Selective Serotonin Reuptake Inhibitors and Intracerebral Hemorrhage Risk and Outcome

Stroke. 2020 Apr;51(4):1135-1141. doi: 10.1161/STROKEAHA.119.028406. Epub 2020 Mar 4.


Background and Purpose- Selective serotonin reuptake inhibitors (SSRIs) have a well-established association with bleeding complications and conflicting reports on outcome after stroke. We sought to evaluate whether pre-intracerebral hemorrhage (ICH) SSRI use increased ICH risk and post-ICH SSRI use improved ICH outcome. Methods- Through post hoc analysis of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage), SSRI use was categorized into no use, pre-ICH only, pre- and post-ICH use (termed "continuous"), and post-ICH only (termed "new"). Using multivariable modeling, associations were sought between pre-ICH SSRI use and ICH risk in the case-control set, and associations between post-ICH SSRI use and 3-month outcome were analyzed in the ICH case set. Exploratory analyses sought to assess influence of race/ethnicity in models. Results- The final study cohort consisted of 2287 ICH cases and 2895 controls. Pre-ICH SSRI use was not associated with ICH risk (odds ratio, 0.824 [95% CI, 0.632-1.074]) nor potentiation of ICH risk with anticoagulant or antiplatelet use. New post-ICH SSRI use was associated with unfavorable modified Rankin Scale score at 3 months after ICH (odds ratio, 1.673 [95% CI, 1.162-2.408]; P=0.006) in multivariable analyses. Additional propensity score analysis indicated a similar trend but did not reach statistical significance (P=0.107). When stratified by race/ethnicity, multivariable modeling demonstrated reduced ICH risk with pre-ICH SSRI use in Hispanics (odds ratio, 0.513 [95% CI, 0.301-0.875]; P=0.014), but not non-Hispanic whites or blacks, and no associations between post-ICH SSRI use and 3-month outcome in any racial/ethnic group. Conclusions- In a large multiethnic cohort, pre-ICH SSRI use was not associated with increased ICH risk, but post-ICH SSRI use was associated with unfavorable 3-month neurological outcome after ICH. Registration- URL:; Unique identifier: NCT01202864.

Keywords: cerebral hemorrhage; hemorrhage; outcomes assessment; risk; serotonin reuptake inhibitors.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • African Americans / ethnology*
  • Aged
  • Case-Control Studies
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / diagnosis*
  • Cerebral Hemorrhage / ethnology*
  • Cohort Studies
  • European Continental Ancestry Group / ethnology*
  • Female
  • Hispanic Americans*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Serotonin Uptake Inhibitors / adverse effects
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Treatment Outcome


  • Serotonin Uptake Inhibitors

Associated data