Electroencephalographic power spectral density profile of the orexin receptor antagonist suvorexant in patients with primary insomnia and healthy subjects

Junshui Ma, Vladimir Svetnik, Ellen Snyder, Christopher Lines, Thomas Roth, W. Joseph Herring

Research output: Contribution to journalArticle

Abstract

Study Objectives: 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.

Design: Phase 2 trial - randomized, double-blind, two-period (4 w per period) crossover. HS studies - randomized, double-blind, crossover.

Setting: Sleep laboratories.

Participants: Insomnia patients (n = 229) or HS (n = 124).

Interventions: 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.

Measurements and 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.

Original languageEnglish (US)
Pages (from-to)1609-1619
Number of pages11
JournalSleep
Volume37
Issue number10
DOIs
StatePublished - Oct 1 2014
Externally publishedYes

Keywords

  • Gaboxadol
  • Orexin
  • Polysomnography
  • QEEG
  • Suvorexant
  • Trazodone
  • Zolpidem

ASJC Scopus subject areas

  • Physiology (medical)
  • Clinical Neurology

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