Electroencephalographic Power Spectral Density Profile of the Orexin Receptor Antagonist Suvorexant in Patients with Primary Insomnia and Healthy Subjects

• Published in: Sleep (New York, N.Y.) Vol. 37; no. 10; pp. 1609 - 1619
• Main Authors: Ma, Junshui, Svetnik, Vladimir, Snyder, Ellen, Lines, Christopher, Roth, Thomas, Herring, W. Joseph
• Format: Journal Article
• Language: English
• Published: United States Associated Professional Sleep Societies, LLC 01.10.2014
• Subjects: Adult; Aged; Azepines - administration & dosage; Azepines - pharmacology; Azepines - therapeutic use; Cross-Over Studies; Double-Blind Method; EEG Power Spectral Density of the Orexin Receptor Antagonist Suvorexant; Electroencephalography - drug effects; Female; Healthy Volunteers; Humans; Isoxazoles - pharmacology; Isoxazoles - therapeutic use; Male; Middle Aged; Orexin Receptor Antagonists; Polysomnography - drug effects; Pyridines - pharmacology; Pyridines - therapeutic use; Sleep - drug effects; Sleep - physiology; Sleep Initiation and Maintenance Disorders - drug therapy; Sleep Initiation and Maintenance Disorders - physiopathology; Triazoles - administration & dosage; Triazoles - pharmacology; Triazoles - therapeutic use; Young Adult; Zolpidem; qEEG; trazodone; zolpidem; orexin; polysomnography; gaboxadol; suvorexant
• ISSN: 0161-8105; 1550-9109; 1550-9109
• DOI: 10.5665/sleep.4068

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. Phase 2 trial--randomized, double-blind, two-period (4 w per period) crossover. HS studies--randomized, double-blind, crossover. Sleep laboratories. Insomnia patients (n = 229) or HS (n = 124). 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. 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. 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.