GABAergic but not Antidepressant Medications Increase Risk for Clostridioides difficile Infection in a National Cohort of Veterans

BACKGROUND: Clostridioides difficile infection (CDI) is primarily mediated by alterations in the host gut ecosystem. While antibiotic use is the primary risk factor for CDI, other medications that modulate the gut ecosystem, particularly those targeting the gut–brain axis, could impact CDI risk. This study aimed to investigate the association between recent antidepressant and gamma-aminobutyric acid (GABA)–ergic medication use with CDI risk in a national cohort of United States veterans. METHODS: This was a retrospective case–control study of patients seen in Veterans Health Administration facilities from October 2002 to September 2014. CDI and non-CDI control patients were propensity score matched 1:1 using a maximum caliper of 0.0001. Antidepressant and GABAergic medication use 90 days before cohort inclusion were analyzed for CDI association using bivariable and multivariable logistic regression models. RESULTS: A total of 85 831 patients were included, and 9287 CDI and 9287 control patients were propensity score matched. Antidepressant use overall was not significantly associated with CDI risk (odds ratio [OR], 1.05; 95% CI, 0.98–1.12), although GABAergic medication use was associated with increased risk (OR, 1.81; 95% CI, 1.70–1.92). In multivariable models of individual medications/classes, benzodiazepines had the strongest CDI association (OR, 1.91; 95% CI, 1.77–2.07). SSRIs (OR, 0.88; 95% CI, 0.81–0.95) and bupropion (OR, 0.67; 95% CI, 0.57–0.78) were negatively associated with CDI. CONCLUSIONS: In this national study of veterans, GABAergic medication use was a positive predictor of CDI risk, though antidepressant use was not. Further research is needed to understand biological mechanisms, and confirmatory studies are needed to validate these findings.