Risk of gastrointestinal bleeding by specific SSRIs and SNRIs: A systematic review and meta-analysis

Abstract

Aim: The purpose of this study is to estimate the risk of gastrointestinal bleeding (GIB) by selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) individual agents.

Methods: A systematic review was conducted for each unique antidepressant (i.e. SSRI: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline; and SNRIs: desvenlafaxine, venlafaxine, and duloxetine) combined with search terms for GIB in PubMed and EMBASE from inception to October 2025. Articles including results on specific antidepressants and GIB risk were included.

Results: From a total of 1218 identified publications, 20 studies were included and analysed using a random-effect meta-analysis. Twelve studies (60%) used a case-control design, three (15%) a cohort study design, one (5%) a case cross-over, one (5%) used both case-control and cross-over designs and three (15%) were randomized control trials (RCTs). Studies sample sizes ranged from 666 235 from a Medicaid population to 1280 from 43 hospitals participating in a RCT. Fluoxetine had the most studies providing evidence (19 studies) and fluvoxamine and duloxetine had the least (five studies). Each antidepressant showed an increased risk of GIB. Venlafaxine had the highest estimated risk (OR 1.50, 95% CI 1.32-1.70), followed by citalopram (OR 1.38, 95% CI 1.17-1.62) and fluoxetine (OR 1.38, 95% CI 1.26-1.51). Paroxetine had the lowest GIB risk (OR 1.31, 95% CI 1.07-1.62).

Conclusion: GIB is an uncommon adverse event, but this analysis demonstrates that the risk of GIB is elevated for commonly used SSRI/SNRI products, highlighting the relevance for those patients with an increased risk of GIB.

Keywords: antidepressive agents; gastrointestinal haemorrhage; selective serotonin reuptake inhibitors; serotonin and noradrenaline reuptake inhibitors.