Skip to main content
SpringerLink
Log in

Frequency of Extrapyramidal Adverse Reactions in Schizophrenic Outpatients Treated with Risperidone, Olanzapine, Quetiapine or Haloperidol

Results of the EIRE Study

  • Original Research Article
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Objective

The EIRE (Estudio de Investigaciön de Resultados en Esquizofrenia — Outcomes Research Study in Schizophrenia) study was initiated in order to assess the frequency of adverse reactions [extrapyramidal symptoms (EPS), hyperprolactinaemia, sexual dysfunction and weight gain] caused by atypical antipsychotics and haloperidol in patients with schizophrenia during routine treatment in clinical practice. This paper presents the results of the assessment of extrapyramidal adverse reactions.

Patients and study design

Outpatients diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of mental disorders, 4th edition (DSM-IV), criteria and receiving a single antipsychotic (risperidone, olanzapine, quetiapine or haloperidol) for at least 4 weeks were consecutively recruited. In this cross-sectional and non-interventional study data were collected in a single visit; this included demographic and clinical characteristics, current antipsychotic and concomitant treatment, and data on several adverse effects listed in a modified version of the UKU (Udvalg for Kliniske Undersogelser — Committee on Clinical Investigations) scale. For paired comparisons of the frequency of adverse reactions between treatments the Chi-squared (χ2) test was used. For estimation of the risk of a given adverse reaction with a given treatment a logistic regression method was used.

Results

636 evaluable patients (of 669 recruited) were assessed. The frequency of EPS with haloperidol (78.3% of the cases) was higher than with risperidone (55.1%), quetiapine (39.5%) and olanzapine (35.8%) [χ2: p < 0.05], and the difference between risperidone and olanzapine was also statistically significant (χ2: p < 0.05). Very similar results were obtained in the individualised analysis of the items as regards the occurrence of akathisia, which was also more frequent in the haloperidol (36.8%) and risperidone (19.7%) groups than in the olanzapine (11.4%) and quetiapine (2.6%) groups (χ2: p < 0.05). Olanzapine, quetiapine and risperidone also showed a lower risk of EPS than haloperidol when adjusting by dose.

Conclusion

Our results suggest that the atypical antipsychotics studied are less likely to induce extrapyramidal adverse reactions compared with haloperidol in stabilised patients, although these reactions are still common.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III
Fig. 1
Table IV
Table V
Table VI

Similar content being viewed by others

References

  1. Arana GW. An overview of side effects caused by typical anti-psychotics. J Clin Psychiatry 2000; 61 Suppl. 8: 5–11

    PubMed  CAS  Google Scholar 

  2. Arana GW, Goff DC, Baldessarini RJ, et al. Efficacy of anti-cholinergic prophylaxis for neuroleptic-induced acute dystonia. Am J Psychiatry 1988; 145: 993–6

    PubMed  CAS  Google Scholar 

  3. Glazer WM, Morgenstern H, Doucette JT. Predicting the long-term risk of tardive dyskinesia in outpatients maintained on neuroleptic medications. J Clin Psychiatry 1993; 54: 133–9

    PubMed  CAS  Google Scholar 

  4. Woerner MG, Alvir JMJ, Saltz BL, et al. Prospective study of tardive dyskinesia in the elderly: rates and risk factors. Am J Psychiatry 1998; 155: 1521–8

    PubMed  CAS  Google Scholar 

  5. Cassens G, Inglis AK, Appelbaum PS, et al. Neuroleptics: effects on neuropsychological function in chronic schizophrenic patients. Schizophr Bull 1990; 16: 477–99

    Article  PubMed  CAS  Google Scholar 

  6. Jeste DV, Lohr JB, Estham JH, et al. Adverse neurobiological effects of long-term use of neuroleptics: human and animal studies. J Psychiatr Res 1998; 32: 201–14

    Article  PubMed  CAS  Google Scholar 

  7. Kane JM. Management issues in schizophrenia. London: Martin Dunitz, 2000

    Google Scholar 

  8. Glazer WM. Extrapyramidal side effects, tardive dyskinesia, and the concept of atypicality. J Clin Psychiatry 2000; 61(3): 16–21

    PubMed  CAS  Google Scholar 

  9. McCreadie RG. The Nithsdale schizophrenia surveys: an overview. Soc Psychiatry Psychiatr Epidemiol 1992; 24: 40–5

    Article  Google Scholar 

  10. Jibson MD, Tandon R. New atypical antipsychotic medications. J Psychiatr Res 1998; 32(3–4): 215–28

    Article  PubMed  CAS  Google Scholar 

  11. Chouinard G, Annable L, Mercier P, et al. A five-year follow-up study of tardive dyskinesia. Psychopharmacol Bull 1986; 22: 259–63

