Objective  Based on the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, to indentity the risk signals of drug-related extrapyramidal symptoms (EPS), and provide a reference for safe medication use in clinical practice.

Methods  The association between drugs and EPS was evaluated using four disproportionate analysis methods in the FAERS database from Q1 2004 to Q1 2025. The clinical outcomes, time to onset, and related risk factors of EPS were further analyzed.

Results  A total of 24,026 EPS cases were collected, and 508 suspected drugs were identified. Data mining analysis showed 36 drugs with positive risk signals for EPS, including antipsychotics, antidepressants, and other drugs. Among the 18,799 reports with complete clinical outcome information, EPS clinical outcomes were characterized by high disability rates and high hospitalization rates. Among the 1,676 reports with complete time to onset information, the median time from starting the drug to EPS onset was 9 days (0–93 days), and about 64.38% of EPS events occurred within 28 days after drug use. Multivariable Logistic regression analysis showed that male, ≥64 years of age, and 23 drugs including metoclopramide were risk factors for drug-related EPS.

Conclusion  The identification of drugs with high EPS risk and with high rates of disability and hospitalization provides important clinical warning signals. These findings can assist clinicians in prioritizing the selection of safer alternative drugs for high-risk populations when managing such risks, thereby reducing the incidence of EPS and ensuring the overall medication safety of patients.

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