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Wednesday 01 December 1999

Ziprasidone for schizophrenia and severe mental illness.

By: Bagnall A, Lewis RA, Leitner ML.

Cochrane Database Syst Rev 2000;(4):CD001945

BACKGROUND: Typical antipsychotic drugs are widely used as the first line treatment for people with schizophrenia. However, the atypical class of antipsychotic drugs are making important inroads into this approach. Atypical is a widely used term used to describe some antipsychotics which have a low propensity to produce movement disorders and raise serum prolactin. There is some suggestion that the different adverse effect profiles of atypical antipsychotic group make them more acceptable to people with schizophrenia. Ziprasidone is one of the newer atypicals with a high serotonin receptor affinity. OBJECTIVES: To determine the effects of ziprasidone compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (January 1999), CINAHL (1982-1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1996), PSYNDEX (1977-1999) and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. Pharmaceutical companies (Pfizer - the manufacturer of ziprasidone - and the manufacturers of all comparator drugs) and first authors of all included trials were contacted. SELECTION CRITERIA: All randomised controlled trials that compared ziprasidone to other treatments for schizophrenia and schizophrenia-like psychoses were included by independent assessment. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. Data were excluded if loss to follow up was greater than 50%. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, weighted mean differences were calculated (WMD). All data were inspected for heterogeneity. MAIN RESULTS: Data for this compound range from very short (one week) studies of the intramuscular preparation, to trials lasting over six months. For measures of mental state ziprasidone seems more effective than placebo (RR 0.8 CI 0.7-0.9) and as effective as haloperidol (RR 0.8 CI 0.7-1). It is less likely than haloperidol to cause movement disorders (RR 0.4 CI 0.2-0.6), but causes more nausea and vomiting (RR 2.1 CI 1.2-3.8). The injected form of the drug causes more pain at the injection site than haloperidol (RR 5.3 CI 1.3-22). REVIEWER'S CONCLUSIONS: Currently data are limited. Ziprasidone may be an effective antipsychotic with less extrapyramidal effects than haloperidol. It also, however, causes more nausea and vomiting than the typical drugs, and, at present, there is no data suggesting that it is different to other atypical compounds. Well planned, conducted and reported long term randomised trials are needed if ziprasidone is to be accepted into everyday use.

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