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

20 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

Funding Information:
In the past few years, E. Spina has participated in speakers/advisory boards and lectured, supported by Arcapharma, Angelini, Janssen Pharmaceuticals, Lundbeck, Otsuka and Recordati. J. de Leon personally develops his presentations for lecturing, has never lectured using any pharmaceutical or pharmacogenetic company presentations, and has never been a consultant for pharmacogenetic or pharmaceutical companies. In the past, J. de Leon received researcher-initiated grants from Eli Lilly (one ended in 2003 and the other, as co-investigator, ended in 2007); from Roche Molecular Systems, Inc. (ended in 2007); and, in a collaboration with Genomas, Inc., from the NIH Small Business Innovation Research program (ended in 2010). J. de Leon has been on the advisory boards of Bristol-Myers Squibb (2003/04) and AstraZeneca (2003). Roche Molecular Systems supported one of his educational presentations, which was published in a peer-reviewed journal (2005). His lectures were supported once by Sandoz (1997), twice by Lundbeck (1999 and 1999), twice by Pfizer (2001 and 2001), three times by Eli Lilly (2003, 2006, and 2006), twice by Janssen (2000 and 2006), once by Bristol-Myers Squibb (2006), and seven times by Roche Molecular Systems, Inc. (once in 2005 and six times in 2006). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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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