Why the study?
With NOAC prescriptions increasingly surpassing warfarin, evidence was assessed regarding the safe concomitant use of NOACs with SSRIs and SNRIs.
Does concomitant treatment with NOACs and SSRI/SNRI antidepressants increase the risk of bleeding?
RCT (n=8,464)
Double-blind
Randomized
Yes
Does concomitant treatment with NOACs and SSRI/SNRI antidepressants increase the risk of bleeding?
Relative Risk: 0.36 (95% CI 0.22–0.54)
Absolute Event Rate: 1.39% vs 3.86%
p-value: p=<0.0001
Caution is advised when co-prescribing NOACs with SSRI/SNRI antidepressants due to a potential increased risk of bleeding from pharmacodynamic interactions.
Introduction: Warfarin has been considered as a “gold standard” in the prevention and treatment of thromboembolic events since 1954. Since the introduction of direct oral anticoagulants in the last few years (NOAC-Non-Vitamin K antagonist Oral Anticoagulants) prescriptions volume for apixaban, edoxaban, dabigatran and rivaroxaban have been gradually surpassing warfarin. The benefits include: anticoagulation from day one, fixed daily dosing, elimination for the need of international normalised ratio (INR) monitoring, fewer interactions with food and co-administered medicines with reduced risk of bleeding and better overall life quality. Objectives: Assessing evidence for the safe use of Non-vitamin K Oral Anticoagulants (NOAC) with Selective Serotonin Reuptake Inhibitors (SSRI) and Serotonin and Noradrenaline Reuptake Inhibitors (SNRI). Method: Review of literature published between 2014 and 2016 was made using the key words: Selective Serotonin Reuptake Inhibitor, Serotonin and Noradrenaline Reuptake Inhibitors, apixaban, dabigatran, edoxaban, rivaroxaban, bleeding, interaction, depression with time description from 2014 to 2018. Evidence within the literature was then compared with guidelines from the National Institute for Health and Care Excellence (UK), British National Formulary (UK), Clinical Excellence Commission (Australia), Thrombophilia and Anticoagulation Clinic (USA) and Summaries of Product Characteristics (SPC). Results: 1. Serotonin plays a critical role in maintaining homeostasis. Use of SSRI/SNRI compromises its platelet reuptake increasing risk of bleeding. 2. Increased tolerability and safety of NOAC over Warfarin, although caution is advised when NOAC is used with SSRI/SNRI with less evidence suggesting pharmacodynamic interactions. 3. It is not recommended to use NOAC with strong CYP and P-gp inhibitors. Conclusions: With limited literature evidence, caution is advised when co-prescribed NOACs with SSRI/SNRI, especially with other cofactors and interacting medicines further increasing risk of bleeding.
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Boguta et al. (2018) conducted an RCT in Elective hip or knee replacement surgery (n=8,464). Apixaban vs. Enoxaparin 40 mg once daily was evaluated on Composite of all VTE and all-cause death (ADVANCE-3 trial) (RR 0.36, 95% CI 0.22-0.54, p=<0.0001).
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