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  • The International Journal of Neuropsychopharmacology, Volume 12, Issue 9
  • October 2009, pp. 1233-1248

Remission in schizophrenia: 196-week, double-blind treatment with ziprasidone vs. haloperidol

  • Steven G. Potkin (a1), Peter J. Weiden (a2), Antony D. Loebel (a3), Lewis E. Warrington (a3), Eric J. Watsky (a3) and Cynthia O. Siu (a4)
  • DOI:
  • Published online: 07 May 2009

To compare the remission rate and its time-course over 196 wk of double-blind treatment with an atypical antipsychotic, ziprasidone (80–160 mg/d given b.i.d., or 80–120 mg/d given q.d.), or a conventional antipsychotic, haloperidol (5–20 mg/d). Outcome assessments included attainment of remission (Andreasen criteria) by longitudinal analysis. Positive and Negative Syndrome Scale (PANSS) scores, Global Assessment of Functioning Scale (GAF) scores, and quality-of-life (QLS) were also assessed in the initial 40-wk study phase (n=599) and the 3-yr extension study (n=186). Discontinuation rates in the initial 40-wk core and follow-up extension studies were comparable between groups: 64% and 65% for the 80–160 mg/d ziprasidone group, 65% and 58% for the 80–120 mg/d ziprasidone group, and 60% and 66% for the 5–20 mg/d haloperidol group, respectively. Mean change scores from baseline to LOCF endpoint (week 40 or early termination) for PANSS negative and GAF (primary efficacy variables) were not statistically significantly different between ziprasidone and haloperidol. During the 3-yr extension study, ziprasidone-treated subjects (80–160 mg/d) were more likely to achieve remission (51%) than haloperidol-treated (40%) subjects (p=0.04), while there was a favourable trend associated with 80–120 mg/d ziprasidone (48%). Compared to the haloperidol group, subjects assigned to the 80–160 mg/d ziprasidone group showed a gradual and persistent improvement in remission (p=0.006) and quality-of-life (p=0.004) in the longitudinal analyses. Significant differences in the trajectory of PANSS total and GAF scores favouring the 80–160 mg/d ziprasidone group were also observed. In this long-term, double-blind study, ziprasidone treatment was more likely to result in remission than haloperidol treatment, and was associated with greater improvement in quality-of-life.

Corresponding author
Address for correspondence: S. G. Potkin, M.D., Department of Psychiatry and Human Behavior, University of California, Irvine, 5251 California Avenue, Suite 240, Irvine, CA 92617, USA. Tel.: (949) 824-8040Fax: (949) 824-3324Email:
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DE Addington , C Pantelis , M Dineen , I Benattia , (2004). Efficacy and tolerability of ziprasidone versus risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder: an 8-week, double-blind, multicenter trial. Journal of Clinical Psychiatry 65, 16241633.

NC Andreasen , WT Carpenter Jr., JM Kane , RA Lasser , (2005). Remission in schizophrenia: proposed criteria and rationale for consensus. American Journal of Psychiatry 162, 441449.

M Arato , R O'Connor , HY Meltzer (2002). A 1-year, double-blind, placebo-controlled trial of ziprasidone 40, 80 and 160 mg/day in chronic schizophrenia: the Ziprasidone Extended Use in Schizophrenia (ZEUS) study. International Clinical Psychopharmacology 17, 207215.

TRE Barnes (1989). A rating scale for drug-induced akathisia. British Journal of Psychiatry 154, 672676.

DG Daniel , DL Zimbroff , SG Potkin , KR Reeves , , for the Ziprasidone Study Group (1999). Ziprasidone 80 mg/day and 160 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 6-week placebo-controlled trial. Neuropsychopharmacology 20, 491505.

M De Hert , R van Winkel , M Wampers , J Kane , (2007). Remission criteria for schizophrenia: evaluation in a large naturalistic cohort. Schizophrenia Research 92, 6873.

PJ Diggle , P Heagerty , KY Liang , SL Zeger (2001). Analysis of Longitudinal Data, 2nd edn.Oxford: Oxford University Press.

RC Hall (1995). Global assessment of functioning. A modified scale. Psychosomatics 36, 267275.

CM Harding , GW Brooks , T Ashikaga , JS Strauss , (1987). The Vermont longitudinal study of persons with severe mental illness. II: Long-term outcome of subjects who retrospectively met DSM-III criteria for schizophrenia. American Journal of Psychiatry 144, 727735.

DW Heinrichs , TE Hanlon , WT Carpenter Jr. (1984). The Quality of Life Scale: an instrument for rating the schizophrenic deficit syndrome. Schizophrenia Bulletin 10, 388398.

MI Herz , WM Glazer , MA Mostert , MA Sheard , (1991). Intermittent vs maintenance medication in schizophrenia. Two-year results. Archives of General Psychiatry 48, 333339.

