Subjective Sleep Onset Research Articles

Efficacy and safety of lemborexant in subjects with insomnia disorder receiving medications for depression or anxiety symptoms.

Individuals with insomnia frequently have comorbid depression or anxiety. This study sought to provide a preliminary indication of the effects of lemborexant (LEM) in subjects treated for mild depression/anxiety symptoms. E2006-G000-303 (NCT02952820; EudraCT 2015-001463-39; SUNRISE-2) was a 12-month, phase 3, randomized, placebo-controlled, double-blind study where subjects with insomnia disorder were randomized (1:1:1) to placebo, LEM 5 mg (LEM5), or LEM 10 mg (LEM10) for 6 months. During the second 6 months (not reported), placebo-treated subjects were re-randomized to LEM5 or LEM10. In this post hoc analysis, changes from baseline (CFB) in subject-reported (subjective) sleep onset latency (sSOL), sleep efficiency (sSE), wake after sleep onset (sWASO), total sleep time (sTST), Fatigue Severity Scale, and Insomnia Severity Index were evaluated in subjects treated with medications for symptoms of depression/anxiety (subpopulation). Of 949 randomized subjects, 61 treated with medications for symptoms of depression/anxiety were included. In the subpopulation, CFB comparing LEM with placebo were generally smaller than the overall population due to a larger placebo response in the subpopulation. However, the magnitudes of CFB within the active treatment groups for sSOL, sWASO, sTST, and sSE were similar between the subpopulation and the overall population. No new safety signals were observed in the subpopulation. LEM treatment benefited subjects with insomnia treated with medications for depression/anxiety symptoms, with no new safety signals. A greater placebo response in the subpopulation than in the overall population decreased the drug versus placebo effect size for LEM, as has been reported for other insomnia medications.

Chronotype, sleep quality, depression and pre-sleep rumination: A diary and actigraphy study.

Eveningness has been associated with both disturbed sleep and depression. It is unclear, however, if deprived sleep explains evening types' vulnerability to depression. The role of pre-sleep rumination in these associations also remains understudied. The present study assessed the relationship between eveningness and sleep quality, as well as the possible mediating effect of pre-sleep rumination and the moderating effect of a history of depression, under naturalistic conditions. Eighty-eight Dutch-speaking participants (87.5% females, 21.4 ± 3.7years) were selected on the basis of their non-intermediate chronotype using the Morningness Eveningness Questionnaire (evening types (n = 53); morning types (n = 35)). Depression status was assessed through a diagnostic interview (healthy (n = 61); remitted depressed (n = 27)). Participants' sleep characteristics were monitored via actigraphy and sleep diaries for seven consecutive days and nights. Pre-sleep rumination was measured via a self-report questionnaire. Evening types had longer subjective and actigraphic sleep onset latency than morning types. Pre-sleep rumination did not mediate the former associations but predicted longer subjective sleep onset latency. Furthermore, the relationship between chronotype and subjective sleep onset latency was moderated by depression history. Remitted depressed evening types reported longer sleep onset latency than healthy evening and morning types, possibly posing the former at a higher risk for depressive relapse. Overall, the current findings address the need to further investigate the physiological signature of circadian rhythms and sleep latency. This could serve as a foundation for the development of prevention and early intervention programs, tailored for mood and sleep disorders.

The effect of regular periocular skin warming before bedtime on sleep and anxiety: a randomised clinical trial.

A randomised, placebo-controlled, parallel-group study was conducted to examine the effect of periocular skin warming before bedtime on sleep and anxiety in female workers with mild sleep difficulty. A total of 64 participants were included in the study, which consisted of a 1-week baseline period and a 4-week intervention period. They were randomly assigned to either the Warm group (N = 32) or the Sham group (N = 32) and were instructed to wear eye masks (warming or sham) before their habitual bedtime during the intervention period. The study found that the Athens Insomnia Scale score after the intervention was significantly lower in the Warm group compared to the Sham group. Additionally, participants in the warm condition showed a decrease in subjective sleep onset latency, better restorative sleep, and improved subjective anxiety before bedtime. A significant reduction in wake after sleep onset was observed in the Warm group at 4 weeks, and this decrease was significantly associated with the degree of improvement in subjective anxiety before bedtime. Furthermore, regular periocular skin warming before bedtime decreased sleep reactivity and improved well-being. In conclusion, the study suggests that periocular skin warming may be an effective approach for female workers with sleep problems, as it can easily be incorporated into daily life.

