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Assessing Prolongation of the Heart Rate Corrected QT Interval in Users of Tricyclic Antidepressants

Advice to Use Fridericia Rather Than Bazett’s Correction

Noordam, Raymond MSc*†; van den Berg, Marten E. MD; Niemeijer, Maartje N. MD; Aarts, Nikkie MSc*†; Leening, Maarten J. G. MD, MSc†§; Deckers, Jaap W. MD, PhD§; Hofman, Albert MD, PhD; Rijnbeek, Peter R. PhD; Eijgelsheim, Mark MD, PhD*†; Kors, Jan A. PhD; Stricker, Bruno H. MMed, PhD*†∥; Visser, Loes E. PharmD, PhD*†¶

Journal of Clinical Psychopharmacology: June 2015 - Volume 35 - Issue 3 - p 260–265
doi: 10.1097/JCP.0000000000000321
Original Contributions

A prolonged heart rate corrected QT interval (QTc) increases the risk of sudden cardiac death. Some methods of heart rate correction (notably Bazett) overestimate QTc in people with high heart rates. Studies suggest that tricyclic antidepressants (TCAs) can prolong the QTc and increase heart rate. Therefore, we aimed to study whether TCA-induced QTc prolongation is a false-positive observation due to overestimation at high heart rates. For this, we included 12,734 participants from the prospective population-based Rotterdam Study, with a total of 27,068 electrocardiograms (ECGs), of which, 331 during TCA use. Associations between use of TCAs, QTc, and heart rate were studied with linear repeated measurement analyses. QT was corrected for heart rate according to Bazett (QTcBazett), Fridericia (QTcFridericia), or a correction based on regression coefficients obtained from the Rotterdam Study data (QTcStatistical). On ECGs recorded during TCA use, QTcBazett was 6.5 milliseconds (95% confidence interval, 4.0–9.0) longer, and heart rate was 5.8 beats per minute (95% confidence interval, 4.7–6.9) faster than during nonuse. QTcFridericia and QTcStatistical were not statistically significantly longer during TCA use than during nonuse. Furthermore, QTcBazett was similar for ECGs recorded during TCA use and nonuse after statistical adjustment for heart rate. According to our results, TCA use does not seem to be associated with QTc prolongation. Therefore, the current advice of regulatory authorities to restrict the use of these drugs and to do regular checkups of the QTc may need to be revised. Other formulas, like Fridericia’s, might be preferred.

From the Departments of *Internal Medicine, †Epidemiology, ‡Medical Informatics, and §Cardiology, Erasmus MC–University Medical Center Rotterdam, Rotterdam: ∥Inspectorate of Health Care; and ¶Apotheek Haagse Ziekenhuizen–HAGA, The Hague, The Netherlands.

Received September 26, 2014; accepted after revision February 27, 2015.

Reprints: Bruno H. Stricker, MMed, PhD, Department of Epidemiology, Erasmus MC–University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands (e-mail:

Funding sources: The Rotterdam Study is supported by the Erasmus MC and Erasmus University Rotterdam; the Netherlands Organisation for Scientific Research (NWO); the Netherlands Organisation for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative; the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. This work was supported by grants from ZonMw (HTA grant 80-82500-98-10208 to B.H.S, Priority Medicine Elderly grants 113101002 [to L.E.V] and 113102005 [to M.E.]).

None of the funders had any role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

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