Review Article| Volume 20, ISSUE 1, P58-71, January 1998

Risperidone versus haloperidol: I. meta-analysis of efficacy and safety

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      Haloperidol is widely considered a reference standard in antipsychotic therapy and is commonly used in comparative studies of the efficacy and safety of antipsychotic medication. Comparative clinical trials have shown that the novel antipsychotic agent risperidone tends to have greater efficacy (ie, clinical response defined as a ≥20% reduction in total scores on the Positive and Negative Syndrome Scale) than haloperidol in patients with chronic schizophrenia and poses less risk of extrapyramidal symptoms (EPS). We used DerSimonian and Laird's random-effects model to analyze pooled patient data from available randomized, double-masked, comparative trials of risperidone and haloperidol in patients with schizophrenia treated for at least 4 weeks at recommended doses. The purpose of the analysis was to determine whether there are significant overall differences in the rates of patient clinical response, prescription of anticholinergic agents, and treatment dropout. Six of the nine trials revealed in a literature search met all criteria for inclusion in the meta-analysis. The meta-analysis showed that in patients with chronic schizophrenia, risperidone therapy is associated with significantly higher response rates, significantly less prescribing of anticholinergic medication, and significantly lower treatment dropout rates than haloperidol. These results demonstrate the greater treatment efficacy associated with risperidone compared with haloperidol and suggest both a lower incidence of EPS and improved treatment compliance.


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        • Janssen PAJ
        • Neimegeers CJE
        • Awouters F
        • et al.
        Pharmacology of risperidone (R64 766), a new antipsychotic with serotonin-S2 and dopamine-D2 antagonist properties.
        J Pharmacol Exp Ther. 1988; 244: 685-693
        • Leysen JE
        • Gommeren W
        • Eens A
        • et al.
        Biochemical profile of risperidone, a new antipsychotic.
        J Pharmacol Exp Ther. 1988; 247: 661-670
        • Johnstone EC
        • Crow TJ
        • Frith C
        Mechanism of the antipsychotic effect in the treatment of acute schizophrenia.
        Lancet. 1978; 1: 848-851
        • Schotte A
        • Janssen PFM
        • Gommeren W
        • et al.
        Risperidone compared with new and reference antipsychotic drugs—in vitro and in vivo receptor binding.
        Psychopharmacology. 1996; 124: 57-73
        • Borison RL
        • Chu C-C
        • Gosenfeld L
        • et al.
        Risperidone versus haloperidol versus placebo in the treatment of schizophrenia.
        Clinical Research Report on R64766 RIS-USA-9001. Janssen Pharmaceutica, Beerse, Belgium1991
        • Chouinard G
        • Jones B
        • Remington G
        • et al.
        A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients.
        J Clin Psychopharmacol. 1993; 13: 25-40
        • Marder SR
        • Meibach RC
        • Risperidone Study Group
        Risperidone in the treatment of schizophrenia.
        Am J Psychiatry. 1994; 151: 825-835
        • Peuskens J
        • Risperidone Study Group
        Risperidone in the treatment of patients with chronic schizophrenia: A multinational, multicenter, double-blind, parallel-group study versus haloperidol.
        Br J Psychiatry. 1995; 166: 712-716
        • Claus A
        • Bollen J
        • De Cuyper H
        • et al.
        Risperidone versus haloperidol in the treatment of chronic schizophrenia in inpatients: A multicenter, double-blind comparative study.
        Acta Psychiatr Scand. 1992; 85: 295-305
        • Blin O
        • Azorin JM
        • Bouhours P
        Antipsychotic and anxiolytic properties of risperidone, haloperidol, and methotrimeprazine in schizophrenic patients.
        J Clin Psychopharmacol. 1996; 16: 38-44
        • Eysenck H
        Meta-analysis and its problems.
        Br Med J. 1994; 309: 789-792
        • Thompson SG
        • Pocock SJ
        Can meta-analysis be trusted?.
        Lancet. 1991; 338: 1127-1130
        • Goodman SN
        Have you ever meta-analysis you didn't like?.
        Ann Intern Med. 1991; 114: 244-246
        • L'Abbé KA
        • Detsky AS
        • O'Rourke K
        Meta-analysis in clinical research.
        Ann Intern Med. 1987; 107: 224-233
        • DerSimonian R
        • Laird N
        Meta-analysis in clinical trials.
        Control Clin Trials. 1986; 7: 177-188
        • Kay SR
        • Fiszbein A
        • Opler LA
        The Positive and Negative Syndrome Scale (PANSS) for schizophrenia.
        Schizophr Bull. 1987; 16: 261-276
        • Overall JF
        • Gorham DR
        The Brief Psychiatric Rating Scale.
        Psychol Rep. 1962; 10: 799-812
        • Ceskova E
        • Svestka J
        Double-blind comparison of risperidone and haloperidol in schizophrenic and schizoaffective psychoses.
        Pharmacopsychiatry. 1993; 26: 121-124
        • Min SK
        • Rhee CS
        • Kim CE
        • Kang DY
        Risperidone versus haloperidol in the treatment of chronic schizophrenic patients: A parallel group, double-blind comparative trial.
        Yonsei Med J. 1993; 34: 179-190
        • Mesotten F
        Risperidone versus haloperidol in chronic psychotic patients: A multicentre double-blind study.
        Clinical Research Report on RIS-BEL-7. Janssen Research Foundation, Beerse, Belgium1991
        • Serejskij MJ
        Terapija psichiceeskich zabolevanij.
        Medgiz Moskva. 1948;
        • Davies A
        • Langley PC
        • Keks NA
        • et al.
        Risperidone versus haloperidol: II. Cost-effectiveness.
        Clin Ther. 1997; 19: 196-213
      1. Risperdal approved product information. Janssen-Cilag Pty. Ltd., Lane Cove, New South Wales, Australia.

