ArticleBMJ (Clinical research ed.)1999
Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study.
Article in BMJ (Clinical research ed.), 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 9 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
115 citing papers in PubMed, 9 syntheses or guidelines pooled it, 452 citations in OpenAlex.
- Risk of gastrointestinal bleeding by specific SSRIs and SNRIs: A systematic review and meta-analysis.British journal of clinical pharmacology · 2026Pooled it
- Guidelines on optimizing the use of proton pump inhibitors: PPI stewardship.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2023Guideline
- Risk of Gastrointestinal Bleeding with Concurrent Use of NSAID and SSRI: A Systematic Review and Network Meta-Analysis.Digestive diseases and sciences · 2023Pooled it
- The impact of CYP2D6 mediated drug-drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine.British journal of clinical pharmacology · 2018Pooled it
- Diving and antidepressants.Diving and hyperbaric medicine · 2017Guideline
- Use of antidepressants and the risk of cardiovascular and cerebrovascular disease: a meta-analysis of observational studies.European journal of clinical pharmacology · 2017Pooled it
- Use of selective serotonin reuptake inhibitors and risk of stroke: a systematic review and meta-analysis.Journal of neurology · 2014Pooled it
- Pooled it
- Validity of diagnostic coding within the General Practice Research Database: a systematic review.The British journal of general practice : the journal of the Royal College of General Practitioners · 2010Pooled it
- Is tramadol associated to bleeding peptic ulcer? A nationwide case-control study in hospitalized Swedish patients.PloS one · 2019Trial
- Trial
- Selective serotonin reuptake inhibitors: measurement of effect on platelet function.Translational research : the journal of laboratory and clinical medicine · 2008Trial
- Effect of CYP2D6 and CYP2C9 genotypes on fluoxetine and norfluoxetine plasma concentrations during steady-state conditions.European journal of clinical pharmacology · 2004Trial
- Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and enteric-coated formulations.BMC clinical pharmacology · 2001Trial
- The Relationship Between Selective Serotonin Reuptake Inhibitor Use and Delayed Bleeding After Colorectal Endoscopic Resection: A Nationwide Retrospective Cohort Study.Digestive diseases and sciences · 2026Article
- Pharmacotherapy of major depressive disorder in older adults: from an evidence-informed stepwise algorithm to precision medicine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- All-Cause Mortality and Bleeding Risks Associated With Serotonin Reuptake Inhibitors in Patients With End-Stage Kidney Disease and Depression: A Nationwide Cohort Study.Psychiatry investigation · 2025Article
- Possible Association Between Concomitant Use of SSRIs with NSAIDs and an Increased Risk of Adverse Events Among People with Depressive Disorders: Data Mining of FDA Adverse Event Reporting System.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Concomitant Use of Selective Serotonin Reuptake Inhibitors With Oral Anticoagulants and Risk of Major Bleeding.JAMA network open · 2024Article
- Multimorbidity patterns and trajectories in young and middle-aged adults: a large-scale population-based cohort study.Frontiers in public health · 2024Article
55 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo examine the association between selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding.
designPopulation based case-control study.
settingGeneral practices included in the UK general practice research database. SUBJECTS: 1651 incident cases of upper gastrointestinal bleeding and 248 cases of ulcer perforation among patients aged 40 to 79 years between April 1993 and September 1997, and 10 000 controls matched for age, sex, and year that the case was identified.
interventionsReview of computer profiles for all potential cases, and an internal validation study to confirm the accuracy of the diagnosis on the basis of the computerised information.
main outcome measuresCurrent use of selective serotonin reuptake inhibitors or other antidepressants within 30 days before the index date.
resultsCurrent exposure to selective serotonin reuptake inhibitors was identified in 3.1% (52 of 1651) of patients with upper gastrointestinal bleeding but only 1.0% (95 of 10 000) of controls, giving an adjusted rate ratio of 3.0 (95% confidence interval 2.1 to 4.4). This effect measure was not modified by sex, age, dose, or treatment duration. A crude incidence of 1 case per 8000 prescriptions was estimated. A small association was found with non-selective serotonin reuptake inhibitors (relative risk 1.4, 1.1 to 1.9) but not with antidepressants lacking this inhibitory effect. None of the groups of antidepressants was associated with ulcer perforation. The concurrent use of selective serotonin reuptake inhibitors with non-steroidal anti-inflammatory drugs increased the risk of upper gastrointestinal bleeding beyond the sum of their independent effects (15.6, 6.6 to 36.6). A smaller interaction was also found between selective serotonin reuptake inhibitors and low dose aspirin (7.2, 3.1 to 17.1).
conclusionsSelective serotonin reuptake inhibitors increase the risk of upper gastrointestinal bleeding. The absolute effect is, however, moderate and about equivalent to low dose ibuprofen. The concurrent use of non-steroidal anti-inflammatory drugs or aspirin with selective serotonin reuptake inhibitors greatly increases the risk of upper gastrointestinal bleeding.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.