QT dynamics during treatment with sertindole

Sertindole is a nonsedating atypical antipsychotic drug with low propensity to cause extrapyramidal side effects but it has been associated with a 20 ms QTc prolongation and increased risk of cardiac events. It is uncertain whether this drug-induced increase in cardiac risk might also be revealed by dynamic measures of the QT interval such as the ratio of QT variability to heart rate variability (variability ratio [VR]). The aim of this study was to investigate the effect of sertindole on QT dynamics.

QTc and the VR were assessed in an observational study using 24-hour Holter monitoring at baseline and after 3 weeks of treatment with sertindole 16 mg. The VR was calculated by dividing the standard deviation of QT intervals with the standard deviation of heart rates. Outcome measures were compared using paired t-test.

A total of 18 patients participated in the study, two were excluded from further analysis due to low amplitude of the T-wave. When patients were shifted to sertindole, the VR increased from 0.192 (SD 0.045) to 0.223 (SD 0.061), p = 0.02. The QTcF interval increased from 388 (SD 16) to 403 ms (SD 14), p = 0.002. There was no difference in heart rate 78 bpm (SD 8) versus 80 bpm (SD 10), p = 0.3 or heart rate variability (SDNN) 127 (SD 40) versus 115 ms (SD 45), p = 0.4.

Sertindole was associated with 19 ms QTc prolongation and an increased ratio of QT variability to heart rate variability. Both measures may contribute to the increased cardiovascular mortality found with sertindole.