Psychotropic drugs associated with corrected QT interval prolongation.
OBJECTIVE
To study whether listed putative corrected QT (QTc)-prolonging psychotropic drugs indeed prolong the QTc interval under everyday circumstances and to evaluate whether this is a class effect or an individual drug effect, we conducted a prospective population-based cohort study.


METHODS
This study was conducted as part of the Rotterdam Study and included 3377 men and 4845 women (>or=55 years) who had triennial electrocardiograms (ECGs). The primary end points of the study were the length of the QTc interval at each ECG, the difference in QTc interval between consecutive ECGs within one person, and the risk of an abnormally prolonged QTc interval. Drug use at the index date was obtained from automated dispensing records. The associations were examined by means of a repeated measurement analysis, adjusted for age, sex, diabetes mellitus, hypertension, myocardial infarction, heart failure, and use of class 1 QTc-prolonging drugs.


RESULTS
Of the 8222 participants, 813 participants (9.9%) developed QTc prolongation during follow-up and 492 participants (74.4% women) used psychotropic drugs at the time of an ECG. Starting tricyclic antidepressants increased the QTc interval significantly with 6.9 milliseconds (95% confidence interval [CI], 3.1-10.7 milliseconds) between consecutive ECGs in comparison with consecutive ECGs of participants not using tricyclic antidepressants, in particular starting amitriptyline (8.5 milliseconds; 95% CI, 2.8-14.2 milliseconds), maprotiline (13.9 milliseconds; 95% CI, 3.6-24.3 milliseconds), and nortriptyline (35.3 milliseconds; 95% CI, 8.0-62.6 milliseconds). Starting lithium also increased the QTc interval significantly (18.6 milliseconds; 95% CI, 4.8-32.4 milliseconds).


CONCLUSIONS
In this population-based prospective cohort study, we confirmed the importance of antidepressants and antipsychotics as potential contributors to QTc prolongation. Especially, starting tricyclic antidepressant drugs (as a class) is associated with a significant intraindividual increase in the QTc interval in comparison to the change in nonusers. The tricyclic antidepressants seem to prolong the QTc interval as a class effect.
van Noord
Charlotte
C
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Straus
Sabine M J M
SM
Sturkenboom
Miriam C J M
MC
Hofman
Albert
A
Aarnoudse
Albert-Jan L H J
AJ
Bagnardi
Vincenzo
V
Kors
Jan A
JA
Newton-Cheh
Christopher
C
Witteman
Jacqueline C M
JC
Stricker
Bruno H C
BH
D000368:Aged; D000369:Aged, 80 and over; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects*; D015331:Cohort Studies; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011619:Psychotropic Drugs / Q000009:adverse effects*
D000929:Antidepressive Agents, Tricyclic; D011619:Psychotropic Drugs