Effects of orexin receptor antagonism on human sleep architecture: A systematic review

Clark, Jacob; Brian, Maddison; Drummond, Sean P.A.; Hoyer, Daniel; Jacobson, Laura H.

doi:10.1016/j.smrv.2020.101332

Cited by 51 publications

(40 citation statements)

References 39 publications

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“…Another potential mechanism may be through the neuropeptide orexin, which regulates sleep-wake cycles and the circadian rhythm and plays a role in cognitive function and the cardiovascular system [58]. Orexin receptor antagonists have been investigated for their potential therapeutic effects for the treatment of insomnia [59]. Sleep disturbances are also associated with compromises in metabolic health and can increase the risk for obesity, dyslipidemia, hypertension, and impaired glucose metabolism, all of which increase the risk for cardiovascular conditions [60].…”

Section: Discussionmentioning

confidence: 99%

Sleep disturbances and the speed of multimorbidity development in old age: results from a longitudinal population-based study

Sindi

Pérez

Vetrano

et al. 2020

BMC Med

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Background Sleep disturbances are prevalent among older adults and are associated with various individual diseases. The aim of this study was to investigate whether sleep disturbances are associated with the speed of multimorbidity development among older adults. Methods Data were gathered from the Swedish National study of Aging and Care in Kungsholmen (SNAC-K), an ongoing population-based study of subjects aged 60+ (N = 3363). The study included a subsample (n = 1189) without multimorbidity at baseline (< 2 chronic diseases). Baseline sleep disturbances were derived from the Comprehensive Psychiatric Rating Scale and categorized as none, mild, and moderate–severe. The number of chronic conditions throughout the 9-year follow-up was obtained from clinical examinations. Linear mixed models were used to study the association between sleep disturbances and the speed of chronic disease accumulation, adjusting for sex, age, education, physical activity, smoking, alcohol consumption, depression, pain, and psychotropic drug use. We repeated the analyses including only cardiovascular, neuropsychiatric, or musculoskeletal diseases as the outcome. Results Moderate–severe sleep disturbances were associated with a higher speed of chronic disease accumulation (ß/year = 0.142, p = 0.008), regardless of potential confounders. Significant positive associations were also found between moderate–severe sleep disturbances and neuropsychiatric (ß/year = 0.041, p = 0.016) and musculoskeletal (ß/year = 0.038, p = 0.025) disease accumulation, but not with cardiovascular diseases. Results remained stable when participants with baseline dementia, cognitive impairment, or depression were excluded. Conclusion The finding that sleep disturbances are associated with faster chronic disease accumulation points towards the importance of early detection and treatment of sleep disturbances as a possible strategy to reduce chronic multimorbidity among older adults.

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Section: Discussionmentioning

confidence: 99%

Sleep disturbances and the speed of multimorbidity development in old age: results from a longitudinal population-based study

Sindi

Pérez

Vetrano

et al. 2020

BMC Med

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“…66,100,101,112 Of note, orexin receptor antagonists do not adversely affect sleep architecture. 113,114 They have been found to shorten REM latency and increase TST, mainly by increasing the time spent in REM sleep. [113][114][115] However the percentage of TST spent in non-REM sleep is left unchanged or possibly lowered.…”

Section: Dual Orexin Receptor Antagonists: a New Class Of Pharmacologic Treatment For Insomniamentioning

confidence: 99%

“…113,114 They have been found to shorten REM latency and increase TST, mainly by increasing the time spent in REM sleep. [113][114][115] However the percentage of TST spent in non-REM sleep is left unchanged or possibly lowered. [113][114][115] They do not appear to be associated with tolerance, withdrawal, or rebound insomnia if abruptly discontinued.…”

Section: Dual Orexin Receptor Antagonists: a New Class Of Pharmacologic Treatment For Insomniamentioning

confidence: 99%

“…[113][114][115] However the percentage of TST spent in non-REM sleep is left unchanged or possibly lowered. [113][114][115] They do not appear to be associated with tolerance, withdrawal, or rebound insomnia if abruptly discontinued. [116][117][118] Importantly, the mechanism of action of DORAs suggests that daytime sleepiness would be further exacerbated in patients with narcolepsy (as they already have impaired orexin-mediated wake signaling).…”

