Risk of Bleeding in Patients on Full-Dose Enoxaparin With Venous Thromboembolism and Selective Serotonin Reuptake Inhibitors

Ann Pharmacother. 2017 Mar;51(3):226-231. doi: 10.1177/1060028016677309. Epub 2016 Nov 13.


Background: Selective serotonin reuptake inhibitors (SSRIs) are very commonly prescribed agents that are also potent antiplatelet agents.

Objective: This study was designed compare the rate of major bleeding events between patients who were treated with low-molecular-weight heparin (LMWH) for venous thromboembolism (VTE) on SSRIs and those not on chronic SSRI therapy.

Methods: This was a retrospective cohort study of 575 patients with a primary or secondary diagnosis of an acute VTE initiated on full-dose enoxaparin with or without an SSRI between October 1, 2009, and October 1, 2014, in a 443-bed, single tertiary care referral county teaching hospital.

Results: No significant difference was found in the incidence of major bleeding in the SSRI versus non-SSRI group (19.6% vs 17.0%, P = 0.548). Ad hoc analysis demonstrated an elevated risk of major bleeding in patients on escitalopram compared with those on any of the other SSRIs (46.2% vs 15.2%, P = 0.018). Multivariate analysis demonstrated that escitalopram use-OR (95% CI) = 18.85 (1.84-193.6)-was associated with increased major bleeding, and acid suppressive therapy-0.24 (0.07-0.90); P = 0.014-was associated with decreased major bleeding in patients reporting alcohol use.

Conclusion: No difference was found in the incidence of major bleeding in patients on LMWH and SSRIs versus those on LMWH but not on SSRIs. However, ad hoc findings showed a significantly higher rate of major bleeding events in patients who received escitalopram and alcohol among patients on full-dose enoxaparin for VTE. These findings merit further exploration.

Keywords: alcohol; bleeding; enoxaparin; escitalopram; gastrointestinal; low-molecular-weight heparin; selective serotonin reuptake inhibitors; venous thromboembolism.

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects*
  • Anticoagulants / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enoxaparin / administration & dosage
  • Enoxaparin / adverse effects*
  • Enoxaparin / therapeutic use
  • Female
  • Hemorrhage / chemically induced*
  • Hemorrhage / epidemiology
  • Heparin, Low-Molecular-Weight / adverse effects
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk
  • Selective Serotonin Reuptake Inhibitors / administration & dosage
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Venous Thromboembolism / drug therapy*


  • Anticoagulants
  • Enoxaparin
  • Heparin, Low-Molecular-Weight
  • Serotonin Uptake Inhibitors