Adverse reactions associated with SSRIs and PD-1/PD-L1 inhibitors: a disproportionality analysis of the FDA Adverse Event Reporting System

Selective serotonin reuptake inhibitors (SSRIs) are the primary choice for antidepressant therapy in cancer patients with depression. Programmed death-1 and programmed cell death-ligand 1 (PD-1/PD-L1) play a critical role in immune checkpoint inhibitors. To date, there have been no studies reporting adverse events (AEs) associated with the real-world use of PD-1/PD-L1 inhibitors-SSRIs combination. This study included a comprehensive evaluation of AE cases covered PD-1/PD-L1 inhibitors-SSRIs combination (first quarter of 2004 to second quarter of 2024) using the FDA Adverse Event Reporting System (FAERS) database, and compared with the use of PD-1/PD-L1 inhibitors or SSRIs alone. By extracting a total of 807 reports of related AEs, the combination therapy was associated with a distinct AE profile characterized by an increased incidence of immune-related and systemic disorders, as well as a higher signal for adverse pregnancy and perinatal outcomes. This study represents the largest report to date on PD-1/PD-L1 inhibitors-SSRIs -related AEs, providing valuable insights into the potential side effects of SSRIs for cancer patients with depression. Clinicians should exercise caution when prescribing SSRIs alongside PD-1/PD-L1 inhibitors, particularly in vulnerable populations such as pregnant women and those with significant comorbidities.