Use of serotonergic antidepressants in patients undergoing antithrombotic therapy: A narrative review of bleeding risk and clinical implications
DOI:
https://doi.org/10.33448/rsd-v15i5.51150Keywords:
Antidepressants, SSRIs, Bleeding, Anticoagulants, Antiplatelet agents.Abstract
Serotonergic antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are among the most frequently prescribed psychotropic medications in contemporary clinical practice. Growing evidence suggests an association between these drugs and increased bleeding risk, especially in patients receiving concomitant antithrombotic therapy. This study critically reviews the main physiopathological mechanisms involved, pharmacological interactions with anticoagulant and antiplatelet agents, and the clinical evidence related to hemorrhagic complications. Available data demonstrate a consistent increase in the risk of major bleeding, gastrointestinal bleeding, and intracranial hemorrhage, particularly among elderly patients, individuals with previous bleeding history, renal or hepatic impairment, polypharmacy, and concomitant use of nonsteroidal anti-inflammatory drugs. Proposed mechanisms include serotonin-mediated platelet dysfunction and pharmacokinetic interactions involving cytochrome P450 enzymes. Despite the methodological limitations of currently available studies, which are predominantly observational, existing evidence supports individualized risk-benefit assessment, careful clinical monitoring, and rational therapeutic management during co-prescription of these medications.
References
Andrade, C., Sandarsh, S., Chethan, K. B., et al. (2010). Serotonin reuptake inhibitor antidepressants and abnormal bleeding: A review for clinicians and a reconsideration of mechanisms. Journal of Clinical Psychiatry, 71(12), 1565–1575. https://doi.org/10.4088/JCP.09r05786blu
Andrade, C., & Sharma, E. (2016). Serotonin reuptake inhibitors and risk of abnormal bleeding. Psychiatric Clinics of North America, 39(3), 413–426. https://doi.org/10.1016/j.psc.2016.04.002
Anglin, R., Yuan, Y., Moayyedi, P., et al. (2014). Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: A systematic review and meta-analysis. American Journal of Gastroenterology, 109(6), 811–819. https://doi.org/10.1038/ajg.2014.82
Celano, C. M., & Huffman, J. C. (2011). Depression and cardiac disease: A review. Cardiology in Review, 19(3), 130–142. https://doi.org/10.1097/CRD.0b013e31820e8106
De Abajo, F. J. (2011). Effects of selective serotonin reuptake inhibitors on platelet function: Mechanisms, clinical outcomes and implications for use in elderly patients. Drugs & Aging, 28(5), 345–367
Douros, A., Ades, M., & Renoux, C. (2018). Risk of intracranial hemorrhage associated with the use of antidepressants inhibiting serotonin reuptake: A systematic review. CNS Drugs, 32(4), 321–334. https://doi.org/10.1007/s40263-018-0517-9
Dragioti, E., Solmi, M., Favaro, A., et al. (2019). Association of antidepressant use with adverse health outcomes: A systematic umbrella review. JAMA Psychiatry, 76(12), 1241–1255. https://doi.org/10.1001/jamapsychiatry.2019.2859
Jensen, M. P., Ziff, O. J., Banerjee, G., et al. (2019). The impact of selective serotonin reuptake inhibitors on the risk of intracranial haemorrhage: A systematic review and meta-analysis. European Stroke Journal, 4(2), 144–152. https://doi.org/10.1177/2396987319836207
Jiang, H. Y., Chen, H. Z., Hu, X. J., et al. (2015). Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding: A systematic review and meta-analysis. Clinical Gastroenterology and Hepatology, 13(1), 42–50. https://doi.org/10.1016/j.cgh.2014.06.021
Komen, J. J., Hjemdahl, P., Mantel-Teeuwisse, A. K., et al. (2020). Concomitant anticoagulant and antidepressant therapy in atrial fibrillation patients and risk of stroke and bleeding. Clinical Pharmacology & Therapeutics, 107(1), 287–294. https://doi.org/10.1002/cpt.1598
Labos, C., Dasgupta, K., Nedjar, H., et al. (2011). Risk of bleeding associated with combined use of selective serotonin reuptake inhibitors and antiplatelet therapy following acute myocardial infarction. Canadian Medical Association Journal, 183(16), 1835–1843. https://doi.org/10.1503/cmaj.100912
Laporte, S., Chapelle, C., Caillet, P., et al. (2017). Bleeding risk under selective serotonin reuptake inhibitor antidepressants: A meta-analysis of observational studies. Pharmacological Research, 118, 19–32. https://doi.org/10.1016/j.phrs.2016.08.017
Lee, M. T., Park, K. Y., Kim, M. S., et al. (2020). Concomitant use of NSAIDs or SSRIs with NOACs requires monitoring for bleeding. Yonsei Medical Journal, 61(9), 741–749. https://doi.org/10.3349/ymj.2020.61.9.741
Loke, Y. K., Trivedi, A. N., & Singh, S. (2008). Meta-analysis: Gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs. Alimentary Pharmacology & Therapeutics, 27(1), 31–40. https://doi.org/10.1111/j.1365-2036.2007.03535.x
Nochaiwong, S., Ruengorn, C., Awiphan, R., et al. (2022). Use of serotonin reuptake inhibitor antidepressants and the risk of bleeding complications in patients on antithrombotic agents: A systematic review and meta-analysis. Annals of Medicine, 54(1), 80–97. https://doi.org/10.1080/07853890.2021.2007692
Patel, D., McConkey, N. D., Sohaney, R., et al. (2013). A systematic review of depression and anxiety in patients with atrial fibrillation: The mind-heart link. Cardiovascular Psychiatry and Neurology, 2013, 159850. https://doi.org/10.1155/2013/159850
Quinn, G. R., Singer, D. E., Chang, Y., et al. (2014). Effect of selective serotonin reuptake inhibitors on bleeding risk in patients with atrial fibrillation taking warfarin. American Journal of Cardiology, 114(4), 583–586. https://doi.org/10.1016/j.amjcard.2014.05.038
Risemberg, R. I. C. et al. (2026). A importância da metodologia científica no desenvolvimento de artigos científicos. E-Acadêmica, 7(1), e0171675. https://eacademica.org/eacademica/article/view/675
Pereira, A. S. et al. (2018). Metodologia da pesquisa científica. Santa Maria: Editora da UFSM.
Ogassawara, D. et al. (2025). Trilhas metodológicas para a revisão narrativa: orientações pragmáticas para sua elaboração. Ensino & Pesquisa, 23(3). https://doi.org/10.33871/23594381.2025.23.3.10317
Renoux, C., Vahey, S., Dell'Aniello, S., et al. (2017). Association of selective serotonin reuptake inhibitors with the risk for spontaneous intracranial hemorrhage. JAMA Neurology, 74(2), 173–180. https://doi.org/10.1001/jamaneurol.2016.4529
Zambrano, J., Celano, C. M., Januzzi, J. L., et al. (2020). Psychiatric and psychological interventions for depression in patients with heart disease: A scoping review. Journal of the American Heart Association, 9(22), e018686. https://doi.org/10.1161/JAHA.120.018686
Zhang, Y., Souverein, P. C., Gardarsdottir, H., et al. (2020). Risk of major bleeding among users of direct oral anticoagulants combined with interacting drugs: A population-based nested case-control study. British Journal of Clinical Pharmacology, 86(6), 1150–1164. https://doi.org/10.1111/bcp.14218
Downloads
Published
Issue
Section
License
Copyright (c) 2026 José Jorge de Miranda Neto, Julia Magalhães Véo, Maria Clara Ricciardi, Miguel Véo Neto
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
