title: Pharmacodynamic effects of suvorexant and zolpidem on EEG during sleep in healthy subjects.
abstract: The objective of this study was to evaluate sleep electrophysiology in healthy subjects after bedtime administration of therapeutic doses of two insomnia treatments - the orexin receptor antagonist suvorexant or the GABAergic agonist zolpidem. Eighteen healthy men received single bedtime doses of suvorexant 20mg, zolpidem 10mg, or placebo in a double-blinded, randomized, balanced 3-period crossover study. EEG power spectral densities during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep were recorded in a polysomnography (PSG) laboratory using a 19-lead EEG recording array. Spectral density was analyzed for each lead for frequencies between 1-32Hz. During NREM and REM sleep, zolpidem treatment reduced spectral density across theta and alpha frequency bands in all leads. In contrast, suvorexant had no significant effects on spectral density in any frequency band during NREM sleep, and modestly increased spectral density in the theta frequency band during REM sleep. Although the study was not designed to detect effects on PSG sleep endpoints in healthy subjects, both suvorexant and zolpidem increased mean total sleep time and sleep efficiency. Zolpidem reduced latency to persistent sleep whereas suvorexant did not. Suvorexant decreased wake after sleep onset, whereas zolpidem did not. These findings suggest that EEG power spectral density profile after administration of suvorexant in healthy subjects more closely approximates placebo sleep physiology than after zolpidem treatment.
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: arie.struyk@merck.com.
authors.forename: Arie
authors.initials: A
authors.lastname: Struyk
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Gargano
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Drexel
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: S Aubrey
authors.initials: SA
authors.lastname: Stoch
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Svetnik
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Junshui
authors.initials: J
authors.lastname: Ma
authors.affiliation: Community Research, Cincinnati, OH, USA.
authors.forename: David
authors.initials: D
authors.lastname: Mayleben
mesh_terms: D000328:Adult; D000368:Aged; D001381:Azepines / Q000009:adverse effects / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D064368:Healthy Volunteers; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D000068796:Orexin Receptor Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D017286:Polysomnography / Q000187:drug effects; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects*; D014230:Triazoles / Q000009:adverse effects / Q000494:pharmacology*; D000077334:Zolpidem
chemical_list: D001381:Azepines; D006993:Hypnotics and Sedatives; D000068796:Orexin Receptor Antagonists; D011725:Pyridines; D014230:Triazoles; C551624:suvorexant; D000077334:Zolpidem
keywords: EEG; Healthy subjects; Sleep; Suvorexant; Zolpidem