SSRIs raise the odds of a stomach bleed by about two thirds; with an NSAID as well, about fourfold
Across 15 case-control studies of 393,268 people, SSRIs carried an odds ratio of 1.66 for upper gastrointestinal bleeding. With an NSAID taken too, 4.25. Number needed to harm: 3,177 in low-risk people, 881 in high-risk.
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: Observational studies pooled; confounding by indication (people with depression may use more NSAIDs or alcohol) cannot be excluded. The authors note earlier reviews had overestimated the SSRI-alone risk.
Serotonin is needed for platelets to clump. Antidepressants that block its reuptake reduce the platelet store, and this meta-analysis measured what that does to the risk of bleeding from the stomach, alone and with an anti-inflammatory painkiller.
Significant findings
Anglin and colleagues (American Journal of Gastroenterology, 2014) searched to April 2013 and included "Fifteen case-control studies (including 393,268 participants) and four cohort studies". "There was an increased risk of upper GI bleeding with SSRI medications in the case-control studies (OR=1.66, 95% CI=1.44,1.92) and cohort studies (OR=1.68, 95% CI=1.13,2.50)."
The absolute numbers: "The number needed to harm for upper GI bleeding with SSRI treatment in a low-risk population was 3,177, and in a high-risk population it was 881." And the combination: "The risk of upper GI bleeding was further increased with the use of both SSRI and NSAID medications (OR=4.25, 95% CI=2.82,6.42)."
The authors' conclusion: "SSRI medications are associated with a modest increase in the risk of upper GI bleeding, which is lower than has previously been estimated. This risk is significantly elevated when SSRI medications are used in combination with NSAIDs, and physicians prescribing these medications together should exercise caution and discuss this risk with patients."
Worth asking
The number needed to harm is the one to hold on to: on an SSRI alone, one extra bleed for roughly every three thousand low-risk people, or every nine hundred high-risk. The combination with regular NSAID use is where the risk stops being modest. If you take an SSRI and buy ibuprofen or naproxen for pain, the question for the pharmacist is what the alternative is, and whether you count as high risk (prior ulcer, older age, anticoagulants, steroids).
Source
Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: a systematic review and meta-analysis — Anglin R, Yuan Y, Moayyedi P, Tse F, Armstrong D, Leontiadis GI (2014)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.1038/ajg.2014.82
DOI: 10.1038/ajg.2014.82
How this was scored
- Study design
- Systematic review of observational studies
- Funding
- Funding not disclosed
- Published in
- Reputable peer-reviewed journal
- Sample size
- 393,268
- Preregistered
- not recorded
- Conflicts disclosed
- not recorded
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published September 21, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "moderate evidence". Reasonable evidence with real limitations. It scores 59 out of 100 on our published rubric. One caveat travels with that badge: Observational studies pooled; confounding by indication (people with depression may use more NSAIDs or alcohol) cannot be excluded. The authors note earlier reviews had overestimated the SSRI-alone risk. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: a systematic review and meta-analysis — Anglin R, Yuan Y, Moayyedi P, Tse F, Armstrong D, Leontiadis GI (2014). Published in: Reputable peer-reviewed journal. DOI: 10.1038/ajg.2014.82. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Systematic review of observational studies. Funding: Funding not disclosed. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.