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Towards More Effective Antipsychotic Treatment

Published online by Cambridge University Press:  06 August 2018

John M. Kane  and
Hugh L. Freeman
John M. Kane*
Affiliation:
Department of Psychiatry, Long Island Jewish Medical Center, New York, USA
Hugh L. Freeman
Affiliation:
University of Salford (current address 21 Montagu Square, London W1H 1RE)
*
Dr John M. Kane, Department of Psychiatry, Hillside Hospital Division, Long Island Jewish Medical Center, 7559 263rd Street, Glen Oaks, New York, NY 11004, USA
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Abstract

The development of antipsychotic drugs has followed two complementary approaches, either towards highly specific actions (e.g. on the dopamine receptor) or targeting a broad range of receptors. The properties of ‘atypical’ agents challenge the original dopamine hypothesis and suggest roles for a variety of dopamine receptors and for other pathways, such as serotonin. Older drugs, despite their proven efficacy in relieving many schizophrenic symptoms, have several drawbacks, being ineffective in some patients, relatively ineffective against negative symptoms, and causing adverse neurological effects which may, in turn, be associated with poor compliance. Among newer agents, currently available ones, such as clozapine and risperidone, offer the possibility of more effective control of negative symptoms and an improved side-effect profile, while others are in earlier stages of development. However, much still remains to be understood about their mechanisms of action.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 165 , Issue S25: New Standards in the Management and Understanding of Schizophrenia , November 1994 , pp. 22 - 31
Copyright
Copyright © 1994 The Royal College of Psychiatrists 

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References

Alvir, J. M. J., Lieberman, J. A., Safferman, A. Z., et al (1993) Clozapine-induced agranulocytosis: incidence and risk factors in the United States. New England Journal of Medicine, 329, 162–167.CrossRefGoogle ScholarPubMed
Baldessarini, R. H., Cohen, B. M. & Teicher, H. M. (1988) Significance of neuroleptic dose and plasma level in pharmacological treatment of psychosis. Archives of General Psychiatry, 45, 79–91.CrossRefGoogle Scholar
Bartels, S. J. & Drake, R. E. (1988) Depressive symptoms in schizophrenia: comprehensive differential diagnosis. Comprehensive Psychiatry, 29, 467–483.CrossRefGoogle ScholarPubMed
Bleich, A., Brown, S. L., Cahn, R., et al (1988) The role of serotonin in schizophrenia. Schizophrenia Bulletin, 14, 297–315.CrossRefGoogle ScholarPubMed
Braude, W. M., Barnes, T. R. E. & Gore, S. N. (1983) Clinical characteristics of akathisia. British Journal of Psychiatry, 143, 134–150.CrossRefGoogle ScholarPubMed
Brenner, H. D., Dencker, S. J., Goldstein, M. J., et al (1990) Defining treatment refractoriness in schizophrenia. Schizophrenia Bulletin, 16, 551–562.CrossRefGoogle ScholarPubMed
Breslin, N. A. (1992) Treatment of schizophrenia: current practice and future promise. Hospital and Community Psychiatry, 43, 877–884.Google ScholarPubMed
Brier, A., Buchanan, R. W., Kirkpatrick, B., et al (1994) Effects of clozapine on positive and negative symptoms in outpatients with schizophrenia. American Journal of Psychiatry, 151, 20–26.Google Scholar
Canton, H., Verriele, L. & Colpaert, F. C. (1990) Binding of typical and atypical antipsychotics to 5-HT1c and 5-HT2 sites. Clozapine potently interacts with 5-HT1c sites. European Journal of Pharmacology, 191, 93–96.CrossRefGoogle ScholarPubMed
Carlsson, A. (1990) Early psychopharmacology and the rise of modern brain research. Journal of Psychopharmacology, 4, 120–126.CrossRefGoogle ScholarPubMed
Carlsson, M. & Carlsson, A. (1990) Interactions between glutamatergic and mono aminergic systems within the basal ganglia – implications for schizophrenia and Parkinson's disease. Trends in Neurological Science, 13, 272–276.CrossRefGoogle Scholar
