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
Further Information

Publication History

Publication Date:
31 December 2001 (online)

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
  • 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
  • 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
  • 4 Ayd F J. A survey of drug-induced extrapyramidal reactions.  JAMA. 1961;  175 1054-1060
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 12 Chouinard G, Ross-Chouinard A, Amiable L. et al . The Extrapyramidal Symptom Rating Scale.  Can J Neurol Sci. 1980;  7 233
  • 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
  • 14 Davis R, Markham A. Ziprasidone.  CNS Drugs. 1997;  8 153-159
  • 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
  • 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
  • 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
  • 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
  • 19 Kurz M, Hummer M, Oberbauer H, Fleischhacker W W. Extrapyramidal side effects of clozapine and haloperidol.  Psychopharmacology. 1995;  118 52-56
  • 20 Lewander T. Placebo response in schizophrenia.  Eur Psychiatry. 1994;  9 119-120
  • 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
  • 22 Marder S R, Meibach R C. Risperidone in the treatment of schizophrenia.  Am J Psychiatry. 1994;  151 825-835
  • 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
  • 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
  • 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
  • 26 Rifkin A, Doddi S, Karajgi B, Borenstein M, Wachspress M. Dosage of haloperidol for schizophrenia.  Arch Gen Psychiatry. 1991;  48 166-170
  • 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
  • 28 Scottish Schizophrenia Research Group . The Scottish first episode schizophrenia study. II. Treatment: pimozide versus flupentixol.  Br J Psychiatry. 1987;  150 334-338
  • 29 Simpson G M, Lindenmayer J P. Extrapyramidal symptoms in patients treated with risperidone.  J Clin Psychopharmacol. 1997;  17 194-201
  • 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
  • 31 Umbricht D, Kane J M. Medical complications of new antipsychotic drugs.  Schizophr Bull. 1996;  22 475-483
  • 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
  • 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
  • 34 Whitworth A B, Fleischhacker W W. Adverse effects of antipsychotic drugs.  Int Clin Psychopharmacol. 1995;  9 (Suppl. 5) 21-27
  • 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
  • 36 Zyprexa (olanzapine) prescribing information. In: Physicians' Desk Reference, 52nd edition. Montvale, New Jersey Medical Economics Data Production 1998

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