QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients

Lancet. 2000 Mar 25;355(9209):1048-52. doi: 10.1016/s0140-6736(00)02035-3.


Background: Sudden unexplained death in psychiatric patients may be due to drug-induced arrhythmia, of which lengthening of the rate-corrected QT interval (QTc) on the electrocardiogram is a predictive marker. We estimated the point prevalence of QTc lengthening in psychiatric patients and the effects of various psychotropic drugs.

Methods: Electrocardiograms were obtained from 101 healthy reference individuals and 495 psychiatric patients in various inpatient and community settings and were analysed with a previously validated digitiser technique. Patients with and without QTc lengthening, QTc dispersion, and T-wave abnormality were compared by logistic regression to calculate odds ratios for predictive variables.

Findings: Abnormal QTc was defined from the healthy reference group as more than 456 ms and was present in 8% (40 of 495) of patients. Age over 65 years (odds ratio 3.0 [95% CI 1.1-8.3]), use of tricyclic antidepressants (4.4 [1.6-12.1]), thioridazine (5.4 [2.0-13.7]), and droperidol (6.7 [1.8-24.8]) were robust predictors of QTc lengthening, as was antipsychotic dose (high dose 5.3 [1.2-24.4]; very high dose 8.2 [1.5-43.6]). Abnormal QT dispersion or T-wave abnormalities were not significantly associated with antipsychotic treatment, but were associated with lithium therapy.

Interpretation: Antipsychotic drugs cause QTc lengthening in a dose-related manner. Risks are substantially higher for thioridazine and droperidol. These drugs may therefore confer an increased risk of drug-induced arrhythmia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use
  • Cause of Death
  • Dose-Response Relationship, Drug
  • Electrocardiography / drug effects*
  • England
  • Female
  • Humans
  • Long QT Syndrome / chemically induced*
  • Long QT Syndrome / diagnosis
  • Long QT Syndrome / mortality
  • Male
  • Mental Disorders / drug therapy*
  • Mental Disorders / mortality
  • Middle Aged
  • Odds Ratio
  • Psychotropic Drugs / adverse effects*
  • Psychotropic Drugs / therapeutic use
  • Risk Factors


  • Antipsychotic Agents
  • Psychotropic Drugs