title: Incident user cohort study of risk for gastrointestinal bleed and stroke in individuals with major depressive disorder treated with antidepressants.
abstract: OBJECTIVE
  To examine the association between exposure to newer antidepressants and risk of gastrointestinal (GI) and other bleeding complications among individuals with major depressive disorder (MDD).
  
  
  METHODS
  This study uses an incident user cohort design to compare associations between incidence of vascular/bleeding events and the relative affinity (low, moderate or high) of the antidepressant for the serotonin transporter during an exposure risk period for each patient.
  
  
  METHODS
  New England healthcare system electronic medical record database.
  
  
  METHODS
  36 389 individuals with a diagnosis of MDD and monotherapy with a selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor or other new-generation antidepressant were identified from among 3.1 million patients in a New England healthcare system.
  
  
  METHODS
  Rates of bleeding or other vascular complications, including acute liver failure, acute renal failure, asthma, breast cancer and hip fractures.
  
  
  RESULTS
  601 GI bleeds were observed in the 21 462 subjects in the high-affinity group versus 333 among the 14 927 subjects in the lower affinity group (adjusted RR: 1.17, 95% CI 1.02 to 1.34). Similarly, 776 strokes were observed in the high-affinity group versus 434 in the lower affinity treatment group (adjusted RR: 1.18, 95% CI 1.06 to 1.32). No significant association with risk for a priori negative control outcomes, including acute liver failure, acute renal failure, asthma, breast cancer and hip fractures, was identified.
  
  
  CONCLUSIONS
  Use of antidepressants with high affinity for the serotonin transporter may confer modestly elevated risk for GI and other bleeding complications. While multiple methodologic limitations must be considered, these results suggest that antidepressants with lower serotonin receptor affinity may be preferred in patients at greater risk for such complications.
authors.affiliation: Partners Research Computing, Partners HealthCare System, Boston, MA.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Castro
authors.forename: Patience J
authors.initials: PJ
authors.lastname: Gallagher
authors.forename: Caitlin C
authors.initials: CC
authors.lastname: Clements
authors.forename: Shawn N
authors.initials: SN
authors.lastname: Murphy
authors.forename: Vivian S
authors.initials: VS
authors.lastname: Gainer
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Weilburg
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Churchill
authors.forename: Isaac S
authors.initials: IS
authors.lastname: Kohane
authors.forename: Dan V
authors.initials: DV
authors.lastname: Iosifescu
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Smoller
authors.forename: Roy H
authors.initials: RH
authors.lastname: Perlis