Association of antidepressants plus antithrombotics and bleeding risk: a pharmacovigilance study

The present study investigated the risk of bleeding when antidepressants are added to antithrombotics. Using data registered in VigiBase®, the WHO pharmacovigilance database, between 01/01/2000 and 31/12/2022, we compared the risk of reporting “serious” bleeding (Reporting Odds Ratio, ROR) with antidepressants + antithrombotics versus antithrombotics alone. Increased values of ROR were found for the association Serotonin Reuptake Inhibitors (SRIs) + Direct Oral Anticoagulants (DOACs) versus DOACs alone (ROR=1.49(1.17-1.89)). Similar results were found for Factor Xa inhibitors or Thrombin inhibitors. This association was also found for other antithrombotics: Vitamin K Antagonists (ROR=1.37(1.12-1.68)), Platelet Aggregation Inhibitors PAIs (ROR=1.38(1.21-1.57)) and Heparins (2.04(1.59-2.62)) but not with other antidepressants (Non-Selective Monoamine Reuptake Inhibitors, NSMRIs). The present study suggests an increased risk of “serious” bleeding when SRIs (but not NSMRIs) are associated with antithrombotics (all antithrombotics and not only DOACs).