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SSRIs and Upper GI Bleeding: Depressing News?

An association between SSRI use and UGIB should be considered, especially in high-risk patients taking aspirin or NSAIDs.

Selective serotonin reuptake inhibitors (SSRIs) are used widely to treat patients with depression because of their efficacy and tolerability. Results of a case-control study from Denmark (BMJ 1999; 319:1106) suggested a possible link between SSRIs and upper gastrointestinal bleeding (UGIB). To evaluate this association further, another Danish research group linked a pharmacy database with a hospital discharge register in 1 county of northern Denmark from 1991 through 1995 (26,005 antidepressant users). Patients with cirrhosis, alcoholism, or histories of GI bleeding before antidepressant use were excluded.

The incidence of hospitalizations for UGIB in SSRI users was 3.6 times the rate found among residents who did not use antidepressants (3.1 per 1000 treatment-years). The risk for hospitalization was even higher when SSRIs were used concomitantly with nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin (risk ratios, 12.2 and 5.2, respectively). Non-SSRI antidepressants were associated with a 2.3-fold increased risk for UGIB, and risks were increased further by aspirin or NSAID use. There was no increase in UGIB hospitalizations among patients taking other antidepressants. The authors concluded that SSRI use increases risk for UGIB and that the risk is potentiated by concomitant use of aspirin or NSAIDs. They postulated that the important role of serotonin in hemostasis may explain the increased risk.

Comment: These provocative data suggest that SSRIs are independent risk factors for UGIB. The study's strengths are its large, population-based cohort and its integration of pharmacy and hospitalization data. However, individual risk factors for UGIB (e.g., Helicobacter pylori infection, smoking, and alcohol use) were not considered; therefore, confounding factors might explain these findings. Although further study is needed, prospective studies of uncommon outcomes, such as UGIB, are difficult and expensive. Thus, the possibility of an association between SSRI use and UGIB should be considered, especially in high-risk patients taking aspirin or NSAIDs.

— David J. Bjorkman, MD, MSPH, SM (Epid.)

Published in Journal Watch Gastroenterology May 13, 2003

Citation(s):

Dalton SO et al. Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: A population-based cohort study. Arch Intern Med 2003 Jan 13; 163:59-64.

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