The International Journal of Neuropsychopharmacology

Research Article

Short-term treatment with risperidone or haloperidol in first-episode schizophrenia: 8-week results of a randomized controlled trial within the German Research Network on Schizophrenia

Hans-Jürgen Möllera1 c1, Michael Riedela1, Markus Jägera1, Florian Wickelmaiera1, Wolfgang Maiera2, Kai-Uwe Kühna2, Gerhard Buchkremera3, Isabella Heusera4, Joachim Klosterköttera5, Markus Gastpara6, Dieter F. Brausa7, Ralf Schlössera8, Frank Schneidera9, Christian Ohmanna10, Mathias Riesbecka11 and Wolfgang Gaebela11

for the German Study Group on First-Episode Schizophrenia

a1 Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany

a2 Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany

a3 Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany

a4 Department of Psychiatry and Psychotherapy, Charité-Campus Benjamin Franklin, Berlin, Germany

a5 Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany

a6 Department of General Psychiatry, Rhein Hospital Essen, Essen, Germany

a7 Central Institute of Mental Health, Mannheim, Germany

a8 Department of Psychiatry and Psychotherapy, University of Jena, Germany

a9 Department of Psychiatry and Psychotherapy, RWTH Aachen University, Germany

a10 Coordinating Centre for Clinical Trials, Heinrich-Heine-University, Duesseldorf, Germany

a11 Department of Psychiatry and Psychotherapy, Heinrich-Heine-University, Duesseldorf, Germany

Abstract

Patients with first-episode schizophrenia appear to respond to lower doses of neuroleptics, and to be more sensitive to developing extrapyramidal side-effects. The authors therefore compared in such patients the efficacy and extrapyramidal tolerability of comparatively low dosages of the atypical neuroleptic risperidone and of the conventional neuroleptic haloperidol. Risperidone was hypothesized to have better extrapyramidal tolerability and efficacy in treating negative symptoms. Patients were randomly assigned under double-blind conditions to receive risperidone (n=143) or haloperidol (n=146) for 8 wk. The primary efficacy criterion was the estimated difference in the mean change in the Positive and Negative Symptom Scale (PANSS) negative score between treatment groups; secondary efficacy criteria were changes on the PANSS total score and other PANSS subscores, and several other measures of psychopathology and general functioning. The primary tolerability criterion was the difference in baseline-adjusted occurrence rates of extrapyramidal side-effects measured with the Simpson–Angus Scale (SAS) compared between treatment groups. The main hypothesis was that risperidone would be superior in terms of improving negative symptoms and lowering the risk of extrapyramidal symptoms. Secondary tolerability criteria were the other extrapyramidal symptoms, measured with the Hillside Akathisia Scale (HAS) and the Abnormal Involuntary Movement Scale (AIMS). The average mean daily doses were 3.8 mg (s.d.=1.5) for risperidone and 3.7 mg (s.d.=1.5) for haloperidol. There were similar, significant improvements in both treatment groups in the primary and secondary efficacy criteria. At week 8 nearly all scores of extrapyramidal side-effects indicated a significantly higher prevalence of extrapyramidal side-effects with haloperidol than with risperidone [SAS: risperidone 36.5% of patients; haloperidol 51.5% of patients; likelihood ratio test, χ2(1)=7.8, p=0.005]. There were significantly fewer drop-outs [risperidone n=55, drop-out rate=38.5%; haloperidol n=79, drop-out rate=54.1%, χ2(1)=7.1, p=0.009] and a longer non-discontinuation time [risperidone: average of 50.8 d to drop-out; haloperidol: average of 44.0 d to drop-out; log rank test, χ2(1)=6.4, p=0.011] in the risperidone group. Risperidone and haloperidol appear to be equally effective in treating negative and other symptoms of first-episode schizophrenia. Risperidone has better extrapyramidal tolerability and treatment retention rate than the equivalent dose of haloperidol in these patients.

(Received August 02 2007)

(Reviewed September 16 2007)

(Revised February 22 2008)

(Accepted March 09 2008)

(Online publication May 09 2008)

Correspondence:

c1 Address for correspondence: Prof. H.-J. Möller, Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Nussbaumstr. 7, 80336 Munich, Germany. Tel.: 0049 89 5160 5501 Fax: 0049 89 5160 5522 E-mail: juergen.moeller@med.uni-muenchen.de

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