title: Effect of selective serotonin reuptake inhibitors on bleeding risk in patients with atrial fibrillation taking warfarin.
abstract: Selective serotonin reuptake inhibitor (SSRI) medications have been linked to increased bleeding risk; however, the actual association among warfarin, SSRI exposure, and bleeding risk has not been well-established. We studied the AnTicoagulation and Risk factors In Atrial fibrillation cohort of 13,559 adults with atrial fibrillation, restricted to the 9,186 patients contributing follow-up time while taking warfarin. Exposure to SSRIs and tricyclic antidepressants (TCAs) was assessed from pharmacy database dispensing data. The main outcome was hospitalization for major hemorrhage. Results were adjusted for bleeding risk and time in international normalized ratio range >3. We identified 461 major hemorrhages during 32,888 person-years of follow-up, 45 events during SSRI use, 12 during TCA-only use, and 404 without either medication. Hemorrhage rates were higher during periods of SSRI exposure compared with periods on no antidepressants (2.32 per 100 person-years vs 1.35 per 100 person-years, p <0.001) and did not differ between TCA exposure and no antidepressants (1.30 per 100 person-years on TCAs, p = 0.94). After adjustment for underlying bleeding risk and time in international normalized ratio range >3, SSRI exposure was associated with an increased rate of hemorrhage compared with no antidepressants (adjusted relative risk 1.41, 95% confidence interval 1.04 to 1.92, p = 0.03), whereas TCA exposure was not (adjusted relative risk 0.82, 95% confidence interval 0.46 to 1.46, p = 0.50). In conclusion, SSRI exposure was associated with higher major hemorrhage risk in patients taking warfarin, and this risk should be considered when selecting antidepressant treatments in those patients.
authors.affiliation: Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. Electronic address: gene.quinn@mail.harvard.edu.
authors.forename: Gene R
authors.initials: GR
authors.lastname: Quinn
authors.affiliation: Clinical Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Singer
authors.affiliation: Clinical Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Yuchiao
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Go
authors.affiliation: Clinical Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Leila H
authors.initials: LH
authors.lastname: Borowsky
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California.
authors.forename: Natalia
authors.initials: N
authors.lastname: Udaltsova
authors.affiliation: Division of Hospital Medicine, University of California, San Francisco, San Francisco, California.
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Fang
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications* / Q000628:therapy; D003863:Depression / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D017367:Selective Serotonin Reuptake Inhibitors; D014859:Warfarin