Respiratory Safety of Lemborexant in Healthy Subjects: A Single-Dose, Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

Background And Objective: Lemborexant is a dual orexin receptor antagonist recently approved in the USA, Japan, and Canada for the treatment of adults with insomnia. Because some pharmacotherapy for insomnia causes respiratory depression, this study assessed the effects of lemborexant treatment on respiratory safety parameters.

Methods: This single-dose, randomized, double-blind, placebo-controlled, three-period crossover study enrolled healthy adult and elderly subjects (n = 17).

Randomized Controlled Trial of Solriamfetol for Excessive Daytime Sleepiness in OSA: An Analysis of Subgroups Adherent or Nonadherent to OSA Treatment.

Background: Solriamfetol, a dopamine-norepinephrine reuptake inhibitor, is approved in the United States to improve wakefulness in adults with excessive daytime sleepiness (EDS) associated with OSA (37.5-150 mg/d).

Research Question: Does solriamfetol have differential effects on EDS based on adherence to primary OSA therapy and does solriamfetol affect primary OSA therapy use?

Study Design And Methods: Participants were randomized to 12 weeks of placebo or solriamfetol 37.

Respiratory safety of lemborexant in healthy adult and elderly subjects with mild obstructive sleep apnea: A randomized, double-blind, placebo-controlled, crossover study.

Lemborexant is a dual orexin receptor antagonist indicated for the treatment of adult and elderly individuals with insomnia. Some current pharmacologic treatments for insomnia cause respiratory depression, a serious safety concern, particularly for individuals with obstructive sleep apnea (OSA). This phase 1, randomized, double-blind, placebo-controlled, two-period crossover study examined respiratory safety parameters in individuals with mild OSA following treatment with lemborexant.

Solriamfetol for Excessive Sleepiness in Obstructive Sleep Apnea (TONES 3). A Randomized Controlled Trial.

Primary treatment of obstructive sleep apnea can be accompanied by a persistence of excessive sleepiness despite adherence. Furthermore, effectiveness of sleep apnea treatment is limited by poor adherence. Currently available pharmacologic options for the treatment of sleepiness in this population are limited.

Pharmacokinetic evaluation of eszopiclone: clinical and therapeutic implications.

Introduction: Eszopiclone is the active S-enantiomer of R,S-zopiclone, and is a cyclopyrrolone hypnotic acting via the GABA-benzodiazepine receptor system. Nearly 6 million prescriptions for eszopiclone are written yearly in the United States.

Areas Covered: This paper addresses the pharmacokinetic properties of eszopiclone and the extent to which the longer half-life of eszopiclone compared to other commonly used hypnotics (immediate-release zolpidem, modified-release zolpidem, triazolam, zaleplon) may translate into either improved efficacy in enhancing sleep maintenance, or increased probability of residual sedative or performance-impairing effects.

Alterations in sleep architecture in response to experimental sleep curtailment are associated with signs of positive energy balance.

Sleep reduction is associated with increased energy intake and weight gain, though few studies have explored the relationship between sleep architecture and energy balance measures in the context of experimental sleep restriction. Fourteen males and 13 females (body mass index: 22-26 kg/m(2)) participated in a crossover sleep curtailment study. Participants were studied under two sleep conditions: short (4 h/night; 0100-0500 h) and habitual (9 h/night; 2200-0700 h), for 5 nights each.

Comparison of actigraphy and polysomnography to assess effects of zolpidem in a clinical research unit.

Objective: This study sought to compare devices that use actigraphy for measuring sleep endpoints in the clinical research unit (CRU) and home environment. The abilities of polysomnography (PSG) and actigraphy monitors to detect drug effects in a CRU were also investigated.

Methods: Eleven healthy subjects were recruited and monitored with PSG for four consecutive nights in a CRU after receiving no treatment (night 1, N1), and then placebo or 5 mg day(-1) or 10 mg day(-1) zolpidem in a randomised, cross-over design.

