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Background: Many pharmaceuticals, including antidepressants, are associated with electrocardiographic (ECG) changes, including QT prolongation, and cardiac dysrhythmias. Concerns that corrected QT (QTc) prolongation may result in torsades de pointes have resulted in medications being removed from the market. In August 2011, the US Food and Drug Administration issued a drug safety warning that citalopram is associated with an increased risk of QTc prolongation at higher doses. Research question: What are the effects of citalopram and other antidepressants on the QTc interval? Methods: This was a cross-sectional study using electronic health records (EHRs) of 38,397 adult patients who had received at least one prescription for an antidepressant between 1990 and 2011. Antidepressants included citalopram, escitalopram, fluoxetine, paroxetine, sertraline, amitriptyline, bupropion, duloxetine, mirtazapine, nortriptyline, and venlafaxine. Methadone was also evaluated to demonstrate assay sensitivity. ECG, prescribing, and clinical data were extracted from EHRs. All ECGs done between 14 and 90 days following a prescription were selected for primary analysis. When multiple ECGs were available during this time frame, the one corresponding to maximum drug dose was obtained. Sensitivity analyses were done by excluding the following subjects: those without a renewal of their initial prescription, individuals without an ECG obtained 14–30 days after receiving a prescription, and individuals prescribed an antipsychotic, astemizole, cisapride, or methadone within 1 year of the ECG. The main outcome measured was the relationship between the antidepressant dose and QTc interval by using linear regression to adjust for confounding variables. Linear regression models included medication dose, age, gender, public versus private health insurance, and selfreported ethnicity. Covariates used to examine potential confounding effects of cardiovascular disease included myocardial infarction, ventricular fibrillation, hypertension, hyperlipidemia, and age-adjusted Charlson comorbidity score. Results: The results were reported in adjusted beta values which represented the increase in QTc, measured in milliseconds, per increase of 1 mg of drug. Therefore, a beta of 0.10 suggests that an increase of 10mgwould result in an increased QTc of 1 ms. Dose–response associations with QTc prolongation were only identified for citalopram (adjusted beta 0.10; SE 0.04), escitalopram (adjusted beta 0.58; 0.15), and amitriptyline (adjusted beta 0.11; 0.03). QTc shortening was identified for bupropion (adjusted beta 0.02; 0.01). Covariates significantly associated with the QTc interval were age, race, gender, insurance, year of ECG, history of major depression, myocardial infarction, ventricular arrhythmia, hypertension or hyperlipidemia, and Charlson comorbidity score. A significant increase in QTc was associated with increased doses of several medications, including the following: citalopram 10 to 20 mg (adjusted beta 9.8; SE 1.6), citalopram 40 to 60 mg (adjusted beta 6.1; 2.1), escitalopram 5 to 10mg (adjusted beta 11; 4.5), escitalopram 10 to 20mg (adjusted beta 4.7; 1.6), and amitriptyline 25 to 50 mg (adjusted beta 3.4; 1.4). Conclusion: The study confirmed a modest prolongation of QTc interval for citalopram, escitalopram, and amitriptyline. Bupropion was associated with a shortening of QTc. Critique: This study included multiple clinical variables in an attempt to identify confounding variables, such as cardiovascular disease, that may affect QTc duration. However, the data There has been no previous presentation of this data.