Antidepressant use was associated with longer overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC) receiving first-line targeted therapy (TT), according to a multicentre retrospective cohort study.
The study included 328 patients with mRCC who received first-line TT between January 2015 and January 2025. Antidepressant use was defined as receiving antidepressant treatment for at least 3 consecutive months during first-line TT.
The researchers assessed progression-free survival (PFS) and OS using Kaplan–Meier survival curves and the log-rank test. Multivariable Cox proportional hazards models were also used to evaluate the association between antidepressant use and survival.
Of the 328 patients included, 81 (24.7%) were classified as antidepressant users. After a median follow-up of 56.3 months, 202 patients (61.6%) had died.
Patients using antidepressants had longer PFS than non-users, with median PFS of 15.2 months compared with 10.3 months, respectively (p=0.023). Median OS was also longer among antidepressant users at 51.2 months versus 33.0 months among non-users (p=0.020).
In multivariable analysis, antidepressant use remained independently associated with improved OS (hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.44–0.90; p=0.010).
The association remained statistically significant after adjustment using an inverse probability of treatment weighting (IPTW) adjusted doubly robust Cox model, which was used to reduce treatment-selection bias (HR: 0.58; 95% CI: 0.39–0.85; p=0.005).
The findings indicated an association between antidepressant use and longer OS in patients with mRCC receiving first-line TT. However, the retrospective nature of the cohort means the results do not establish that antidepressants caused the observed survival difference.
The study authors emphasised that the findings were hypothesis-generating and did not support prescribing antidepressants with the aim of improving survival.
Further research would therefore be needed to clarify the relationship between antidepressant treatment and outcomes in patients with mRCC receiving targeted therapy. In clinical practice, the reported association should not be interpreted as evidence for using antidepressants as an anticancer intervention.
Reference
Aktepe OH et al. Association between antidepressant use and overall survival in metastatic renal cell carcinoma treated with first-line targeted therapy. Sci Rep. 2026;DOI:10.1038/s41598-026-65116-0.
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