Antimicrobial Exposure and Risk for Incident Major Depressive Disorder

Antibacterials are among the most frequently prescribed medications. Antibacterial drugs have the unintended consequence of destroying healthy gut flora, which can lead to known adverse events such as Clostridium difficile infection. Given emerging research concerning the role of these microorganisms in the gut-brain axis and some limited epidemiological studies, the objective of this study was to determine if antimicrobial exposure is associated with increased risk for depression.

National Veterans Health Administration administrative data were used to identify 878,405 veteran patients prescribed an incident antimicrobial during calendar year 2018. Sequence symmetry analysis was used to compare the incidence of a depressive disorder in the 6 months before and after antibacterial exposure, with additional analyses conducted with other antimicrobial classes as negative controls including antifungals, antivirals, and nonsystemic antibacterials.

Antibacterial initiation was associated with a small but significant increase in the risk of incident depression (symmetry ratio [SR] = 1.04, 95% confidence interval [CI]: 1.03, 1.05), which was limited to the first 8 weeks following exposure. The strength of association varied with categories of antibacterial spectrum, from SR = 0.98 (95% CI: 0.95, 1.01) with the narrowest spectrum regimens, to SR = 1.12 (95% CI: 1.09, 1.15) with the broadest regimens. No significant association with incident depression was observed for antifungals, antivirals, and nonsystemic antibacterials.

Antibacterial exposure was associated with increased risk for a depressive disorder. These findings are consistent with emerging literature and support the need for further research investigating a causal relationship between antibacterial exposure and risk for adverse mental health outcomes.