Plasma concentrations of antipsychotics and QTc prolongation: a pilot study

Abstract

Background: Certain antipsychotics are known to cause QTc interval prolongation, which has been associated with increased risk of arrhythmia and sudden death. Previous studies have investigated whether there is an association between oral antipsychotic dose and QTc interval prolongation, however only few have examined the association between antipsychotic plasma concentrations and QTc interval.

Material and methods: We performed a cross-sectional study with 22 forensic psychiatric in-patients. We measured the plasma concentration of the prescribed antipsychotics and performed an ECG simultaneously. We used Bazett's formula to calculate QTc and defined QTc as prolonged when: >460 ms for women and >450 ms for men.

Results: Seventy-seven percent (n = 17) of the subjects were men (mean age = 40 years) and 91% (n = 20) were diagnosed with schizophrenia. QTc’s ranged from 369 to 437 ms. Patients receiving QTc prolonging drugs had significantly greater QTc interval compared to patients receiving non-prolonging drugs. Weak to moderate negative correlations were found between QTc interval and both defined daily dose (DDD) and antipsychotic plasma concentration. There was no statistical difference between the correlations for DDD and plasma concentration versus QTc interval.

Conclusion: We did not find a stronger association between antipsychotic plasma concentration and QTc than between antipsychotic dose and QTc. We suggest close monitoring with regular electroencephalogram’s until the development of a better marker for predicting the risk of cardiac arrhythmia.

Keywords:

• Antipsychotics
• QTc prolongation
• plasma concentration

Acknowledgements

The authors thank emeritus consultant Jørgen Jensen for statistical help.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

The study was funded by the Department of Organic Psychiatry and the Department of Forensic Psychiatry, Aarhus University Hospital Psychiatry, Denmark.

Notes on contributors

Lene Høimark

Lene Høimark, MD, is a medical doctor trained at Aarhus University, Denmark. Since 2004, Dr. Høimark holds a position as senior registrar at the Department of Clinical Pharmacology, Aarhus University Hospital, Denmark. She also holds a position as consultant in the Department of Psychoses, Aarhus University Hospital, Denmark.

Lisbeth Uhrskov Sørensen

Lisbeth Uhrskov Sørensen completed a Master of Science in Health Policy and Planning, 1998, at London School of Hygiene and Tropical Medicine of London School of Economics and Political Science, and a PhD in Geriatric psychiatry 2000 at the University of Aarhus, Faculty of Health. She is consultant, leader of reseach at Department of Forensic Psychiatry, Aarhus University Hospital Psychiatry and associate professor at Aarhus University Health.

Ljubica Vukelic Andersen

Ljubica Vukelic Andersen, MD, PhD is a trained medical doctor from Aarhus University, Faculty of Health, Denmark, where she also was awarded with PhD degree in cardiology in 2011. Ljubica holds a position as physician at the Department of Cardiology, Aalborg University Hospital. She is associate professor of Clinical pharmacology and cardiology at Aarhus University and Aalborg University, Denmark.