Reliability and validity of the brief insomnia questionnaire in the America insomnia survey.

Study Objectives: to evaluate the reliability and validity of the Brief Insomnia Questionnaire (BIQ), a fully structured questionnaire developed to diagnose insomnia according to hierarchy-free Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR), International Classification of Diseases-10 (ICD-10), and research diagnostic criteria/International Classification of Sleep Disorders-2 (RDC/ICSD-2) general criteria without organic exclusions in the America Insomnia Survey (AIS).

Design: probability subsamples of AIS respondents, oversampling BIQ positives, completed short-term test-retest interviews (n = 59) or clinical reappraisal interviews (n = 203) to assess BIQ reliability and validity.

Setting: the AIS is a large (n = 10,094) epidemiologic survey of the prevalence and correlates of insomnia.

The effect of vestibular stimulation in a four-hour sleep phase advance model of transient insomnia.

Study Objectives: To determine if vestibular stimulation is an effective therapy for transient insomnia in a sleep phase advance model.

Design: Multi-site, double-blind, randomized, parallel-group, sham-controlled trial

Setting: This study was carried out at 6 sites in the United States.

Participants: 198 healthy normal sleepers.

Short sleep duration as a risk factor for hypercholesterolemia: analyses of the National Longitudinal Study of Adolescent Health.

Study Objectives: To explore the relationship between sleep duration in adolescence and hypercholesterolemia in young adulthood. Experimental sleep restriction has been shown to significantly increase total cholesterol and LDL cholesterol levels in women. Short sleep duration has been found in cross sectional studies to be associated with higher total cholesterol and lower HDL cholesterol levels.

Impact of nighttime awakenings on worker productivity and performance.

Objective: To describe the relationship between nighttime awakenings and work performance.

Methods: Employees (N = 4188) at four US companies described their sleep patterns and completed the Work Limitations Questionnaire. Participants were categorized by number of nighttime awakenings: 0 (n = 464; 11%), 1 to 2 (n = 2373; 58%), 3 to 4 (n = 984; 24%), or > or =5 (n = 289; 7%).

Insomnia and sleep duration as mediators of the relationship between depression and hypertension incidence.

Background: Depression has been found to predict the incidence of hypertension and other adverse cardiovascular events in prospective studies. Insomnia and short sleep duration, which are typical symptoms of depression, have also been shown to increase the risk for hypertension incidence. Insomnia is associated with increased activation of the hypothalamic-pituitary-adrenal axis, and short sleep duration raises average 24-h blood pressure, which over time could lead to structural adaptations that gradually reset the entire cardiovascular system to operate at an elevated pressure equilibrium.

Sleep duration associated with mortality in elderly, but not middle-aged, adults in a large US sample.

Study Objectives: To explore age differences in the relationship between sleep duration and mortality by conducting analyses stratified by age. Both short and long sleep durations have been found to be associated with mortality. Short sleep duration is associated with negative health outcomes, but there is little evidence that long sleep duration has adverse health effects.

Efficacy and safety of as-needed, post bedtime dosing with indiplon in insomnia patients with chronic difficulty maintaining sleep.

Objective: To evaluate the efficacy and tolerability of immediate release indiplon capsules in patients with chronic insomnia using an "as-needed" dosing strategy in response to difficulty falling back to sleep following a middle of the night, nocturnal awakening.

Methods: Adult outpatients (N=264; 71% female; age, 46 years) who met DSM-IV criteria for primary insomnia, with average total sleep time (TST) < 6.5 hours and >8 nights in the past month with nocturnal awakenings, were randomized to 4 weeks of double-blind treatment with 10 mg or 20 mg indiplon capsules, or placebo.

Sleep duration as a risk factor for diabetes incidence in a large U.S. sample.

