Table 2.

Effects of hypocretin/orexin receptor antagonists on sleep/wake parameters in clinical studies

Drugs	Subject Population	WASO	TST	SOL	SWSL	NREM/SWS	REM	REML	LPS	SE	Refs
DORAs
Almorexant	Healthy control samples	NC	NC	N/R	↓	NC	↑	↓	↓	NC	[15, 93]
“	Adult chronic insomnia samples (≥100 mg)	↓	↑	↓	↓	↑	↑	↓	↓	↑	[93]
“	Elderly patients with primary insomnia	↓	↑	N/R	NC	NC	↑	↓	↓	N/R	[94]
Daridorexant	Insomnia disorder	↓	↑	N/R	N/R	N/R	N/R	N/R	↓	N/R	[27]
“	Elderly with Insomnia	↓	↑	N/R	N/R	N/R	N/R	N/R	↓	N/R	[28]
Filorexant	Clinical insomnia samples	↓	↑	N/R	N/R	NC	↑	↓	↓	↑	[31]
Lemborexant	Clinical insomnia samples	↓	N/R	N/R	N/R	N/R	NC	N/R	↓	↑	[23, 24]
SB-649868	Healthy control samples	↓	↑	N/R	N/R	↓	↑	↓	↓	N/R	[95]
“	Healthy control sample in situational insomnia	↓	↑	N/R	N/R	↑	↑	↓	↓	↑	[96]
“	Clinical insomnia samples	↓	↑	N/R	↓	↓	↑	↓	↓	↑	[97]
Suvorexant	Healthy control samples	↓	↑	N/R	N/R	↑	↑	N/R	↓	↑	[21, 98]
“	Clinical insomnia samples	↓	↑	↓	N/R	↑	↑	↓	↓	↑	[82, 99]
“	Insomnia with obstructive sleep apnea	↓	↑	N/R	N/R	↑	↑	N/R	NC	↑	[100]
“	Chronic obstructive pulmonary disorder	↓	↑	N/R	N/R	↑	↑	N/R	↓	↑	[101]
2-SORAs
Seltorexant	Healthy control samples	N/R	↑ (Somnolence)	N/R	N/R	N/R	N/R	N/R	N/R	N/R	[102]
“	Insomnia without psychiatric comorbidity	↓	↑	↓	N/R	NC(N3)	↑	↓	↓	↑	[25]
“	Major depressive disorder (MDD)	NC	NC	N/R	N/R	N/R	N/R	N/R	↓	↑	[78]
“	MDD with persistent insomnia	NC	↑	N/R	N/R	NC (N2 & N3)	NC	N/R	↓	↑	[76]
MK-1064	Healthy control samples	↓	↑	N/R	N/R	↑	↑	↓	↓	↑	[84]

LPS, latency to persistent sleep; N2, Stage N2 sleep; N3 Stage N3 sleep; NC, no change; N/R, not reported; NREM/SWS, non-rapid-eye movement/slow-wave sleep; REM, rapid-eye-movement; REML, rapid-eye-movement sleep latency; SE, sleep efficiency; SOL, sleep onset latency; SWSL, slow wave sleep latency; TST, total sleep time; WASO, wake after sleep onset