The impact of antidepressant use on antibiotic treatment outcomes in urinary tract infections and pneumonia: A population‐based cohort study

Aims Antidepressants may induce antibiotic resistance, yet their impact on antibiotic treatment outcomes in clinical settings remains unexplored. This study investigates the association between antidepressant use and antibiotic treatment failure in outpatients with urinary tract infections (UTIs) and pneumonia, conditions with distinct pathogen origins. Methods Using Taiwan's National Health Insurance database (2010–2021), this cohort study analyzed new outpatient antibiotic treatments for UTIs ( n = 4,176,347) and pneumonia ( n = 498,156). Antidepressant use was defined as prescriptions within 6 months before treatment initiation. Treatment failure occurring between days 4 and 14 after antibiotic initiation was defined as any antibiotic change, hospitalization, or emergency department visit. Subgroup analyses considered age, gender, comorbidities, and antibiotic types, along with antidepressant usage patterns. Results Antidepressant use was linked to a higher risk of treatment failure in UTIs (adjusted hazard ratio = 1.11 [1.09, 1.13]) but not pneumonia. The risk was higher in females than in males and higher in older adults than in middle‐aged individuals. In addition, the use of specific antidepressants (e.g., imipramine, citalopram, paroxetine, sertraline, fluvoxamine, trazodone, and mirtazapine), particularly in combination (polypharmacy), was associated with a further increase in risk. Conclusion Antidepressants are associated with a modest rise in UTI treatment failure risk, possibly due to antibiotic resistance or other mechanisms. Despite this, their essential role in mental health management outweighs the small risk, emphasizing the need for judicious use, particularly in females and older adults. Further research is warranted to clarify underlying mechanisms.