Safety signals for drug-related respiratory depression: a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS).

BACKGROUND

Drug-induced respiratory depression is a severe and potentially life-threatening adverse event (AE); however, its systematic risk profile based on real-world data remains incomplete. Using real-world data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), this study systematically identified drugs associated with respiratory depression and generated reporting safety signals to provide exploratory evidence for optimizing clinical medication safety.

METHODS

The reporting odds ratio (ROR) was used to evaluate reports of drug-induced respiratory depression from the first quarter of 2015 to the third quarter of 2025. Single-factor, least absolute shrinkage and selection operator (LASSO), and multi-factor regression models were employed to analyze the association between various medications and respiratory depression events. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the associated risks.

RESULTS

A total of 869 drugs associated with respiratory depression were identified, with nervous system drugs being the predominant category. Multivariate analysis identified 16 of 17 LASSO-screened drugs and male patients under 41 years of age as significant safety signals for respiratory depression, exhibiting strong disproportionate reporting signals. The median duration of drug-related respiratory depression was 1 day [interquartile range (IQR), 23 days], with approximately 75% of AEs occurring within this 23-day period.

CONCLUSIONS

These findings assist clinicians in the early identification of the risk of drug-related respiratory depression, underscoring the necessity for proactive assessment and management of this risk in both analgesia and disease treatment.