Drug‐induced respiratory depression in FDA Adverse Event Reporting System for 20 years

Background Drug‐induced respiratory depression (DIRD) is a common and highly prevalent condition in clinical practice, necessitating early prevention and intervention. This study aimed to identify the association between specific medications and DIRD, providing evidence‐based insights for clinical risk assessment and management. Methods Data were extracted from the FDA Adverse Event Reporting System (FAERS) database, covering reports of DIRD from 2004 to 2024. Four disproportionality analyses (reporting odds ratio [ROR], proportional reporting ratio, Bayesian confidence propagation neural network [BCPNN], and multi‐item Gamma Poisson Shrinker) were employed to detect signals of respiratory depression associated with medications, and the highest‐risk drug classes were statistically analyzed. Results A total of 10,975 DIRD reports were identified in the FAERS database. Male patients (47.03%) were more frequently reported than females (40.58%), and the most affected age group was 48–68 years. The primary outcomes included death (32.01%) and prolonged hospitalization (24.56%). Disproportionality analyses revealed that opioids posed the highest risk, with fentanyl (ROR = 22.29), morphine (ROR = 31.24), and methadone (ROR = 41.38) showing the strongest signals. The BCPNN algorithm further identified methadone (IC025 = 5.14), diazepam (IC025 = 4.89), and morphine (IC025 = 4.70) as high‐risk drugs. Notably, the combination of opioids and benzodiazepines (e.g., midazolam and ROR = 39.04) significantly increased the risk of respiratory depression, aligning with Food and Drug Administration warnings. Conclusion This study highlights the association between specific medications and DIRD, particularly emphasizing the high risk of opioids and their interactions with benzodiazepines. The findings underscore the need for enhanced monitoring of high‐risk patient groups, improved awareness of drug safety among clinicians, and optimized clinical practice to mitigate DIRD‐related risks.