Association between antidepressant use and overall survival in metastatic renal cell carcinoma treated with first-line targeted therapy

Depression is common among patients with metastatic renal cell carcinoma (mRCC), yet the prognostic relevance of antidepressant (AD) use during targeted therapy (TT) remains unclear. This study evaluated the association between AD use and overall survival (OS) in mRCC patients receiving first-line TT. This multicenter retrospective cohort study included 328 patients with mRCC treated with first-line TT between January 2015 and January 2025. AD use was defined as receiving AD treatment for at least three consecutive months during first-line TT. Survival outcomes were evaluated through Kaplan–Meier survival curves, compared with the log-rank test, and further analyzed using multivariable Cox proportional hazards models. An inverse probability of treatment weighting (IPTW)-adjusted doubly robust Cox model was additionally fitted to reduce treatment-selection bias. Overall, 81 patients (24.7%) were classified as AD users. After a median follow-up of 56.3 months, 202 patients (61.6%) had died. AD users had significantly longer progression-free survival (PFS) than non-users, with a median PFS of 15.2 versus 10.3 months, respectively ( p = 0.023). AD users also had longer OS than non-users, with a median OS of 51.2 versus 33.0 months, respectively ( p = 0.020). In multivariable analysis, AD use was independently associated with improved OS (hazard ratio [HR]: 0.63, 95% confidence interval [CI]: 0.44–0.90; p = 0.010). This association remained significant in the IPTW-adjusted doubly robust model (HR: 0.58, 95% CI: 0.39–0.85; p = 0.005). AD use was associated with longer OS in this retrospective cohort of patients with mRCC receiving first-line TT. These findings are hypothesis-generating and do not support prescribing ADs to improve survival.