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Original Investigation
August 31, 2020

Association of Selective Serotonin Reuptake Inhibitor Use After Intracerebral Hemorrhage With Hemorrhage Recurrence and Depression Severity

Author Affiliations
  • 1Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center, Boston, Massachusetts
  • 2Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts
  • 3Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts
  • 4Henry and Allison McCance Center for Brain Health, Massachusetts General Hospital, Boston, Massachusetts
  • 5Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
JAMA Neurol. 2021;78(1):61-67. doi:10.1001/jamaneurol.2020.3142
Key Points

Question  Among intracerebral hemorrhage (ICH) survivors with depression treated with selective serotonin reuptake inhibitors (SSRIs), what is the risk of recurrent cerebral bleeding vs decrease in severity of depressive symptoms?

Findings  In this cohort study, SSRIs were associated with both remission of post-ICH depression and higher risk of ICH recurrence. Selective serotonin reuptake inhibitor use is associated with a larger increase in recurrent ICH risk among patients with preexisting clinical, genetic, or neuroimaging risk factors for hemorrhagic stroke.

Meaning  Clinical history, genetics, and neuroimaging data may identify depressed survivors of ICH at higher risk of recurrent cerebral bleeding, for whom SSRI use warrants careful consideration.


Importance  Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat poststroke depression but are associated with increased incidence of first-ever intracerebral hemorrhage (ICH) in the general population. The decision to treat ICH survivors with SSRIs must therefore balance potential risks of ICH recurrence with presumed benefits on depressive symptoms.

Objective  To determine whether SSRI use among survivors of primary ICH was associated with ICH recurrence and decreased severity of depressive symptoms.

Design, Setting, and Participants  Longitudinal ICH cohort study at a tertiary care center enrolling from January 2006 to December 2017, with follow-up for a median of 53.2 months (interquartile range, 42.3-61.2 months). The study included 1279 consenting individuals (1049 White, 89 Black, 77 Hispanic, and 64 other race/ethnicity) of 1335 eligible patients presenting with primary ICH and who were discharged alive from initial hospitalization for stroke.

Main Outcomes and Measures  We conducted univariable and multivariable analyses for ICH recurrence risk and depression severity, including subset analyses for patients with 1 or more of the following characteristics associated with high ICH recurrence risk: (1) lobar ICH; (2) presence of the apolipoprotein ε2/ε4 gene variants; (3) prior history of ICH/TIA/ischemic stroke; and (4) Black or Hispanic race/ethnicity.

Results  Mean age of study participants was 71.3 years, with 602 women (47%); of the 1279 participants, 1049 were White, 89 were Black, 77 were Hispanic, and 64 were other race/ethnicity. SSRI exposure was associated with both ICH recurrence (subhazard ratio [SHR], 1.31; 95% CI, 1.08-1.59) and resolution of post-ICH depression (SHR, 1.53; 95% CI, 1.12 2.09). Among those individuals at high risk for recurrent ICH, SSRIs were associated with further elevation in risk for ICH recurrence (SHR, 1.79; 95% CI, 1.22-2.64) compared with all other survivors of ICH (SHR, 1.20; 95% CI, 1.01-1.42; P = .008 for comparison of effect sizes). The association of SSRI with reduced depressive symptoms did not differ between high those at high risk for recurrent ICH and all other ICH survivors.

Conclusions and Relevance  Selective serotonin reuptake inhibitor exposure after ICH is associated with both improvement in depressive symptoms and increased risk of recurrent hemorrhagic stroke. Clinical history, neuroimaging data, and genetic biomarkers may help to identify survivors of ICH more likely to safely tolerate SSRI use.

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