Clinically relevant drug interactions between newer antidepressants and oral anticoagulants

Edoardo Spina, Maria Antonietta Barbieri, Giuseppe Cicala, Antonio Bruno, Jose de Leon

Research output: Contribution to journalReview articlepeer-review

28 Scopus citations


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.

Original languageEnglish
Pages (from-to)31-44
Number of pages14
JournalExpert Opinion on Drug Metabolism and Toxicology
Issue number1
StatePublished - Jan 2 2020

Bibliographical note

Publisher Copyright:
© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.


  • Newer antidepressants
  • direct-acting oral anticoagulants
  • drug interactions
  • oral anticoagulants
  • pharmacodynamics
  • pharmacokinetics
  • vitamin K antagonists
  • warfarin

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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