Section: Dual Orexin Receptor Antagonists: a New Class Of Pharmacologic Treatment For Insomniamentioning

confidence: 99%

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Advances in the Treatment of Chronic Insomnia: A Narrative Review of New Nonpharmacologic and Pharmacologic Therapies

Rosenberg¹,

Citrome²,

Drake³

2021

NDT

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Chronic insomnia disorder, which affects 6–10% of the population, is diagnostically characterized by ongoing difficulties with initiating or maintaining sleep occurring at least three times per week, persisting for at least 3 months, and associated with daytime impairment. While chronic insomnia is often considered a condition primarily related to impaired sleep, the disorder can also adversely affect domains of physical and mental health, quality of life, and daytime function, which highlights the importance of treating the multidimensional sleep disorder. Owing to misperceptions about the safety and effectiveness of treatment options, many individuals with insomnia may not seek professional treatment, and alternatively use ineffective home remedies or over-the-counter medications to improve sleep. Some physicians may even believe that insomnia is remediated by simply having the patient “get more sleep”. Unfortunately, treatment of insomnia is not always that simple. The disorder’s complex underlying pathophysiology warrants consideration of different nonpharmacologic and pharmacologic treatment options. Indeed, recent insights gained from research into the pathophysiology of insomnia have facilitated development of newer treatment approaches with more efficacious outcomes. This narrative review provides a summary of the diagnostic criteria and pathophysiology of insomnia and its subtypes. Further, this review emphasizes new and emerging nonpharmacologic and pharmacologic treatments for chronic insomnia, including recent enhancements in approaches to cognitive behavioral therapy for insomnia (CBT-I) and the new dual orexin receptor antagonist (DORA) pharmacologics. These advances in treatment have expanded the treatment options and are likely to result in improved outcomes in patients with chronic insomnia.

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“…They reduce orexin signaling by blocking both orexin receptors 1 and 2, thereby inhibiting arousal and inducing a state of sleep [7]. There are potential benefits of DORAs over traditional insomnia pharmacotherapeutics, such as promoting rapid eye movement (REM) sleep in addition to non-rapid eye movement (NREM) sleep in adults [8]. There is no evidence of habit and tolerance formation as with sedative hypnotics, benzodiazepines and antihistamines, or metabolic side effects as with atypical antipsychotics [7].…”

Section: Introductionmentioning

confidence: 99%

Dual orexin receptor antagonists for insomnia in youth with neurodevelopmental disorders: a case series and review

Besterman

Jeste

2021

Eur Child Adolesc Psychiatry

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Insomnia is a common, impairing, and difficult-to-treat comorbidity in children with neurodevelopmental disorders (NDDs). Behavioral interventions can be challenging because of developmental and behavioral features that interfere with treatment. Medication management also can be difficult due to a high burden of side effects, a high rate of paradoxical responses, and frequent treatment resistance. Therefore, new treatment options for insomnia in children with NDDs are needed. Dual orexin receptor antagonists (DORAs) are a relatively new class of pharmacotherapeutics that induce sleep by inhibiting the orexin signaling pathway. To date, there is little safety or efficacy data on the use of DORAs in children with NDDs. We present four patients with NDDs and insomnia that we treated with the DORA, suvorexant. We found that patients had a wide range of responses, with one patient displaying a robust improvement in sleep onset and maintenance, while another had significant improvement in insomnia symptoms on combination therapy with trazodone. Our final two patients had mild or no benefit from suvorexant therapy. Further research is necessary to establish the safety and efficacy of DORAs in this population and to identify predictive factors, such as specific neurogenetic diagnoses or clinical features, of a positive treatment response.

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Effects of orexin receptor antagonism on human sleep architecture: A systematic review

Cited by 51 publications

References 39 publications

Sleep disturbances and the speed of multimorbidity development in old age: results from a longitudinal population-based study

Sleep disturbances and the speed of multimorbidity development in old age: results from a longitudinal population-based study

Advances in the Treatment of Chronic Insomnia: A Narrative Review of New Nonpharmacologic and Pharmacologic Therapies

Dual orexin receptor antagonists for insomnia in youth with neurodevelopmental disorders: a case series and review

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