Daytime Functioning Research Articles

Sleep spindles are reduced in children with Down syndrome and sleep-disordered breathing

BackgroundChildren with Down syndrome (DS) are at increased risk of sleep-disordered breathing (SDB). We investigated sleep spindle activity, as a marker of sleep quality, and its relationship with daytime functioning in children with DS compared to typically developing (TD) children.MethodsChildren with DS and SDB (n = 44) and TD children matched for age, sex and SDB severity underwent overnight polysomnography. Fast or Slow sleep spindles were identified manually during N2/N3 sleep. Spindle activity was characterized as spindle number, density (number of spindles/h) and intensity (density × average duration) on central (C) and frontal (F) electrodes. Parents completed the Child Behavior Check List and OSA-18 questionnaires.ResultsIn children with DS, spindle activity was lower compared to TD children for F Slow and F Slow&Fast spindles combined (p < 0.001 for all). Furthermore, there were no correlations between spindle activity and CBCL subscales; however, spindle activity for C Fast and C Slow&Fast was negatively correlated with OSA-18 emotional symptoms and caregiver concerns and C Fast activity was also negatively correlated with daytime function and total problems.ConclusionsReduced spindle activity in children with DS may underpin the increased sleep disruption and negative effects of SDB on quality of life and behavior.ImpactChildren with Down syndrome (DS) are at increased risk of sleep-disordered breathing (SDB), which is associated with sleep disruption affecting daytime functioning.Sleep spindles are a sensitive marker of sleep quality.We identified for the first time that children with DS had reduced sleep spindle activity compared to typically developing children matched for SDB severity.The reduced spindle activity likely underpins the more disrupted sleep and may be associated with reduced daytime functioning and quality of life and may also be an early biomarker for an increased risk of developing dementia later in life in children with DS.

Potential therapeutic benefit of spinal cord stimulation in restless legs syndrome: scoping review and mechanistic considerations.

Restless legs syndrome (RLS) is a prevalent sensorimotor disorder that can dramatically impair sleep quality, daytime function, and quality of life. Although many patients benefit from standard pharmacological therapy, some patients suffer from insufficient treatment response or medication intolerance. Novel treatment approaches are therefore necessary. Given the overlap between RLS and pain syndromes in both pathophysiological mechanisms and certain treatment options, we aimed to perform a scoping review of the available evidence on spinal cord stimulation (SCS) for RLS and discuss potential mechanistic implications. We identified a total of 16 cases of patients with RLS who underwent SCS, all from case reports or case series. The published evidence is insufficient to assess SCS efficacy in patients with RLS, but SCS remains a promising investigational therapy in RLS on the basis of its potential mitigatory effects in the central hyperexcitability of the sensorimotor cortex through neuromodulation of spinal, subcortical, and cortical areas. A call for further research in this field is presented, with suggestions for future directions and trial designs.

General practitioner assessment and management of insomnia in adults.

Sleep disturbance is among the most prevalent presentations in Australian general practice. Insomnia, the most common sleep disorder, is associated with impaired daytime, social and occupational function, reduced quality of life and substantially increased risk of future depression. Guidelines from Australian and international general practice, sleep and medical societies strongly recommend cognitive behavioural therapy for insomnia (CBT-i) as the first-line treatment for chronic insomnia. This is because CBT-i targets the underlying causes of insomnia, results in sustained improvements and commonly improves comorbid conditions such as depression and pain. This article aims to provide an overview of evidence-based assessment, management and referral options for insomnia in Australian general practice. Access to brief insomnia assessment andevidenced-based treatments are becoming increasingly available to Australian general practitioners. CBT-i can be delivered through self-guided online programs or by suitably trained general practitioners and psychologists.

Insomnia

Patients with insomnia suffer from problems falling asleep and/or maintaining sleep. This has a negative effect on their daytime wellbeing and performance. Insomnia is primarily diagnosed by a detailed clinical history, supplemented by questionnaires and sleep diaries. Polysomnography may be necessary for the differential diagnosis of organic sleep disorders. Insomnia is a frequent comorbidity of most mental disorders and many physical diseases. It is treated according to guidelines with cognitive behavioural therapy for insomnia (CBT-I). CBT-I is offered in individual or group format as well as online-supported treatment. If behavioural therapy is not effective or not available, pharmacotherapy can be discussed.

