Abstract
BACKGROUND/AIM: Benzodiazepine receptor agonists (BZRAs) are well-known hypnotics. Although the research is scarce, relatively newer hypnotics such as melatonin receptor agonists (MRAs) and dual orexin receptor antagonists (DORAs), can be associated with respiratory depression. The association between hypnotic use and respiratory depression in clinical practice was investigated in this study. PATIENTS AND METHODS: A total of 733,296 reports from the Japanese Adverse Event Reporting Database published between April 2004 and September 2023 were analyzed. The reporting odds ratios (RORs) and 95% confidence intervals (CIs) for respiratory depression associated with each hypnotic condition were calculated after adjusting for potential confounders. RESULTS: Among all the reports, 5,147 involved respiratory depression. After adjustments for sex, age, reporting year, concomitant medications, and medical history the associations with non-benzodiazepines (adjusted ROR=1.06; 95% CI=0.92-1.23) and DORAs (adjusted ROR=0.94; 95% CI=0.70-1.27) were not significant. In contrast, significant associations remained for BZRAs (adjusted ROR=1.34; 95% CI=1.20-1.49) and MRAs (adjusted ROR=2.03; 95% CI=1.56-2.64). The stratified analyses showed that BZRAs were associated with respiratory depression regardless of age, whereas MRAs were associated regardless of opioid use. CONCLUSION: The associations between hypnotics and respiratory depression varied depending on the drug administered. In addition to BZRAs, MRAs may also have a potential risk for respiratory depression.