Exploratory Study Examining the Risk of Gastrointestinal Bleeding for Patients on Selective Serotonin Reuptake Inhibitor Therapy

Abstract

Purpose: Selective Serotonin Reuptake Inhibitors (SSRIs) are highly used in the treatment of depression; however their use has been associated with bleeding. There is current debate in the literature whether SSRIs are associated with gastrointestinal bleeding (GIB). This exploratory, retrospective claims-based analysis aimed to compare the incidence of GIB in patients continuously using SSRIs for at least 6 months compared with age and sex matched controls and examine factors that may be associated with the risk of GIB among SSRI users. Methods: The MarketScan database (2001–2005) was used to identify patients ≥ 18 years, newly initiated on SSRI therapy. Inclusion criteria: continuous enrollment in the 12 months before and after the first SSRI prescription (index claim); consecutive SSRI use without a gap of >31 days between prescriptions for at least 6 months. Exclusion criteria: received an SSRI prescription or had a GIB diagnoses within 1 year before the index claim. Logistic regression examined impact of age, gender, exposure (days supply of filled prescriptions) of SSRI, NSAID, gastrotoxic agents (GTAs; warfarin, corticosteroids, antiplatelets and calcium channel blockers), and gastroprotective agents (GPAs; proton pump inhibitors, histamine2-receptor antagonists) on odds of GIB. Results: Sample had 149,647 SSRI users that met the inclusion criteria; mean SSRI exposure in follow-up period was 358 days (SD 79). SSRI incidence of GIB was 8.3/1000, compared to 6.4/1000 in controls. Percent use of NSAID, GTA, and GPA in SSRI patients ranged from 24–36% in the pre or post period. Mean days (across all patients) of NSAID, GTA, and GPA exposure was 39, 63, and 53 in the pre-period, and 48, 89, and 75 days in the follow-up period. Compared to 18–34 year old SSRI users, those 65+ years were 12 times(x) more likely to have GIB, rates were 6× and 3× higher for those aged 55–64 and 45–54. Female SSRI users were 1.4× more likely to have GIB compared to males. GTA users were 2% more likely to have GIB for each additional 30 days of exposure (pre-period or follow-up period). Conclusion: New SSRI users were 1.3× more likely than controls to experience GIB. Among SSRI patients, older age, females, and use of GTAs were associated with having GIB. Additional research will investigate time to onset of GIB, and the influence of GIB events on subsequent SSRI, GTA, NSAID, and GPA use in the SSRI population.