Intrafamilial associations of sleep multitrajectory groups between ages of 3 and 60 months in the SEPAGES cohort

ObjectivesWe investigated intrafamilial sleep evolution by identifying children’s sleep multitrajectory groups between 3- and 60-month of age and their association with parental sleep multitrajectory groups. MethodsWe included 180 children from the SEPAGES cohort (Grenoble, France) whose parents belonged to previously identified sleep multitrajectory groups, through group-based multitrajectory modeling, between 3 and 36months postpartum, using nighttime (NSD) and weekend daytime (DSD) sleep durations and subjective sleep loss, comprising “No,” “Subjective,” and “Global” sleep problems groups. Child sleep information (NSD, DSD, subjective sleep loss, night waking, and sleep onset difficulties) was collected by parental questionnaires at 3-, 12-, 36-, and 60-month. We identified sleep multitrajectory groups using group-based multitrajectory modeling in children and examined their associations with parental sleep multitrajectory groups using multinomial logistic regressions. ResultsWe identified three sleep multitrajectory groups in children: the “No/few” group (29.4%) had moderate NSD, long DSD, low subjective sleep loss/night waking/sleep onset difficulties prevalence, the “Moderate” group (60.0%) had long NSD and moderate DSD, and medium subjective sleep loss/night waking/sleep onset difficulties prevalence, and the “Global” group (10.6%) had the shortest NSD and DSD, and the highest subjective sleep loss/night waking/sleep onset difficulties prevalence. After adjusting for covariates, mothers in the “Global” group were more likely to have children in the same group, and mothers in “Subjective” and “Global” groups were less likely to have children in the “Moderate” group than in the “No/few” group. No association was identified with paternal or couple sleep multitrajectory groups. ConclusionsThe observed associations between parent-child sleep multitrajectory groups suggest greater maternal sensitivity to or involvement in the child’s sleep than the fathers. Early preventive sleep actions could improve sleep in children and mothers.

Digital cognitive–behavioural therapy application compared with zolpidem for the treatment of insomnia: protocol for an exploratory randomised controlled trial

IntroductionInsomnia is a common health problem and cognitive–behavioural therapy (CBT) is recommended as a treatment. As there is a critical shortage of CBT-trained therapists, we developed a digital CBT application...

Safety and Efficacy of Lemborexant in Insomnia Patients: Results of a Postmarketing Observational Study of Dayvigo® Tablets.

A prospective, postmarketing observational study was conducted to evaluate the safety and efficacy of lemborexant (LEM) tablets in daily clinical practice in Japan. No other studies of a similar size have been conducted since the marketing approval of LEM, making this the first report of its kind. Insomnia patients (n=550) administered LEM (5-10 mg daily) for the first time were enrolled. Adverse events were collected for target events (somnolence, parasomnia, narcolepsy and associated conditions, suicidal ideation and suicidal behavior). Overall improvement of insomnia symptoms was assessed by the investigator based on the patient's complaint. Subjective sleep onset latency (sSOL) and subjective total sleep time (sTST) were investigated as sleep parameters. A case report form was obtained from 539 patients. The incidence of adverse drug reactions (ADRs) was 7.65% for somnolence, 1.76% for nightmares, 0.59% for abnormal dreams, and 0.20% for sleep paralysis. No serious ADRs or ADRs related to suicidal ideation or suicidal behavior were observed. The efficacy rate at the final evaluation was 80.83%. Decreased sSOL and increased sTST were observed as assessed starting from Week 8 of treatment. Based on the results of this study, the safety result was consistent with the safety profile described in the current package insert. Efficacy results also indicated that LEM is clinically useful.

