Strong Evidence for Harm When Combining SSRIs and Blood Thinners

Serotonin is a key mediator of coagulation via its direct effects on platelet activation. As such, bleeding is a natural side effect of selective serotonin reuptake inhibitors (SSRIs), which are commonly used to treat mental health disorders like depression and anxiety.

Prior studies have identified an amplified risk of bleeding when SSRIs are combined with oral anticoagulants (OACs). However, these retrospective studies suffered from several limitations, notably exposure misclassification, possible informative censoring, residual confounding, and limited statistical power. Hence, the true magnitude of this potentially hazardous combination remains undefined.

In this installment of Talking Therapeutics, we explore a new paper that attempts to tackle this key gap in existing literature.

Talking Point: Harm Exists Regardless of OAC

Authors performed a nested case-control study among patients with atrial fibrillation (AFib) initiating OACs between January 2, 1998, and March 29, 2021, from approximately 2,000 general practices in the UK. The primary endpoints were the incidence rate ratios (IRRs) of hospitalization for bleeding or death due to bleeding.

Concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding compared with OACs alone (IRR, 1.33; 95% CI, 1.24-1.42). Importantly, the risk was present when both SSRIs and direct oral anticoagulants (DOACs) (IRR, 1.25; 95% CI, 1.12-1.40) and SSRIs and vitamin K agonists (VKAs) were combined (IRR, 1.36; 95% CI, 1.25-1.47).

Talking Point: Enhanced Monitoring Required During Initiation of Therapy

The results of this study confirm what has long been suspected regarding the bleeding risk associated with combining OACs with SSRIs. This study also unfortunately shows that the hazard persists even when the chosen anticoagulant is a DOAC.

Fortunately, this study showed that the risk peaked during the first 30 days of treatment and persisted for up to 6 months. This indicates that the enhanced monitoring required for this combination of drugs can be directed at the highest risk period, which is right after the medication is started.