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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 Möller (a1), Michael Riedel (a1), Markus Jäger (a1), Florian Wickelmaier (a1), Wolfgang Maier (a2), Kai-Uwe Kühn (a2), Gerhard Buchkremer (a3), Isabella Heuser (a4), Joachim Klosterkötter (a5), Markus Gastpar (a6), Dieter F. Braus (a7), Ralf Schlösser (a8), Frank Schneider (a9), Christian Ohmann (a10), Mathias Riesbeck (a11) and Wolfgang Gaebel (a11)...

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.

Corresponding author
Address for correspondence: Prof. H.-J. Möller, Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Nussbaumstr. 7, 80336 Munich, Germany. Tel.: 0049 89 5160 5501Fax: 0049 89 5160 5522E-mail:
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A Agresti (2002). Categorical Data Analysis. New York: Wiley.

D Addington , J Addington , B Schissel (1990). A depression rating scale for schizophrenics. Schizophrenia Research 3, 247251.

NC Andreasen (1982). Negative symptoms in schizophrenia. Definition and reliability. Archives of General Psychiatry 39, 784788.

EL Coldham , J Addington , D Addington (2002). Medication adherence of individuals with a first episode of psychosis. Acta Psychiatrica Scandinavica 106, 286290.

JG Csernansky , R Mahmoud , R Brenner (2002). A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. New England Journal of Medicine 346, 1622.

RA Emsley , the Risperidone Working Group (1999). Risperidone in the treatment of first-episode psychotic patients: a double-blind multicenter study. Risperidone Working Group. Schizophrenia Bulletin 25, 721729.

WW Fleischhacker , KJ Bergmann , R Perovich , LK Pestreich , M Borenstein , JA Lieberman , JM Kane (1989). The Hillside Akathisia Scale: a new rating instrument for neuroleptic-induced akathisia. Psychopharmacology Bulletin 25, 222226.

W Gaebel , HJ Moller , G Buchkremer , C Ohmann , M Riesbeck , W Wolwer , M Von Wilmsdorff , R Bottlender , S Klingberg (2004). Pharmacological long-term treatment strategies in first episode schizophrenia – study design and preliminary results of an ongoing RCT within the German Research Network on Schizophrenia. European Archives of Psychiatry and Clinical Neuroscience 254, 129140.

W Gaebel , M Riesbeck , W Wölwer , A Klimke , M Eickhoff , M Von Wilmsdorff , MC Jockers-Scherübl , K Kühn , M Lemke , A Bechdolf , (2007). Maintenance treatment with risperidone or low-dose haloperidol in first-episode schizophrenia: one-year results of a randomized controlled trial within the German Research Network on Schizophrenia. Journal of Clinical Psychiatry 68, 17631774.

AI Green , JA Lieberman , RM Hamer , ID Glick , RE Gur , RS Kahn , JP McEvoy , DO Perkins , AJ Rothschild , T Sharma , (2006). Olanzapine and haloperidol in first episode psychosis: two-year data. Schizophrenia Research 86, 234243.

GL Haas , JA Sweeney (1992). Premorbid and onset features of first-episode schizophrenia. Schizophrenia Bulletin 18, 373386.

M Hamilton (1960). A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry 23, 5662.

SR Kay , A Fiszbein , LA Opler (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261276.

RS Keefe , LJ Seidman , BK Christensen , RM Hamer , T Sharma , MM Sitskoorn , RR Lewine , DA Yurgelun-Todd , RC Gur , M Tohen , (2004). Comparative effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: a randomized, double-blind trial of olanzapine versus low doses of haloperidol. American Journal of Psychiatry 161, 985995.

RS Keefe , JA Sweeney , H Gu , RM Hamer , DO Perkins , JP McEvoy , JA Lieberman (2007). Effects of olanzapine, quetiapine, and risperidone on neurocognitive function in early psychosis: a randomized, double-blind 52-week comparison. American Journal of Psychiatry 164, 10611071.

L Kopala , J Rabinowitz , M Davidson (2003). Extra-pyramidal signs and symptoms (EPS) in recent onset schizophrenia: a comparison of risperidone and haloperidol. European Neuropsychopharmacology 13 (Suppl. 4), S338.

K-Y Liang , SL Zeger (1986). Longitudinal data analysis using generalized linear models. Biometrika 73, 1322.

S Leucht , G Pitschel-Walz , D Abraham , W Kissling (1999). Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials. Schizophrenia Research 35, 5168.

JA Lieberman , TS Stroup , JP McEvoy , MS Swartz , RA Rosenheck , DO Perkins , RS Keefe , SM Davis , CE Davis , BD Lebowitz , J Severe , JK Hsiao (2005). Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. New England Journal of Medicine 353, 12091223.

JA Lieberman , G Tollefson , M Tohen , AI Green , RE Gur , R Kahn , J McEvoy , D Perkins , T Sharma , R Zipursky , H Wei , RM Hamer (2003). Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol. American Journal of Psychiatry 160, 13961404.

SR Marder , SM Glynn , WC Wirshing , DA Wirshing , D Ross , C Widmark , J Mintz , RP Liberman , KE Blair (2003). Maintenance treatment of schizophrenia with risperidone or haloperidol: 2-year outcomes. American Journal of Psychiatry 160, 14051412.

