Hostname: page-component-78c5997874-4rdpn Total loading time: 0 Render date: 2024-11-05T00:50:44.377Z Has data issue: false hasContentIssue false

Risperidone in the Treatment of Patients with Chronic Schizophrenia: a Multi-National, Multi-Centre, Double-Blind, Parallel-Group Study versus Haloperidol

Published online by Cambridge University Press:  02 January 2018

Abstract

Background

This study was performed in order to evaluate the short-term efficacy and safety of fixed risperidone doses compared to haloperidol.

Method

In a multi-national, parallel-group, double-blind study, patients with chronic schizophrenia (DSM–III–R) were randomly assigned to risperidone 1, 4, 8, 12 or 16 mg or haloperidol 10 mg daily for 8 weeks. Efficacy was assessed by the Positive and Negative Syndrome Scale for schizophrenia (PANSS) and clinical global impression (CGI), and safety primarily by the Extrapyramidal Symptom Rating Scale (ESRS).

Results

One thousand three hundred and sixty-two patients were evaluated. The optimum risperidone doses were 4 mg and 8 mg, with response rates of 63.4% (56.8%; 69.7%) and 65.8% (59.2%; 71.9%) respectively. Response rate in haloperidol-treated patients was 58.7% (52.0%; 65.3%); the 95% confidence intervals (CI) of the differences between risperidone 4 mg or 8 mg and haloperidol were (–4.3%; 13.7%) and (–1.9%; 16.0%) respectively. There were no significant differences in CGI scores at endpoint between risperidone 4 mg, 8 mg, 12 mg and 16 mg and haloperidol (3.0, 3.0, 3.2, 3.1 and 3.1 respectively); the 95% CI of the differences between risperidone 4 mg or 8 mg and haloperidol were (–0.4; 0.1) and (–0.3; 0.2) respectively. Mean shifts to the maximum total ESRS scores versus baseline (mean (confidence interval)) were significantly greater in haloperidol-treated patients (5.1 (4.0; 6.2)) than in the risperidone 1, 4, 8 and 12 mg groups (1.1 (0.3; 1.9); 1.8 (0.9; 2.7); 2.7 (1.8; 3.6) and 3.2 (2.3; 4.1) respectively (P< 0.05)).

Conclusion

Risperidone is an effective antipsychotic for the treatment of chronic schizophrenia; doses of 4 and 8 mg seem to be optimal and have a lower incidence of side-effects than haloperidol.

Type
Papers
Copyright
Copyright © Royal College of Psychiatrists, 1995 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

