Electroencephalographic power spectral density profile of the orexin receptor
antagonist suvorexant in patients with primary insomnia and healthy subjects.
Author(s): Ma J(1), Svetnik V(1), Snyder E(1), Lines C(1), Roth T(2), Herring WJ(1).
Affiliation(s): Author information:
(1)Merck & Co., Inc., Whitehouse Station, NJ. (2)Henry Ford Hospital Sleep
Center, Detroit, MI.
Publication date & source: 2014, Sleep. , 37(10):1609-19
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.
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