Suicidal ideation associated with daridorexant treatment in insomnia patients: Comparator-restricted disproportionality analysis and assessment of potential heterogeneity in reporting patterns

PURPOSE: Daridorexant, a novel dual orexin receptor antagonist, holds promise for managing insomnia. Although previous studies have identified a significant signal for suicidal ideation associated with daridorexant when compared with all other drugs, the significance when compared specifically with insomnia medications and the potential differences in reporting patterns of suicidal ideation across subgroups remain unclear. METHODS: This study utilized the data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Comparator-restricted disproportionality analyses were conducted using the reports with insomnia indication and commonly prescribed insomnia medications as comparators. Sensitivity analyses, stratified analyses, and subgroup comparative analyses were then performed to explore the potential differences in reporting patterns of suicidal ideation across subgroups. RESULTS: The signal for suicidal ideation was no longer significant based on comparator-restricted disproportionality analyses. Sensitivity analyses revealed a reduction in the signal strength for suicidal ideation after excluding reports with depression-related co-reported adverse events, and depression was the only significant concurrent event that occurred simultaneously with suicidal ideation, suggesting that the co-reported depression may partly contribute to the reporting of suicidal ideation. Additionally, there may be potential differences in reporting patterns of daridorexant-associated suicidal ideation across subgroups. CONCLUSIONS: Although prior studies have identified a significant signal for suicidal ideation associated with daridorexant, the underlying relationship is likely multifactorial, with potential confounders such as underlying insomnia and co-reported depression. In addition, this study underscores the potential need for further verification of the differences in reporting daridorexant-associated suicidal ideation. The establishment of a definitive pharmacoepidemiological relationship between daridorexant and suicidal ideation warrants further research.