    PubMed  CAS  Google Scholar 

  12. Saltz BL, Woerner MG, Kane JM, et al. Prospective study of tardive dyskinesia incidence in the elderly. JAMA 1991; 266: 2402–6

    Article  PubMed  CAS  Google Scholar 

  13. Beasley CM, Dellva MA, Tamura RN, et al. Randomised double-blind comparison of the incidence of tardive dyskinesia in patients with schizophrenia during long-term treatment with olanzapine or haloperidol. Br J Psychiatry 1999; 174: 23–30

    Article  PubMed  CAS  Google Scholar 

  14. Van Putten T. Why do schizophrenic patients refuse to take their drugs? Arch Gen Psychiatry 1974; 31: 67–72

    Article  PubMed  Google Scholar 

  15. Hogan TP, Awad AG. Subjective response to neuroleptics and outcome in schizophrenia: a re-examination comparing two measures. Psychol Med 1992; 22(2): 347–52

    Article  PubMed  CAS  Google Scholar 

  16. Levinson DF, Simpson GM, Singh H, et al. Fluphenazine dose, clinical response, and extrapyramidal symptoms during acute treatment. Arch Gen Psychiatry 1990; 47: 761–8

    Article  PubMed  CAS  Google Scholar 

  17. McEvoy JP, Schooler NR, Wilson WH. Predictors of therapeutic response to haloperidol in acute schizophrenia. Psychopharmacol Bull 1991; 27: 97–101

    PubMed  CAS  Google Scholar 

  18. Goldstein JM. Quetiapine Fumarate (Seroquel) a new atypical antipsychotic. Drugs of Today 1999; 35: 193–210

    PubMed  CAS  Google Scholar 

  19. Jauss M, Schroder J, Pantel J, et al. Severe akathisia during olanzapine treatment of acute schizophrenia. Pharmaco-psychiatry 1998; 31: 146–8

    CAS  Google Scholar 

  20. Kurzthaler I, Hummer M, Kohl C, et al. Propranolol treatment of olanzapine-induced akathisia [letter]. Am J Psychiatry 1997; 154: 1316

    PubMed  CAS  Google Scholar 

  21. Norquist G, Lebowitz B, Hyman S. Expanding the frontier of treatment research. Prevention & Treatment 1999; I: 0002a, posted June 26 1998 at: www.journal.apa.org/prevention/volume1/pre0010002a.html

  22. Fleischhacker WW, Hummer M. Do phase III trials have clinical value? J Clin Psychopharmacol 1999; 19: 391–2

    Article  PubMed  CAS  Google Scholar 

  23. Guy W. Early clinical drug evaluation (ECSDU): assessment manual. Rockville: National Institute Mental Health, 1976

    Google Scholar 

  24. Lingjærde O, Ahlfors UG, Bech P, et al. The UKU side effects rating scale. Acta Psychiatr Scand 1987; 76 Suppl. 334: 1–100

    Article  Google Scholar 

  25. SPSS para Windows Version 10.0. Programa informático. Chicago 1999: SPSS Inc. Fsd.

  26. Keks NA. Minimizing the non-extrapyramidal side-effects of antipsychotics. Acta Psychiatr Scand 1996; 94: 18–24

    Article  Google Scholar 

  27. Geddes J, Freemantle N, Harrison P, et al. Atypical antipsychotics in the treatment of schizophrenia: systematic overview and metaregression analysis. BMJ 2000; 321: 1371–6

    Article  PubMed  CAS  Google Scholar 

  28. Tollefson GD, Beasley CM Jr, Tran P, et al. Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial. Am J Psychiatry 1997; 154: 457–65

    PubMed  CAS  Google Scholar 

  29. Arvanitis LA, Miller BG. Seroquel trial 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: 233–46

    Article  PubMed  CAS  Google Scholar 

  30. Chouinard G, Jones B, Remington G, et al. A Canadian multi-center placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. J Clin Psychopharmacol 1993; 13: 25–40

    Article  PubMed  CAS  Google Scholar 

  31. Marder SR, Meibach RC. Risperidone in the treatment of schizophrenia. Am J Psychiatry 1994; 151: 825–35

    PubMed  CAS  Google Scholar 

  32. Peuskens J, on behalf of the Risperidone Study Group. Risperidone in the treatment of patients with chronic schizophrenia: a multi-national, multi-centre, double-blind, parallel-group study versus haloperidol. Br J Psychiatry 1995; 166: 712–26