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., Cohen, B. M., Teicher, M. H. (1988) Significance of neuroleptic dose and plasma level in the pharmacological treatment of psychoses. Archives of General Psychiatry, 45, 7991.Google ScholarPubMed
Barnes, T. R. E. (1987) The present status of tardive dyskinesia and akathisia in the treatment of schizophrenia. Psychiatric Developments, 4, 301319.Google Scholar
Bersani, G., Bressa, G. M., Meco, G., et al (1990) Combined serotonin 5-HT2 and dopamine-D2 antagonism in schizophrenia: clinical, extrapyramidal and neuroendocrine response in a preliminary study with risperidone (R64766). Human Psychopharmacology, 5, 225231.CrossRefGoogle Scholar
Borison, R. L., Pathiraja, A. P., Diamond, B. I., et al (1992) Risperidone: Clinical safety and efficacy in schizophrenia. Psychopharmacology Bulletin 28(2), 213218.Google ScholarPubMed
Castelao, J. F., Ferreira, L., Gelders, Y. G., et al (1989) The efficacy of the D2 and 5-HT2 antagonist risperidone (R64766) in the treatment of chronic psychosis: an open dose-finding study. Schizophrenia Bulletin, 2, 411415.Google Scholar
Ceulemans, D. L. S., Gelders, Y. G., Hoppenbrouwers, M-L. J. A., et al (1985) Effect of serotonin antagonism in schizophrenia: a pilot study with setoperone. Psychopharmacology, 85, 329332.CrossRefGoogle ScholarPubMed
Chouinard, G., Annable, L., Ross-Chouinard, A., et al (1979) Ethopropazine and benztropine in neuroleptic-induced Parkinsonism. Journal of Clinical Psychiatry, 40, 147152.Google ScholarPubMed
Chouinard, G., Jones, B., Remington, G., et al (1993) A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. Journal of Clinical Psychopharmacology, 13, 2540.CrossRefGoogle ScholarPubMed
Chouinard, G., Ross-Chouinard, A., Annable, L., et al (1980) The Extrapyramidal Symptom Rating Scale. Canadian Journal of Neurological Sciences, 7, 233.Google Scholar
Claus, A., Bollen, J., De Cuyper, H., et al (1992) Risperidone versus haloperidol in the treatment of chronic schizophrenic inpatients: a multicenter double-blind comparative study. Acta Psychiatrica Scandinavica, 85, 295305.CrossRefGoogle Scholar
Crow, T. J. (1985) The two-syndrome concept: origins and status. Schizophrenia Bulletin, 11, 471486.Google ScholarPubMed
Drake, R. E. & Ehrlich, J. (1985) Suicide attempts associated with akathisia. American Journal of Psychiatry, 142, 499501.Google ScholarPubMed
Farde, L., Hall, H. (1992) Positron emission tomography. Examination of chemical transmission in the living human brain. Arzneim-Forsch/Drug Research, 42, 260264.Google ScholarPubMed
Gelders, Y. G. (1989) Thymosthenic agents, a novel approach in the treatment of schizophrenia. British Journal of Psychiatry, 155(suppl 5), 3336.CrossRefGoogle Scholar
Gelders, Y. G., Heylen, S. L. E., Vanden Bussche, G., et al (1990) Pilot clinical investigations of risperidone in the treatment of psychotic patients. Pharmacopsychiatry, 23, 206211.CrossRefGoogle ScholarPubMed
Guy, W. (1976) ECDEU Assessment Manual for Psychopharmacology (revised). Published by DHEW, No (ADM) 76–338, Rockville, MD: National Institute of Mental Health.Google Scholar
Janssen, P. A. J., Niemegeers, C. J. E., Awouters, F., et al (1988) Pharmacology of risperidone (R64766), a new antipsychotic with serotonin-S2 and dopamine-D2 antagonistic properties. Journal of Pharmacological Experimental Therapeutics, 244, 685693.Google ScholarPubMed
Kalinowski, L. B. (1958) Appraisal of the “tranquillisers” and their influences on other somatic treatment in psychiatry. American Journal of Psychiatry, 115, 94300.Google Scholar
Kay, S. R., Fiszbein, A. & Opler, L. A. (1987) The Positive and Negative Syndrome Scale (PANSS) for Schizophrenia. Schizophrenia Bulletin, 13, 261276.CrossRefGoogle ScholarPubMed
Kay, S. R., Opler, L. A. & Lindenmayer, J. P. (1988) Reliability and validity of the Positive and Negative Syndrome Scale for Schizophrenics. Psychiatric Research, 23, 99110.CrossRefGoogle ScholarPubMed
Kay, S. R. & Sevy, S. (1990) Pyramidical model of schizophrenia. Schizophrenia Bulletin, 16, 537545.CrossRefGoogle ScholarPubMed
Lehmann, E. L. (1975) Nonparametric Statistical Methods, Statistical Methods based on Ranks. San Francisco: Holden-Day.Google Scholar
Leysen, J. E., Gommeren, W., Eens, A., et al (1988) The biochemical profile of risperidone, a new antipsychotic. Journal of Pharmacological Experimental Therapeutics, 247, 661670.Google ScholarPubMed
Lingjaerde, O., Ahlfors, U. G., Bech, P., et al (1987) The UKU Side-Effect Rating Scale. Acta Psychiatrica Scandinavica, 76(suppl 334), 8194.Google Scholar
Marder, S. R., Meibach, R. C. (1994) Risperidone in the treatment of schizophrenia. American Journal of Psychiatry, 151, 18251835.Google ScholarPubMed
Meco, G., Bedini, L., Bonifati, V., et al (1989) Risperidone in the treatment of chronic schizophrenia with tardive dyskinesia: a single-blind crossover study versus placebo. Current Therapeutic Research, 46, 876883.Google Scholar
Mesotten, F., Suy, E., Pietquin, M., et al (1989) Therapeutic effect and safety of increasing doses of risperidone (R64766) in psychotic patients. Psychopharmacology, 99, 445449.CrossRefGoogle ScholarPubMed
Nordström, A. L., Farde, L., Halldin, C. (1992) Time course of D2-dopamine receptor occupancy examined by PET after single oral doses of haloperidol. Psychopharmacology, 106, 433438.CrossRefGoogle ScholarPubMed
Overall, J. F. & Gorham, D. R. (1962) The Brief Psychiatric Rating Scale. Psychological Reports, 10, 799812.CrossRefGoogle Scholar
Pocock, S. J. (1983) Methods of randomisation: Preparing the randomisation list. In Clinical Trials. A Practical Approach, pp 7380. Chichester: John Wiley & Sons.Google Scholar
Reyntjens, A. J. M., Gelders, Y. G., Hoppenbrouwers, M.-L. J. A., et al (1986) Thymosthenic effects of ritanserin (R55667), a centrally acting serotonin-S2 receptor blocker. Drug Development and Research, 8, 205211.CrossRefGoogle Scholar
Shear, K., Frances, A. & Weiden, P. (1983) Suicide associated with akathisia and depot fluphenazine treatment. Journal of Clinical Psychopharmacology, 3, 235236.CrossRefGoogle ScholarPubMed
Turri, M., Stein, G. (1986) The determination of practically useful doses of new drugs: some methodological considerations. Statistics in Medicine, 5, 449457.Google ScholarPubMed
Van Putten, T. (1974) Why do schizophrenic patients refuse to take their drugs? Archives of General Psychiatry, 31, 6772.CrossRefGoogle ScholarPubMed
Van Putten, T. (1984) Akathisia with haloperidol and thiothixene. Archives of General Psychiatry, 41, 10361039.CrossRefGoogle ScholarPubMed
Van Putten, T. & Marder, S. R. (1987) Behavioral toxicity of antipsychotic drugs. Journal of Clinical Psychiatry, 48(suppl 9), 1319.Google ScholarPubMed
Van Putten, T., Marder, S. R. & Mintz, J. (1990) A controlled dose comparison of haloperidol in newly admitted schizophrenic patients. Archives of General Psychiatry, 47, 754758.CrossRefGoogle ScholarPubMed
Submit a response

eLetters

No eLetters have been published for this article.