Neural mechanisms and clinical features of anti‐influenza drug‐related psychiatric adverse events

Abstract Influenza is a highly pathogenic acute respiratory viral infection. Anti‐influenza drugs remain the cornerstone of treatment in current clinical practice; however, the incidence of psychiatric adverse events (pAEs) associated with these medications has shown a significant upward trend. This study sought to comprehensively investigate the clinical characteristics and underlying molecular mechanisms of anti‐influenza drug‐related pAEs. The epidemiological characteristics of anti‐influenza drug‐related pAEs were systematically evaluated based on large pharmacovigilance databases FDA Adverse Event Reporting System (FAERS) and VigiBase. Mouse models treated with oseltamivir phosphate and baloxavir marboxil were established, and cognitive‐motor functions were assessed using behavioral test systems (including pole test, open‐field test, novel object recognition, and Morris water maze test). Neuronal pathological changes in the hippocampal CA1 region were evaluated through Nissl staining, combined with transcriptome sequencing analysis to elucidate molecular mechanisms. Data mining analysis revealed that the reporting rates of anti‐influenza drug‐related pAEs reached 22.9% and 17.4% in FAERS and VigiBase databases, respectively. Stratified analysis indicated that individuals under 45 years of age and male patients were high‐risk populations for pAEs. Animal experiments confirmed that treated mice exhibited significant cognitive impairment and motor coordination deficits, accompanied by marked reduction in hippocampal CA1 neurons. Transcriptomic analysis revealed that multiple signaling pathways, including cell junction, apoptotic cell clearance, and neurotransmitter release, play crucial roles in the development of pAEs. This study systematically reveals, for the first time, the epidemiological characteristics and potential molecular mechanisms of anti‐influenza drug‐related pAEs, providing important reference for clinical medication safety.