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SSRIs nearly doubled risk for upper GI bleeding

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Selective serotonin reuptake inhibitors, or SSRIs, were found to be associated with a nearly twofold increased risk for upper gastrointestinal bleeding in a recent study.

Aiming to better understand the relationship between SSRI use and risk for upper GI bleeding (UGIB), researchers from China performed a systematic review and meta-analysis of 22 studies (six cohort, 16 case-control) published between 1999 and 2014 involving more than 1,073,000 individuals (56,290 UGIB cases).

They found that SSRI use was associated with a 55% increase in UGIB incidence (OR=1.55; 95% CI, 1.35-1.78), but there was considerable heterogeneity across studies (P<.001). When restricting analysis to studies reporting risk estimations of SSRI use only, the association persisted (OR=1.95; 95% CI, 1.44-2.63) but so did the heterogeneity across studies (P<.001). Subgroup analysis showed the association was greatest for patients receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs; OR=3.72; 95% CI, 3.01-4.67) or antiplatelet drugs (OR=2.48; 95% CI, 1.7-3.61), but there was no association with concurrent acid-suppressing drugs (OR=0.81; 95% CI, 0.43-1.53).

“In summary, the present meta-analysis suggests that SSRI use was associated significantly with the risk of UGIB, especially among patients with high risk (concurrent NSAID and antiplatelet drug use),” the researchers concluded. “Such risk may be reduced significantly through the concomitant use of acid-suppressing drugs. However, large-scale, well-designed, prospective studies with consideration of more confounding factors are warranted to show the strength of this association.”

In an accompanying editorial, Laura E. Targownik, MD, MSHS, from the IBD Clinical and Research Centre at the University of Manitoba in Canada, wrote that the data confirm a moderate estimate of magnitude of the SSRI-UGIB association, but “none of these analyses of observed data can directly answer whether this association truly is causal.”

“Although the causality of the SSRI-UGIB association has not been proven definitely,” Targownik said, “the weight of the current evidence does not deny the possibility of causality, and the likelihood of more definitive evidence becoming available is low. In the interim, given the widespread use of SSRIs in high-risk patients, it seems reasonable to provide [proton pump inhibitor]-based gastroprotection to long-term NSAID users who also are being prescribed SSRIs, and to consider bleeding risk when initiated SSRI-based therapy.” 

For more information:

Jiang HY. Clin Gastroenterol Hepatol. 2015;13:42-50.

Targownik LE. Clin Gastroenterol Hepatol. 2014;13:51-54.

Disclosure: The researchers report no relevant financial disclosures. Targownik reports various financial ties with AbbVie, AstraZeneca, Janssen, Merck, Pfizer and Takeda.