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.