Perfect Enough to Sleep? Perfectionism and Actigraphy-Determined Markers of Insomnia

ABSTRACT Objectives Perfectionism is an important factor in insomnia development and maintenance. Previous studies exploring the relationship between perfectionism and insomnia have predominantly relied on self-reported sleep measures. Therefore, this study sought to assess whether actigraphy-measured sleep parameters were associated with perfectionism. Methods Sixty adults (85% females, mean age 30.18 ± 11.01 years) were sampled from the Australian general population. Actigraphy-derived objective sleep measures, subjective sleep diary measures, the Frost Multidimensional Perfectionism Scale (FMPS), Hewitt-Flett Multidimensional Perfectionism Scale (HFMPS) and Depression, Anxiety and Stress Scale 21 (DASS-21) were collected. Results High perfectionism levels were associated with poor sleep, but these relationships differed between objective and subjective measures. Perfectionism via FMPS total score and subscales of Concern over Mistakes, Doubts about Actions, Personal Standards and Self-oriented Perfectionism correlated with subjective sleep onset latency and sleep efficiency with moderate effects (r = .26 to .88). In contrast, perfectionism via HFMPS total score and subscales of Socially Prescribed Perfectionism and Parental Expectations predicted objective sleep onset latency and sleep efficiency. Additionally, stress mediated the relationships between objective sleep efficiency and Concern over Mistakes and Doubts about Actions. Conclusions Perfectionism demonstrated stronger associations with subjective than objective sleep measures. Higher Parental Expectations and Socially Prescribed Perfectionism may increase one’s vulnerability to objectively measured poor sleep. Therefore, perfectionism may be important in preventing and treating insomnia.

Subjective sleep onset latency is influenced by sleep structure and body heat loss in human subjects.

The present study examined the relationship between subjective sleep onset latency (SOL), sleep structure, changes in skin and body temperature, and subjective evaluation of sleep in healthy young adults to elucidate the pathophysiological mechanisms of insomnia. A total of 28 participants (age 21.54 [0.50] years) with no sleep problems participated in a 1-h polysomnographic recording that obtained objective sleep parameters during the daytime while skin and body temperatures were recorded. The distal-proximal skin temperature gradient (DPG) was calculated. Subjective parameters, such as subjective SOL, sleep time, and restorative sleepiness, were evaluated before and after sleep. Most participants estimated their sleep latency as being longer than their actual SOL (13.7 versus 7.6 min). Objective SOL was significantly correlated with each sleep stage parameter whereas subjective SOL was negatively correlated with Stage N2 sleep duration (Rho = -0.454, p = 0.020), slow-wave activity and delta power (Rho = -0.500, p = 0.011 and Rho = -0.432, p = 0.031, respectively), and ΔDPG (the degree of reduction of heat loss before and after lights-off). Stepwise regression analysis showed that ΔDPG was the strongest predictive factor in explaining the length of subjective SOL. The degree of heat dissipation before and after lights-off contributed most to the sensation of falling asleep in healthy young adults. This finding may be helpful for elucidating the physiological mechanisms of insomnia and its treatment.

Cannabidiol for moderate-severe insomnia: a randomized controlled pilot trial of 150 mg of nightly dosing.

Low-dose cannabidiol (CBD) has become readily available in numerous countries; however, little consensus exists on its efficacy as a sleep aid. This trial explored the efficacy of 150 mg of CBD (n = 15) compared with placebo (n = 15) as a sleep aid in primary insomnia. CBD supplementation was hypothesized to decrease insomnia symptoms and improve aspects of psychological health, relative to placebo. Using a randomized, placebo-controlled, parallel design featuring a single-blind placebo run-in week followed by a 2-week double-blind randomized dosing phase, participants consumed the assigned treatment sublingually 60 minutes before bed nightly. Wrist-actigraphy and sleep diaries measured daily sleep. Sleep quality, sleep effort, and well-being were measured weekly over 4 in-laboratory visits. Insomnia severity and trait anxiety were measured at screening and study conclusion. Insomnia severity, self-reported sleep-onset latency, sleep efficiency, and wake after sleep onset did not differ between treatments throughout the trial (all P > .05). Compared with placebo, the CBD group reported greater well-being scores throughout the trial (trial end mean difference = 2.60; standard error: 1.20), transient elevated behavior following wakefulness scores after 1 week of treatment (mean difference = 3.93; standard error: 1.53), and had superior objective sleep efficiency after 2 weeks of treatment (mean difference = 6.85; standard error: 2.95) (all P < .05). No other significant treatment effects were observed. Nightly supplementation of 150 mg CBD was similar to placebo regarding most sleep outcomes while sustaining greater well-being, suggesting more prominent psychological effects. Additional controlled trials examining varying treatment periods and doses are crucial. Registry: Australian New Zealand Clinical Trials Registry; Name: Cannabidiol (CBD) treatment for insomnia; URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000070932; Identifier: ACTRN12620000070932. Narayan AJ, Downey LA, Rose S, Di Natale L, Hayley AC. Cannabidiol for moderate-severe insomnia: a randomized controlled pilot trial of 150 mg of nightly dosing. J Clin Sleep Med. 2024;20(5):753-763.

