An Association Between Selective Serotonin Reuptake Inhibitor Use and Serious Upper Gastrointestinal Bleeding

Background & Aims

In vitro studies have shown that selective serotonin reuptake inhibitors (SSRIs) inhibit platelet aggregation. It is controversial whether use of SSRIs is a cause of clinically important bleeding; results from observational studies have been equivocal.

Methods

A population-based case-control study was conducted in Denmark. The 3652 cases all had a first discharge diagnosis of serious upper gastrointestinal bleeding (UGB) from 1995 to 2006. Controls (n = 36,502), matched for age and sex, were selected by risk-set sampling. Data on drug exposure and medical history were retrieved from a prescription database and the county's patient register. Confounders were controlled for by conditional logistic regression and the case-crossover design.

Results

The adjusted odds ratio (OR) of UGB among current, recent, and past users of SSRIs was 1.67 (95% confidence interval [CI], 1.46–1.92), 1.88 (95% CI, 1.42–2.5), and 1.22 (95% CI, 1.07–1.39). The adjusted OR for concurrent use of SSRI and nonsteroidal anti-inflammatory drugs (NSAIDs) was 8.0 (95% CI, 4.8–13). The adjusted OR for the concurrent use of NSAID, aspirin, and SSRI was 28 (95% CI, 7.6–103). Of the UGB cases, 377 were current users of SSRI; the adjusted OR for UGB in the case crossover analysis was 2.8 (95% CI, 2.2–3.6). The adjusted OR among users of proton pump inhibitors was 0.96 (95% CI, 0.50–1.82).

Conclusions

Use of SSRI was associated with UGB, consistent with its antiplatelet effects. SSRIs should be prescribed with caution for patients at high risk for UGB.

Abbreviations used in this paper: ASA, acetylsalicylic acid, ATC, anatomical-therapeutic-chemical, CI, confidence interval, COPD, chronic obstructive pulmonary disease, DDD, defined daily dose, FPAS, Funen County Patient Administrative System, ICD- 8, 9, and 10, International Classification of Diseases 8th, 9th, and 10th versions, NNTH, the number of patients needed to be treated for 1 additional patient to be harmed, NSAIDs, nonsteroidal anti-inflammatory drugs, OPED, Odense University Pharmaco-Epidemiological Database, OR, odds ratio, OTC, over-the-counter, PPI, proton pump inhibitor, SSRIs, selective serotonin reuptake inhibitors, TCA, tricyclic antidepressant, UGB, upper gastrointestinal bleeding