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Risk of Upper Gastrointestinal Bleeding With Selective Serotonin Reuptake Inhibitors With or Without Concurrent NonSteroidal Anti-Inflammatory Use: A Systematic Review and Meta-Analysis
Abstract
Objectives There is emerging concern that selective serotonin reuptake inhibitors (SSRIs) may be associated with an increased risk of upper gastrointestinal (GI) bleeding, and that this risk may be further increased by concurrent use of nonsteroidal anti-inflammatory (NSAID) medications. Previous reviews of a relatively small number of studies have reported a substantial risk of upper GI bleeding with SSRIs; however, more recent studies have produced variable results. The objective of this study was to obtain a more precise estimate of the risk of upper GI bleeding with SSRIs, with or without concurrent NSAID use. Methods MEDLINE, EMBASE, PsycINFO, the Cochrane central register of controlled trials (through April 2013), and US and European conference proceedings were searched. Controlled trials, cohort, case-control, and cross-sectional studies that reported the incidence of upper GI bleeding in adults on SSRIs with or without concurrent NSAID use, compared with placebo or no treatment were included. Data were extracted independently by two authors. Dichotomous data were pooled to obtain odds ratio (OR) of the risk of upper GI bleeding with SSRIs +/- NSAID, with a 95% confidence interval (CI). The main outcome and measure of the study was the risk of upper GI bleeding with SSRIs compared with placebo or no treatment. Results Fifteen case-control studies (including 393,268 participants) and four cohort studies were included in the analysis. There was an increased risk of upper…
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“coadministration of NSAIDs with selective serotonin reuptake inhibitors (SSRIs) more than doubles the odds of gastrointestinal bleeding [9,10]”
From Comparing Artificial Intelligence (ChatGPT, Gemini, DeepSeek) and Oral Surgeons in Detecting Clinically Relevant Drug–Drug Interactions in Dental Therapy (2025) · cites this paper as [10]
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“Also, in the present study, no information about concomitant nonsteroidal anti‐inflammatory drug intake was available, which has been shown to have an impact on bleeding events when combined with SSRI or anticoagulants.(37,38) Furthermore, we were not able to assess adherence to the medications for which prescriptions…”
Lin, X., Young, S.-H., Luo, J., Peng, Y., Chen, P., Lin, C.-C., Chen, W., Hou, M., & Lee, F. (2017) · Pain Medicine · doi:10.1093/pm/pnx097 · Cited by 11
Alqdwah‐Fattouh, R., Rodríguez‐Martín, S., de Abajo, F. J., González‐Bermejo, D., Gil, M., García‐Lledó, A., & Bolúmar, F. (2020) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.14299 · Cited by 11
“After 4–8 weeks of SSRIs use, the serotonin content in platelets is almost depleted(42) and, through this mechanism, SSRIs could alter platelet function, which is clinically expressed by a prolongation of bleeding time(43) and an increase in the risk of bleeding,(22) with particularly strong evidence being upper gastr…”
Metadata
- Authors
- Anglin, R., Yuan, Y., Moayyedi, P., Tse, F., Armstrong, D., & Leontiadis, G. I.
- Affiliations
- McMaster University (CA)
- Corresponding author
- Anglin, Rebecca
- Venue
- American Journal of Gastroenterology
- Published
- 2014-06
- Volume
- 109
- Issue
- 6
- Pages
- 811-819
- ISSN
- 0002-9270 (ISSN-L)
- OpenAlex
- W1970727094
- Cited by
- 234
- References
- 44
- Citations by year
- 2026: 18 · 2025: 17 · 2024: 14 · 2023: 12 · 2022: 21 · 2021: 16 · 2020: 14 · 2019: 22 · 2018: 24 · 2017: 35 · 2016: 19 · 2015: 17 · 2014: 4
- FWCI
- 4.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal Bleeding Diagnosis and Treatment
- Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
- Health Sciences › Medicine › Gastroenterology › Helicobacter pylori-related gastroenterology studies
- Keywords
- upper gastrointestinal bleeding, selective serotonin reuptake inhibitors, nonsteroidal anti-inflammatory drugs, drug-drug interactions, adverse drug reactions, antidepressant safety, number needed to harm, risk estimation, combination therapy, prescribing precautions, depression treatment, antidepressant side effects, NSAID adverse effects, antidepressant discontinuation
- MeSH terms
- Anti-Inflammatory Agents, Non-Steroidal, Drug Therapy, Combination, Gastrointestinal Hemorrhage, Humans, Risk Factors, Incidence, Selective Serotonin Reuptake Inhibitors, Risk Assessment, Upper Gastrointestinal Tract
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