Original article
Systematic reviews and meta-analyses
Use of Selective Serotonin Reuptake Inhibitors and Risk of Upper Gastrointestinal Bleeding: A Systematic Review and Meta-analysis

https://doi.org/10.1016/j.cgh.2014.06.021Get rights and content

Background & Aims

Selective serotonin reuptake inhibitors (SSRIs) are used to treat various psychiatric disorders. However, there are concerns that SSRIs increase the risk for upper gastrointestinal bleeding (UGIB).

Methods

We performed a systematic review and meta-analysis of controlled observational studies to determine whether SSRI use affects the risk for UGIB. Our analysis included all observational studies that compared UGIB development among patients receiving SSRIs vs no treatment. We calculated pooled odds ratios using random- and fixed-effects models.

Results

A total of 22 studies (6 cohort and 16 case-control studies) involving more than 1,073,000 individuals were included in our meta-analysis. In comparing SSRI users with patients who had not taken SSRIs, the odds for developing UGIB were 1.55-fold higher (odds ratio, 1.55; 95% confidence interval, 1.35–1.78). In subgroup analyses, the association was greatest for patients who received concurrent therapy with nonsteroidal anti-inflammatory or antiplatelet drugs; we found no significant increase in the risk of developing UGIB among patients receiving concurrent acid-suppressing drugs.

Conclusions

SSRI use was associated with an almost 2-fold increase in the risk of developing UGIB, especially among patients at high risk for GI bleeding (concurrent use of nonsteroidal anti-inflammatory or antiplatelet drugs). This risk might be reduced significantly by concomitant use of acid-suppressing drugs.

Section snippets

Methods

This meta-analysis was conducted following guidance provided by the Cochrane Handbook11 and Kanwal and White,12 and is reported according to the meta-analysis of Observational Studies in Epidemiology guidelines. All steps in the literature search, study identification, study selection, quality, and data extraction were performed independently by 2 investigators from different subspecialties (H.-Y.J. and Y.-H.Z.). Disagreements were resolved by discussion, and consensus was achieved in the

Search Results

By using keywords, a total of 2819 potentially eligible articles were identified by searching the 3 databases and relevant reference sections. Of these, 2494 articles were excluded after reading the title and abstract, and the remaining 163 articles underwent detailed full-text evaluation. From these articles, 225, 6, 7, 8, 9, 10, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 (18 published as full articles and 4 as abstracts) met our inclusion criteria. Four studies5, 7, 20, 21

Discussion

In this comprehensive meta-analysis of 22 studies analyzing the effect of SSRIs on the risk of UGIB in more than 1,073,000 patients, we found that current SSRI use was associated with a 55% increased risk of UGIB. Most of the results of the individual studies were consistent with the overall results. The effect was stable across both case-control and cohort studies. A more pronounced risk of UGIB was found with concurrent use of SSRIs and NSAIDs or antiplatelet drugs, which was increased even

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    Conflicts of interest The authors disclose no conflicts.

    Funding Supported by Fundamental Research Funds for the Central Universities (2014XZZX008).

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    Authors share co-first authorship.

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