Risk of Gastrointestinal Bleeding with Concurrent Use of NSAID and SSRI: A Systematic Review and Network Meta-Analysis.

ABSTRACT

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used over-the-counter medications that can increase the risk of gastrointestinal (GI) bleeding through antiplatelet effects and loss of GI protection. Selective serotonin reuptake inhibitors (SSRIs), commonly used for mental and behavioral health, are another group of medications that can cause platelet dysfunction. Previous literature has shown a possible increased risk of GI bleeding with concurrent use of SSRIs and NSAIDs. We performed a network meta-analysis comparing NSAIDs, SSRIs, and combined SSRI/NSAIDs to assess the risk of GI bleeding. METHODS: The following databases were searched MEDLINE, Embase, Web of Science Core Collection, SciELO, KCI, and Cochrane database. All comparative studies, i.e., case-control, cohort, and randomized controlled trials were included. Direct and network meta-analysis was conducted using DerSimonian-Laird approach and random effect. For binary outcomes, odds ratio (OR) with 95% confidence interval (CI) and p value were calculated. RESULTS: After a comprehensive search through November 10th, 2021, 15 studies with 82,605 patients were identified. 11 studies reported higher rates of GI bleeds in SSRI/NSAID than SSRI users (36.9% vs 22.8%, OR 2.14, 95% CI 1.52-3.02, p < 0.001, I2 = 86.1%). 10 studies compared SSRI/NSAID to NSAID users with higher rates of bleeds in SSRI/NSAID group (40.9% vs 34.2%, OR 1.49, 95% CI 1.20-1.84, p < 0.001, I2 = 68.8%). The results were consistent using network meta-analysis as well. CONCLUSION: Given higher risk of bleeding with concurrent NSAIDs and SSRIs, prescribers should exercise caution when administering NSAIDs and SSRIs concurrently especially in patients with higher risks of GI bleeding.