LPS and its relationship with subjective–objective discrepancies of sleep onset latency in patients with psychiatric disorders

Subjective–objective discrepancies in sleep onset latency (SOL), which is often observed among psychiatric patients, is attributed partly to the definition of sleep onset. Recently, instead of SOL, latency to persistent sleep (LPS), which is defined as the duration from turning out the light to the first consecutive minutes of non-wakefulness, has been utilized in pharmacological studies. This study aimed to determine the non-awake time in LPS that is most consistent with subjective sleep onset among patients with psychiatric disorders. We calculated the length of non-awake time in 30-s segments from lights-out to 0.5–60 min. The root mean square error was then calculated to determine the most appropriate length. The analysis of 149 patients with psychiatric disorders showed that the optimal non-awake time in LPS was 12 min. On the other hands, when comorbid with moderate or severe obstructive sleep apnea (OSA), the optimal length was 19.5 min. This study indicates that 12 min should be the best fit for the LPS non-awake time in patients with psychiatric disorders. When there is comorbidity with OSA, however, a longer duration should be considered. Measuring LPS minimizes discrepancies in SOL and provides important clinical information.

P060 Effectiveness of current digital interventions for children and adolescents with sleep problems: a systematic review and meta-analysis

Abstract Introduction Sleep problems occur in up to 50% of typically developing children. Sleep problems include difficulty initiating sleep, frequent night waking, daytime sleepiness, or frequent nightmares, which lead to poor quality sleep. We conducted a systematic review and meta-analysis to examine the effectiveness of digital sleep interventions for children and adolescents. Method Databases (MEDLINE, PubMed, PsycINFO, Scopus, EMBASE, CENTRAL and Web of Science) were searched for studies published from January 2012 to April 2023. Within-subject studies or randomised controlled trials reporting the effects of a digital sleep-based intervention were included. Random-effects meta-analyses estimated pooled standardised mean difference to assess effectiveness. Nine studies involving 484 children/adolescents were included in this review. Results Digital sleep interventions were effective in reducing insomnia symptoms, decreasing subjective sleep onset latency and wake after sleep onset, and increasing subjective sleep efficiency. Objective measures of SOL, WASO and SE were all unchanged following digital sleep intervention. However, objective but not subjective increases in TST were identified. Discussion These results suggest that digital sleep interventions are effective in improving children and adolescent’s perceptions of their sleep but are less effective at improving some objective measures of sleep. Further, uptake of current digital sleep interventions was low, therefore future interventions should aim to address this, potentially through co-design, and integrating treatment components to enhance young people’s motivation. In order to achieve a clear understanding of how digital sleep interventions compare to other behavioural interventions, additional high-quality randomised controlled trials comparing digital interventions to traditional in person modalities are needed.

Efficacy of melatonin and ramelteon for the acute and long-term management of insomnia disorder in adults: A systematic review and meta-analysis.

