Real-world pharmacovigilance analysis of depression associated with antineoplastic agents

Cancer remains a major global health threat. Although antineoplastic agents have significantly improved survival outcomes, growing evidence indicates that they may also induce neuropsychiatric adverse events (AEs), particularly depressive symptoms. Such effects can severely compromise patients' quality of life and adherence to therapy. However, this issue has not been systematically evaluated. In this study, we investigated depression-related AEs submitted to the FDA Adverse Event Reporting System from Q1 2004 to Q4 2024. We included reports involving antineoplastic agents (Anatomical Therapeutic Chemical [ATC] code L01) with oncology-related indications and excluded those with concomitant antidepressant use (ATC N06A) for depression-related indications. Disproportionality analyses were performed using the Reporting Odds Ratio (ROR) and the Bayesian Confidence Propagation Neural Network. A total of 211 antineoplastic agents potentially associated with depression and suicide/self-injury were identified, and class-specific risks were evaluated. Most reports involved female patients, and 56.3 % concerned individuals older than 45 years. Protein kinase inhibitors and other antineoplastics exhibited the strongest associations. Notably, significant signals were observed for docetaxel (ROR = 3.7; IC025 = 1.8), palbociclib (ROR = 2.03; IC025 = 0.98), and ibrutinib (ROR = 1.83; IC025 = 0.83). These signals call for heightened clinical vigilance and may inform safer prescribing. Prospective, multicenter studies integrating pharmacovigilance, mechanistic, and clinical data are needed to guide personalized strategies aimed at improving patient outcomes.