Network analysis to estimate central insomnia symptoms among daytime workers at-risk for insomnia

Although insomnia complaints are associated with mental health problems and reduced work productivity, the central insomnia symptoms in workers at-risk for insomnia remain unclear. This study aimed to identify the central insomnia symptoms among daytime workers at risk for insomnia. The participants were 881 Japanese daytime workers at-risk for insomnia with a mean age of 49.33 ± 9.92 years. At-risk for insomnia was defined as an Athens Insomnia Scale score of six or higher. The Athens Insomnia Scale was used as a screening for at-risk insomnia because it has higher sensitivity and specificity than other insomnia screening scales. The Insomnia Severity Index is recommended as a mechanism of insomnia and an outcome measure; therefore, a network analysis was conducted with the seven items of the Insomnia Severity Index. The important variables in the connections between insomnia symptoms were estimated from centrality indices, which were interpretable only for strength. The strength value results suggest that difficulty staying asleep and worry about sleep problems were the central insomnia symptoms. The connections were stronger for difficulty staying asleep and problem waking up too early, difficulty staying asleep and difficulty falling asleep, and interference with daytime functions and noticeable to others. Worry about sleep problems was strongly associated with variables other than nocturnal insomnia symptoms. Therefore, difficulty staying asleep and worry about sleep problems are important variables in daytime workers at-risk for insomnia and are key points for improvement or exacerbation of insomnia symptoms.

Understanding daytime functioning in insomnia: responder and correlation analyses in patients treated with daridorexant

BackgroundImproving daytime functioning is a key treatment goal for patients with insomnia disorder. In a phase 3 study, using the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ), daridorexant 50 mg significantly improved daytime functioning in adults with insomnia, as well as sleep parameters. These data are further analyzed to evaluate the clinically meaningful changes in IDSIQ scores at weekly intervals and investigate the correlation between the effects of daridorexant on daytime functioning and on sleep quality and quantity.MethodsNine hundred thirty patients with insomnia randomized to daridorexant 25 mg (n = 310), 50 mg (n = 310) or placebo (n = 310) for 12 weeks were analyzed, with focus on daridorexant 50 mg and placebo. Patients recorded daily their daytime functioning using the IDSIQ and their self-reported total sleep time (sTST) and sleep quality using a sleep diary questionnaire; weekly mean changes from baseline were calculated. A clinically meaningful improvement (‘response’) at a given week was defined as a ≥ 20-point decrease in IDSIQ total score from baseline.ResultsWeekly responder rates increased over time in both groups but were consistently higher each week with daridorexant. Overall, 53% (n = 165/310) of patients in the daridorexant 50 mg group perceived a response for ≥ 1 week versus 41% in the placebo group (n = 126/310). This response, which could be achieved at any time during the 12 weeks of the study, was more often continuous on daridorexant and more often intermittent on placebo. Time-to-first response was significantly different between daridorexant and placebo (hazard ratio 1.55; 95% confidence intervals [CI] 1.22, 1.97; p = 0.0003) with shorter time observed in daridorexant. Patient perception of the response also lasted longer on daridorexant than placebo (mean number of continuous responder weeks; 9.2 vs. 7.9 respectively). A decrease in IDSIQ total score was correlated with an increase in sTST and sleep quality and a decrease in morning sleepiness, from Week 1 onwards.ConclusionPatients with insomnia are more likely to perceive a clinically meaningful improvement in their daytime functioning each week with daridorexant 50 mg than placebo. The response, which can fluctuate over time, is also perceived earlier and sustained for longer than placebo. The correlations between improved daytime functioning and improved sleep quantity and quality support the benefits of daridorexant on both the night and daytime symptoms in patients with insomnia disorder.Trial registrationClinicalTrials.gov: NCT03545191.

