Sertindole causes distinct electrocardiographic T-wave morphology changes

Eur Neuropsychopharmacol. 2009 Oct;19(10):702-7. doi: 10.1016/j.euroneuro.2009.04.011. Epub 2009 May 19.

Abstract

Sertindole's propensity to prolong the QT interval relates to blockade of the KCNH2 (HERG) encoded Ikr potassium channel, but there has been limited detailed data on T-wave morphology changes. Digital 12-lead ECG was recorded at baseline and at steady-state in 37 patients switched to sertindole. ECG was analyzed for quantitative T-wave morphology changes and Fridericia-corrected QT duration (QTcF). Prominent T-wave morphology changes occurred during sertindole treatment and in some cases without concomitant prolongation of the QTcF interval. Four patients developed notched T-waves during sertindole treatment. Mean QTc prolongation was 19 ms. The mean effect size was higher for T-wave morphology combination score (MCS) (ES=1.92; 95% CI: 1.35-2.49) compared to the mean effect size for QTcF (ES=0.88; 95% CI: 0.52-1.24). The use of T-wave morphology analysis may become clinically relevant, particularly if shown to be associated with drug-induced arrhythmia risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Cohort Studies
  • Electrocardiography / drug effects*
  • Female
  • Humans
  • Imidazoles / adverse effects*
  • Imidazoles / therapeutic use
  • Indoles / adverse effects*
  • Indoles / therapeutic use
  • Male
  • Schizophrenia / drug therapy

Substances

  • Antipsychotic Agents
  • Imidazoles
  • Indoles
  • sertindole