Ziprasidone in the management of schizophrenia : the QT interval issue in context.

Ziprasidone is a new atypical antipsychotic recently marketed in a number of countries. Its main advantage over other atypical and typical drugs is its low propensity for causing weight gain. However, ziprasidone has been shown to prolong to some extent the cardiac corrected QT (QTc) interval, a property shared by a number of other antipsychotics. Prolongation of the QTc interval is linked to the ventricular tachyarrhythmia torsade de pointes, which is occasionally fatal, although the precise association between QTc changes and risk of sudden cardiac death has not been determined. QTc prolongation is certainly linked in some way to an increased risk of sudden cardiac death, and this may explain the recent, somewhat preliminary, reports of increased risk associated with use of some antipsychotics. Ziprasidone prolongs QTc to a moderate degree, though to a greater extent than quetiapine, risperidone, olanzapine and haloperidol. There is also preliminary evidence that ziprasidone blocks the delayed potassium rectifier channel in cardiac cells. Because of this, and despite the fact that no increased risk of arrhythmia or sudden death has been demonstrated for ziprasidone, some caution is required. Ziprasidone should be avoided in patients with some types of cardiac disease and with uncontrolled electrolyte disturbance. Coprescription of ziprasidone with other drugs that prolong the QT interval should be avoided where possible. When cross-tapering with other antipsychotics, care should be taken to avoid high total load of antipsychotics, and cross-tapering with drugs known to prolong QT interval at normal clinical doses should be avoided. Under most clinical circumstances, however, ziprasidone may be safely used without ECG monitoring or other special precautions. Its effect on QT interval and possible effect on risk of arrhythmia should be balanced with the observation that the drug has a more favourable effect on bodyweight and glucose homeostasis (and so perhaps cardiac risk) than many other antipsychotics.