Analysis of the QTc Interval During Olanzapine Treatment of Patients With Schizophrenia and Related Psychosis

Article Abstract

Background: There may be a temporal associationbetween some antipsychotics and prolongation of theheart-rate-corrected QT interval (QTc) representing a delay inventricular repolarization. QTc prolongation significantlyexceeding normal intraindividual and interindividual variationmay increase the risk of ventricular tachydysrhythmias,especially torsade de pointes, and therefore, sudden cardiacdeath.

Method: Electrocardiogram recordings obtained aspart of the safety assessment of olanzapine in 4 controlled,randomized clinical trials (N = 2700) were analyzed. Theseanalyses were conducted to characterize any change in QTctemporally associated with olanzapine, compared with placebo,haloperidol, and risperidone, in acutely psychotic patients(DSM-III-R and DSM-IV) and to characterize variability andtemporal course of the QTc in this patient population. Changesfrom baseline to minimum and maximum QTc were tested forsignificance, and baseline to acute-phase endpoint change in meanQTc was tested for significance within treatments and fordifferences between olanzapine and comparators. The possibilityof a linear relationship between dose of olanzapine and meanchange in QTc, as well as incidence of treatment-emergentprolongation of QTc (change from = 430 msec at endpoint), was tested.

Results: The incidence of maximum QTc >= 450msec during treatment was approximately equal to the incidence ofQTc >= 450 msec at baseline.

Conclusion: Results of these analyses suggestthat olanzapine, as therapeutically administered to patients withschizophrenia and related psychoses, does not contribute to QTcprolongation resulting in potentially fatal ventriculararrhythmias.

Volume: 62

Quick Links: Neurologic and Neurocognitive , Neurology

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