S Hirsch , W Kissling , J Bauml , A Power , (2002). A 28-week comparison of ziprasidone and haloperidol in outpatients with stable schizophrenia. Journal of Clinical Psychiatry 63, 516523.

G Huber , G Gross , R Schuttler (1975). A long-term follow-up study of schizophrenia: psychiatric course of illness and prognosis. Acta Psychiatrica Scandinavica 52, 4957.

PB Jones , TR Barnes , L Davies , G Dunn , (2006). Randomized controlled trial of the effect on Quality of Life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Archives of General Psychiatry 63, 10791087.

RS Kahn , WW Fleischhacker , H Boter , M Davidson , (2008). Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 371, 10851097.

JM Kane , DT Crandall , RN Marcus , J Eudicone , (2007). Symptomatic remission in schizophrenia patients treated with aripiprazole or haloperidol for up to 52 weeks. Schizophrenia Research 95, 143150.

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

P Keck Jr., A Buffenstein , J Ferguson , J Feighner , (1998). Ziprasidone 40 and 120 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 4-week placebo-controlled trial. Psychopharmacology (Berlin) 140, 173184.

HC Kraemer , GT Wilson , CG Fairburn , WS Agras (2002). Mediators and moderators of treatment effects in randomized clinical trials. Archives of General Psychiatry 59, 877883.

AC Leon , CH Mallinckrodt , C Chuang-Stein , DG Archibald , (2006). Attrition in randomized controlled clinical trials: methodological issues in psychopharmacology. Biological Psychiatry 59, 10011005.

S Leucht , RR Engel , J Bauml , JM Davis (2007). Is the superior efficacy of new generation antipsychotics an artifact of LOCF? Schizophrenia Bulletin 33, 183191.

JA Lieberman , TS Stroup , JP McEvoy , MS Swartz , (2005). Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. New England Journal of Medicine 353, 12091223.

SR Marder , SM Glynn , WC Wirshing , DA Wirshing , (2003). Maintenance treatment of schizophrenia with risperidone or haloperidol: 2-year outcomes. American Journal of Psychiatry 160, 14051412.

A Marneros , A Deister , A Rohde , EM Steinmeyer , (1989). Long-term outcome of schizoaffective and schizophrenic disorders: a comparative study. I. Definitions, methods, psychopathological and social outcome. European Archives of Psychiatry & Neurological Sciences 238, 118125.

MC Mauri , A Colasanti , M Rossattini , LS Volonteri , (2007). Ziprasidone outcome and tolerability: a practical clinical trial with plasma drug levels. Pharmacopsychiatry 40, 8992.

JP McEvoy , JA Lieberman , DO Perkins , RM Hamer , (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.

J Modestin , A Huber , E Satirli , T Malti , (2003). Long-term course of schizophrenic illness: Bleuler's study reconsidered. American Journal of Psychiatry 160, 22022208.

AM Mortimer (2007). Symptom rating scales and outcome in schizophrenia. British Journal of Psychiatry Supplement 50, S7–14.

B Parsons , DB Allison , A Loebel , K Williams , (2009). Weight effects associated with antipsychotics: a comprehensive database analysis. Schizophrenia Research. Published online: 25 March 2009. doi:10.1016/j.schres.2008.09.025.

RA Rosenheck , DL Leslie , J Sindelar , EA Miller , (2006). Cost-effectiveness of second-generation antipsychotics and perphenazine in a randomized trial of treatment for chronic schizophrenia. American Journal of Psychiatry 163, 20802089.

GM Simpson , JW Angus (1970). A rating scale for extrapyramidal side effects. Acta Psychiatrica Scandinavica (Suppl.) 212, 1119.

GM Simpson , ID Glick , PJ Weiden , SJ Romano , (2004). Randomized, controlled, double-blind multicenter comparison of the efficacy and tolerability of ziprasidone versus olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder. American Journal of Psychiatry 161, 18371847.

GM Simpson , P Weiden , T Pigott , S Murray , (2005). Six-month, blinded, multicenter continuation study of ziprasidone versus olanzapine in schizophrenia. American Journal of Psychiatry 162, 15351538.

MT Tsuang , RF Woolson , JA Fleming (1979). Long-term outcome of major psychoses. I. Schizophrenia and affective disorders compared with psychiatrically symptom-free surgical conditions. Archives of General Psychiatry 36, 12951301.

JB Willett , JD Singer , NC Martin (1998). The design and analysis of longitudinal studies of development and psychopathology in context: statistical models and methodological recommendations. Development and Psychopathology 10, 395426.

MC Wu , PS Albert , BU Wu (2001). Adjusting for drop-out in clinical trials with repeated measures: design and analysis issues. Statistics in Medicine 20, 93–108.

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  • ISSN: 1461-1457
  • EISSN: 1469-5111
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