Concomitant SSRI, Oral Anticoagulants Increase Risk for Hemorrhage in Ischemic Stroke

CT scan of brain
CT scan of brain
The relationship between selective serotonin-reuptake inhibitor use and outcomes after ischemic stroke was examined.

In patients with acute ischemic stroke, preadmission treatment with selective serotonin-reuptake inhibitors (SSRIs) does not significantly increase the risk for postthrombolysis symptomatic intracerebral hemorrhage (sICH), according to a recent multicenter retrospective analysis published in Stroke. A subgroup analysis, however, found that concomitant use of oral anticoagulants and SSRIs did increase the risk for sICH.

Jan F. Scheitz, MD, from the Center for Stroke Research Berlin, Germany, and colleagues pooled data from 1998 to 2016 from 7 European stroke centers that operate prospective registries of patients treated with intravenous thrombolysis. Patients treated with intravenous thrombolysis within 4.5 hours of stroke onset were eligible for inclusion in the study. The investigators assessed the association between preadmission treatment with SSRIs and sICH or unfavorable 3-month outcome.

Of the 6242 patients included, 4.3% (N=266) used SSRIs before hospital admission for stroke. The overall sICH rate was 3.9%.

sICH frequency did not differ among patients who were and were not using SSRIs before hospital admission (4.9% [95% CI, 2.9%-8.2%] vs 3.9% [95% CI, 3.4%-4.4%]; unadjusted odds ratio [OR], 1.28; 95% CI, 0.72-2.27; P =.40).

However, the investigators did find a significant interaction between concomitant use of oral anticoagulants (international normalized ratio, <1.7) and SSRIs for the incidence of sICH (P =.01). sICH occurred in 23.1% of patients taking both an oral anticoagulant and an SSRI (OR, 7.65) compared with patients using neither drug.

Patients taking both antiplatelet drugs and SSRIs did not have a significantly higher risk for sICH compared with patients taking neither drug.

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Of note, preadmission treatment with SSRIs increased the risk for an unfavorable outcome at 3 months. The authors, however, suggest that this was confounded by the presence of preadmission depression, as a history of depression has been associated with poorer outcomes in patients with stroke.

The authors noted a number of study limitations, including the lack of data on SSRI use, treatment dose, and time since drug initiation; the sample size, which did not allow in-detail subgroup analyses on type or dose of SSRIs; the potential for residual confounders; and the lack of ethnic diversity in the study population.


Scheitz JF, Turc G, Kujala L, et al. Intracerebral hemorrhage and outcome after thrombolysis in stroke patients using selective serotonin-reuptake inhibitors. Stroke. 2017;48(12):3239-3244.