SSRI co‐medication with NOAC or VKA does not increase hospitalisation for bleeding: A retrospective nationwide cohort study in Austria 2010‐2015

Abstract

Objectives Non‐vitamin K oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) are used for the prophylaxis and treatment of thromboembolic events. A potential drug–drug interaction and increased bleeding events have been reported with co‐medication of selective serotonin receptor inhibitors (SSRIs) and VKA. The aim of this study was to investigate the bleeding risk of a coprescription of NOAC or VKA with SSRI. Methods Patients with prescription of NOAC or VKA and an antidepressant drug therapy (ADTx) were selected from the drug reimbursement database of 13 Austrian health insurance funds. For this cohort, hospital discharge diagnoses for gastrointestinal bleeding, cerebral haemorrhage, and bleeding anaemia between 2010 and 2015 were analysed. Results Data were available from 50 196 female and 31 308 male patients. Among these, 892 patients had 987 hospitalisations with bleeding events. The most frequent bleeding cases were gastrointestinal bleedings with 588 events (59.6%), followed by cerebral haemorrhage with 344 (34.8%), and bleeding anaemia with 55 events (5.6%), respectively. The risk of bleeding events was similar between SSRI and other ADTx, when combined with oral anticoagulants (p = 0.51). Concomitant treatment of patients with SSRI or other ADTx and NOAC was associated with an increased bleeding risk compared with cotreatment with VKA (1.21, 95% CI: 1.05‐1.40; p = 0.0097). Conclusion Co‐medication of SSRI with VKA or NOAC has little if any impact on hospital discharge diagnoses for bleeding events compared with cotreatment of those anticoagulants with other antidepressant medications.

Adverse drug reactions with oral anticoagulants: data from sicilian spontaneous reporting system database

“…Moreover, if the coadministration of apixaban and venlafaxine is necessary, it is useful to monitor the patient closely for a possible additive effect on haemostasis 79,89 . On the other hand, an Austrian cohort study indicated that the co‐medication of SSRIs and OACs has no substantial impact on bleeding events, compared with the concomitant administration of OACs with other antidepressants 90 . Other concomitant bleeding‐risk medicines include nonsteroidal anti‐inflammatory drugs (NSAIDs) such as ketoprofen and ibuprofen, having an additive effect on haemostasis 76,91,92 .…”

Association of Type of Antidepressant Initiation with Bleeding Risk in Atrial Fibrillation Patients Taking Oral Anticoagulants

“…Previous studies have reported the association of antidepressant use with bleeding risk in OAC users. SSRI use has been associated with an increased risk of bleeding among OAC users in some studies [26,27], but not others [28][29][30]. The findings could potentially be explained by SSRIs' interference with hepatic cytochrome P-450 isoenzyme metabolic pathways, which are responsible for warfarin metabolism [31].…”

“…Approximately one fifth of eligible study participants included in our analysis were DOAC users. Since few published studies have assessed the risk of bleeding associated with concomitant use of antidepressant and DOAC [ 28 , 30 ], we performed additional stratified analyses and tested for interaction between antidepressant type and OAC type. Results from prior studies showed that SSRI use is not associated with an increased risk of bleeding among AF patients on DOAC [ 28 , 30 ].…”

“…Since few published studies have assessed the risk of bleeding associated with concomitant use of antidepressant and DOAC [ 28 , 30 ], we performed additional stratified analyses and tested for interaction between antidepressant type and OAC type. Results from prior studies showed that SSRI use is not associated with an increased risk of bleeding among AF patients on DOAC [ 28 , 30 ]. In our study, we did not find any evidence supporting a differential effect of antidepressant type on bleeding by type of OAC, other than a potential weaker association of SSRI versus TCA with bleeding risk in warfarin users than in DOAC users.…”

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

“…However, little is known regarding the clinical relevance of these drug-drug interactions. Previous studies to explore the effects of antidepressants on bleeding risk in patients taking DOACs also demonstrate conflict results (Sheikh Rezaei et al, 2019;Komen et al, 2020;Marchena et al, 2020). To address this important question, we conducted a nationwide retrospective cohort study to compare the major bleeding risk of patients with AF concurrently treated with DOACs and antidepressants and those who took DOACs alone.…”