56, 239247.
McClelland, H. A., Dutta, D., Metcalfe, A., et al (1986) Mortality and facial dyskinesia. British Journal of Psychiatry, 148, 310316.
McMillen, B. A. & Shore, P. A. (1978) Comparative effects of clozapine and alpha-adrenoceptor blocking drugs on regional noradrenaline metabolism in rat brain. European Journal of Pharmacology, 52, 225230.
Meltzer, H. Y. & Luchins, D. J. (1984) Effect of clozapine in severe tardive dyskinesia: a case report. Journal of Clinical Psychopharmacology, 4, 286287.
Reynolds, G. P., Garret, N. J., Rupniak, N., et al (1983) Chronic clozapine treatment of rats down-regulates cortical 5–HT2 receptors. European Journal of Pharmacology, 89, 325326.
Rosengarten, H., Schweitzer, J. W. & Friedhoff, A. J. (1986) Selective dopamine D2 receptor reduction enhances a D1 mediated oral dyskinesia in rats. Life Science, 39, 2935.
Rupniak, N. M. J., Hall, M. D., Mann, S., et al (1985) Chronic treatment with clozapine, unlike haloperidol, does not induce changes in striatal D2 receptor function in the rat. Biochemical Pharmacology, 34, 27552763.
Savers, A. C., Burki, H. R., Ruch, W., et al (1975) Neuroleptic-induced hypersensitivity of striatal dopamine receptors in the rat as a model of tardive dyskinesia. Effects of clozapine, haloperidol, loxapine and chlorpromazine. Psychopharmacology, 41, 97104.
Schmutz, J. & Eichenberger, E. (1982) Clozapine. Chronicles Drug Discovery, 1, 3959.
Simpson, G., Lee, J. H. & Shrivastava, R. K. (1978) Clozapine in tardive dyskinesia. Psychopharmacology, 56, 7580.
Small, J. G., Milstein, V., Marhenke, J. D., et al (1987) Treatment outcome with clozapine in tardive dyskinesia, neuroleptic sensitivity, and treatment-resistant psychosis. Journal of Clinical Psychiatry, 48, 263267.
Yassa, R. & Jones, B. (1985) Complications of tardive dyskinesia: a review. Psychosomatics, 26, 305313.
Youssef, H. A. & Waddington, J. L. (1987) Morbidity and mortality in tardive dyskinesia: associations in chronic schizophrenia. Acta Psychiatrica Scandinavica, 75, 7477.
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The Effects of Clozapine on Tardive Dyskinesia

  • Jeffrey A. Lieberman (a1), Bruce L. Saltz (a2), Celeste A. Johns (a3), Simcha Pollack (a4), Michael Borenstein (a3) and John Kane (a5)...
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