Analysis of the Characteristics of Psychiatric Immune - related Adverse Events Induced by Immune Checkpoint Inhibitors in Immunotherapy from 2004 to 2025

Objective To explore the occurrence characteristics, risk factors, and potential mechanisms of neuropsychiatric immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs), and to provide evidence for clinical management. Methods Data on ICI-related neuropsychiatric adverse events from 2004 to 2025 were extracted from the U.S. FDA Adverse Event Reporting System (FAERS). After preprocessing with SAS and Navicat, the data were standardized and classified with reference to the MedDRA dictionary. Disproportionality analysis was performed using Reporting Odds Ratio (ROR). The distribution patterns were explored through stratification by gender, age, geography, and onset time. Results A total of 181,482 reports were included, with nivolumab (1,820 cases) and pembrolizumab (1,539 cases) accounting for the highest proportions. Delirium was the most frequently reported adverse reaction across all subgroups. Tislelizumab showed significantly strong signals for dysphoria (ROR = 11.82) and listlessness (ROR = 15.46). Demographically, males (2,462 cases), patients aged ≥ 65 years (2,005 cases), and populations in North America had the highest reporting rates. In terms of temporal distribution, more than 60% of events occurred within the first 60 days of treatment initiation. Mechanistic analysis suggested that immune-mediated processes such as cytokine dysregulation and microglial activation may be key triggers. Conclusion ICI-related neuropsychiatric irAEs have distinct population and temporal risk characteristics, requiring stratified monitoring for high-risk groups. This study provides real-world evidence for optimizing the safety of ICI treatment, but limited by the voluntary reporting bias of FAERS, prospective studies are still needed to verify the mechanisms and management strategies.