Analysis of the QTc interval during olanzapine treatment of patients with schizophrenia and related psychosis
Czekalla, J.; Beasley, C.M.; Dellva, M.A.; Berg, P.H.; Grundy, S.
Journal of Clinical Psychiatry 62(3): 191-198
2001
ISSN/ISBN: 0160-6689 PMID: 11305706 Document Number: 535668
Background: There may be a temporal association between some antipsychotics and prolongation of the heart-rate-corrected QT interval (QTc) representing a delay in ventricular repolarization. QTc prolongation significantly exceeding normal intraindividual and interindividual variation may increase the risk of ventricular tachydysrhythmias, especially torsade de pointes, and therefore, sudden cardiac death. Method: Electrocardiogram recordings obtained as part of the safety assessment of olanzapine in 4 controlled, randomized clinical trials (N = 2700) were analyzed. These analyses were conducted to characterize any change in QTc temporally associated with olanzapine, compared with placebo, haloperidol, and risperidone, in acutely psychotic patients (DSM-III-R and DSM-IV) and to characterize variability and temporal course of the QTc in this patient population. Changes from baseline to minimum and maximum QTc were tested for significance, and baseline to acute-phase endpoint change in mean QTc was tested for significance within treatments and for differences between olanzapine and comparators. The possibility of a linear relationship between dose of olanzapine and mean change in QTc, as well as incidence of treatment-emergent prolongation of QTc (change from < 430 msec at baseline to gtoreq 430 msec at endpoint), was tested. Results: The incidence of maximum QTc gtoreq 450 msec during treatment was approximately equal to the incidence of QTc gtoreq 450 msec at baseline. Conclusion: Results of these analyses suggest that olanzapine, as therapeutically administered to patients with schizophrenia and related psychoses, does not contribute to QTc prolongation resulting in potentially fatal ventricular arrhythmias.