Selective serotonin re-uptake inhibitor use and risk of gastrointestinal bleeding in aspirin users

Both aspirin and selective serotonin reuptake inhibitors (SSRIs) have been linked to an increased risk of gastrointestinal (GI) bleeding, while the interaction between the combined use of these two drugs on GI bleeding remains unclear. We aimed to explore the association between SSRIs use and risk of GI bleeding among aspirin users.

This is a prospective cohort study of 12,712 new aspirin users with a history of ischemic cardiovascular disease from the UK Biobank. Information on aspirin or SSRIs prescriptions was retrieved from primary care records, and GI bleeding data from hospital inpatient admissions. A competing risk model was used to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs).

The incidence rate was 7.44 and 4.99 per 1000 person-years in the group of SSRIs and non-SSRIs use, respectively. A significant positive association was observed between SSRIs use and GI bleeding risk among aspirin users (Adjusted HR,1.27; 95 % CI, 1.01-1.58). The observed association was more pronounced in younger adults, females, individuals with a history of GI bleeding or those using PPIs. Besides, the association varied across different types of SSRIs, with paroxetine users showing the highest risk of GI bleeding (Adjusted HR, 1.73; 95 % CI, 1.06-2.83).

This study indicated an additional risk of GI bleeding associated with SSRIs use in aspirin users, especially when combining paroxetine with aspirin. This finding underscores the necessity for further investigation into the differential risks of specific SSRIs to guide personalized polypharmacy.