        • American Psychiatric Association
        3rd ed. Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association, Washington, DC1987: 187-198 (revised)
      2. Manual of the International Classification of Diseases, Injuries and Causes of Death Based on the Recommendations of the Ninth Revision Conference. World Health Organization, Geneva1977: 182-185
        • Carman J
        • Peuskens J
        • Vangeneugden A
        Risperidone in the treatment of negative symptoms of schizophrenia: A meta-analysis.
        Int Clin Psychopharmacol. 1995; 10: 207-213
        • Chouinard G
        • Ross-Chouinard A
        • Annable L
        • Jones BD
        The Extrapyramidal Rating Scale.
        Can J Neurol Sci. 1980; 73: 233
        • Kane JM
        Am J Psychiatry. 1994; 151: 802-803
      3. 2nd ed. Victorian Drug Usage Advisory Committee Psychotropic Drug Guidelines 1993. Victorian Medical Postgraduate Foundation, Inc, North Melbourne, Australia1993: 68
      4. Reynolds JEF 31st ed. Martindale: The Extra Pharmacopoiea. Royal Pharmaceutical Society, London1996: 714-715
        • Frances A
        • Docherty JP
        • Kahn DA
        Treatment of schizophrenia.
        J Clin Psychiatry. 1996; 57 (Suppl 12B): 25
      5. Australian Medical Index. 4. IMS Australia, Australia1994 (Crows Nest)
        • Van Putten T
        • Marder SR
        • Mintz J
        • et al.
        A controlled dose comparison of haloperidol in newly admitted schizophrenic patients.
        Arch Gen Psychiatry. 1990; 47: 754-758
        • Umbricht D
        • Kane JM
        Risperidone safety and efficacy.
        Schizophr Bull. 1995; 21: 593-606
        • Borison RJ
        Clinical efficacy of serotonin-dopamine antagonists relative to classical neuroleptics.
        J Clin Psychopharmacol. 1995; 15 (Suppl 1): 24S-29S
        • Song F
        • Sheldon T
        Meta-analysis of relative efficacy and side effects of risperidone in the treatment of schizophrenia.
        Pharmacoepidemiol Drug Saf. 1995; 4 (Abstract): S5