SLEEPexpert+: Blending Internet-Based Cognitive Behavioral Therapy for Insomnia with In-Person Psychotherapy—A Feasibility Study in Routine Care

Insomnia is characterized by frequent and persistent difficulties initiating and maintaining sleep, along with impaired daytime functioning. Blended treatments are increasingly popular for treating psychological disorders such as depression. Blended treatments combine elements of face-to-face therapy and online interventions. A single-arm pre-post study investigated the feasibility of a blended treatment combining face-to-face cognitive behavioral therapy for insomnia and internet-based cognitive behavioral therapy for insomnia (SLEEPexpert+). The findings show that the therapists have a positive attitude toward blended CBT-I (b-CBT-I) and that they feel supported by the online components of the treatment. Possible barriers to implementing blended treatments are integrating the online materials into the face-to-face sessions and adapting one’s therapeutic style to the blended treatment approach. No definitive statements about the effectiveness of the b-CBT-I treatment can be made. However, of the six presented cases, five patients showed notably higher sleep efficiency and fewer insomnia symptoms at the end of the therapy. Program usage data indicate that participants mainly used the online components at the beginning of their treatment. Future studies should investigate the effectiveness of b-CBT-I with a sufficiently powered randomized controlled trial comparing b-CBT-I with an adequate control group in routine care.

Reliability and validity of the Chinese version of the Athens insomnia scale for non-clinical application in Chinese athletes.

This study aimed to revise and examine the reliability and validity of the Chinese version of the Athens Insomnia Scale for Non-clinical Application (AIS-NCA) among Chinese athletes. Additionally, the study tested the scale in non-athlete individuals with similar sleep management practices to further analyze its cultural specificity among Chinese athletes and make preliminary inferences about its applicability in other Chinese populations. Four hundred twenty-six Chinese professional athletes and 779 high school students participated in this research. Both athletes and students were divided into two parallel groups for exploratory and confirmatory factor analyses. Additionally, three athlete samples and one student sample were established for reliability and validity assessments. Among athletes, the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, the Athlete Sleep Screening Questionnaire, and the Warwick-Edinburgh Mental Well-Being Scale were employed to evaluate convergent and discriminant validity. Re-test reliability was evaluated at intervals of 1 and 2 weeks. In the case of students, convergent and discriminant validity were tested using the Pittsburgh Sleep Quality Index and the General Self-Efficacy Scale, with re-test reliability assessed at two-week intervals. The Chinese version of the AIS-NCA consists of six items, categorized into two dimensions: sleep problems and daytime functioning. This structure explained 65.08% (athletes) and 66.22% (students) of the variance. Confirmatory factor analysis revealed good model fit, with values of χ2/df = 2.217, CFI = 0.975, AGFI = 0.929, TLI = 0.953, and RMSEA = 0.076 among athletes, and χ2/df = 3.037, CFI = 0.979, AGFI = 0.947, TLI = 0.961, and RMSEA = 0.072 among students. The scale demonstrated a reasonable degree of measurement invariance. The overall scale and two subscales exhibited strong reliability and validity among athletes. Similar results in terms of reliability and validity were also observed within the student sample. The Chinese version of the AIS-NCA shows promise as an assessment tool for evaluating the sleep quality of Chinese athletes. It effectively captures both sleep-related concerns and daytime functionality within the athlete population. The scale demonstrates solid reliability and validity in professional athletes and holds potential for application across various other demographic groups in China.

An eHealth Program for Insomnia in Children With Neurodevelopmental Disorders (Better Nights, Better Days): Protocol for an Economic Evaluation of a Randomized Controlled Trial.

