Objectives: To examine the effect of olanzapine on QTc in a population of children with autism who participated in a clinical trial of olanzapine monotherapy.
Methods: Patients were 35 children (26 males), aged 3-11.9 years (mean, 6.3 ± 2), diagnosed with autistic disorder. The study included a six-week randomized, double-blind, placebo-controlled phase, followed by a six-week open treatment phase. Responders at the end of the 6 week open treatment phase continued to receive open olanzapine for an additional 20 week (32 weeks total study drug exposure). Concomitant medication use was not permitted during the study. Electrocardiograms (ECG) were obtained at baseline, week 12, and week 32. They were obtained in a fasting state between 9 and 10 AM, when drug was at its trough level. To investigate whether there were any QTc increases associated with olanzapine administration, paired t-tests were performed comparing the QTcs obtained at baseline to the QTcs obtained at weeks 12 and 32.
Results: The mean QTc was 409.3 ± 19.1 msec at baseline, 407.3 ± 25.2 msec at week 12, and 411.3 ± 40.1 msec at week 32. Thus the change in QTc from baseline to week 12 was -2.1 ± 29 msec (t = 0.42, df = 34, p = 0.68). The mean QTc change from baseline to week 32 was 2.28 ± 42.7 msec (t = -0.226, df = 17, p = 0.824). No child had a QTc greater than 500 msec during this study. One child with a baseline QTc of 388 msec had an increase of ≥ 60 msec at weeks 12 and 32 compared to baseline. His maximum QTc was 452 msec at week 32.
Conclusions: The results of this study suggest that olanzapine monotherapy does not significantly affect the QTc when administered to children with autism.
References:
1. Czekalla, J et al. (2001). J Clin Psychiatry, 62(3):191-198.
2. Welch, R, Chue P. (2000). J Psychiatry Neurosci, 25:154-160.