Novel class of medications, orexin receptor antagonists, in the treatment of insomnia – critical appraisal of suvorexant

Figures & data

Table 1 Selected pharmacokinetic parameters of US FDA-approved medications for insomnia treatment

Drug	Dose (mg)	Tmax (hours)	t1/2 (hours)
Benzodiazepine receptor antagonists
Estazolam	0.5–2	2	10–24
Flurazepam	15–30	0.5–1	74–90
Lorazepam	2–4	2	12
Quazepam	7.5–15	2	39
Temazepam	7.5–30	1.2–1.6	3.5–18.4
Triazolam	0.125–0.5	2	1.5–5.5
Nonbenzodiazepine receptor antagonists
Eszopiclone	1–3	1–1.5	6
Zaleplon	5–20	1	1
Zolpidem	5–10	1.6	2–2.6
Zolpidem ER	6.25–12.5	1.6	2–2.6
Zolpidem SL	1.75–3.5	1.6	2–2.6
Zolpidem SL (Canada)	5–10	1.6	2–2.6
Melatonin receptor agonist
Ramelteon	8	0.5–1.5	1–2.6
Tricyclic antidepressant
Doxepin	3–6	3.5	15.3
Orexin receptor antagonist
Suvorexant	10–20	2	12

Abbreviations: FDA, Food and Drug Administration; ER, extended release; SL, sublingual; T_max, median time to maximum concentration; t_1/2, terminal half-life.

Table 2 Suvorexant Phase III clinical trial data

Study	Intervention	N	Female (%)	N <65 years (%)	Baseline sTST (minutes)	Baseline sTSO (minutes)	Change in sTST at month 3 (minutes)	Change in sTSO at month 3 (minutes)	Change in sTST at month 12 (minutes)	Change in sTSO at month 12 (minutes)
Herring et al,^Citation11 trial 1	Suvorexant 20/15 mg	254	162 (63.8)	147 (57.9)	322	63	10.7*	−5.2*	–	–
	Suvorexant 30/40 mg	383	230 (60.1)	222 (58)	316	68	19.7*	−8.4*	–	–
	Placebo	384	245 (63.8)	223 (58.1)	316	67	–	–	–	–
Herring et al,^Citation11 trial 2	Suvorexant 20/15 mg	239	157 (65.7)	144 (60.3)	298	86	22.1*	−7.6*	–	–
	Suvorexant 30/40 mg	387	267 (69)	229 (59.2)	315	74	25.1*	−13.2*	–	–
	Placebo	383	247 (64.5)	226 (59)	310	81	–	–	–	–
Michelson et al^Citation12	Suvorexant 40/30 mg	521	287 (55)	213 (41)	320.4	65.9	–	–	27.5*	−9.7*
	Placebo	238	149 (58)	107 (42)	330.1	64.9	–	–	–	–

Notes:

* P<0.05. Doses listed are for nonelderly/elderly study participants.

Abbreviations: sTSO, subjective time to sleep onset; sTST, subjective total sleep time.

HerringWJConnorKMIvgy-MayNSuvorexant in patients with insomnia: results from two 3-month randomized controlled clinical trialsBiol Psychiatry201679213614825526970

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MichelsonDSnyderEParadisESafety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind, placebo-controlled trialLancet Neurol201413546147124680372

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