Melatonin has gained growing interest as a treatment of insomnia, despite contradictory findings, and a low level of evidence. A systematic review and meta-analysis was conducted following PRISMA criteria, to assess the efficacy of melatonin and ramelteon compared with placebo on sleep quantity and quality in insomnia disorder, while also considering factors that may impact their efficacy. This review included 22 studies, with 4875 participants, including 925 patients treated with melatonin, 1804 treated with ramelteon and 2297 receiving a placebo. Most studies evaluated the acute efficacy of prolonged release (PR) melatonin in insomnia disorder. Compared with placebo, PR melatonin appears efficacious with a small to medium effect size on subjective sleep onset latency (sSOL) (p = 0.031; weighted difference = -6.30 min), objective sleep onset latency (oSOL) (p < 0.001; weighted difference = -5.05 min), and objective sleep efficiency (oSE) (p = 0.043; weighted difference = 1.91%). For the subgroup mean age of patients ≥55, PR melatonin was efficacious on oSE with a large effect size (p < 0.001; weighted difference = 2.95%). Ramelteon was efficacious with a large effect size at 4 weeks on objective total sleep time (oTST) (p = 0.010; weighted difference = 17.9 min), subjective total sleep time (sTST) (p = 0.006; weighted difference = 11.7 min), sSOL (p = 0.009; weighted difference = -8.74 min), and oSOL (p = 0.017; weighted difference = -14 min). Regarding long-term effects, ramelteon has a large effect size on oTST (p < 0.001; weighted difference = 2.02 min) and sTST (p < 0.001; weighted difference = 14.5 min). PR melatonin and ramelteon appear efficacious compared with placebo for insomnia symptoms with PR melatonin showing mostly small to medium effect sizes. PR melatonin for individuals with a mean age ≥ 55 and ramelteon show larger effect sizes.

0729 Grandparents Raising Grandchildren: Does Caregiving Status Moderate the Relationship between Stress and Sleep

Abstract Introduction The close relationship between high stress and poor sleep is well known. Less is known whether this relationship is stronger for a certain population group who may experience more stress. Grandparents responsible for raising their grandchildren are such a vulnerable group, as increased caregiving responsibilities are associated with increased stress levels. To test this hypothesis, we examined whether grandparent caregiving status moderated the relationship between subjective stress and sleep. Methods The sample was a subset of individuals recruited in the second wave of the MIDUS biomarkers project completed in 2009 who answered the sleep, caregiving, and stress variables of interest. Participants included grandparents who reported having been responsible for the care of their grandchildren for at least 1 year (N=63, age M=61.80, 64% female) and grandparents who were not responsible for their grandchildren (N=423, age M=62.98, 56.2% female). Multiple regressions (SPSS PROCESS) examined whether caregiving status (1=yes, 0=no) moderated associations between subjective stress (Perceived Stress Scale) and sleep (subjective Sleep Onset Latency-SOL and sleep quality) over the past month. Analyses controlled for age and gender. Results Caregiving status interacted with stress (t(1, 484)=3.81, p=.04) in its association with SOL (R2=.15, p=.001). Specifically, increased stress was associated with greater SOL in caregiving grandparents and to a lesser (but not significant) extent in non-caregiving grandparents (Z =1.49, p=.13). Caregiving status interacted with stress (t(1, 484)=5.76, p=.02) in its association with sleep quality (R2=.33, p&amp;lt; 001). Specifically, increased stress was associated with worse sleep quality in caregiving grandparents and to a less extent in non-caregiving grandparents (Z =2.67, p=.01). Conclusion These results suggest that caregiving status may contribute to an increase in the positive relationship between subjective stress and sleep problems. Future research should utilize longitudinal and experimental methodology to determine the causality of these relationships as well as examine physiological measures of stress. In addition, studies should investigate whether addressing stress in behavioral sleep treatments may improve caregiving grandparents’ sleep. Support (if any) National Institute on Aging (P01AG020166, R37AG027343; McCrae, PI: R01AG061976)

The course of insomnia symptoms during the acute treatment of major depressive disorder: A CAN-BIND-1 report

