Orexin receptor antagonism for treatment of insomnia

Herring, W. Joseph; Snyder, Ellen; Budd, Kerry; Hutzelmann, Jill; Snavely, Duane; Liu, Kenneth; Lines, Christopher; Roth, Thomas; Michelson, David

doi:10.1212/wnl.0b013e31827688ee

Cited by 281 publications

(254 citation statements)

References 22 publications

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“…1,2 Sixteen years later, in 2014, suvorexant became the first agent specifically targeting the orexin system (via orexin receptor antagonism) to be approved as a therapeutic agent, for the treatment of insomnia. [3][4][5][6][7][8] This relatively rapid progress reflects advances in understanding orexin biology. The orexin signaling system comprises of a restricted number (50,000-80,000) of orexin neurons which originate from the lateral hypothalamus and project widely throughout the central nervous system.…”

Section: Introductionmentioning

confidence: 99%

Suvorexant in Patients with Insomnia: Pooled Analyses of Three-Month Data from Phase-3 Randomized Controlled Clinical Trials

Herring

Connor

Snyder

et al. 2016

Journal of Clinical Sleep Medicine

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Study Objectives: Suvorexant is an orexin receptor antagonist approved for treating insomnia at a maximum dose of 20 mg. Phase-3 trials evaluated two age-adjusted (non-elderly/elderly) dose-regimes of 40/30 mg and 20/15 mg with the primary focus on 40/30 mg. We report here results from pooled analyses of the 20/15 mg dose-regime, which was evaluated as a secondary objective in the trials. Methods: Prespecified analysis of pooled data from two identical randomized, double-blind, placebo-controlled, parallel-group, 3-month trials in non-elderly (18-64 years) and elderly (≥ 65 years) patients with insomnia. Patients were randomized to suvorexant 20/15 mg (non-elderly/elderly), suvorexant 40/30 mg (non-elderly/elderly), or placebo; by design, fewer patients were randomized to 20/15 mg. Efficacy was assessed by self-reported and polysomnography (PSG; subset of patients) sleep maintenance and onset endpoints. Results: Suvorexant 20/15 mg (N = 493 treated) was effective compared to placebo (N = 767 treated) on patient-reported and PSG sleep maintenance and onset endpoints at Night-1 (PSG endpoints) / Week-1 (subjective endpoints), Month-1 and Month-3, except for effects on PSG sleep onset at Month-3. Suvorexant 20/15 mg was generally well tolerated, with 3% of patients discontinuing due to adverse events over 3 months vs. 5.2% on placebo. Somnolence was the most common adverse event (6.7% vs. 3.3% for placebo). There was no systematic evidence of rebound or withdrawal signs or symptoms when suvorexant was discontinued after 3 months of nightly use.

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Section: Introductionmentioning

confidence: 99%

Suvorexant in Patients with Insomnia: Pooled Analyses of Three-Month Data from Phase-3 Randomized Controlled Clinical Trials

Herring

Connor

Snyder

et al. 2016

Journal of Clinical Sleep Medicine

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“…Initial studies suggest that it has efficacy in combating insomnia (6)(7)(8). Suvorexant works by diminishing alertness (4)(5)(6)(7)(8). In May 2013, suvorexant was approved by an advisory panel for the United States Food and Drug Administration (FDA) for the treatment of patients with sleep difficulties (9).…”

Section: Suvorexantmentioning

confidence: 99%

“…In animal research, suvorexant has less effect on reducing attention or memory as compared with benzodiazepines (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). In rodents, it reduced wakefulness and increased rapid eye movement (REM) and non-REM sleep (4).…”

Section: Studiesmentioning

confidence: 99%

“…Subjects prescribed suvorexant do not exhibit rebound insomnia or evidence withdrawal upon abrupt discontinuation of the drug following 4 weeks of ingestion (6). Suvorexant usage does not induce disruption in sleep architecture nor sleep fragmentation (6)(7)(8)(9)(10)(11)(12).…”

Section: Studiesmentioning

confidence: 99%

“…Suvorexant has been tested in several different strength versions; the manufacturer offered to market in tablets of 10, 15, and 20 mg formulations (6). The initial dosing regimens have been under review (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15).…”

Section: Dosagementioning

confidence: 99%

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Suvorexant: something new for sleep?

Reddy

Puvvada

Kommisetti

et al. 2014

Acta Neuropsychiatr.

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Orexin, also called hypocretin, is a neuropeptide that acts on central nervous system receptors to promote arousal. Suvorexant, its receptor antagonist, generates interest as a medication to treat insomnia. Suvorexant helps in decreasing wakefulness by counteracting orexin activity. Its low side effect potential may offer considerable benefit. Compared with other sleep aids, diminished drowsiness and less cognitive dysfunction is an advantage. Now approved for clinical use, an apparent lack of rebound insomnia or drug dependence potential might make suvorexant a good choice pharmacotherapy for patients with insomnia.

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