Children with neurodevelopmental disorders have a high risk of sleep disturbances, with insomnia being the most common sleep disorder (ie, chronic and frequent difficulties with going and staying asleep). Insomnia adversely affects the well-being of these children and their caregivers. Pediatric sleep experts recommend behavioral interventions as the first-line treatment option for children. Better Nights, Better Days for Children with Neurodevelopmental Disorders (BNBD-NDD) is a 5-session eHealth behavioral intervention delivered to parents to improve outcomes (eg, Pediatric Quality of Life Inventory [PedsQL]) for their children (ages 4-12 years) with insomnia and who have a diagnosis of mild to moderate attention-deficit/hyperactivity disorder, autism spectrum disorder, cerebral palsy, or fetal alcohol spectrum disorder. If cost-effective, BNBD-NDD can be a scalable intervention that provides value to an underserved population. This protocol outlines an economic evaluation conducted alongside the BNBD-NDD randomized controlled trial (RCT) that aims to assess its costs, efficacy, and cost-effectiveness compared to usual care. The BNBD-NDD RCT evaluates the impacts of the intervention on children's sleep and quality of life, as well as parents' daytime functioning and psychosocial health. Parent participants were randomized to the BNBD-NDD treatment or to usual care. The economic evaluation assesses outcomes at baseline and 8 months later, which include the PedsQL as the primary measure. Quality of life outcomes facilitate the comparison of competing interventions across different populations and medical conditions. Cost items include the BNBD-NDD intervention and parent-reported usage of private and publicly funded resources for their children's insomnia. The economic evaluation involves a reference case cost-effectiveness analysis to examine the incremental cost of BNBD-NDD per units gained in the PedsQL from the family payer perspective and a cost-consequence analysis from a societal perspective. These analyses will be conducted over an 8-month time horizon. Research funding was obtained from the Kids Brain Health Network in 2015. Ethics were approved by the IWK Health Research Ethics Board and the University of Calgary Conjoint Health Research Ethics Board in January 2019 and June 2022, respectively. The BNBD-NDD RCT data collection commenced in June 2019 and ended in April 2022. The RCT data are currently being analyzed, and data relevant to the economic analysis will be analyzed concurrently. To our knowledge, this will be the first economic evaluation of an eHealth intervention for insomnia in children with neurodevelopmental disorders. This evaluation's findings can inform users and stakeholders regarding the costs and benefits of BNBD-NDD. ClinicalTrial.gov NCT02694003; https://clinicaltrials.gov/study/NCT02694003. DERR1-10.2196/46735.

Longitudinal course and outcome of social jetlag in adolescents: A 1-year follow-up study of the adolescent sleep health epidemiological cohorts.

The discrepancy in sleep timing between weekdays and weekends - social jetlag (SJL) - is known to negatively affect student quality of life (QOL). However, the association between social jetlag and physical/mental QOL among adolescents and the precise effect of social jetlag on depressive symptoms and daytime sleepiness remains unknown. This study investigated the longitudinal course, risk factors, and effects of social jetlag, a circadian misalignment, in a school-based cohort. The participants were 427 students (13.3 ± 0.6 years, 45.2% girls) from five junior high schools. We performed a baseline survey in 2019 and a 1-year follow-up survey in 2020. Depressive symptoms, QOL, and daytime sleepiness were assessed using the Birleson Depression Self-Rating Scale for Children, Paediatric Quality of Life Inventory, and Paediatric Daytime Sleepiness Scale. In the baseline survey, 49.6% of the students reported SJL ≥1 h, and 17.1% reported SJL ≥2 h. Among them, 37.2% and 6.8% reported persistent SJL at follow-up, respectively. New incidences of SJL ≥1 h were associated with older age, non-attainment of menarche or voice changes, and longer duration of smartphone use, whereas its persistence was associated with a later chronotype. Persistence of SJL ≥1 h and ≥2 h predicted depressive symptoms and daytime sleepiness at follow-up, whereas new incidences of SJL ≥2 h predicted lower QOL. In conclusion, social jetlag has a persistent course, and daytime functioning can deteriorate as social jetlag becomes chronic. Our findings suggest the need for intensive interventions for social jetlag among adolescents.

Internet-delivered cognitive behavioral therapy for adolescents with insomnia: Feasibility and preliminary efficacy.

