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Comparative Study
. 2013 Jan 29:346:f288.
doi: 10.1136/bmj.f288.

QT interval and antidepressant use: a cross sectional study of electronic health records

Victor M Castro  1 , Caitlin C Clements, Shawn N Murphy, Vivian S Gainer, Maurizio Fava, Jeffrey B Weilburg, Jane L Erb, Susanne E Churchill, Isaac S Kohane, Dan V Iosifescu, Jordan W Smoller, Roy H Perlis
Affiliations
Comparative Study

QT interval and antidepressant use: a cross sectional study of electronic health records

Victor M Castro et al. BMJ. .

Abstract

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.

Design: 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.

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

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

Main outcome measures: 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.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: RHP has received consulting fees from or served on scientific advisory boards for Proteus Biomedical, Pamlab, Genomind, and RIDventures, and has received research grant support from Proteus Biomedical and royalties from Concordant Rater Systems. JWS has served as a consultant for the Medical Letter. DVI has received payment for lectures including service on speakers’ bureaus from the Massachusetts General Hospital Psychiatry Academy and has served as a consultant for CNS Response. MF has received consulting fees from or served on scientific advisor boards for Abbott Laboratories, Affectis Pharmaceuticals AG, Alkermes, Amarin Pharma, Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management, BioMarin Pharmaceuticals, Biovail Corporation, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, CNS Response, Compellis Pharmaceuticals, Cypress Pharmaceutical, DiagnoSearch Life Sciences, Dinippon Sumitomo Pharma, Dov Pharmaceuticals, Edgemont Pharmaceuticals, Eisai, Eli Lilly, EnVivo Pharmaceuticals, ePharmaSolutions, EPIX Pharmaceuticals, Euthymics Bioscience, Fabre-Kramer Pharmaceuticals, Forest Pharmaceuticals, GenOmind, GlaxoSmithKline, Grunenthal GmbH, i3 Innovus/Ingenis, Janssen Pharmaceutica, Jazz Pharmaceuticals, Johnson & Johnson Pharmaceutical Research & Development, Knoll Pharmaceuticals, Labopharm, Lorex Pharmaceuticals, Lundbeck, MedAvante, Merck, MSI Methylation Sciences, Naurex, Neuralstem, Neuronetics, NextWave Pharmaceuticals, Novartis AG, Nutrition 21, Orexigen Therapeutics, Organon Pharmaceuticals, Otsuka Pharmaceuticals, Pamlab, Pfizer, PharmaStar, Pharmavite, PharmoRx Therapeutics, Precision Human Biolaboratory, Prexa Pharmaceuticals, Puretech Ventures, PsychoGenics, Psylin Neurosciences, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche, Sanofi-Aventis US, Sepracor, Servier Laboratories, Schering-Plough, Solvay Pharmaceuticals, Somaxon Pharmaceuticals, Somerset Pharmaceuticals, Sunovion Pharmaceuticals, Supernus Pharmaceuticals, Synthelabo, Takeda Pharmaceutical, Tal Medical, Tetragenex Pharmaceuticals, TransForm Pharmaceuticals, Transcept Pharmaceuticals, Vanda Pharmaceuticals. MF has equity holdings in Compellis and has received research grant support from Abbot Laboratories, Alkermes, Aspect Medical Systems, AstraZeneca, BioResearch, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Clintara, Covance, Covidien, Eli Lilly, ElMindA, EnVivo Pharmaceuticals, Euthymics Bioscience, Forest Pharmaceuticals, Ganeden Biotech, GlaxoSmithKline, Icon Clinical Research, i3 Innovus/Ingenix, Johnson & Johnson Pharmaceutical Research & Development, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, National Alliance for Research on Schizophrenia & Depression (NARSAD), National Center for Complementary and Alternative Medicine (NCCAM), National Institute of Drug Abuse (NIDA), National Institute of Mental Health (NIMH), Novartis AG, Organon Pharmaceuticals, PamLab, Pfizer, Pharmavite, Photothera, Roche Pharmaceuticals, RCT Logic (formerly Clinical Trials Solutions), Sanofi-Aventis, Shire, Solvay Pharmaceuticals, Synthelabo, Wyeth-Ayerst Laboratories. MF also holds a patent for Sequential Parallel Comparison Design (SPCD), which is licensed by MGH to RCT Logic, and copyright for the MGH Cognitive & Physical Functioning Questionnaire (CPFQ), Sexual Functioning Inventory (SFI), Antidepressant Treatment Response Questionnaire (ATRQ), Discontinuation-Emergent Signs & Symptoms (DESS), and SAFER; Lippincott, Williams & Wilkins; Wolkers Kluwer; World Scientific Publishing.

Figures

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Mean (SD) corrected QT (QTc) interval recorded on electrocardiogram 14–90 days after prescription of antidepressant or methadone, by drug dose
See this image and copyright information in PMC

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