CNS Drugs. 17(6):423-430, 2003.
Taylor, David
Abstract:
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.
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No Significant QTc Interval Changes with High-Dose Ziprasidone: A Case Series.

ARTICLES
Journal of Psychiatric Practice. 10(4):227-232, July 2004.
LEVY, WOODBURNE O. MD; ROBICHAUX-KEENE, NICOLE R. PsyD, ARNP; NUNEZ, CLAUDIA MD
Abstract:
This study examined the effects of high-dose ziprasidone on the electrocardiograms (ECGs) of adult inpatients. This was done in an effort to assess the incremental risk of QTc interval prolongation when using ziprasidone in doses above the maximum dose of 160 mg/day approved by the Food and Drug Administration. We retrospectively examined pre- and post-treatment QTc intervals in 15 subjects at the James A. Haley Veterans Affairs Medical Center who had received high doses of ziprasidone, ranging from 240 to 320 mg/day, due to intractable psychotic symptoms. Pure baseline ECGs were not always attainable, since the majority of the subjects were taking concomitant medications at the time that ziprasidone was initiated. Analysis yielded an average increase of 3.4 msec from pre- to post-treatment, with a maximum post-treatment interval of 452 msec and no cases having a pre- to post- treatment QTc interval increase > 20 msec. These findings are statistically insignificant and do not approach the 500 msec threshold of concern. This study suggests that high-dose ziprasidone does not have a significant incremental effect on QTc interval prolongation in certain subsets of patients. However, it does not rule out the possibility that ziprasidone could have deleterious effects in higher risk populations or that ziprasidone could have rare, idiosyncratic cardiogenic effects. Limitations of the study are identified and recommendations for future research are presented.
(C) 2004 Lippincott Williams & Wilkins, Inc.