Ziprasidone: an atypical antipsychotic drug for the treatment of schizophrenia.

Background: Over the past decade, use of the atypical antipsychotic drugs clozapine, risperidone, olanzapine, and quetiapine has significantly changed the treatment of schizophrenia in the United States. The ability to make optimal drug choices will depend on determining whether there are clinically important differences between these drugs.

Objective: This review describes ziprasidone, the most recently introduced antipsychotic drug. Its mechanism of action, pharmacokinetics, and adverse-effect profile are discussed, and the results of clinical efficacy trials are summarized.

Methods: This review of ziprasidone is based on data from premarketing clinical efficacy and safety trials, a briefing document from the US Food and Drug Administration Psychopharmacological Drugs Advisory Committee, published studies, and abstracts presented at national and international meetings. International Pharmaceutical Abstracts and MEDLINE were searched for relevant citations, with no limitation on year.

Results: Ziprasidone has been reported to be an effective antipsychotic drug for both positive and negative symptoms of schizophrenia, and long-term use has been effective in preventing relapse. Its 5-hydroxytryptamine (HT)1D-antagonist and 5-HT(1A)-agonist activity are consistent with a potential for antidepressant and anxiolytic activity beyond its antipsychotic effects. Ziprasidone has been associated with a low incidence of sedative effects, a low likelihood of extrapyramidal symptoms and postural hypotension, and no anticholinergic effect, although it may cause transient hyperprolactinemia. Unlike most atypical antipsychotic drugs, ziprasidone is not associated with weight gain, hyperlipidemia, or elevated plasma glucose levels. It is, however, more likely than other atypical antipsychotic drugs to increase the QTc interval (QT interval corrected for heart rate). For acute psychotic symptoms in patients with schizophrenia, schizoaffective disorder, or acute mania, ziprasidone is administered twice daily at a usual daily dose of 80 to 160 mg, whereas 40 mg/d may be an effective maintenance dose.

Conclusions: Differences in efficacy and tolerability between existing atypical antipsychotic drugs allow individualization of drug therapy for patients with schizophrenia or schizoaffective disorder. Ziprasidone differs from other atypical antipsychotic drugs in several clinically important ways, although further experience is necessary to clarify the significance of these differences.