Updated Insomnia Guidelines and Latest Real-World Evidence Data on Daridorexant

Abstract

During this symposium, held at the 10^th Congress of the European Academy of Neurology (EAN), speakers highlighted that chronic insomnia disorder (CID) is under-recognised and under-treated. Comorbid disorders associated with CID include psychiatric conditions, neurological disorders, and cardiovascular disease. Untreated, CID can negatively impact mental, physical, and occupational health. Consequently, the presence of CID should be evaluated and actively treated independent of comorbidities. The concept of CID is characterised by a perpetuating cycle of hyperarousal. It is proposed that dual orexin receptor antagonists (DORAs) reduce hyperarousal and restore sleep–wake balance via antagonism of orexin 1 and orexin 2 receptors. The European Insomnia Guidelines 2023 recommend cognitive behavioural therapy for insomnia (CBTi) as first-line treatment in adults. CBTi can be administered in-person or digitally. However, CBTi is not always available, can be costly in terms of time and resources, and not all individuals respond to therapy. Where CBTi is not effective or practical, the guidelines recommend short-term therapy (≤4 weeks) with benzodiazepines, benzodiazepine receptor agonists, the DORA daridorexant, or low-dose sedating antidepressants. DORAs can be used for >3 months in some cases, and prolonged-release melatonin for up to 3 months in individuals aged ≥55 years. In Phase III trials, daridorexant reduced electroencephalography (EEG) features associated with hyperarousal in individuals with CID, reduced cumulative night-time waking, particularly time spent in long wake bouts, and improved daytime functioning. Real-world evidence showed that daridorexant improved sleep parameters in individuals with CID, including those with and without neurologic and psychiatric comorbidities.