QTc prolongation: is clozapine safe? Study of 82 cases before and after clozapine treatment

Hum Psychopharmacol. 2011 Aug;26(6):397-403. doi: 10.1002/hup.1221. Epub 2011 Aug 9.

Abstract

Objective: The most feared cardiological consequence of clozapine is sudden cardiac death. A potential marker of it is QTc interval (QTc) prolongation. This study aimed to determine the prevalence of QTc prolongation in patients before and after 18 weeks of clozapine treatment and to detect predictors of QTc prolongation.

Methods: Patients undergoing treatment with clozapine who had been given an electrocardiogram prior to the treatment and had their electrocardiogram, serum clozapine and norclozapine levels taken on the 18th week were selected. Exclusion criteria were thioridazine, pimozide, diuretics or beta-blocker treatment, electrolytic alteration, heart diseases and substance misuse diagnosis. Prolonged QTc was defined as >450 ms in men and >470 ms in women.

Results: No significant differences were detected in prevalence of prolonged QTc or mean QTc before and after 18 weeks of clozapine treatment (p = 0.15, p = 0.32, respectively). Age, heart rate at 18th week and QTc prior to clozapine treatment had significant effects on QTc at follow-up. Prolonged QTc during previous treatment and heart rate >95 beats/min at 18 weeks were found to be predictors of QTc prolongation.

Conclusion: No significant differences were detected in prevalence of QTc prolongation or mean QTc among patients before and after 18 weeks on clozapine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / pharmacokinetics
  • Antipsychotic Agents / therapeutic use
  • Clozapine / adverse effects*
  • Clozapine / pharmacokinetics
  • Clozapine / therapeutic use
  • Electrocardiography
  • Female
  • Follow-Up Studies
  • Heart Rate
  • Humans
  • Long QT Syndrome / chemically induced
  • Long QT Syndrome / epidemiology*
  • Long QT Syndrome / etiology
  • Male
  • Middle Aged
  • Prevalence
  • Retrospective Studies
  • Risk Factors
  • Young Adult

Substances

  • Antipsychotic Agents
  • Clozapine