Orexin receptor antagonism, a new sleep-enabling paradigm: a proof-of-concept clinical trial

Hoever, P; Dorffner, G; Beneš, H; Penzel, T; Danker-Hopfe, H; Barbanoj, M J; Pillar, G; Saletu, B; Polo, O; Kunz, D; Zeitlhofer, J; Berg, S; Partinen, M; Bassetti, C L; Högl, B; Ebrahim, I O; Holsboer-Trachsler, E; Bengtsson, H; Peker, Y; Hemmeter, U-M; ... (2012). Orexin receptor antagonism, a new sleep-enabling paradigm: a proof-of-concept clinical trial. Clinical pharmacology & therapeutics, 91(6), pp. 975-85. New York, N.Y.: Nature Publishing Group 10.1038/clpt.2011.370

Full text not available from this repository. (Request a copy)

The orexin system is a key regulator of sleep and wakefulness. In a multicenter, double-blind, randomized, placebo-controlled, two-way crossover study, 161 primary insomnia patients received either the dual orexin receptor antagonist almorexant, at 400, 200, 100, or 50 mg in consecutive stages, or placebo on treatment nights at 1-week intervals. The primary end point was sleep efficiency (SE) measured by polysomnography; secondary end points were objective latency to persistent sleep (LPS), wake after sleep onset (WASO), safety, and tolerability. Dose-dependent almorexant effects were observed on SE , LPS , and WASO . SE improved significantly after almorexant 400 mg vs. placebo (mean treatment effect 14.4%; P < 0.001). LPS (–18 min (P = 0.02)) and WASO (–54 min (P < 0.001)) decreased significantly at 400 mg vs. placebo. Adverse-event incidence was dose-related. Almorexant consistently and dose-dependently improved sleep variables. The orexin system may offer a new treatment approach for primary insomnia.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Bassetti, Claudio




Nature Publishing Group




Factscience Import

Date Deposited:

04 Oct 2013 14:39

Last Modified:

17 Mar 2015 21:32

Publisher DOI:


PubMed ID:


Web of Science ID:



https://boris.unibe.ch/id/eprint/15886 (FactScience: 223380)

Actions (login required)

Edit item Edit item
Provide Feedback