Introduction: Chronic insomnia disorder significantly affects cognitive, emotional, and physical health. Recently, the dual orexin receptor antagonist (DORA) daridorexant was approved for treating chronic insomnia in several countries. Given the limited evidence available, expert consensus was sought to clarify key clinical issues, inform practice, and guide future research. Methods: Thirteen Italian sleep experts employed the Nominal Group Technique (NGT) to identify and rank important clinical questions. The process involved independent thought generation, group discussion, and online voting using a 5-point Likert scale. Results: The NGT process resulted in 55 statements across five key clinical questions, with relevance scores guiding their categorization into three tiers. Key findings highlight daridorexant’s mechanism of action, safety profile, efficacy on night and day parameters, and suitability for long-term use. The experts emphasized cross-tapering strategies for switching from other hypnotics, the importance of sleep psychoeducation, and using the Insomnia Severity Index and sleep diaries for treatment evaluation. Discussion: Daridorexant may address insomnia without increasing sedation via its dual orexin receptor antagonism. Daridorexant seems to be effective and safe even in special patient populations, such as the elderly and those with comorbid conditions (neurodegenerative disorders and cognitive impairment, comorbid insomnia and sleep apnea, psychiatric conditions and mood disorders, epilepsy, and restless leg syndrome), thus representing a new, promising option for insomnia treatment. Conclusion: The expert consensus provides a comprehensive framework for daridorexant clinical application, advocating for further research to expand the evidence base and refine best practices, as well as underscoring the importance of a multidisciplinary approach that combines both pharmacological and psychosocial interventions to optimize outcomes.