Insomnia is common in adolescents. This study evaluated feasibility and preliminary efficacy of a six-week internet-delivered cognitive-behavioral therapy for insomnia (ICBT-I) in adolescents. In this uncontrolled pilot study, participants (n = 27, 78% female) completed assessments pre- and post intervention. Data on recruitment, adherence to treatment, treatment activity, satisfaction and credibility was collected to assess feasibility. Self-reported insomnia symptoms, sleep parameters as well as depression, anxiety and daytime function were also assessed. Participants showed good adherence to treatment and found the intervention overall credible and satisfactory. From pre- to post-assessment, statistically significant improvements were found for insomnia symptoms (p < .001; d = 1.02), sleep onset latency (p < .001; d = .39), wake after sleep onset (p = .001; d = .34), sleep efficiency (p < .001; d = .5) and depression (p = .01, d = .37). Changes in scores of total sleep time, generalized anxiety, daytime sleepiness and functional disability were not significant. The present study indicates that ICBT-I is well accepted by adolescents, that insomnia symptoms and sleep parameters can improve following the intervention, and that co-morbid symptoms of depression can be reduced. Due to the limited sample size and the uncontrolled design, the suggested results need to be replicated in well-powered controlled clinical trials.

General practitioner management of comorbid insomnia and sleep apnoea.

Insomnia and obstructive sleep apnoea are the two most common sleep disorders and frequently co-exist. Patients with comorbid insomnia and sleep apnoea experience worse daytime function, mental health and physical health than patients with either disorder alone. General practitioners may face unique challenges in the assessment and management of this prevalent and debilitating condition. This article aims to provide an overview of the prevalence, consequences, assessment and management of patients with comorbid insomnia and sleep apnoea in Australian general practice. Patients with either insomnia or sleep apnoea should be assessed for both conditions. Treatments for both disorders should be offered to patients with both conditions. The recommended treatment for insomnia is cognitive behavioural therapy, whereas the recommended first-line treatment for moderate and severe obstructive sleep apnoea is lifestyle/weight management advice (where relevant) and continuous positive airway pressure therapy.

Co-morbid insomnia and sleep apnea (COMISA): recent research and future directions.

Insomnia and obstructive sleep apnea have previously been viewed as completely independent conditions. However, there is now increasing recognition that insomnia and sleep apnea frequently co-occur. Co-morbid insomnia and sleep apnea (COMISA) is a highly prevalent condition that is associated with impairment of sleep, daytime function, mental health and physical health outcomes, and mortality risk. This review aims to provide an update on COMISA prevalence, consequences, treatment approaches, and future research directions. People with COMISA experience worse sleep, mental health, physical health, quality of life and longevity compared to people with neither condition, and often compared to those with insomnia alone and sleep apnea alone. Emerging evidence suggests that cognitive behavioral therapy for insomnia is an effective treatment in the presence of treated and untreated sleep apnea, that may also improve manifestations and subsequent management of sleep apnea. Future research is required to understand the etiology of COMISA, and to develop and implement tailored treatment approaches. It is important for sleep and respiratory technicians, researchers and clinicians to be aware of the high co-morbidity rates, consequences, and treatment requirements of patients with co-morbid insomnia and sleep apnea.

The burden of untreated insomnia disorder in a sample of 1 million adults: a cohort study

