Abstract
Background: Since warfarin has a very narrow therapeutic index, the interaction between
warfarin and antidepressants is very critical and has potentially severe consequences. It is unclear
whether clinicians have sufficient knowledge about the risk of bleeding when warfarin and antidepressants
are used concomitantly.
Objective: In this systematic review, we discuss the main considerations when using warfarin with
antidepressants.
Methods: The information about warfarin-antidepressant interactions was obtained from Google
Scholar®, PubMed/MEDLINE® and a hand search of the published literature. The following research
terms which were systematically combined with each other to find articles: warfarin, anticoagulant,
interactions, antidepressant (and each antidepressant name individually), SSRI, SNRI, TCA, MAOI.
Results: Several possible mechanisms that can cause bleeding when antidepressants and warfarin
are used concomitantly, have been discussed. According to the available data, sertraline and citalopram/
escitalopram are safer antidepressants to use with warfarin, whereas fluoxetine and fluvoxamine
have a higher interaction potential with warfarin. The remaining antidepressants appear to lie
somewhere in between and have little empirical data to guide the clinicians.
Conclusion: It is recommended that when an antidepressant is prescribed to a patient using warfarin,
patient’s international normalized ratio (INR) level should be checked regularly. In this review,
the interaction between warfarin and antidepressants, including new ones, were evaluated
inclusively and in detail.
Keywords:
Anticoagulant, antidepressant, cytochrome, interaction, SSRI, SNRI, warfarin.
Graphical Abstract
[1]
Jeffrey IW. Antithrombotic drugs Hematology: basic principles and practice. 6th ed. Philadelphia, PA, USA: Elsevier 2013; pp. 2102-19.
[8]
Rang HP, Dale MM, Ritter JM, Moore PK. Pharmacology. 5th ed. London: Churchill Linvingston 2004.
[9]
Moss PA, Pettit JE. Platelets, blood coagulation and haemostasis.In: Hoffbrand AV, Ed Hoffbrant’s essential haematology. 7th ed. New Jersey: Wiley 2016; pp. 264-77.
[10]
David P. Steensma. Thrombosis 2: treatment. In: Hoffbrand AV,
Ed. Hoffbrant’s essential haematology, 7th Ed. New Jersey: Wiley
2016; pp. 311-320..
[12]
Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The
pharmacology and management of the vitamin K antagonists: the
Seventh ACCP Conference on Antithrombotic and Thrombolytic
Therapy Chest. 126(3 Suppl): 204S-233S..
[20]
Komen JJ, Hjemdahl P, Mantel-Teeuwisse AK, Klungel OH,
Wettermark B, Forslund T. Concomittant oral anticoagulant and
antidepressant therapy in patients with atrial fibrillation and risk of
stroke and bleeding: a population based cohort study. ESC
Congress 2019 together with World Congress of Cardilogy. 31
August- 4 September 2019; Paris, France. P4745. 2019..
[26]
Allen SN, John S, Shannon J, Ferrara J. Treatment of depression in patients on anticoagulation therapy: antidepressant-warfarin drug interactions. US Pharm 2013; 38(11): 23-6.
[65]
Sjöqvist F. Drug interactionsFASS 2005 (the Swedish Physicians’ Desk Reference) 2005.
[66]
Ronfeld RA, Shaw GL, Tremaine LM. Distribution and pharmacokinetics of the selective 5-HT uptake blocker sertraline in man, rat, and dog. Psychopharmacology (Berl) 1988; 96(Suppl.): 269.
[70]
Wilner KD, Lazar JD, Apseloff G, Gerber N, Yurkewick L. The effects of sertraline on the pharmacodynamics of warfarin in healthy volunteers. Biol Psychiatry 1991; 29: 354-5.
[108]
Norton J, Quarles E. Mirtazapine-induced warfarin toxicity. Prim Psychiatry 2002; 9: 30-1.