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

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.

• Authors: Junshui Ma, Vladimir Svetnik, Ellen Snyder, Christopher Lines, Thomas Roth, W Joseph Herring
• Journal: Sleep (Sleep) Vol. 37 Issue 10 Pg. 1609-19 (Oct 01 2014) ISSN: 1550-9109 [Electronic] United States
• PMID: 25197807 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Associated Professional Sleep Societies, LLC.

Chemical References

• Azepines
• Isoxazoles
• Orexin Receptor Antagonists
• Pyridines
• Triazoles
• suvorexant
• Zolpidem
• gaboxadol

Topics

• Adult
• Aged
• Azepines (administration & dosage, pharmacology, therapeutic use)
• Cross-Over Studies
• Double-Blind Method
• Electroencephalography (drug effects)
• Female
• Healthy Volunteers
• Humans
• Isoxazoles (pharmacology, therapeutic use)
• Male
• Middle Aged
• Orexin Receptor Antagonists
• Polysomnography (drug effects)
• Pyridines (pharmacology, therapeutic use)
• Sleep (drug effects, physiology)
• Sleep Initiation and Maintenance Disorders (drug therapy, physiopathology)
• Triazoles (administration & dosage, pharmacology, therapeutic use)
• Young Adult
• Zolpidem