BackgroundInsomnia disorder is a highly prevalent, significant public health concern associated with substantial and growing health burden. There are limited real-world data assessing the burden of insomnia disorder on daytime functioning and its association with comorbidities. The objective of this study was to leverage large-scale, real-world data to assess the burden of untreated insomnia disorder in terms of daytime impairment and clinical outcomes.MethodsThis United States medical claims database study compares patients diagnosed with insomnia disorder but not receiving treatment (‘untreated insomnia’ cohort) to patients without an insomnia disorder diagnosis and without treatment (‘non-insomnia’ cohort). International Classification of Disease, Tenth Revision codes were used as a proxy to represent the three symptom domains (Sleepiness, Alert/Cognition, Mood) of the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ), a newly developed and validated tool used in clinical studies to assess daytime functioning in insomnia disorder. Chronic Fatigue (R53.83) and Other Fatigue (R53.83), Somnolence (R40.0) and Disorientation (R41.0) were selected as categories representing one or more IDSIQ domains. Clinical outcomes included cardiovascular events, psychiatric disorders, cognitive impairment and metabolic disorders.ResultsApproximately 1 million patients were included (untreated insomnia: n = 139,959; non-insomnia: n = 836,975). Compared with the ‘non-insomnia’ cohort, the ‘untreated insomnia’ cohort was more likely to experience daytime impairments, with mean differences in occurrences per 100 patient-years for: (a) fatigue, at 27.35 (95% confidence interval [CI] 26.81, 27.77, p < 0.01); (b) dizziness, at 4.66 (95% CI 4.40, 4.90, p < 0.01); (c) somnolence, at 4.18 (95% CI 3.94, 4.43, p < 0.01); and (d) disorientation, at 0.92 (95% CI 0.77, 1.06, p < 0.01). During the 1-year look-back period, patients in the ‘untreated insomnia’ cohort were also more likely to have been diagnosed with arterial hypertension (40.9% vs. 26.3%), psychiatric comorbidities (40.1% vs. 13.2%), anxiety (29.2% vs. 8.5%), depression (26.1% vs. 8.1%) or obesity (21.3% vs. 11.1%) compared with those in the ‘non-insomnia’ cohort.ConclusionsThis large-scale study confirms the substantial burden of insomnia disorder on patients in a real-world setting, with significant daytime impairment and numerous comorbidities. This reinforces the need for timely insomnia disorder diagnosis and treatments that improve both sleep, as well as daytime functioning.

Associated Risk Factors of Insomnia among Elderly People in Banepa Municipality

Background &amp; Objective: Insomnia is defined as a difficulty with the initiation, maintenance, duration, or quality of sleep that results in the impairment of daytime functioning. The prevalence of insomnia increases steadily with age and is often a persistent problem, particularly in older adults and is often mistaken as a normal part of ageing. The objective was to identify the associated risk factors of insomnia among elderly. Material and Methods: A descriptive cross-sectional research design was adopted. The data was collected from respondents in 60 samples using probability systematic random sampling technique. Data was collected using standard questionnaire tool i.e. Pittsburgh Insomnia Rating Scale 20 version. Descriptive statistics (frequency and percentage) and inferential statistics (Chi-square) were applied using Statistical Package for Social Science (SPSS) Version 16 for data analysis. Results: Study finding revealed that the mean age of the respondents was 77.5. Half of respondents i.e. (50.0%) had insomnia. There is significant association between insomnia and drinking alcohol (p=0.045), fear of death (p=0.032) and alter sleep due to bad dreams (p=0.035) and there is no significant association between insomnia and co-morbidity (p&gt;0.05). Conclusion: It was concluded that 50% of the respondents had insomnia. Drinking alcohol, fear of death and alter sleep due to bad dreams are significant association with insomnia. Therefore, it would be better if awareness programs regarding stress management and lifestyle modification are given to the patient to improve the quality of life.

A phospho-dawn of protein modification anticipates light onset in the picoeukaryote Ostreococcus tauri.

Diel regulation of protein levels and protein modification had been less studied than transcript rhythms. Here, we compare transcriptome data under light-dark cycles with partial proteome and phosphoproteome data, assayed using shotgun MS, from the alga Ostreococcus tauri, the smallest free-living eukaryote. A total of 10% of quantified proteins but two-thirds of phosphoproteins were rhythmic. Mathematical modelling showed that light-stimulated protein synthesis can account for the observed clustering of protein peaks in the daytime. Prompted by night-peaking and apparently dark-stable proteins, we also tested cultures under prolonged darkness, where the proteome changed less than under the diel cycle. Among the dark-stable proteins were prasinophyte-specific sequences that were also reported to accumulate when O. tauri formed lipid droplets. In the phosphoproteome, 39% of rhythmic phospho-sites reached peak levels just before dawn. This anticipatory phosphorylation suggests that a clock-regulated phospho-dawn prepares green cells for daytime functions. Acid-directed and proline-directed protein phosphorylation sites were regulated in antiphase, implicating the clock-related casein kinases 1 and 2 in phase-specific regulation, alternating with the CMGC protein kinase family. Understanding the dynamic phosphoprotein network should be facilitated by the minimal kinome and proteome of O. tauri. The data are available from ProteomeXchange, with identifiers PXD001734, PXD001735, and PXD002909.