Carpenter, W. T. Jr, Heinrichs, D. W. & Alphs, L. D. (1985) Treatment of negative symptoms. Schizophrenia Bulletin, 11, 440–452.CrossRefGoogle ScholarPubMed
Casey, D. E. (1989) Clozapine: neuroleptic induced EPS and tardive dyskinesia. Psychopharmacology, 99, 547–555.CrossRefGoogle ScholarPubMed
Chouinard, G., Jones, B., Remington, G., et al (1993) A Canadian multicentre placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. Journal of Clinical Psychopharmacology, 13, 25–40.CrossRefGoogle Scholar
Committee on Safety of Medicines (1993) Remoxipride – aplastic anaemia. Current Problems in Pharmacovigilance, 19, 9–10.Google Scholar
Cookson, J. (1987) The development of new drugs for the treatment of schizophrenia. British Journal of Hospital Medicine, December, 542–548.Google Scholar
Cookson, J., Natorf, B., Hunt, N., et al (1989) Efficacy, safety and tolerability of raclopride, a specific D2 receptor blocker, in acute schizophrenia: an open trial. International Clinical Psychopharmacology, 4, 61–70.CrossRefGoogle ScholarPubMed
Crow, T. J. (1985) The two syndrome concept: origins and current status. Schizophrenia Bulletin, 11, 471–486.CrossRefGoogle ScholarPubMed
Davis, J. M. (1991) Treatment of schizophrenia. Current Opinion in Psychiatry, 4, 28–33.CrossRefGoogle Scholar
Deutch, A. Y., Moghaddem, B., Innis, R. B., et al (1991) Mechanisms of action of atypical antipsychotic drugs. Schizophrenia Research, 4, 121–156.CrossRefGoogle ScholarPubMed
Farde, L., Wiesel, F. A., Nordstrom, A. L. (1989) D1 and D2 dopamine receptor occupancy during treatment with conventional and atypical neuroleptics. Psychopharmacology, 99, S28–S31.CrossRefGoogle ScholarPubMed
Farde, L., Wiesel, F. A., Stone-Elander, S., et al (1990) D2 dopamine receptors in neuroleptic-naïve schizophrenic patients. Archives of General Psychiatry, 47, 213–219.CrossRefGoogle ScholarPubMed
Farde, L., Nordstrom, A. L. & Wiesel, F. A. (1992) Positron emission tomography analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Archives of General Psychiatry, 49, 538–544.CrossRefGoogle ScholarPubMed
Gaebel, W. & Pietzcker, A. (1985) One year outcome of schizophrenic patients – the interaction of chronicity and neuroleptic treatment. Pharmacopsychiatry, 18, 235–239.CrossRefGoogle Scholar
Gelders, Y. G. (1989) Thymosthenic agents, a novel approach in the treatment of schizophrenia. British Journal of Psychiatry, 155 (suppl. 5), 33–36.CrossRefGoogle Scholar
Gerlach, J. (1991) New antipsychotics: classification, efficacy and adverse effects. Schizophrenia Bulletin, 17, 289–309.CrossRefGoogle ScholarPubMed
Gerlach, J., Behnke, K., Heltberg, J., et al (1985) Sulpiride and haloperidol in schizophrenia: a double-blind cross-over study of therapeutic effects, side effects and plasma concentrations. British Journal of Psychiatry, 147, 283–288.CrossRefGoogle ScholarPubMed
Gerlach, J. & Casey, D. E. (1994) Drug treatment of schizophrenia: myths and realities. Current Opinion in Psychiatry, 7, 65–70.CrossRefGoogle Scholar
Goldberg, C. S. (1985) Negative and deficit symptoms in schizophrenia do respond to neuroleptics. Schizophrenia Bulletin, 11, 453–456.CrossRefGoogle ScholarPubMed
Halstead, S. M., Barnes, T. R. E. & Speller, J. C. (1994) Akathisia: prevalence and associated dysphoria in an inpatient with chronic schizophrenia. British Journal of Psychiatry, 164, 177–183.CrossRefGoogle Scholar
Hirsch, S. R., Gaind, R., Rohde, P. D., et al (1973) Outpatient maintenance of chronic schizophrenic patients with long-acting fluphenazine: double-blind placebo trial. British Medical Journal, i, 633–637.CrossRefGoogle Scholar
Hirsch, S. R. & Puri, B. K. (1993) Clozapine: progress in treating refractory schizophrenia. British Medical Journal, 306, 1427–1428.CrossRefGoogle ScholarPubMed
Kallioniemi, H. & Syvalahti, E. (1992) Citalopram, a specific inhibitor of serotonin reuptake in the treatment of psychotic and borderline patients. Nordic Journal of Psychiatry, 46, 181–187.CrossRefGoogle Scholar
Kane, J. M. (1985) Compliance issues in outpatient treatment. Journal of Clinical Psychopharmacology, 5, 22–27.CrossRefGoogle ScholarPubMed
