J. Czekalla et al., Analysis of the QTc interval during olanzapine treatment of patients with schizophrenia and related psychosis, J CLIN PSY, 62(3), 2001, pp. 191-198
Background: There may be a temporal association between some antipsychotics
and prolongation of the heart-rate-corrected QT interval (QTc) representin
g a delay in ventricular repolarization. QTc prolongation significantly exc
eeding normal intraindividual and interindividual variation may increase th
e risk of ventricular tachydysrhythmias, especially torsade de pointes, and
therefore, sudden cardiac death.
Method: Electrocardiogram recordings obtained as part of the safety assessm
ent of olanzapine in 4 controlled, randomized clinical trials (N = 2700) we
re analyzed. These analyses were conducted to characterize any change in QT
c 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 f
or significance, and baseline to acute-phase endpoint change in mean QTc wa
s tested for significance within treatments and for differences between ola
nzapine and comparators. The possibility of a linear relationship between d
ose of olanzapine and mean change in QTc, as well as incidence of treatment
-emergent prolongation of QTc (change from < 430 msec at baseline to <great
er than or equal to> 430 msec at endpoint), was tested.
Results: The incidence of maximum QTc greater than or equal to 450 msec dur
ing treatment was approximately equal to the incidence of QTc greater than
or equal to 450 msec at baseline.
Conclusion: Results of these analyses suggest that olanzapine, as therapeut
ically administered to patients with schizophrenia and related psychoses, d
oes not contribute to QTc prolongation resulting in potentially fatal ventr
icular arrhythmias.