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Pharmacopsychiatry 2001; 34(3): 104-110
DOI: 10.1055/s-2001-14282
Original Paper
© Georg Thieme Verlag Stuttgart · New York

A Qualitative Assessment of the Neurological Safety of Antipsychotic Drugs; an Analysis of a Risperidone Database

W. W. Fleischhacker1 , P. Lemmens2 , B. van Baelen2
  • 1Dept. of Biological Psychiatry, Innsbruck University Clinics, Innsbruck, Austria
  • 2Janssen Research Foundation, Beerse, Belgium
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Publication History

Publication Date:
31 December 2001 (online)

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Background: Neurological side effects of antipsychotic agents limit the use of these drugs, and development of newer antipsychotic agents has been focused on a reduced risk of extrapyramidal symptoms (EPS) as well as effective symptom control. Methods: A qualitative analysis of EPS was performed using Extrapyramidal Symptom Rating Scale (ESRS) data from 11 double-blind risperidone trials. An ESRS factor analysis and maximum changes in ESRS scores were compared for the risperidone, haloperidol, and placebo groups. Results: The factor analysis revealed five factors. Between-group comparisons showed no differences between placebo and 1 to 2 mg/day-risperidone groups. Parkinsonism, tremor, akathisia, and sialorrhea were more likely to occur with haloperidol than with placebo or risperidone at 1 to 6 mg/day. Similar results were noted by maximum changes in ESRS scores. At risperidone doses of more than 8 mg/day, acute EPS severity lay between that of the placebo and haloperidol groups. The severity of tardive dyskinesia was greater in patients receiving placebo than in those receiving either active treatment. Conclusions: As the results described above were derived from a post hoc analysis of an existing database, conclusions must remain tentative. To provide more definitive answers, EPS assessments in future studies should be refined to more accurately predict the type of EPS expected with a given agent in clinical practice.