Study Objectives: To explore the relationship between sleep duration and diabetes incidence over an 8- to 10-year follow-up period in data from the First National Health and Nutrition Examination Survey (NHANES I). We hypothesized that prolonged short sleep duration is associated with diabetes and that obesity and hypertension act as partial mediators of this relationship. The increased load on the pancreas from insulin resistance induced by chronically short sleep durations can, over time, compromise beta-cell function and lead to type 2 diabetes.

Long-term efficacy and safety of zolpidem extended-release 12.5 mg, administered 3 to 7 nights per week for 24 weeks, in patients with chronic primary insomnia: a 6-month, randomized, double-blind, placebo-controlled, parallel-group, multicenter study.

Study Objectives: To evaluate long-term efficacy and safety of zolpidem extended-release 3 to 7 nights/week for chronic primary insomnia.

Design: Multicenter, 25-week, phase IIIb, randomized, double-blind, placebo-controlled, parallel-group.

Setting: Outpatient; visits every 4 weeks.

Ramelteon: a novel hypnotic indicated for the treatment of insomnia.

Ramelteon is a hypnotic with a novel mechanism of action and is the only melatonin agonist currently indicated for the treatment of insomnia. This drug acts at the MT1 and MT2 receptors to promote sleep and exert an effect on circadian rhythms. Unlike traditional hypnotics, ramelteon demonstrates no affinity for any CNS receptors commonly associated with sedation (GABA, dopamine, opiate, serotonin).

Sleep and residual sedation after administration of zaleplon, zolpidem, and placebo during experimental middle-of-the-night awakening.

Study Objectives: To assess the efficacy of zaleplon 10 mg and zolpidem 10 mg administered during experimental middle-of-the-night awakenings in patients with sleep-maintenance insomnia using objective polysomnographic measures and to assess daytime residual sedation 4 to 7 hours after dosing using sleep-latency testing.

Design: A randomized, double-blind, placebo-controlled, 3-period, crossover design was used to study 37 adults with insomnia who received treatment during an experimental awakening 4 hours after bedtime. Latency to persistent sleep and total sleep time before and after awakening were recorded.

The prevalence, morbidities, and treatments of insomnia.

Insomnia is a common condition that often is co-morbid with other illnesses. It is associated with significant morbidities, including nighttime distress, impaired cognitive functioning, impaired daytime functioning, and increased risk of accidents. People with insomnia utilize healthcare services more often than those without insomnia, and they are at greater risk for the development of certain health problems; most notably psychiatric illness such as depression.

Dynamics and kinetics of a modified-release formulation of zolpidem: comparison with immediate-release standard zolpidem and placebo.

Modified-release (MR) zolpidem was developed to maintain effective plasma concentrations during the 3- to 6-hour post-dosage interval, corresponding to the middle portion of the typical sleep interval. Modified-release zolpidem (12.5 mg), standard immediate-release (IR) zolpidem (10 mg), and placebo were compared in a double-blind, single-dose, 3-way crossover daytime study of healthy volunteers (n = 70 completers).

A polysomnography study of eszopiclone in elderly patients with insomnia.

Objective: To evaluate the safety and efficacy of eszopiclone 2 mg in elderly patients (aged 64-86 years) with chronic insomnia.

Methods: This was a randomized, double-blind, placebo-controlled 2-week study. Patients meeting DSM-IV criteria for primary insomnia and screening polysomnography criteria (wakefulness after sleep onset [WASO] >or= 20 min and latency to persistent sleep >or= 20 min) were randomized to 2 weeks of nightly treatment with eszopiclone 2 mg (n = 136) or placebo (n = 128).

Short sleep duration as a risk factor for hypertension: analyses of the first National Health and Nutrition Examination Survey.

Depriving healthy subjects of sleep has been shown to acutely increase blood pressure and sympathetic nervous system activity. Prolonged short sleep durations could lead to hypertension through extended exposure to raised 24-hour blood pressure and heart rate, elevated sympathetic nervous system activity, and increased salt retention. Such forces could lead to structural adaptations and the entrainment of the cardiovascular system to operate at an elevated pressure equilibrium.