The clinical effects of digital cognitive behavioral therapy for insomnia in a heterogenous study sample: Results from a randomized controlled trial.

Numerous studies worldwide have reported beneficial effects of digital cognitive behavioral therapy for insomnia (dCBT-I). However, few focus on real-world study samples that reflect people in regular care. To test whether dCBT-I is suitable within German regular care, we designed a randomized controlled trial recruiting a heterogenous insomnia population. Participants aged 18+ who met the criteria for insomnia disorder were randomized to 8-weeks dCBT-I + care-as-usual (CAU) or they were set on a waitlist + CAU. The intervention group was followed up at six and 12-months. Primary outcome was self-reported insomnia severity, assessed with the Insomnia Severity Index (ISI) at eight-weeks post-randomization. A one-way ANCOVA with baseline score as covariate was fitted to determine group-differences. Secondary outcomes included measures on daytime functioning, quality of life, depression, anxiety, dreams, and nightmares. Of the N = 238 participants (67.6% female), age range 19 to 81 years, n = 118 were randomized to dCBT-I and n = 120 to the control group. At post-treatment, the use of dCBT-I was associated with a large reduction on the ISI (Diffadj = -7.60) in comparison to WLC (d = - 2.08). This clinical improvement was also reflected in responder and remission rates. Treatment effects were also observed for daytime functioning, quality of life, symptoms of depression and anxiety (ds = 0.26 - 1.02) and at long-term follow-up (intervention group only; ds = 0.18 - 1.65). No effects were found for dream and nightmare frequency. This study showed that dCBT-I reduces insomnia symptoms and improves daytime functioning in a heterogenous insomnia population in Germany with sustained long-term treatment effects in the intervention group. Our results underscore the potential of digital health applications, their suitability within regular care, and their role in facilitating widespread implementation of CBT-I as first-line treatment for insomnia.

Number, Duration, and Distribution of Wake Bouts in Patients with Insomnia Disorder: Effect of Daridorexant and Zolpidem.

Daridorexant, a dual orexin receptor antagonist approved in early 2022, reduces wake after sleep onset without reducing the number of awakenings in patients with insomnia. The objective of this post hoc analysis was to explore the effect of daridorexant on the number, duration, and distribution of night-time wake bouts, and their correlation with daytime functioning. Adults with insomnia disorder were randomized 1:1:1:1:1:1 to placebo, zolpidem 10mg, or daridorexant 5, 10, 25, or 50mg in a phase II dose-finding study, and 1:1:1 to placebo or daridorexant 25 or 50mg in a pivotal phase III study. We analyzed polysomnography data for daridorexant 25 and 50mg, zolpidem 10mg, and placebo groups. Polysomnography was conducted at baseline, then on Days 1/2, 15/16, and 28/29 in the phase II study, and Months 1 and 3 in the phase III study. The number, duration, and distribution of wake bouts (≥ 0.5min) were assessed. Data from 1111 patients (phase II study: daridorexant 50mg [n = 61], zolpidem 10mg [n = 60], placebo [n = 60]; phase III study: daridorexant 25mg [n = 310], daridorexant 50mg [n = 310], placebo [n = 310]) were analyzed. Long wake bouts were defined as > 6min. Compared with placebo, daridorexant 50mg reduced overall wake time (p < 0.05; all time points, both studies), the odds of experiencing long wake bouts (p < 0.001; Months 1 and 3, phase III study), and the cumulative duration of long wake bouts (p < 0.01; all time points, both studies). Reductions in long wake bouts were sustained through the second half of the night and correlated with improvements in daytime functioning. An increase in the cumulative duration of short wake bouts was observed with daridorexant 50mg (p < 0.01 vs placebo, Months 1 and 3, phase III study); this was uncorrelated with daytime functioning. Daridorexant reduced the number and duration of longer wake bouts throughout the night compared with placebo, corresponding with improved daytime functioning. Clinicaltrials.gov NCT02839200 (registered July 20, 2016), NCT03545191 (registered June 4, 2018).

