title: Suvorexant for the treatment of insomnia.
abstract: Suvorexant (Belsorma(®)) is the first orexin receptor antagonist approved by the US FDA (August 2014) for insomnia treatment. Following comprehensive Phase II/III studies, with up to 12 months of treatment in adult and elderly patients, there is little doubt that suvorexant induces and maintains sleep. However, the FDA and sponsor disagreed about effective versus safe doses (November 2012). The FDA considered that 5-15 mg were efficient and probably safe, whereas the sponsors had proposed 15-40 mg. The final approved doses are 5, 10, 15 and 20 mg. The major issues are next-morning somnolence and safety as seen in driving tests, with possible signs of muscle weakness, weird dreams, sleep walking, other nighttime behaviors and suicidal ideation. Despite its limitations, suvorexant's market entry offers a truly novel treatment for insomnia, paving the way for follow-up compounds and opening therapeutic avenues in other disorders for orexin receptor modulating compounds.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Laura H
authors.initials: LH
authors.lastname: Jacobson
authors.forename: Gabrielle E
authors.initials: GE
authors.lastname: Callander
authors.forename: Daniel
authors.initials: D
authors.lastname: Hoyer
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D017277:Drug Approval; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000068796:Orexin Receptor Antagonists; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D001381:Azepines; D006993:Hypnotics and Sedatives; D000068796:Orexin Receptor Antagonists; D014230:Triazoles; C551624:suvorexant
keywords: Belsorma; FDA; NDA; SB649868; almorexant; drug development; hypocretin; insomnia; orexin; orexin receptor antagonists; pharmacodynamics; pharmacokinetics; sleep disorders; suvorexant