    Article  PubMed  CAS  Google Scholar 

  33. Goff DC, Posever T, Herz L, et al. An exploratory haloperidol-controlled dose-fixing study of ziprasidone in hospitalised patients with schizophrenia or schizoaffective disorder. J Clin Psychopharmacol 1998; 18(4): 296–304

    Article  PubMed  CAS  Google Scholar 

  34. Petit M, Raniwalla J, Tweed J, et al. A comparison of an atypical and typical antipsychotic, zotepine versus haloperidol in patients with acute exacerbation of schizophrenia: a parallel group, double-blind trial. Psychopharmacol Bull 1996; 32: 81–7

    PubMed  CAS  Google Scholar 

  35. Muller-Siecheneder F, Muller MJ, Hillert A, et al. Risperidone versus haloperidol and amitriptyline in the treatment of patients with a combined psychotic and depressive syndrome. J Clin Psychopharmacol 1998; 18(2): 111–20

    Article  PubMed  CAS  Google Scholar 

  36. Nemeroff CB. Dosing the antipsychotic medication olanzapine. J Clin Psychiatry 1997; 58 Suppl. 10: 45–9

    PubMed  CAS  Google Scholar 

  37. Jeste DV, Klausner M, Brecher M, et al. A clinical evaluation of risperidone in the treatment of schizophrenia: a 10-week, open-label, multicenter trial. ARCS Study Group. Assessment of risperdal in a clinical setting. Psychopharmacology (Berl) 1997; 131(3): 239–47

    Article  CAS  Google Scholar 

  38. McEvoy JP, Schifler PL, Frances A, et al. The Expert Consensus Guideline Series. Treatment of schizophrenia 1999. J Clin Psychiatry 1999; 60 Suppl. 11: 1–80

    Google Scholar 

  39. Cada DJ, Levien T, Baker SD. Ziprasidone. Hosp Pharm 2001; 96(6): 645–56

    Google Scholar 

  40. Keck PE, McElroy SL, Arnold LM. Ziprasidone: a new atypical antipsychotic. Expert Opin Pharmacother 2001; 2(6): 1033–42

    Article  PubMed  CAS  Google Scholar 

  41. Hoge SK, Appelbaum PS, Lawlor T, et al. A prospective, multi-center study of patients’ refusal of antipsychotic medication. Arch Gen Psychiatry 1990; 47(10): 949–56

    Article  PubMed  CAS  Google Scholar 

  42. Kapur S, Remington G. Atypical antipsychotics. Patients value the lower incidence of extrapyramidal side effects. BMJ 2000; 321: 1360–1

    Article  PubMed  CAS  Google Scholar 

  43. Fakhoury WKH, Wright D, Wallace M. Prevalence and extent of distress of adverse reactions of antipsychotics among callers to a United Kingdom National Mental Health Helpline. Int Clin Psychopharmacol 2001; 16: 153–62

    Article  PubMed  CAS  Google Scholar 

  44. Sainati SM, Hubbard JW, Chi E, et al. Safety, tolerability, and effect of food on the pharmacokinetics of iloperidone (HP 873), a potential atypical antipsychotic. J Clin Pharmacol 1995; 35(7): 713–20

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study received a grant from Pfizer SA, Madrid, Spain.

Previous presentations: preliminary results presented at the American Psychiatric Association (APA) Annual Meeting, New Orleans, 5–10 May 2001, and at the International Society for Pharmacoeconomics and Outcomes Research Fourth Annual European Congress (ISPOR), Cannes (France), 11–13 November 2001.

Author information

Authors and Affiliations

  1. Departamento de Psiquiatría, Universidad de Oviedo, C/Julián Clavería, Oviedo, 6, 33006, Spain

    Julio Bobes & M. P. García-Portilla

  2. Outcomes Research Unit & Medical Division, Laboratorios Pfizer SA, Madrid, Spain

    J. Rejas

  3. Biométrica, Barcelona, Spain

    M. Garcia-Garcia & F. Rico-Villademoros

  4. Medical Division, Laboratorios Pfizer SA, Madrid, Spain

    M. Madrigal & G. Hernández

Authors
  1. Julio Bobes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Rejas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Garcia-Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. Rico-Villademoros
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. P. García-Portilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Madrigal
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G. Hernández
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Julio Bobes.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bobes, J., Rejas, J., Garcia-Garcia, M. et al. Frequency of Extrapyramidal Adverse Reactions in Schizophrenic Outpatients Treated with Risperidone, Olanzapine, Quetiapine or Haloperidol. Clin. Drug Investig. 22, 609–622 (2002). https://doi.org/10.2165/00044011-200222090-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00044011-200222090-00006

Keywords

Search

Navigation