Despite considerable efforts to study the relationship between insomnia and depression, there is minimal research investigating whether insomnia symptoms change over time during a course of antidepressant pharmacotherapy. This study investigated the course of insomnia symptoms during the acute treatment of major depressive disorder (MDD) using a secondary analysis of data from MDD patients (N = 180) who were treated with open-label escitalopram (10–20 mg/day) for 8-weeks. Montgomery-Asberg Depression Rating Scale without sleep item (modified-MADRS) assessed depression and Self-reported Quick Inventory Depressive Scale (QIDS-SR) measured subjective sleep-onset, mid-nocturnal, and early-morning insomnia throughout 8-weeks of treatment. Pittsburgh Sleep Quality Index (PSQI) was used to assess subjective sleep quality, duration, onset latency, and efficiency throughout 8-weeks of treatment. Remission of depression was defined as modified-MADRS ≤10 at week-8. Mixed model repeated measures (MMRMs) were conducted with remission status as an independent variable and each sleep variable as a dependent variable. MMRMs demonstrated that remitters had significantly lower QIDS-SR sleep-onset and mid-nocturnal insomnia scores as well as a significantly lower PSQI sleep quality score than non-remitters throughout 8-weeks of treatment. Monitoring subjective sleep-onset and mid-nocturnal insomnia during the course of treatment with serotonergic antidepressants may be useful for predicting acute remission of depression.

The Virtual Sleep Lab—A Novel Method for Accurate Four-Class Sleep Staging Using Heart-Rate Variability from Low-Cost Wearables

Sleep staging based on polysomnography (PSG) performed by human experts is the de facto "gold standard" for the objective measurement of sleep. PSG and manual sleep staging is, however, personnel-intensive and time-consuming and it is thus impractical to monitor a person's sleep architecture over extended periods. Here, we present a novel, low-cost, automatized, deep learning alternative to PSG sleep staging that provides a reliable epoch-by-epoch four-class sleep staging approach (Wake, Light [N1 + N2], Deep, REM) based solely on inter-beat-interval (IBI) data. Having trained a multi-resolution convolutional neural network (MCNN) on the IBIs of 8898 full-night manually sleep-staged recordings, we tested the MCNN on sleep classification using the IBIs of two low-cost (<EUR 100) consumer wearables: an optical heart rate sensor (VS) and a breast belt (H10), both produced by POLAR®. The overall classification accuracy reached levels comparable to expert inter-rater reliability for both devices (VS: 81%, κ = 0.69; H10: 80.3%, κ = 0.69). In addition, we used the H10 and recorded daily ECG data from 49 participants with sleep complaints over the course of a digital CBT-I-based sleep training program implemented in the App NUKKUAA™. As proof of principle, we classified the IBIs extracted from H10 using the MCNN over the course of the training program and captured sleep-related changes. At the end of the program, participants reported significant improvements in subjective sleep quality and sleep onset latency. Similarly, objective sleep onset latency showed a trend toward improvement. Weekly sleep onset latency, wake time during sleep, and total sleep time also correlated significantly with the subjective reports. The combination of state-of-the-art machine learning with suitable wearables allows continuous and accurate monitoring of sleep in naturalistic settings with profound implications for answering basic and clinical research questions.

Poor quality sleep is associated with greater carotid intima media thickness among otherwise healthy resident doctors.

Sleep is important for maintaining the metabolic processes in the body, and hence, disruption in sleep leads to metabolic derangement and accelerated atherosclerosis. The effect of sleep duration on subclinical atherosclerosis has been examined in several studies; however, data regarding sleep quality is lacking. The study aimed to assess the association between sleep quality and carotid intima-media thickness among healthy young doctors. This was an observational cross-sectional study among 110 healthy young resident doctors. Anthropometric data were recorded and morning fasting venous blood samples were collected to assess fasting blood sugar, lipid profile and glycosylated haemoglobin (HbA1c). Pittsburgh Sleep Quality Index and Berlin questionnaire assessed subjective sleep quality and risk for obstructive sleep apnea, respectively. Carotid ultrasonography was done to detect the intima-media thickness. Average age of the participants was 26.45 (±1.43) years, and 51.8% were male. Self-reported poor sleep quality was found in 54.5%. Carotid intima-media thickness (CIMT) was increased among 44.5% of participants. In the multivariate analysis, only poor sleep quality appeared to be associated with higher CIMT (P < 0.001, OR = 7.4; 95% CI = 2.70-20.32). When different components of sleep quality was analyzed through multivariate logistic regression, subjective sleep onset latency (>30 min), sleep efficiency (<85%) and sleep disturbance was found to be associated with the increased CIMT. Poor sleep quality, especially prolonged sleep onset latency, poor sleep efficiency, and sleep disturbance are associated with increased carotid intima-media thickness among healthy young adults.