Kane, J. M. (1990) Treatment programme and long-term outcome in chronic schizophrenia. Acta Psychiatrica Scandinavica, 82 (suppl. 358), 151–157.CrossRefGoogle Scholar
Kane, J. M. (1992) New developments in the pharmacological treatment of schizophrenia. Bulletin of the Menninger Clinic, 56, 62–75.Google ScholarPubMed
Kane, J. M. (1993) Risk benefit of antipsychotic treatment. Presented at the 146th meeting of the American Psychiatric Association, May 22–27, 1993, San Francisco.Google Scholar
Kane, J. M. & Smith, J. N. (1982) Tardive dyskinesia. Prevalance and risk factors 1959–1979. Archives of General Psychiatry, 39, 473–481.CrossRefGoogle Scholar
Kane, J. M., 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.CrossRefGoogle ScholarPubMed
Kane, J. M. & Mayerhoff, D. (1989) Do negative symptoms respond to pharmacological treatment? British Journal of Psychiatry, 155 (suppl. 7), 115–118.CrossRefGoogle Scholar
Kane, J. M., Jeste, D. V. & Barnes, T. R. E. (1992) Tardive Dyskinesia: A Task Force Report of the American Psychiatric Association. Washington, DC: American Psychiatric Association.Google Scholar
Kane, J. M. & Marder, S. R. (1993) Psychopharmacologic treatment of schizophrenia. Schizophrenia Bulletin, 19, 287–302.CrossRefGoogle ScholarPubMed
Kerwin, R. W. (1993) Adverse reaction reporting and new antipsychotics. Lancet, 342, 1440.CrossRefGoogle ScholarPubMed
Kerwin, R. W. (1994) The new atypical antipsychotics. British Journal of Psychiatry, 164, 141–148.CrossRefGoogle ScholarPubMed
King, D. J., Blomqvist, M., Cooper, S. J., et al (1992) A placebo controlled trial of remoxipride in the prevention of relapse in chronic schizophrenia. Psychopharmacology, 107, 175–179.CrossRefGoogle ScholarPubMed
Kinon, B. J., Kane, J. M., Johns, C., et al (1993) Treatment of neuroleptic resistant schizophrenic relapse. Psychopharmacology Bulletin, 29, 309–314.Google ScholarPubMed
Kissling, W. (1992) Ideal and reality of neuroleptic relapse prevention. British Journal of Psychiatry, 161 (suppl. 18), 133–139.CrossRefGoogle Scholar
Krupp, P. & Barnes, P. (1992) Clozapine-associated agranulocytosis: risk and aetiology. British Journal of Psychiatry, 160 (suppl. 17), 38–40.CrossRefGoogle Scholar
Lader, M. (1979) Monitoring plasma concentrations of neuroleptics. Pharmacopsychology, 9, 170–177.CrossRefGoogle Scholar
Lambert, P. A. (1964) Essai de systématisation des associations de neuroleptiques. L'encéphale, 1, 262–275.Google Scholar
Lancet (1992) Editorial. Lancet, 339, 276–277.Google Scholar
Levinson, D. F. (1991) Pharmacologic treatment of schizophrenia. Clinical Therapeutics, 13, 326–352.Google ScholarPubMed
Mackay, A. V. P. (1980) Positive and negative schizophrenic symptoms and the role of dopamine. British Journal of Psychiatry, 170, 379–386.CrossRefGoogle Scholar
Madras, B. K. (1992) Dopamine receptors and schizophrenia: significance of D1–D5 . In Schizophrenia: New Developments in its Understanding & Treatment (ed. Hirsch, S. R.). London: IBC Technical Services.Google Scholar
Malmberg, A. H., Jackson, D. M., Eriksson, A., et al (1993) Unique binding characteristics of antipsychotic agents interacting with human dopamine D2A, D2B and D3 receptors. Molecular Pharmacology, 43, 749–754.Google ScholarPubMed
Meltzer, H. Y. (1989) Clinical studies on the mechanism of action of clozapine: the dopamine–serotonin hypothesis of schizophrenia. Psychopharmacology, 99, S18–S27.CrossRefGoogle ScholarPubMed
Meltzer, H. Y. (1991) The mechanism of action of novel antipsychotic drugs. Schizophrenia Bulletin, 17, 263–287.CrossRefGoogle ScholarPubMed
Meltzer, H. Y. (1992) Dimensions of outcome with clozapine. British Journal of Psychiatry, 160 (Suppl. 17), 46–53.CrossRefGoogle Scholar
Meltzer, H. Y., Sommers, A. A. & Luchins, D. J. (1986) Effects of neuroleptics and other psychotropic drugs on negative symptoms in schizophrenia. Journal of Clinical Psychopharmacology, 6, 329–338.CrossRefGoogle ScholarPubMed
Nutt, D. J. (1990) Specific anatomy, non-specific drugs: the present state of schizophrenia. Journal of Psychopharmacology, 4, 171–175.CrossRefGoogle ScholarPubMed
