ORIGINAL RESEARCH article
Front. Med.
Sec. Precision Medicine
Association between Concomitant Use of Direct Oral Anticoagulants(DOACs) with Antidepressants and an Increased Risk of Haemorrhage: Analysis of the Food and Drug Administration Adverse Event Reporting System(FAERS) Database
Provisionally accepted
- Department of Pharmacy, People’s Hospital of Chongqing Liangjiang New Area, Chongqing, Chongqing, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Direct Oral Anticoagulants (DOACs) and antidepressants are often co-administered, but their combined effect on bleeding risk in real-world settings is poorly quantified. This study aimed to evaluate this risk using pharmacovigilance data. Methods: Data spanning quarter 3(Q3) 2010 to quarter 1(Q1) 2025 were analyzed from the Food and Drug Administration Adverse Event Reporting System (FAERS) database, comparing bleeding adverse events reported for DOACs monotherapy versus DOACs combined with antidepressants. Bleeding signals were assessed using the Reporting Odds Ratio (ROR). Results: The proportion of bleeding events was 31.00%(64,165/207,000) in the DOACs monotherapy group versus 57.92%(307/530) in the DOACs-antidepressant combination therapy group. Concomitant use of DOACs with antidepressants was associated with a significant increase in overall bleeding risk (reporting odds ratio [ROR] = 1.45, 95% confidence interval [CI]: 1.29– 1.63). Selective serotonin reuptake inhibitors(SSRIs) presented the highest class risk (ROR 1.78, 95% CI 1.54–2.04), with apixaban plus paroxetine showing the strongest signal (ROR 14.12, 95% CI 7.62–26.15). Nervous system bleeding was also elevated (ROR 1.86, 95% CI 1.44–2.40). Notably, mirtazapine significantly increased nervous system bleeding risk (ROR 9.83, 95% CI 4.92– 19.67) despite its non-SSRI mechanism. Conclusions: Co-administration of antidepressants and DOACs significantly elevates bleeding risk, especially for the nervous system. Clinicians must exercise heightened caution, particularly with SSRIs and when using mirtazapine, and further validation studies are needed.
Keywords: Antidepressants, bleeding risk, direct oral anticoagulants, Drug Interaction, FAERS
Received: 11 Dec 2025; Accepted: 10 Feb 2026.
Copyright: © 2026 Ran, Zhang, Cai and Hailin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Liu Hailin
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.