Supplementary figures and tables. Figure A: Study schematic
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1 Supplementary figures and tables Figure A: Study schematic
2 Figure B: Percent of patients with a normal (green), borderline (beige), abnormal (brown), or high (red) electrocardiogram days after prescription of (A) an or methadone (positive control) by dose or (B) other antidepressants or methadone, by dose
3 Castro et al. 3 Table A: Demographic and clinical feature comparisons between study cohort and patients receiving an antidepressant or methadone but no EKG in the drug exposure window* Antidepressant/ methadone users with EKG (14-90 days post-dose) Antidepressant/ methadone users with no EKG in exposure window p-value N 38, ,911 Demographics Age, mean years (SD) 58.3 (16.2) 49.4 (17.2) < Female gender 23,020 (60.0) (66.3) < Race/ethnicity < White 30,637 (80.0) 163,874 (80.8) African American 2,759 (7.2) 9,262 (4.6) Hispanic 2,987 (7.8) 12,911 (6.4) Asian 451 (1.2) 2,772 (1.4) Other 1,528 (4.0) 14,172 (7.0) Insurance < Public 20,052 (52.2) 69,559 (34.3) Private 15,851 (41.3) 115,615 (57.0) Other / Unknown 2,494 (6.5) 17,817 (8.8) Year of EKG, median (IQR) 2007 ( ) 2007 ( ) < Comorbidities (lifetime history) Major depression 10,930 (28.5) 34,772 (17.1) < Myocardial infarction 10,391 (27.1) 15,535 (7.7) < Ventricular arrhythmia 7,968 (20.8) 53,085 (26.2) < Hypertension 28,145 (73.3) 81,384 (40.1) < Hyperlipidemia 23,384 (60.9) 72,499 (35.7) < Age-adjusted Charlson comorbidity index 6 (3-10) 2 (0-5) < Pharmacotherapy < Citalopram 9,777 (25.5) 48,690 (24.3) Escitalopram 2,364 (6.2) 15,821 (7.8) Fluoxetine 5,721 (14.9) 35,230 (17.4) Paroxetine 4,205 (11.0) 21,793 (10.7) Sertraline 6,293 (16.4) 36,034 (17.8) Other antidepressants Duloxetine 1,912 (5.0) 10,402 (5.1) Venlafaxine 2,480 (6.5) 15,853 (7.8) Bupropion 5,064 (13.2) 35,259 (17.4) Mirtazapine 3,487 (9.1) 11,337 (5.6) Amitriptyline 4,228 (11.0) 25,206 (12.4) Nortriptyline 1,978 (5.2) 12,632 (6.2) Opiate antagonist Methadone (known QTc-prolonging agent) 2,255 (5.9) 7,830 (3.9) *All values indicate patient count (% of cohort) unless otherwise specified. comparison using Students t-test; comparison using χ 2 ; Comparison using Kruskal-Wallis non-parametric test Race and ethnicity are collected using a single field in the electronic health record, so subjects who identify as Hispanic are not further characterized.
4 Table B: Overall effect of medication dose on continuous QTc measured days after medication dose Unadjusted model Adjusted model Antidepressant Beta (SE) Beta (SE) Citalopram 0.04 (0.04) 0.10 (0.04) ** Escitalopram 0.60 (0.17) *** 0.62 (0.17) *** Fluoxetine (0.03) 0.04 (0.03) Paroxetine (0.07) 0.04 (0.07) Sertraline (0.01) 0.01 (0.01) TCA/Other Amitriptyline 0.12 (0.03) *** 0.12 (0.03) *** Bupropion (0.01) *** (0.01) * Duloxetine 0.00 (0.05) 0.02 (0.05) Mirtazapine (0.08) (0.08) Nortriptyline 0.01 (0.04) 0.06 (0.04) Venlafaxine 0.01 (0.01) 0.01 (0.01) Positive control Methadone 0.30 (0.06) *** 0.31 (0.06) *** Castro et al. 4 Statistical significance at *** α = 0.001; ** α = 0.01; * α = 0.05 Model is adjusted for age, gender, race, type of insurance, year of EKG, history of major depression, history of myocardial infarction, history of ventricular arrhythmia, history of hypertension, and history of hyperlipidemia and log-transformed age-adjusted Charlson comorbidity score.
5 Castro et al. 5 Table C: Overall effect of medication dose on continuous QTc measured days after medication dose. Prescriptions with a concomitant prescription of a typical or atypical antipsychotic or other known QT prolonging agent are excluded. Unadjusted model Adjusted model Antidepressant Beta (SE) Beta (SE) Citalopram 0.01 (0.04) 0.08 (0.04) * Escitalopram 0.49 (0.17) ** 0.54 (0.17) *** Fluoxetine 0.02 (0.04) 0.09 (0.04) * Paroxetine 0.00 (0.08) 0.08 (0.08) Sertraline (0.01) * 0.01 (0.01) TCA/Other Amitriptyline 0.09 (0.03) *** 0.10 (0.03) *** Bupropion (0.01) 0.00 (0.01) Duloxetine 0.03 (0.05) 0.04 (0.05) Mirtazapine (0.11) * (0.11) Nortriptyline (0.05) 0.02 (0.04) Venlafaxine 0.01 (0.01) 0.01 (0.01) Statistical significance at *** α = 0.001; ** α = 0.01; * α = 0.05 Model is adjusted for age, gender, race, type of insurance, year of EKG, history of major depression, history of myocardial infarction, history of ventricular arrhythmia, history of hypertension, and history of hyperlipidemia and log-transformed age-adjusted Charlson comorbidity score.
6 Table D: Overall effect of medication dose on continuous QTc measured days after medication dose where a prescription re-fill occurs with 30 days of the end of supply Unadjusted model Adjusted model Antidepressant Beta (SE) Beta (SE) Citalopram 0.04 (0.04) 0.10 (0.04) ** Escitalopram 0.60 (0.17) *** 0.62 (0.17) *** Fluoxetine (0.03) 0.04 (0.03) * Paroxetine (0.07) 0.04 (0.07) Sertraline (0.01) 0.01 (0.01) TCA/Other Amitriptyline 0.12 (0.03) *** 0.12 (0.03) *** Bupropion (0.01) *** (0.01) * Duloxetine (0.05) 0.02 (0.05) Mirtazapine (0.08) (0.08) Nortriptyline 0.01 (0.04) 0.06 (0.04) Venlafaxine 0.01 (0.01) 0.01 (0.01) Positive control Methadone 0.30 (0.06) *** 0.31 (0.06) *** Castro et al. 6 Statistical significance at *** α = 0.001; ** α = 0.01; * α = 0.05 Model is adjusted for age, gender, race, type of insurance, year of EKG, history of major depression, history of myocardial infarction, history of ventricular arrhythmia, history of hypertension, and history of hyperlipidemia and log-transformed age-adjusted Charlson comorbidity score.
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