QT interval and antidepressant use: a cross sectional study of electronic health records.
OBJECTIVE
To quantify the impact of citalopram and other selective serotonin reuptake inhibitors on corrected QT interval (QTc), a marker of risk for ventricular arrhythmia, in a large and diverse clinical population.


METHODS
A cross sectional study using electrocardiographic, prescribing, and clinical data from electronic health records to explore the relation between antidepressant dose and QTc. Methadone, an opioid known to prolong QT, was included to demonstrate assay sensitivity.


METHODS
A large New England healthcare system comprising two academic medical centres and outpatient clinics.


METHODS
38,397 adult patients with an electrocardiogram recorded after prescription of antidepressant or methadone between February 1990 and August 2011.


METHODS
Relation between antidepressant dose and QTc interval in linear regression, adjusting for potential clinical and demographic confounding variables. For a subset of patients, change in QTc after drug dose was also examined.


RESULTS
Dose-response association with QTc prolongation was identified for citalopram (adjusted beta 0.10 (SE 0.04), P<0.01), escitalopram (adjusted beta 0.58 (0.15), P<0.001), and amitriptyline (adjusted beta 0.11 (0.03), P<0.001), but not for other antidepressants examined. An association with QTc shortening was identified for bupropion (adjusted beta 0.02 (0.01) P<0.05). Within-subject paired observations supported the QTc prolonging effect of citalopram (10 mg to 20 mg, mean QTc increase 7.8 (SE 3.6) ms, adjusted P<0.05; and 20 mg to 40 mg, mean QTc increase 10.3 (4.0) ms, adjusted P<0.01).


CONCLUSIONS
This study confirmed a modest prolongation of QT interval with citalopram, and identified additional antidepressants with similar observed risk. Pharmacovigilance studies using electronic health record data may be a useful method of identifying potential risk associated with treatments.
Partners Research Computing, Partners HealthCare System, One Constitution Center, Boston, MA 02129, USA.
Victor M
VM
Castro
Caitlin C
CC
Clements
Shawn N
SN
Murphy
Vivian S
VS
Gainer
Maurizio
M
Fava
Jeffrey B
JB
Weilburg
Jane L
JL
Erb
Susanne E
SE
Churchill
Isaac S
IS
Kohane
Dan V
DV
Iosifescu
Jordan W
JW
Smoller
Roy H
RH
Perlis
D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000453:epidemiology* / Q000503:physiopathology; D003430:Cross-Sectional Studies; D003863:Depression / Q000188:drug therapy; D004562:Electrocardiography / Q000187:drug effects*; D057286:Electronic Health Records; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009511:New England / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors
D000928:Antidepressive Agents