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Michele Thomas, PharmD, BCPP
CPNP Recertification Editorial Board

This session can be purchased in CPNP University.

Antidepressants, such as serotonin reuptake inhibitors (SRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs), are commonly prescribed as first line pharmacotherapy in treating depression and anxiety disorders due to their favorable safety profile and established efficacy. There is a concern among psychiatric pharmacists about the risk of bleeding with antidepressants in patients receiving antiplatelet or anticoagulant therapy. Cynthia  A. Gutierrez, PharmD, MS, BCPP shared her expertise at CPNP 2017 in her presentation entitled,  Management of Antidepressant Therapy in the Presence of Increased Bleeding Risk. Dr. Gutierrez is currently the Clinical Pharmacy Program Manager, Mental Health at the South Texas Veterans Health Care System.

Do antidepressants cause bleeding? This was the first question Dr. Guiterrez addressed. She explained that in the platelet aggregation cascade serotonin is a weak platelet activator although it is not produced by the platelets. It must be taken up into the platelet by a serotonin transporter1. SRIs block this transporter, thus there is less serotonin available in the platelet to activate platelet aggregation2. This may reduce platelet aggregation.

Do antidepressants cause clinically relevant bleeding? Dr. Guiterrez explained that there are many case reports and observational studies describing an increased bleeding risk in patients receiving SRIs1. One meta- analysis demonstrated a small increase in the risk of bleeding with SRI exposure3. This meta-analysis showed one severe bleed for every 8000 prescriptions of SRIs. Gastrointestinal (GI) bleeding is the most frequently reported type of bleed, and patients on nonsteroidal anti-inflammatory drugs (NSAIDs) along with a SRI are at an elevated risk4. GI bleeding can occur at any time during SRI therapy although the highest risk is in the early part of treatment. She also shared data showing a small increase risk of intracranial bleeding with SRI therapy5. Patients taking an anticoagulant and a SRI have a greater risk of an intracranial hemorrhage compared to those taking only an anticoagulant.  

Can antidepressants be used in patients receiving anticoagulation or antiplatelet therapy? There is consistent data that SRIs increase the risk of bleeding, especially GI bleeding, when given to a patient taking aspirin1. Observational studies show that SRIs increase the risk of bleeding when used with warfarin. There is less data available with the Direct Oral Anticoagulants (DOACs). SRIs can have both pharmacokinetic and pharmacodynamic drug interactions with anticoagulants and aspirin.

How can risk of bleeding with antidepressant therapy be assessed and managed? Unfortunately, there is no data on risk assessment with SRI therapy and bleeding. Clinical judgement is the best guide. Patient risk factors as well as drug interactions must be considered.

Take Home Messages

  • Antidepressants that inhibit the serotonin reuptake into the platelets may reduce platelet aggregation. 
  • There is data that shows SRIs increase the risk of bleeding, especially GI bleeding; however, the number needed to harm is very large. 
  • When using an antidepressant in a patient on an anticoagulant or antiplatelet agent, the pharmacodynamic interaction of increased risk of bleeding plus any pharmacokinetic interactions must be considered.


  1. Andrade C, Sandarsh S, Chethan KB, Nagesh KS. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry. 2010;71(12):1565-75. DOI: 10.4088/JCP.09r05786blu. PubMed PMID: 21190637.
  2. Mercado CP, Kilic F. Molecular mechanisms of SERT in platelets: regulation of plasma serotonin levels. Mol Interv. 2010;10(4):231-41. DOI: 10.1124/mi.10.4.6. PubMed PMID: 20729489.
  3. Laporte S, Chapelle C, Caillet P, Beyens M-N, Bellet F, Delavenne X, et al. Bleeding risk under selective serotonin reuptake inhibitor (SSRI) antidepressants: A meta-analysis of observational studies. Pharmacol Res. 2017;118:19-32. DOI: 10.1016/j.phrs.2016.08.017. PubMed PMID: 27521835.
  4. Anglin R, Yuan Y, Moayyedi P, Tse F, Armstrong D, Leontiadis GI. Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: a systematic review and meta-analysis. Am J Gastroenterol. 2014;109(6):811-9. DOI: 10.1038/ajg.2014.82. PubMed PMID: 24777151.
  5. Hackam DG, Mrkobrada M. Selective serotonin reuptake inhibitors and brain hemorrhage: a meta-analysis. Neurology. 2012;79(18):1862-5. DOI: 10.1212/WNL.0b013e318271f848. PubMed PMID: 23077009.
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