Owens, D. G. C., Johnstone, E. C. & Frith, C. D. (1982) Spontaneous involuntary disorders of movement. Archives of General Psychiatry, 39, 452–461.CrossRefGoogle ScholarPubMed
Peroutka, S. J. & Snyder, S. H. (1980) Relationship of neuroleptic drug effects to brain dopamine, serotonin, adrenergic and histamine receptors and clinical potency. American Journal of Psychiatry, 137, 1518–1523.Google ScholarPubMed
Philpott, N. J., Marsh, J. C. W., Gordon-Smith, E. C., et al (1993) Aplastic anaemia and remoxipride (letter). Lancet, 342, 1244–1245.CrossRefGoogle Scholar
Pilowsky, L. S., Costa, D. C., Ell, P. J., et al (1994) D2 dopamine receptor binding in the basal ganglia in antipsychotic-free schizophrenic patients. British Journal of Psychiatry, 164, 16–26.CrossRefGoogle ScholarPubMed
Prosser, E. S., Csernansky, J. G., Kaplan, J., et al (1987) Depression, parkinsonian symptoms and negative symptoms in schizophrenics treated with neuroleptics. Journal of Nervous and Mental Disease, 157, 100–105.CrossRefGoogle Scholar
Reynolds, G. P. (1989) Beyond the dopamine hypothesis. British Journal of Psychiatry, 155, 305–316.CrossRefGoogle ScholarPubMed
Reynolds, G. P. (1992) Developments in the drug treatment of schizophrenia. Trends in Pharmacological Science, 13, 116–121.CrossRefGoogle ScholarPubMed
Rifkin, A. (1987) Extrapyramidal side effects: a historical perspective. Journal of Clinical Psychiatry, 48 (suppl. 9), 3–6.Google ScholarPubMed
Rifkin, A., Quitkin, F., Rabiner, C. J., et al (1977) Fluphenazine decanoate, fluphenazine hydrochloride given orally, and placebo in remitted schizophrenics. I. Relapse rates after one year. Archives of General Psychiatry, 34, 43–47.CrossRefGoogle ScholarPubMed
Rifkin, A., Quitkin, F., Kane, J., et al (1978) Are prophylactic anti-parkinson drugs necessary? Archives of General Psychiatry, 35, 483–489.CrossRefGoogle ScholarPubMed
Sachdev, P. & Loneragan, C. (1991) The present status of akathisia. Journal of Nervous and Mental Disease, 179, 381–391.CrossRefGoogle ScholarPubMed
Saltz, B., Woerner, M. & Kane, J. M. (1991) Prospective study of tardive dyskinesia in the elderly. Journal of the American Medical Association, 266, 2402–2406.CrossRefGoogle ScholarPubMed
Schwartz, J. T. & Brotman, A. W. (1992) A clinical guide to antipsychotic drugs. Drugs, 44, 981–992.CrossRefGoogle ScholarPubMed
Schwartz, J. T., Levesque, D., Martres, M-P., et al (1993) Dopamine D3 receptor: basic and clinical aspects. Clinical Neuropharmacology, 16, 295–314.CrossRefGoogle ScholarPubMed
Seeman, P. (1980) Brain dopamine receptors. Pharmacology Review, 32, 229–313.Google ScholarPubMed
Seeman, P. (1992) Dopamine receptor sequences. Therapeutic levels of neuroleptics occupy D2 receptors. Clozapine occupies D4 . Neuropsychopharmacology, 7, 261–284.Google ScholarPubMed
Serban, G., Siegel, S. & Gaffney, G. (1992) Response of negative symptoms of schizophrenia to neuroleptic treatment. Journal of Clinical Psychiatry, 53, 229–234.Google ScholarPubMed
Stephens, J. H. (1970) Long-term course and prognosis in schizophrenia. Seminars in Psychiatry, 2, 464–485.Google ScholarPubMed
Strauss, S. J. & Carpenter, W. T. (1972) The prediction of outcome in schizophrenia. I: Characteristics of outcome. Archives of General Psychiatry, 27, 739–746.CrossRefGoogle ScholarPubMed
Tsuang, M. T. (1982) Long-term outcome in schizophrenia. Trends in Neuroscience, June, 203–207.CrossRefGoogle Scholar
Van Putten, T., May, P. R. A. & Marder, S. R. (1984) Akathisia with haloperidol and thiothixene. Archives of General Psychiatry, 41, 1036–1039.CrossRefGoogle ScholarPubMed
Wirshing, W. C. & Marder, S. R. (1993) Drug treatment in schizophrenia. Current Opinion in Psychiatry, 6, 85–89.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, 1558–1563.CrossRefGoogle ScholarPubMed
Wyatt, R. J. (1992) Neuroleptics and the natural course of schizophrenia. Schizophrenia Bulletin, 17, 325–351.CrossRefGoogle Scholar
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