Major Bleeding Risk in Patients With Non-valvular Atrial Fibrillation Concurrently Taking Direct Oral Anticoagulants and Antidepressants

Abstract

Direct oral anticoagulants (DOACs) are commonly prescribed with antidepressants that may increase bleeding risk. Here we assessed the association between DOACs with and without concurrent antidepressants and major bleeding risk in patients with atrial fibrillation (AF) by a retrospective cohort study included patients with AF who received prescriptions of DOACs in Taiwan’s National Health Insurance database between 2012 and 2017. Adjusted rate ratio (ARR) of major bleeding was calculated by comparing incidence rate adjusted with Poisson regression and inverse probability of treatment weighting using the propensity score between patient-times with and without antidepressants. Among 98863 patients with AF, concurrent use of bupropion with DOACs increased the risks of all major bleeding (ARR: 1.49, 95% CI: 1.02–2.16) and gastrointestinal hemorrhage (ARR: 1.57, 95% CI: 1.04–2.33). An increased risk of intracerebral hemorrhage (ICH) was associated with the combinations of DOACs with selective serotonin reuptake inhibitors (SSRIs, ARR: 1.38, 95% CI: 1.08–1.76), particularly in paroxetine (ARR: 2.11, 95% CI: 1.17–3.81), and tetracyclic antidepressants (TeCAs, ARR: 1.34, 95% CI: 1.01–1.78). In subgroup analyses stratified by individual NOACs, SSRIs increased the risk of ICH in the dabigatran-treated patients (ARR: 1.55, 95% CI: 1.04–2.33). The combinations of apixaban and serotonin-norepinephrine reuptake inhibitors (SNRIs) were associated with a higher risk of all major bleeding (ARR: 1.63, 95% CI: 1.04–2.55). These results clearly indicate the drug–drug interactions between DOACs and antidepressants, which should be carefully considered when prescribing DOACs in adult patients. Careful monitoring for bleeding should be performed while concurrently prescribing DOACs with bupropion, SSRI, SNRI, and TeCA. Concomitant use of DOACs and TCAs may be a relatively safe strategy for patients with AF.

Impact of Selective Serotonin-Reuptake Inhibitors in Hemorrhagic Risk in Anticoagulated Patients Taking Non–Vitamin K Antagonist Anticoagulants

“…The electronic database yielded 480 references. After applying inclusion/exclusion criteria, 8 studies were included 7–14 . The main characteristics of the included studies are depicted in Table 1.…”

“…After applying inclusion/exclusion criteria, 8 studies were included. [7][8][9][10][11][12][13][14] The main characteristics of the included studies are depicted in Table 1.…”

A review on increasing risk for gastrointestinal bleeding associated with dabigatran

“…Retrospective cohort studies on patients with atrial fibrillation revealed the combined use of DOACs and selective serotonin reuptake inhibitors (SSRIs). Further, the use of bupropion was associated with an elevated risk of bleeding in the digestive tract in patients with atrial fibrillation treated with dabigatran [53].…”

Drug-Drug Interactions of Direct Oral Anticoagulants (DOACs): From Pharmacological to Clinical Practice

“…Antidepressants are widely used in the treatment of patients with stroke [68]. A retrospective cohort study conducted in patients with AF documented an increased risk of intracerebral hemorrhage in patients treated with the combination of DOACs with SSRIs (+38%), particularly with paroxetine and tetracyclic antidepressants [69]. These results, although from a retrospective study, indicate a clinically relevant DDI between DOACs and antidepressants, which should be carefully considered when prescribing DOACs in adult patients (Table 6).…”