Clinically relevant drug interactions between newer antidepressants and oral anticoagulants

Expert Opin Drug Metab Toxicol. 2020 Jan;16(1):31-44. doi: 10.1080/17425255.2020.1700952. Epub 2019 Dec 10.


Introduction: This is a review of the drug interactions (DIs) between newer antidepressants and oral anticoagulants (OACs): vitamin K antagonists (VKAs) and direct-acting OACs (DOACs).Areas covered: Articles were obtained from PubMed searches performed for each of the newer antidepressants and oral anticoagulants. The basic pharmacokinetic and pharmacodynamic mechanisms for DIs with these drugs were summarized. Some newer antidepressants are inhibitors of a number of cytochrome P450 (CYP) isoforms and many antidepressants appear to have potential to impair serotonin platelet function and increase bleeding risk.Expert opinion: Clinicians should not forget that the DIs between newer antidepressants and VKAs can be potentially lethal. Among SSRIs, fluoxetine and fluvoxamine appear to be associated with the highest DI risk with warfarin, the most commonly prescribed VKA worldwide. Case reports featuring duloxetine, mirtazapine and trazadone suggested potential for interaction with warfarin. As CYP3A4 is an important metabolic pathway for all DOACs except dabigatran, it appears reasonable to recommend avoiding the co-prescription of fluoxetine and fluvoxamine (weak to moderate CYP3A4 inhibitors) and St John's wort (CYP3A4 inducer). Many package inserts for the newer antidepressants include a warning regarding an increased risk of bleeding events with concomitant use of these agents with OACs.

Keywords: Newer antidepressants; direct-acting oral anticoagulants; drug interactions; oral anticoagulants; pharmacodynamics; pharmacokinetics; vitamin K antagonists; warfarin.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Anticoagulants / pharmacokinetics
  • Antidepressive Agents / administration & dosage*
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / pharmacology
  • Cytochrome P-450 Enzyme Inhibitors / administration & dosage
  • Cytochrome P-450 Enzyme Inhibitors / pharmacology
  • Drug Interactions*
  • Hemorrhage / chemically induced
  • Humans
  • Vitamin K / antagonists & inhibitors
  • Warfarin / administration & dosage
  • Warfarin / adverse effects
  • Warfarin / pharmacokinetics


  • Anticoagulants
  • Antidepressive Agents
  • Cytochrome P-450 Enzyme Inhibitors
  • Vitamin K
  • Warfarin