McIntyre et al. (2024) explore whether dual orexin receptor antagonists (DORAs) such as suvorexant, lemborexant, and daridorexant are linked to suicidality, a concern noted in their FDA-approved package inserts, in their article "Association between dual orexin receptor antagonists (DORAs) and suicidality: reports to the United States Food and Drug Administration Adverse Event Reporting System (FAERS)." Using the reporting odds ratio (ROR) with trazodone as a control, the study analyzed data from FAERS, determining disproportionate reporting when 95% confidence intervals (CIs) did not encompass 1.0, and calculating information components (ICs) to evaluate significant increases. The findings revealed that suvorexant (0.025 ROR), lemborexant (0.019 ROR), and daridorexant (0.002 ROR) were associated with significantly lower odds of reported completed suicides compared to trazodone (p < 0.05). There were no significantly increased RORs for the DORAs concerning suicidal ideation, depression suicidal, suicidal behavior, and suicide attempts, with the IC analysis showing nonsignificant associations for all suicidality parameters for each DORA. The conclusion indicates no significant association between DORAs and any aspect of suicidality as captured in FAERS. However, it emphasizes the importance of evaluating all patients treated for insomnia, whether pharmacologically or non-pharmacologically, for any emergence or worsening of suicidality. Future research should focus on conducting long-term observational studies to monitor suicidality over extended periods in patients using DORAs, examining the effects of DORAs on suicidality across different demographic groups, investigating the biological mechanisms underlying the potential impact of DORAs on mood and suicidality, comparing the risk of suicidality between DORAs and other insomnia treatments, and designing randomized controlled trials specifically targeting the assessment of suicidality in patients treated with DORAs to provide high-quality evidence on this safety concern.

Reference:
McIntyre RS et al. Expert Opin Drug Saf 2024;1-5. Abstract