FAERS‐Based Pharmacovigilance Study on Drug‐Induced Extrapyramidal Disorder: Risk Signals and Mechanistic Insights

Purpose This study aimed to identify high‐risk drugs for drug‐induced extrapyramidal disorder (EPD) and explore their molecular mechanisms by integrating pharmacovigilance analytics with genetic and computational approaches. Methods We performed disproportionality analysis on FAERS data (2004–2024) to detect EPD signals, time‐to‐onset analysis to assess risk timing, Mendelian randomization (MR) to infer causal effects of drug–target gene expression (e.g., HTR1D, ADRA2B) on EPD risk, and molecular docking to evaluate drug–target binding affinities. Results Metoclopramide, risperidone, and haloperidol decanoate showed the strongest EPD signals. TTO analysis revealed an early failure pattern (Weibull β < 1), indicating highest risk during initial treatment. MR identified brain‐expressed HTR1D and ADRA2B as causally linked to EPD risk. Molecular docking confirmed strong binding of risperidone and paliperidone to these targets. Conclusions This study is the first to integratively link pharmacovigilance signals with genetic causality and structural binding insights for EPD. Our findings support deprescribing high‐risk agents, preemptive genetic screening, and enhanced early monitoring to mitigate drug‐induced EPD, offering a translational framework for precision pharmacovigilance.