Background: Selective serotonin reuptake inhibitors (SSRI) are widely used in the treatment of psychiatric disorders such as post-stroke depression. Some studies have reported an association between SSRI use and increased bleeding risk, including intracerebral hemorrhage (ICH). We evaluated this association in two large ICH case control studies. We also tested to see whether SSRI use potentiates the bleeding risk associated with warfarin use and prior ischemic stroke.
Methods: ICH cases and controls from the Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS) and Ethnic Racial Variations in ICH (ERICH) studies were combined in an unmatched case-control analysis. SSRI use and variables previously associated with ICH risk were tested in univariate and multivariate analyses. Interaction terms for SSRI use plus warfarin use and SSRI use plus prior ischemic stroke were included.
Results: There were 4134 ICH cases with 303 pre-stroke SSRI users (7.3%) and 4945 controls with 419 SSRI users (8.5%). Results of the multivariate analysis are presented in the table. In univariate analysis, SSRI use was protective (OR 0.85, CI 0.73-1.00, p = .05), however in multivariate analysis this became non-significant. Although the combination of an SSRI and warfarin produced a higher point estimate for ICH risk than warfarin alone, the interaction term did not reach significance (p = .09). There was no interaction found for SSRI use plus history of ischemic stroke.
Conclusions: In this large case control analysis, SSRI use was not associated with increased risk of ICH. We also failed to confirm an interaction between SSRI use, warfarin use, and ICH risk, although a modest effect cannot be excluded. While a history of ischemic stroke is a risk factor for ICH, SSRI use did not increase that risk.