Antidepressants and risk of pneumonia in older adults: a nationwide self-controlled case series

BACKGROUND: Pneumonia is a leading cause of morbidity and mortality in older adults, and antidepressant use is increasing globally. Although biologically plausible links exist, comprehensive, population-based evidence remains limited. We evaluated the association of antidepressant use with pneumonia hospitalisation and potential effect modifiers. METHODS: We conducted a nationwide self-controlled case series using Korea National Health Insurance Service-Senior Cohort data on adults aged 60-80 years who initiated antidepressants and were hospitalised for pneumonia (2008-2019). The risk period was defined as 90 days (three 30-day intervals) after antidepressant initiation, with baseline periods as the reference. Incidence rate ratios (IRRs) were calculated using conditional Poisson regression adjusted for age and season. Subgroup analyses were performed according to demographics, comorbidities, and the anticholinergic/sedative burden. RESULTS: Among 15,478 individuals, pneumonia hospitalisation risk was higher during the 90-day risk period (IRR 2.48, 95% CI 2.35-2.61), peaking in the first 30 days (IRR 3.53, 95% CI 3.31-3.76). Risk remained elevated in later intervals and declined during washout. Stronger associations were observed in older age and neurologic comorbidities. A graded pattern by pharmacological burden showed the highest risk in those with both high anticholinergic and sedative loads. CONCLUSION: Antidepressant use was associated with an increased pneumonia hospitalisation in older adults. The risk was further elevated in patients with neurologic conditions or a high anticholinergic/sedative burden, highlighting the need for individualised prescriptions and routine medication reviews.