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Cited by 389Gastrointestinal Bleeding Diagnosis and TreatmentPharmacovigilance and Adverse Drug ReactionsInflammatory mediators and NSAID effects

Use of Selective Serotonin Reuptake Inhibitors and Risk of Upper Gastrointestinal Tract Bleeding: A Population-Based Cohort Study

Dalton, Susanne Oksbjerg, Johansen, Christoffer, Mellemkjær, Lene, Sørensen, Henrik Toft, Nørgård, Bente, Olsen, Jørgen H.·2003·Archives of Internal Medicine
DOI 10.1001/archinte.163.1.59
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Abstract

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have been suspected of increasing the risk of bleeding. We examined the risk of upper gastrointestinal tract (GI) bleeding with use of antidepressant medication. METHODS: All users of antidepressants in the county of North Jutland, Denmark, from January 1, 1991, to December 31, 1995, were identified in the Pharmaco-Epidemiologic Prescription Database of North Jutland. In the Hospital Discharge Register, hospitalizations for upper GI bleeding were searched among the 26 005 users of antidepressant medications and compared with the number of hospitalizations in the population of North Jutland who did not receive prescriptions for antidepressants. RESULTS: During periods of SSRI use without use of other drugs associated with upper GI bleeding, we observed 55 upper GI bleeding episodes, which was 3.6 times more than expected (95% confidence interval, 2.7-4.7), corresponding to a rate difference of 3.1 per 1000 treatment years. Combined use of an SSRI and nonsteroidal anti-inflammatory drugs or low-dose aspirin increased the risk to 12.2 (95% confidence interval, 7.1-19.5) and 5.2 (95% confidence interval, 3.2-8.0), respectively. Non-SSRIs increased the risk of upper GI bleeding to 2.3 (95% confidence interval, 1.5-3.4), while antidepressants without action on the serotonin receptor had no significant effect on the risk of upper GI bleeding. The risk with SSRI use returned to unity after termination of SSRI use, while the risks were similarly increased during periods of use and nonuse of non-SSRIs. CONCLUSION: Selective serotonin reuptake inhibitors increase the risk of upper GI bleeding, and this effect is potentiated by concurrent use of nonsteroidal anti-inflammatory drugs or low-dose aspirin, whereas an increased risk of upper GI bleeding could not be attributed to other types of antidepressants.

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Authors
Dalton, S. O., Johansen, C., Mellemkjær, L., Sørensen, H. T., Nørgård, B., & Olsen, J. H.
Affiliations
Danish Cancer Society (DK)
ORCID
Venue
Archives of Internal Medicine
Publisher
American Medical Association (AMA)
Published
2003-01-13
Volume
163
Issue
1
Pages
59
ISSN
0003-9926 (ISSN-L)
DOI
10.1001/archinte.163.1.59
OpenAlex
W2043177024
Cited by
389
References
32
Citations by year
2026: 5 · 2025: 7 · 2024: 10 · 2023: 9 · 2022: 9 · 2021: 9 · 2020: 8 · 2019: 8 · 2018: 12 · 2017: 13 · 2016: 15 · 2015: 17 · 2014: 25 · 2013: 17 · 2012: 20
FWCI
22.88
Type
journal article
Language
en
Open access
closed
Locations
  • Archives of Internal Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Kræftens Bekæmpelse
  • Sundhed og Sygdom, Det Frie Forskningsråd (9700677)
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal Bleeding Diagnosis and Treatment
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
  • Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
Keywords
selective serotonin reuptake inhibitors, upper gastrointestinal bleeding, antidepressants, nonsteroidal anti-inflammatory drugs, low-dose aspirin, drug-drug interactions, bleeding risk, hospitalization
MeSH terms
Aged, Anti-Inflammatory Agents, Non-Steroidal, Antidepressive Agents, Denmark, Drug Synergism, Female, Gastrointestinal Hemorrhage, Humans, Male, Middle Aged, Population Surveillance, Risk Factors, Cohort Studies, Selective Serotonin Reuptake Inhibitors, Risk Assessment

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