The clinical efficacy of orexin antagonists for primary insomnia- A review of the evidence

Introduction Primary insomnia is frequently present in the general population, with epidemiologic research reporting prevalence values from 10% to as high 60%. Chronic associated a significant impact on professional, academic, and daily life functionality, it also may be responsible for decreasing quality of life. Multiple generations drugs have been launched clinical use last decades, but each class pharmacological agents has its shortcomings (i.e., low efficacy, risk addiction, diurnal sedation, falls fractures, etc.). Initially, orexin receptor antagonists considered enthusiasm, due these agents’ adverse events good safety profile medium long term. Objectives To assess evidence supporting efficiency treatment insomnia. Methods A literature review was performed through main electronic databases (PubMed, Cochrane, Clarivate/Web Of Science, EMBASE) using search paradigm “primary insomnia” AND “orexin modulators”. All papers published between January 2000 September 2022 were included. Results Suvorexant dual antagonist 1 2 receptors (DORA), FDA-approved insomnia, both difficulties falling staying asleep. Daridorexant another DORA, approved by FDA EMA same indications suvorexant, considers „additional monitoring” necessary this drug. Lemborexant DORA US Japan, while vornorexant, which included class, under development sleep apnea (in phase trials, respectively). Almorexant that discontinued hepatic concerns. Seltorexant an (SORA2) explored II trials Somnolence fatigue are most reported DORAs, sleepwalking driving, paralysis, or hypnopompic hypnagogic hallucinations described studies. somnolence, headache, nausea. Conclusions Dual antagonism mechanism produced three currently available other applications still investigation. At least one agent investigation, therefore potential utility DORAs far being exhausted. Also, selective could promising action Disclosure Interest None Declared