Effects of Suvorexant, an Orexin Receptor Antagonist, on Sleep Parameters as Measured by Polysomnography in Healthy Men

Sun, Hong; Kennedy, William P.; Wilbraham, Darren; Lewis, Nicole; Calder, Nicole; Li, Xiaodong; Ma, Junshui; Yee, Ka Lai; Ermlich, Susan J.; Mangin, Eric; Lines, Christopher; Rosen, Laura; Chodakewitz, Jeffrey A.; Murphy, Gail

doi:10.5665/sleep.2386

Cited by 94 publications

(156 citation statements)

References 23 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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“…Among them suvorexant is a potent and selective dual orexin receptor antagonist; this diazepine-based substance is the one most prominently considered (7)(8)(9)(10)(11). Orexin receptor antagonists counteract the effect of orexin at central nervous system receptors and might be advantageous for patients with trouble in sleeping (12).…”

Section: Suvorexantmentioning

confidence: 99%

“…These same properties might make it particularly desirable in patients with psychiatric illness, where the primary conditions, or their treatments, might be associated with inattention or reduced cognitive function. In addition, without sedative properties, it may be less likely to cause falling, especially in geriatric populations (11,12).…”

Section: Indicationsmentioning

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%

“…Reportedly, it does not have side effects of sedation or cognitive disturbances (12), which are associated with sedative hypnotics, including benzodiazepines and related drugs (4). Thus, suvorexant might offer an advantage in treating persons with the aforementioned adversities.…”

Section: Indicationsmentioning

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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Effect of Suvorexant vs Placebo on Total Daytime Sleep Hours in Shift Workers

et al. 2020

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IMPORTANCE Many shift workers have difficulty sleeping during the daytime owing to an inappropriately timed circadian drive for wakefulness. OBJECTIVE To determine whether a dual hypocretin receptor antagonist would enable shift workers to have more daytime sleep. DESIGN, SETTING, AND PARTICIPANTS This double-blind, placebo-controlled randomized clinical trial included 2 weeks of baseline data and 3 weeks of intervention data, from March 2016 to December 2018. Individuals were recruited through poster advertisements in the broader San Francisco Bay area in California. From an initial voluntary recruitment cohort of 38 shift workers, 19 individuals with self-reported difficulty sleeping during the daytime following night work shift were included. Data were analyzed from Janaury to March 2019. INTERVENTIONS 1 week of 10 mg suvorexant or placebo, titrated upward to 20 mg suvorexant or placebo for 2 additional weeks. MAIN OUTCOMES AND MEASURES Objective (ie, actigraphy) and subjective (ie, sleep logs) measures of sleep. RESULTS Among 19 participants who completed the study (mean [SD] age, 37.7 [11.1] years; 13[68%] men), 8 participants (42%) were assigned to the suvorexant group and 11 participants (58%) were assigned to the placebo group. Compared with individuals in the placebo group, individuals in the suvorexant group increased their objective total sleep time by a mean (SE) of 1.04 (0.53) hours (P = .05) at the end of 1 week of 10-mg doses and by 2.16 (0.75) hours (P = .004) by the end of the 2 weeks of 20-mg doses. Subjective sleep was similarly improved as, compared with the placebo group, individuals in the suvorexant group increased their subjective total sleep time by a mean (SE) of 2.08 (0.47) hours (P < .001) at the end of 1 week of 10-mg doses and by 2.97 (0.56) hours (P < .001) by the end of the 2 weeks of 20-mg doses. Physician ratings of daytime sleep aligned with these measures, as there was no change in the placebo group and a much improved change in the suvorexant group. No adverse events were reported in the suvorexant group.CONCLUSIONS AND RELEVANCE This pilot study found that the use of a dual hypocretin receptor antagonist in shift workers under real-world conditions resulted in more than 2 extra hours of daytime sleep per episode. Future research should confirm this pilot finding in a larger sample size and examine whether, over the long term, use of this medication has a concomitant improvement in medical and psychiatric health as well as workplace performance and safety.

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Effects of Suvorexant, an Orexin Receptor Antagonist, on Sleep Parameters as Measured by Polysomnography in Healthy Men

Abstract: In healthy young men without sleep disorders, suvorexant promoted sleep with some evidence of residual effects at the highest doses.

Cited by 94 publications

References 23 publications

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

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

Suvorexant: something new for sleep?

Effect of Suvorexant vs Placebo on Total Daytime Sleep Hours in Shift Workers

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