Does Concomitant Use of Antidepressants and Direct Oral Anticoagulants Increase the Risk of Bleeding?: A Systematic Review and Meta-Analysis.

Purpose: To evaluate the risk of bleeding associated with the simultaneous administration of antidepressants (ADs) and direct oral anticoagulants (DOACs).

Methods: PubMed, Embase, and Scopus databases were searched for papers that focused on the concomitant administration of ADs and DOACs and presented data on the bleeding outcomes. The comparator group of interest consisted of subjects who received only DOACs. Besides the overall pooled analysis, irrespective of the primary disease condition, we were also interested in studies involving patients with atrial fibrillation (AF). We therefore included studies with relevant comparisons (AD with DOACs, compared to DOACs alone), regardless of the reported underlying condition. Thereafter, we conducted a sensitivity analysis to refine estimates specific to AF. Clinical trials and observational studies were eligible. Pooled effect sizes were reported as relative risk (RR) for studies with cohort design and as odds ratio (OR) for case-control studies.

Results: Ten studies were included. Overall pooled analysis showed that treatment with both DOAC and selective serotonin reuptake inhibitor and serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) was associated with significantly higher risk of major bleeding (cohort: RR 1.25, 95% CI: 1.07-1.47; case-control: OR 1.40, 95% CI: 1.15-1.69). The risk of intracranial bleeding was found to be increased when cohort studies were pooled (RR 1.44, 95% CI: 1.24-1.66), but not with pooling of case-control studies (OR 1.58, 95% CI: 0.43-5.75). The risk of gastrointestinal bleeding and transient ischemic attack (TIA)/ischemic stroke was comparable between the 2 groups (DOAC + SSRI/SNRI vs DOAC only group).

Conclusions: Our results indicate that combined SSRIs/SNRIs and DOAC treatment may be associated with increased incidence of major and intracranial bleeding, further emphasizing the importance of caution when considering their concomitant use.