A new study published in JAMA Neurology reports that treatment with selective serotonin reuptake inhibitors (SSRIs) and antidepressants in general with strong inhibition of serotonin reuptake is associated with a greater risk of intracranial hemorrhage.

SSRIs have been previously linked to an increase in intracranial hemorrhage, however, whether antidepressants that are strong inhibitors of serotonin reuptake actually raise the risk for intracranial hemorrhage is still unknown. 

Researchers from the Jewish General Hospital and McGill University set out to evaluate the risk for intracranial hemorrhage with the use of SSRIs vs. tricyclic antidepressants (TCAs) among new users. Risk was assessed based on the relative affinity of the antidepressant for the serotonin transporter and to assess whether concomitant antithrombotics altered the risk. They performed a population-based cohort study from January 1, 1995 to June 30, 2014. Using a nested case-control method, each case of a first intracranial hemorrhage identified during follow-up was matched with up to 30 control individuals.  

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The study’s main outcome was the incidence rate ratios (RRs) of intracranial hemorrhage stratified by current use of SSRIs vs. TCAs as well as strong vs. weak serotonin reuptake inhibitors. 

The cohort included 1,363,990 incident users of antidepressants of which the majority (63.2%) were female. A total of 3,036 cases of intracranial hemorrhage were identified during the follow-up period and were matched to 89,702 controls. 

The study found that current SSRI use was associated with a higher risk for intracranial hemorrhage (RR 1.17, 95% CI: 1.02–1.35) vs. TCAs, with highest risk during the first 30 days of use (RR 1.44, 95% CI: 1.04–1.99). The risk for intracranial hemorrhage was 25% higher with the use of strong inhibitors (RR 1.25, 95% CI: 1.01–1.54) and was at the highest during the first 30 days of use (RR 1.68, 95% CI: 0.90–3.12). Moreover, the risk was much greater with concomitant anticoagulants (RR 1.73, 95% CI: 0.89–3.39). 

For more information visit jamanetwork.com.