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Spotlight on Ziprasidone in Schizophrenia and Schizoaffective Disorder

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Abstract

Ziprasidone is a novel antipsychotic agent with a pharmacological profile distinct from that of other currently available novel or classical antipsychotics. In preclinical studies, ziprasidone was predicted to have efficacy against positive, negative and affective symptoms of schizophrenia with a favourable tolerability profile, including a low propensity to induce extrapyramidal adverse effects. p ]The drug has been administered orally to >300 patients with an acute exacerbation of schizophrenia or schizoaffective disorder in published 4- to 6-week randomised, double-blind trials. When given twice daily at dosages of between 80 and 160 mg/day, ziprasidone produced significantly greater improvements in overall symptomatology than placebo. In the largest study, ziprasidone 80 or 160 mg/day was also significantly more effective than placebo in reducing negative symptoms and, at 160 mg/day, was significantly more effective than placebo in improving depressive symptoms in patients with associated clinically significant depression. Data from a 4-week trial indicate that ziprasidone 160 mg/day has similar efficacy to haloperidol 15 mg/day.

Ziprasidone 40 to 160 mg/day was more effective than placebo with respect to prevention of impending relapse and improvement of negative symptoms in 294 stable patients with chronic schizophrenia who were treated for up to 1 year. In addition, significantly more ziprasidone than haloperidol recipients achieved a negative symptom response in a 28-week study involving 301 stable patients with chronic or subchronic schizophrenia.

In general, oral ziprasidone is well tolerated with an overall incidence of adverse events similar to placebo. Importantly, the drug has a low propensity to induce extrapyramidal effects and a negligible effect on body weight. Ziprasidone is associated with slight prolongation of the QTc interval; the clinical significance of this is not yet clear. The drug does not appear to be associated with sustained elevation of plasma prolactin levels. Preliminary data indicate that long-term oral ziprasidone treatment is well tolerated.

Ziprasidone is the only novel antipsychotic currently available in a rapid-acting intramuscular formulation. Short-term treatment with intramuscular ziprasidone was effective and well tolerated in patients with acute agitation associated with psychosis. In addition, intramuscular ziprasidone reduced agitation scores by a significantly greater extent than haloperidol in a study involving patients with acute agitation associated with psychosis.

Conclusions: Ziprasidone is a promising new antipsychotic that has shown significant efficacy in the oral treatment of patients with schizophrenia or schizoaffective disorder. The drug is well tolerated with a low propensity to induce extrapyramidal effects and a negligible effect on bodyweight. In addition, intramuscular ziprasidone shows efficacy and good tolerability in the treatment of acute agitation associated with psychotic disorders.

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Acknowledgements

The full text article in Drugs 2002; 62 (8): 1217-1251 was reviewed by: C. Bench, Department of Psychiatry, Imperial College of Science, Technology and Medicine, London, UK; J.C. Chou, Nathan Kline Institute, New York University School of Medicine, Orangeburg, New York, USA; D.G. Daniel, Bioniche Development Inc, Falls Church, Virginia, USA; W. Fleischhacker, Department of Biological Psychiatry, University of Innsbruck Medical School, Innsbruck, Austria; N. Gerber, Department of Pharmacology, Ohio State University, Columbus, Ohio, USA; R. Kerwin, Institute of Psychiatry, London, UK; D.J. King, Department of Therapeutics and Pharmacology, Queen’s University Belfast, Belfast, Northern Ireland; C.A. Tamminga, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland, USA; R. Tandon, Department of Psychiatry, University of Michigan Medical Center, Ann Arbor, Michigan, USA.

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  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Nishan S. Gunasekara, Caroline M. Spencer & Gillian M. Keating

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  1. Nishan S. Gunasekara
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  3. Gillian M. Keating
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Correspondence to Gillian M. Keating.

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This spotlight is derived from abstract and summary text of an Adis Drug Evaluation originally published in full in Drugs2002; 62 (8): 1217–1251

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Gunasekara, N.S., Spencer, C.M. & Keating, G.M. Spotlight on Ziprasidone in Schizophrenia and Schizoaffective Disorder. Mol Diag Ther 16, 645–652 (2002). https://doi.org/10.2165/00023210-200216090-00005

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