Sex difference in QTc prolongation in chronic institutionalized patients with schizophrenia on long-term treatment with typical and atypical antipsychotics

Psychopharmacology (Berl). 2011 Jul;216(1):9-16. doi: 10.1007/s00213-011-2188-5. Epub 2011 Feb 9.


Objective: The rate-corrected electrocardiographic QT (QTc) interval may significantly increase in patients with schizophrenia taking antipsychotics. The objective of this naturalistic study was to assess the prevalence of prolonged QTc interval in a large population of inpatients with chronic schizophrenia and to explore QTc relationship with demographic variables and prescribed treatments.

Materials and methods: Electrocardiograms were obtained from age- and sex-matched 456 controls and 1,006 inpatients with schizophrenia (male/female = 689/317) taking antipsychotics. QTc prolongation was defined as a mean value of two standard deviations above the controls. The adjusted relative risk was calculated using logistic regression analysis.

Results: QTc prolongation was present in 45 (4.5%) of 1,006 patients overall. Fewer men (3.2%, 22 of 689) than women (7.3%, 23 of 317) displayed QTc prolongation (p < 0.004). Moreover, QTc intervals were shorter in male (391 ± 31 ms) than female subjects (400 ± 37 ms) (p < 0.001). Clozapine was found to produce a longer QTc intervals compared to risperidone and typical antipsychotics. Furthermore, multiple regression analysis showed that significant predictors for QTc prolongation were comorbid cardiovascular disease, antipsychotic types, sex, and age (all p < 0.01).

Conclusion: Our present findings suggest that there are sex differences in the prevalence of QTc prolongation and QTc lengthening in schizophrenia. Antipsychotic types are risk factors for QTc prolongation, and risks are substantially higher for clozapine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Chronic Disease
  • Cross-Sectional Studies
  • Electrocardiography
  • Female
  • Hospitals, Psychiatric
  • Humans
  • Institutionalization
  • Long QT Syndrome / chemically induced
  • Long QT Syndrome / epidemiology
  • Long QT Syndrome / etiology*
  • Male
  • Middle Aged
  • Prevalence
  • Regression Analysis
  • Schizophrenia / complications
  • Schizophrenia / drug therapy*
  • Schizophrenia / epidemiology
  • Sex Characteristics*
  • Time Factors


  • Antipsychotic Agents