Association between long-term alcohol consumption and insomnia symptoms in civil servants: Aichi Workers' Cohort Study.

The influence of habitual alcohol consumption on insomnia symptoms in healthy workers remains unclear. In this study, we evaluated the association between habitual alcohol consumption among civil servants and insomnia symptoms such as difficulty falling asleep, difficulty staying asleep, and tiredness after sleep, using longitudinal data. We enrolled civil servants in a prospective cohort study who completed questionnaires at baseline. Of those, 2861 participants were revaluated in a 5-year follow-up survey. Insomnia symptoms during the past month were assessed using self-reporting. Alcohol drinking habits were assessed by querying the frequency of drinking alcohol as well as the amount of alcohol usually consumed per one occasion. Drinking alcohol every day was less likely to have difficulty falling asleep (odds ratio, 0.42 95% confidence interval, 0.20-0.89), and drinking alcohol 3 or more days a week was associated with difficulty staying asleep (odds ratio, 1.48; 95% confidence interval, 1.16-1.90). Drinking alcohol every day may produce subjective improvement in sleep onset. However, drinking alcohol 3 or more days a week may increase arousal during sleep, which contributes to reduced sleep quality. These results suggest the possibility that long-term daily habitual drinking may reinforce a sense of improvement in subjective sleep onset but may possibly induce sleep disturbance.

0440 Subjective Sleep Outcomes with Lemborexant Among Subjects with Insomnia and Clinically Meaningful Decreases on the Insomnia Severity Index

Abstract Introduction Lemborexant (LEM) is a dual orexin receptor antagonist approved in multiple countries for the treatment of adults with insomnia. In Study 303 (NCT02952820), LEM provided significant benefit on sleep outcomes including patient-reported (subjective) sleep onset latency (sSOL) and wake after sleep onset (sWASO) versus placebo (PBO). This post-hoc analysis assessed these measures in Insomnia Severity Index (ISI) responders, defined as subjects with clinically meaningful reductions (≥7 points) in ISI total scores (ISI-TS). Methods Study 303 was a 12-month, PBO-controlled (first 6mo), randomized, double-blind, phase 3 study in subjects with ISI-TS ≥15 (moderate to severe insomnia). Subjects (n=949; Full Analysis Set [FAS]) received LEM (5mg [LEM5]; 10mg [LEM10]) or PBO for 6mo. Changes from baseline (CFB) in sSOL (min) and sWASO (min) at 6mo were analyzed in ISI responders from the FAS and in subjects with severe insomnia (baseline ISI-TS ≥22), using mixed-effect model repeated measurement analysis. Results At 6mo, 175 (LEM5), 151 (LEM10), and 124 (PBO) subjects were ISI responders; of these, 46 (LEM5), 48 (LEM10) and 29 (PBO) had severe insomnia. CFB in the FAS in median sSOL was significantly greater with LEM5 (−21.8) and LEM10 (−28.2) versus PBO (−11.4; both P&amp;lt;0.001). ISI responders also had significantly greater decreases in sSOL with LEM (LEM5: −26.7, P&amp;lt;0.01; LEM10: −32.6, P&amp;lt;0.001) than PBO (−18.0). In ISI responders from the severe insomnia subgroup, greater CFB in median sSOL was observed with LEM10 (−41.4) than with PBO (−32.1; P&amp;gt;0.05), but not with LEM5 (−32.9, P&amp;gt;0.05).Least-squares mean (standard error) CFB in sWASO in the FAS was −46.8(3.7) with LEM5 (P&amp;lt;0.001), −42.0(3.7) with LEM10 (P&amp;lt;0.05), versus −29.3(3.6) with PBO. In ISI responders, CFB in sWASO was greater with LEM10 (−52.7[4.0], P&amp;gt;0.05) and significantly greater with LEM5 (−58.9[3.8], P&amp;lt;0.01) versus PBO (−43.6[4.4]). In ISI responders from the severe insomnia subgroup, greater CFB was observed with LEM5 (−91.6[9.5]) versus PBO (−70.2[11.1]); P&amp;gt;0.05); CFB with LEM10 (−71.4[9.0]) was similar to PBO. Conclusion ISI responders including those from the severe insomnia subgroup reported greater CFB in sSOL and sWASO than the FAS that was somewhat dose dependent. LEM generally showed benefit versus PBO. Support (If Any) Eisai Inc.

