Chapter 30.Ziprasidone

Ziprasidone (CP-88059) is an atypical, or second-generation, antipsychotic agent that has activity for treating positive, negative, cognitive, and affective symptoms of schizophrenia and schizoaffective disorder and for treating mania and mixed states in bipolar disorder, with limited adverse extrapyramidal, sedative, anticholinergic, and cardiometabolic effects. First approved in 2001, this antipsychotic was initially part of a new drug application for the treatment of psychotic disorders submitted to the U.S Food and Drug Administration (FDA) in 1997. Because of concerns regarding an increase in the mean duration of the QT interval, an electrocardiographic measure of the ventricular depolarization and repolarization phases of cardiac conduction, the application was not initially approved. Further studies, designed in collaboration with the FDA, quantified the limited extent of the QTc interval lengthening effect seen with ziprasidone compared with that seen with other agents in wide use; these studies established the safety of ziprasidone with respect to cardiac conduction and a benchmark for the approach to evaluating drug effects on the QT interval that has subsequently been applied to other agents evaluated by the FDA. Ziprasidone has received regulatory approval and is available in more than 92 countries.