Relative risk was about one-third higher when anticoagulated patients also were taking SSRIs.

Selective serotonin reuptake inhibitors (SSRIs) inhibit platelet uptake of serotonin, which is one of many promoters of platelet aggregation. Many (but not all) studies in the past 15 years have shown that risk for major bleeding is higher with concomitant use of SSRIs and oral anticoagulants than with oral anticoagulants alone. Investigators used a UK general practice database to conduct a case-control study that involved 42,000 patients with atrial fibrillation who were prescribed oral anticoagulants and then had major bleeding events (i.e. hospitalisation or death) and more than one million controls.

During a mean follow up of nearly five years, incidence of major bleeding with oral anticoagulants was about 28 per 1000 person-years. Adjusted relative risk for major bleeding was 33% higher with concomitant use of an SSRI, translating to an absolute excess risk of about nine events per 1000 person-years. Risk was similar for various types of bleeding (e.g. intracranial, gastrointestinal) and did not vary with potency of SSRI. Excess relative risk was slightly less with direct-acting oral anticoagulants than with vitamin K antagonists (25% vs 36%).

Comment: This population-based study reinforces longstanding concerns about risk for bleeding in patients with atrial fibrillation and concomitant use of SSRIs and anticoagulants. In patients with strong indications for both drugs, the relatively small absolute excess risk might be acceptable. However, in patients for whom the indication for either the SSRI or the anticoagulant is marginal, the excess bleeding risk might be a reason to avoid prescribing both drugs together. Finally, note that changing from a high- to a low-potency SSRI does not appear to offer any risk mitigation.

Thomas L. Schwenk, MD, Professor Emeritus, Family and Community Medicine, University of Nevada School of Medicine, Reno, USA.

Rahman AA, et al. Concomitant use of selective serotonin reuptake inhibitors with oral anticoagulants and risk of major bleeding. JAMA Netw Open 2024 Mar 4; 7: e243208.

This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine, Hospital Medicine.