0151 Subjective sleep onset latency is influenced by the sleep structure and body heat loss in human subjects

Abstract Introduction Humans can estimate the time that has elapsed during sleep (time estimation ability; TEA). Although research on the TEA during sleep has advanced in the field of sleep research, few studies have focused on the relationship between the subjective sleep onset latency (SOL), which is an indicator of TEA, and objective sleep structures, body heat loss, and body temperature. This paper investigates the association of the subjective SOL with sleep structures such as the objective SOL, duration of each sleep stage, subjective sleep parameters, and body heat loss in healthy young participants. Methods Twenty six participants (7 men and 19 women, mean age of 21.5 ± 0.5 years) having no sleep problems participated in a 1-hour polysomnographic recording that obtained objective sleep parameters during the daytime while temperatures of the skin (i.e., dorsum of the hand and foot, forehead, and subclavian) and eardrum were recorded at intervals of 1 min. The distal–proximal skin temperature gradient (DPG), which is a good predictor of body heat loss and sleepiness, was calculated. Subjective parameters, such as the subjective SOL, sleep time, sleep depth, sleepiness, and mood, were evaluated before and after sleep. We examined the association of the subjective SOL with objective sleep parameters, DPG, and other subjective parameters. Results Most participants estimated their sleep latency to be longer than their actual SOL (mean objective SOL of 7.6 min vs. subjective SOL of 13.7 min). The objective SOL was significantly correlated with each sleep stage parameter whereas the subjective SOL was negatively correlated with the stage N2 sleep duration (Rho = −0.454, p = 0.020) and correlated with the stage N2 sleep latency (Rho = 0.402, p = 0.051). Participants who estimated a shorter subjective SOL had a higher DPG before sleep periods than that after sleep onset (Rho = −0.692, p &amp;lt; 0.001). Additionally, the subjective SOL was correlated with the subjective sleep depth, subjective wake after sleep onset, and restorative sleep. Conclusion The subjective sleep onset latency in the healthy young participants was affected by the degree of body heat loss before sleep onset and stable shallow nonrapid-eye-movement sleep. Support (If Any)

Periocular Skin Warming Promotes Sleep Onset Through Heat Dissipation From Distal Skin in Patients With Insomnia Disorder.

Study ObjectivesPeriocular skin warming before bedtime has been demonstrated to improve subjective sleep initiation in healthy adults with sleep difficulties scored six or higher in the Pittsburgh Sleep Questionnaire Index. This study aimed to investigate the effects of periocular skin warming on sleep initiation and thermoregulation processes in patients with insomnia disorder.MethodsParticipants included those with sleep difficulty (n = 22) and those with insomnia disorder (n = 16). Individuals from both groups were assessed at baseline (habitual sleep-wake schedule) and after two intervention conditions (use of a warming eye mask or a sham eye mask before habitual bedtime). The subjective and electroencephalographic sleep onset latency, along with proximal and distal skin temperature after periocular skin warming, were evaluated.ResultsPeriocular skin warming reduced objective sleep onset latency in independently of the group. Foot temperature and foot-proximal temperature gradient after getting into bed increased with periocular skin warming in independently of the group. However, the increase in hand temperature was observed only in the insomnia disorder group. Periocular skin warming also increased the normalized high frequency component of heart rate variability in independently of the group. The reduction of objective sleep onset latency was strongly associated with heat dissipation from the foot skin region.ConclusionThese results suggest that periocular skin warming promotes sleep initiation by enhancing heat dissipation from the distal skin regions in individuals with sleep difficulty and insomnia disorder. Periocular skin warming could thus be a novel non-pharmacological therapy for insomnia disorder.