title: Electroencephalographic power spectral density profile of the orexin receptor antagonist suvorexant in patients with primary insomnia and healthy subjects.
abstract: OBJECTIVE
  Suvorexant, an orexin receptor antagonist, improves sleep in healthy subjects (HS) and patients with insomnia. We compared the electroencephalographic (EEG) power spectral density (PSD) profile of suvorexant with placebo using data from a phase 2 trial in patients with insomnia. We also compared suvorexant's PSD profile with the profiles of other insomnia treatments using data from 3 HS studies.
  
  
  METHODS
  Phase 2 trial--randomized, double-blind, two-period (4 w per period) crossover. HS studies--randomized, double-blind, crossover.
  
  
  METHODS
  Sleep laboratories.
  
  
  METHODS
  Insomnia patients (n = 229) or HS (n = 124).
  
  
  METHODS
  Phase 2 trial--suvorexant 10 mg, 20 mg, 40 mg, 80 mg, placebo; HS study 1--suvorexant 10 mg, 50 mg, placebo; HS study 2--gaboxadol 15 mg, zolpidem 10 mg, placebo; HS study 3--trazodone 150 mg, placebo.
  
  
  RESULTS
  The PSD of the EEG signal at 1-32 Hz of each PSG recording during nonrapid eye movement (NREM) and rapid eye movement (REM) sleep were calculated. The day 1 and day 28 PSD profiles of suvorexant at all four doses during NREM and REM sleep in patients with insomnia were generally flat and close to 1.0 (placebo) at all frequencies. The day 1 PSD profile of suvorexant in HS was similar to that in insomnia patients. In contrast, the other three drugs had distinct PSD profiles in HS that differed from each other.
  
  
  CONCLUSIONS
  Suvorexant at clinically effective doses had limited effects on power spectral density compared with placebo in healthy subjects and in patients with insomnia, in contrast to the three comparison insomnia treatments. These findings suggest the possibility that antagonism of the orexin pathway might lead to improvements in sleep without major changes in the patient's neurophysiology as assessed by electroencephalographic.
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ.
authors.forename: Junshui
authors.initials: J
authors.lastname: Ma
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Svetnik
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ.
authors.forename: Ellen
authors.initials: E
authors.lastname: Snyder
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lines
authors.affiliation: Henry Ford Hospital Sleep Center, Detroit, MI.
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ.
authors.forename: W Joseph
authors.initials: WJ
authors.lastname: Herring
mesh_terms: D000328:Adult; D000368:Aged; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000068796:Orexin Receptor Antagonists; D017286:Polysomnography / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000503:physiopathology*; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D055815:Young Adult; D000077334:Zolpidem
chemical_list: D001381:Azepines; D007555:Isoxazoles; D000068796:Orexin Receptor Antagonists; D011725:Pyridines; D014230:Triazoles; C551624:suvorexant; D000077334:Zolpidem; C015542:gaboxadol
keywords: gaboxadol; orexin; polysomnography; qEEG; suvorexant; trazodone; zolpidem