References

  • 1 American Psychiatric Association .Diagnostic and statistical manual of mental disorders. 3rd ed. Washington, DC: APA 1987
    Google Scholar
  • 2 Arana G W, Goff D C, Baldessarini R J, Keepers G A. Efficacy of anticholinergic prophylaxis for neuroleptic-induced acute dystonia.  Am J Psychiatry. 1988;  145 993-996
    PubMedGoogle Scholar
  • 3 Arvanitis L A, Miller B G. the Seroquel Trial 13 Study Group . Multiple fixed doses of “Seroquel” (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo.  Biol Psychiatry. 1997;  42 233-246
    CrossrefPubMedGoogle Scholar
  • 4 Ayd F J. A survey of drug-induced extrapyramidal reactions.  JAMA. 1961;  175 1054-1060
    CrossrefPubMedGoogle Scholar
  • 5 Blin O, Azorin J M, Bouhours P. Antipsychotic and anxiolytic properties of risperidone, haloperidol, and methotrimeprazine in schizophrenic patients.  J Clin Psychopharmacol. 1996;  16 38-44
    CrossrefPubMedGoogle Scholar
  • 6 Bondolfi G, Baumann P, Patris M, May J P, Billeter U, Eap C B. et al . Risperidone versus clozapine for treatment-resistant chronic schizophrenia a randomized double-blind trial study.  Am J Psychiatry. 1998;  155 499-504
    PubMedGoogle Scholar
  • 7 Borison R L, Arvanitis L A, Miller B G. ICI 204,636, an atypical antipsychotic: efficacy and safety in a multicenter, placebo-controlled trial in patients with schizophrenia.  J Clin Psychopharmacol . 1996;  16 158-169
    CrossrefPubMedGoogle Scholar
  • 8 Borison R L, Pathiraja A P, Diamond B I. et al . Risperidone: clinical safety and efficacy in schizophrenia.  Psychopharmacol Bull. 1992;  28 213-218
    PubMedGoogle Scholar
  • 9 Casey D E, Keepers G A. Neuroleptic side effects: acute extrapyramidal syndromes and tardive dyskinesia. In: Casey DE, Christensen AV, editor Psychopharmacology: current trends. Berlin: Springer 1988: 74-93
    Google Scholar
  • 10 Chakos M H, Mayerhoff D I, Loebel A D, Alvir J M, Lieberman J A. Incidence and correlates of acute extrapyramidal symptoms in first episode of schizophrenia.  Psychopharmacol Bull. 1992;  28 81-86
    PubMedGoogle Scholar
  • 11 Chouinard G, Jones B, Remington G, Bloom D, Addington D, MacEwan G W. 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
    PubMedGoogle Scholar
  • 12 Chouinard G, Ross-Chouinard A, Amiable L. et al . The Extrapyramidal Symptom Rating Scale.  Can J Neurol Sci. 1980;  7 233
    PubMedGoogle Scholar
  • 13 Claus A, Bollen J, De Cuyper H, Eneman M, Malfroid M, Peuskens J. et al . Risperidone versus haloperidol in the treatment of chronic schizophrenic inpatients: a multicentre double-blind comparative study.  Acta Psychiatr Scand. 1992;  85 295-305
    PubMedGoogle Scholar
  • 14 Davis R, Markham A. Ziprasidone.  CNS Drugs. 1997;  8 153-159
    PubMedGoogle Scholar
  • 15 Høyberg O J, Fensbo C, Remvig J, Lingjaerde O, Sloth-Nielsen M, Salvesen I. Risperidone versus perphenazine in the treatment of chronic schizophrenic patients with acute exacerbations.  Acta Psychiatr Scand. 1993;  88 395-402
    PubMedGoogle Scholar
  • 16 Hummer M, Fleischhacker W W. Compliance and outcome in patients treated with antipsychotics: the impact of extrapyramidal syndromes.  CNS Drugs. 1996;  5 (Suppl. 1) 13-20
    PubMedGoogle Scholar
  • 17 Huttunen M O, Piepponen T, Rantanen H, Larmo I, Nyholm R, Raitasuo V. Risperidone versus zuclopenthixol in the treatment of acute schizophrenic episodes: a double-blind parallel-group trial.  Acta Psychiatr Scand. 1995;  91 271-277
    PubMedGoogle Scholar
  • 18 Kane J, Honigfeld G, Singer J, Meltzer H. Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlorpromazine.  Arch Gen Psychiatry. 1988;  45 789-796
    Google Scholar
  • 19 Kurz M, Hummer M, Oberbauer H, Fleischhacker W W. Extrapyramidal side effects of clozapine and haloperidol.  Psychopharmacology. 1995;  118 52-56
    PubMedGoogle Scholar
  • 20 Lewander T. Placebo response in schizophrenia.  Eur Psychiatry. 1994;  9 119-120
    PubMedGoogle Scholar
  • 21 Lieberman J, Jody D, Geisler S, Vital-Herne J, Alvir J M, Walsleben J. et al . Treatment outcome of first-episode schizophrenic patients.  Psychopharmacol Bull. 1989;  25 92-96
    PubMedGoogle Scholar
  • 22 Marder S R, Meibach R C. Risperidone in the treatment of schizophrenia.  Am J Psychiatry. 1994;  151 825-835
    PubMedGoogle Scholar
  • 23 Min S K, Rhee C S, Kirn C E, Kang D Y. Risperidone versus haloperidol in the treatment of chronic schizophrenic patients: a parallel group double-blind comparative trial.  Yonsei Med J. 1993;  34 179-190
    PubMedGoogle Scholar
  • 24 Peacock L, Solgaard T, Lublin H, Gerlach J. Clozapine versus typical antipsychotics. A retro- and prospective study of extrapyramidal side effects.  Psychopharmacology. 1996;  124 188-196
    PubMedGoogle Scholar
  • 25 Peuskens J. the Risperidone Study Group . Risperidone in the treatment of chronic schizophrenic patients: a multinational, multicentre, double-blind, parallel-group study versus haloperidol.  Br J Psychiatry. 1995;  166 712-726
    CrossrefPubMedGoogle Scholar
  • 26 Rifkin A, Doddi S, Karajgi B, Borenstein M, Wachspress M. Dosage of haloperidol for schizophrenia.  Arch Gen Psychiatry. 1991;  48 166-170
    CrossrefPubMedGoogle Scholar
  • 27 Saltz B L, Woerner M G, Kane J M, Lieberman J A, Alvir J M, Bergmann K J. et al . Prospective study of tardive dyskinesia incidence in the elderly.  JAMA. 1991;  266 2402-2406
    CrossrefPubMedGoogle Scholar
  • 28 Scottish Schizophrenia Research Group . The Scottish first episode schizophrenia study. II. Treatment: pimozide versus flupentixol.  Br J Psychiatry. 1987;  150 334-338
    PubMedGoogle Scholar
  • 29 Simpson G M, Lindenmayer J P. Extrapyramidal symptoms in patients treated with risperidone.  J Clin Psychopharmacol. 1997;  17 194-201
    CrossrefPubMedGoogle Scholar
  • 30 Tran P V, Dellva M A, Tollefson G D, Beasley C M , Potvin J H, Kiesler G M. Extrapyramidal symptoms and tolerability of olanzapine versus haloperidol in the acute treatment of schizophrenia.  J Clin Psychiatry. 1997;  58 205-211
    PubMedGoogle Scholar
  • 31 Umbricht D, Kane J M. Medical complications of new antipsychotic drugs.  Schizophr Bull. 1996;  22 475-483
    PubMedGoogle Scholar
  • 32 Van Kammen D P, McEvoy J P, Targum S D, Kardatzke D, Sebree T B. A randomized, controlled, dose-ranging trial of sertindole in patients with schizophrenia.  Psychopharmacology. 1996;  124 168-175
    PubMedGoogle Scholar
  • 33 Van Putten T, May P R, Marder S R. Response to antipsychotic medication: the doctor's and the consumer's view.  Am J Psychiatry. 1984;  141 16-19
    PubMedGoogle Scholar
  • 34 Whitworth A B, Fleischhacker W W. Adverse effects of antipsychotic drugs.  Int Clin Psychopharmacol. 1995;  9 (Suppl. 5) 21-27
    PubMedGoogle Scholar
  • 35 Zimbroff D L, Kane J M, Tamminga C A, Daniel D G, Mack R J, Wozniak P J. et al . Controlled, dose-response study of sertindole and haloperidol in the treatment of schizophrenia.  Am J Psychiatry. 1997;  154 782-791
    Google Scholar
  • 36 Zyprexa (olanzapine) prescribing information. In: Physicians' Desk Reference, 52nd edition. Montvale, New Jersey Medical Economics Data Production 1998
    Google Scholar

Prof. Dr. med. W. Wolfgang Fleischhacker


Department of Biological Psychiatry
Innsbruck University Clinics

Anichstrasse 35

6020 Innsbruck

Austria

Phone: +43 512 504 3669

Phone: +43 512 504 5267

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