title: Clinical Outcomes of Concomitant Use of Warfarin and Selective Serotonin Reuptake Inhibitors: A Multidatabase Observational Cohort Study.
abstract: BACKGROUND
  Patients treated with warfarin are often coprescribed selective serotonin reuptake inhibitors (SSRIs) for coexisting depression. Some SSRIs are potent CYP2C9 inhibitors that may increase warfarin plasma concentrations and the risk of bleeding. We aimed to examine the effect of the putative CYP2C9-mediated warfarin-SSRI interaction on clinical outcomes.
  
  
  METHODS
  We conducted an observational cohort study among warfarin initiators who had a subsequent SSRI prescription in 5 US claims databases. Patients were followed for up to 180 days as long as they were exposed to both warfarin and their index SSRI groups. Cox regression models were used to estimate hazard ratios and 95% confidence intervals for bleeding events, ischemic or thromboembolic events, and mortality comparing patients treated with SSRIs that are potent CYP2C9 inhibitors (fluoxetine, fluvoxamine) with those treated with other SSRIs after propensity score matching.
  
  
  RESULTS
  The eligible cohort comprised 52,129 patients. Hazard ratios were 1.14 (95% confidence interval [CI], 0.94-1.38) for bleeding events, 1.03 (95% CI, 0.87-1.21) for ischemic or thromboembolic events, and 0.90 (95% CI, 0.72-1.14) for mortality. Results were consistent across individual component outcomes, different warfarin stabilization periods, and subgroup analyses.
  
  
  CONCLUSIONS
  Patients concomitantly treated with warfarin and SSRIs that are potent CYP2C9 inhibitors had comparable rates of bleeding events, ischemic or thromboembolic events, and mortality as did patients cotreated with warfarin and other SSRIs, although small but potentially meaningful effects on bleeding cannot be completely excluded. SSRI inhibition of CYP2C9 does not appear to affect major safety or effectiveness outcomes of warfarin treatment in clinical practice, where patients may be closely monitored.
authors.affiliation: From the *Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; †Faculty of Pharmacy, National Yang-Ming University, Taipei, Taiwan; ‡Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA; and §Division of Pharmacy Practice and Science, College of Pharmacy, The Ohio State University, Columbus, OH.
authors.forename: Yaa-Hui
authors.initials: YH
authors.lastname: Dong
authors.forename: Katsiaryna
authors.initials: K
authors.lastname: Bykov
authors.forename: Niteesh K
authors.initials: NK
authors.lastname: Choudhry
authors.forename: Macarius M
authors.initials: MM
authors.lastname: Donneyong
authors.forename: Krista F
authors.initials: KF
authors.lastname: Huybrechts
authors.forename: Raisa
authors.initials: R
authors.lastname: Levin
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schneeweiss
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Gagne
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D065690:Cytochrome P-450 CYP2D6 Inhibitors / Q000009:adverse effects*; D016208:Databases, Factual; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D065690:Cytochrome P-450 CYP2D6 Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors; D014859:Warfarin