Association between antidepressant exposure and prognosis in breast cancer: A systematic review and meta-analysis

To date, the prognostic impact of antidepressant (AD) use on breast cancer (BC) outcomes remains unclear. The present study investigated the relationship between AD exposure and survival outcomes in patients with BC. PubMed, Web of Science, Embase and the Cochrane Library databases were systematically searched from inception to October 2025. The hazard ratio (HR) with its 95% confidence interval (CI) was used as the effect size. The primary outcomes of the present study were overall survival (OS) and BC-specific survival (BCSS). The protocol was registered with the International Prospective Register of Systematic Reviews database (study no. CRD420251232706). In total, nine studies comprising ~90,000 AD-exposed and >300,000 unexposed patients with BC were included. AD-exposed patients had worse OS (HR=1.28; 95% CI, 1.22-1.34; P<0.001) and BCSS (HR=1.16; 95% CI, 1.09-1.25; P<0.001) compared with the control group. In geographical subgroup analyses, AD-exposed patients in Europe demonstrated worse OS (HR=1.27; P<0.001) and BCSS (HR=1.18; P<0.001), and those in Asia had worse BCSS (HR=1.30; P<0.001); by contrast, for North America (P=0.671), no significant difference in BCSS was observed compared with non-exposed patients. By drug class, patients exposed to selective serotonin reuptake inhibitors (SSRIs) had worse OS (HR=1.34; P<0.001) and BCSS (HR=1.21, P<0.001) compared with non-exposed patients. Among individual SSRIs, no significant differences in BCSS were observed for sertraline (P=0.547), paroxetine (P=0.063) or fluoxetine (P=0.647), whereas citalopram exposure (HR=1.29; P<0.001) had worse BCSS compared with non-exposed patients. Tricyclic ADs demonstrated worse BCSS (HR=1.26; P<0.001) compared with the control group. Regarding exposure timing, both continuous (OS: HR=1.24; P<0.001; BCSS: HR=1.14; P<0.001) and post-diagnosis (OS: HR=1.32; P<0.001; BCSS: HR=1.22; P=0.001) exposure had worse prognosis compared with the control group. In conclusion, observational evidence suggested that AD exposure may be associated with worse BC prognosis, and this association appeared to be influenced by geographical regions and drug classes.