JP McEvoy , JA Lieberman , DO Perkins , RM Hamer , H Gu , A Lazarus , D Sweitzer , C Olexy , P Weiden , SD Strakowski (2007). Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, double-blind 52-week comparison. American Journal of Psychiatry 164, 10501060.

MC Merlo , H Hofer , W Gekle , G Berger , J Ventura , I Panhuber , G Latour , SR Marder (2002). Risperidone, 2 mg/day vs. 4 mg/day, in first-episode, acutely psychotic patients: treatment efficacy and effects on fine motor functioning. Journal of Clinical Psychiatry 63, 885891.

HJ Möller (2000a). Definition, psychopharmacological basis and clinical evaluation of novel/atypical neuroleptics: methodological issues and clinical consequences. World Journal of Biological Psychiatry 1, 7591.

HJ Möller (2000b). State of the art of drug treatment of schizophrenia and the future position of the novel/atypical antipsychotics. World Journal of Biological Psychiatry 1, 204214.

HJ Möller (2003). Management of the negative symptoms of schizophrenia. New treatment options. CNS Drugs 17, 793823.

HJ Möller (2004). Course and long-term treatment of schizophrenic psychoses. Pharmacopsychiatry 37 (Suppl. 2), 126135.

HJ Möller (2005). Antidepressive effects of traditional and second generation antipsychotics: a review of the clinical data. European Archives of Psychiatry and Clinical Neuroscience 255, 8393.

HJ Möller (2007). Clinical evaluation of negative symptoms in schizophrenia. European Psychiatry 22, 380386.

HJ Möller , R Bottlender , A Groß , P Hoff , J Wittmann , U Wegner , A Strauss (2002). The Kraepelinian dichotomy: preliminary results of a 15-year follow-up study on functional psychoses: focus on negative symptoms. Schizophrenia Research 56, 8794.

HJ Möller , W Schmid Bode , C Cording-Tömmel , HU Wittchen , M Zaudig , D von Zerssen (1988). Psychopathological and social outcome in schizophrenia versus affective/schizoaffective psychoses and prediction of poor outcome in schizophrenia. Results from a 5–8 year follow-up. Acta Psychiatrica Scandinavica 77, 379389.

HJ Möller , R Bottlender , U Wegner , J Wittmann , A Strauß (2000). Long-term course of schizophrenic, affective and schizoaffective psychosis: focus on negative symptoms and their impact on global indicators of outcome. Acta Psychiatrica Scandinavica 102 (Suppl. 407), 5457.

HJ Möller , HM van Praag , B Aufdembrinke , P Bailey , TR Barnes , J Beck , H Bentsen , FX Eich , L Farrow , WW Fleischhacker , (1994). Negative symptoms in schizophrenia: considerations for clinical trials. Working group on negative symptoms in schizophrenia. Psychopharmacology (Berlin) 115, 221228.

MJ Muller , P Marx-Dannigkeit , R Schlosser , H Wetzel , D Addington , O Benkert (1999). The Calgary Depression Rating Scale for Schizophrenia: development and interrater reliability of a German version (CDSS-G). Journal of Psychiatric Research 33, 433443.

P Oosthuizen , R Emsley , TH Jadri , N Keyter (2004). A randomized, controlled comparison of the efficacy and tolerability of low and high doses of haloperidol in the treatment of first-episode psychosis. International Journal of Neuropsychopharmacology 7, 125131.

C Rummel , J Hamann , W Kissling , S Leucht (2003). New generation antipsychotics for first episode schizophrenia. Cochrane Database of Systematic Reviews. Issue 4. Art. no.: CD004410.

TM Sanger , JA Lieberman , M Tohen , S Grundy , C Beasley Jr., GD Tollefson (1999). Olanzapine versus haloperidol treatment in first-episode psychosis. American Journal of Psychiatry 156, 7987.

N Schooler , J Rabinowitz , M Davidson , R Emsley , PD Harvey , L Kopala , PD McGorry , HI Van , M Eerdekens , W Swyzen , G De Smedt (2005). Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial. American Journal of Psychiatry 162, 947953.

PE Shrout , JL Fleiss (1979). Intraclass correlations: uses in assessing rater reliability. Psychological Bulletin 86, 420428.

SJ Siegel , F Irani , CM Brensinger , CG Kohler , WB Bilker , JD Ragland , SJ Kanes , RC Gur , RE Gur (2006). Prognostic variables at intake and long-term level of function in schizophrenia. American Journal of Psychiatry 163, 433441.

AJ Vickers , DG Altman (2001). Analysing controlled trials with baseline and follow up measurements. British Medical Journal 323, 11231124.

JS Strauss , WT Carpenter Jr. (1978). The prognosis of schizophrenia: rationale for a multidimensional concept. Schizophrenia Bulletin 4, 5667.

W Wolwer , G Buchkremer , H Hafner , J Klosterkotter , W Maier , HJ Moller , W Gaebel (2003). German research network on schizophrenia-bridging the gap between research and care. European Archives of Psychiatry and Clinical Neuroscience 253, 321329.

RC Young , JT Biggs , VE Ziegler , DA Meyer (1978). A rating scale for mania: reliability, validity and sensitivity. British Journal of Psychiatry 133, 429435.

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