Use of melatonin in children and adolescents with idiopathic chronic insomnia: a systematic review, meta-analysis, and clinical recommendation.

Melatonin prescriptions for children and adolescents have increased substantially during the last decade. Existing clinical recommendations focus on melatonin as a treatment for insomnia related to neurodevelopmental disorders. To help guide clinical decision-making, we aimed to construct a recommendation on the use of melatonin in children and adolescents aged 5-20 years with idiopathic chronic insomnia. A systematic search for guidelines, systematic reviews and randomised controlled trials (RCT) were performed in Medline, Embase, Cochrane Library, PsycInfo, Cinahl, Guidelines International Network, Trip Database, Canadian Agency for Drugs and Technologies in Health, American Academy of Sleep Medicine, European Sleep Research Society and Scandinavian Health Authorities databases. A search for adverse events in otherwise healthy children and adolescents was also performed. The latest search for guidelines, systematic reviews, and adverse events was performed on March 18, 2023. The latest search for RCTs was performed on to February 6, 2023. The language was restricted to English, Danish, Norwegian, and Swedish. Eligible participants were children and adolescents (5-20 years of age) with idiopathic chronic insomnia, in whom sleep hygiene practices have been inadequate and melatonin was tested. There were no restrictions on dosage, duration of treatment, time of consumption, or release formula. Primary outcomes were quality of sleep, daytime functioning and serious adverse events. Secondary outcomes included total sleep time, sleep latency, awakenings, drowsiness, quality of life, all-cause dropouts, and non-serious adverse events. Outcomes were assessed at different time points to assess short-term and long-term effects. Meta-analysis was performed using inverse variance random-effects model and risk of bias was assessed using Cochrane risk of bias tool. If possible, funnel plots would be constructed to investigate publication bias. Heterogeneity was calculated via I2 statistics. A multidisciplinary guideline panel formulated the recommendation according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). The certainty of evidence was considered either high, moderate, low or very low depending on the extent of risk of bias, inconsistency, imprecision, indirectness, or publication bias. The evidence-to-decision framework was subsequently used to discuss the feasibility and acceptance of the constructed recommendation alongside the impact on resources and equity. The protocol is registered with the Danish Health Authority. We included eight RCTs with 419 children and adolescents with idiopathic chronic insomnia. Melatonin led to a moderate increase in total sleep time by 30.33min (95% confidence interval (CI) 18.96-41.70, 4 studies, I2=0%) and a moderate reduction in sleep latency by 18.03min (95% CI-26.61 to-9.44, 3 studies, I2=0%), both as assessed by sleep diary. No other beneficial effects were found. None of the studies provided information on serious adverse events, yet the number of participants experiencing non-serious adverse events was increased (Relative risk 3.44, 95% CI 1.25-9.42, 4 studies, I2=0%). Funnel plots were not constructed due to the low number of studies. The certainty of evidence was very low on the quality of sleep and low for daytime functioning. Evidence of very low certainty shows that benefits are limited and unwanted events are likely when melatonin is used to treat otherwise healthy children and adolescents with chronic insomnia. Melatonin should never be the first choice of treatment for this particular population, yet carefully monitored short-term use may be considered if sleep hygiene practices and non-pharmacological interventions have proven inadequate, and only if daytime function is compromised. The Danish Health Authority and the Parker Institute, Bispebjerg and Frederiksberg Hospital supported by the Oak Foundation.

Daridorexant, a Recently Approved Dual Orexin Receptor Antagonists (DORA) in the Treatment of Insomnia.

Insomnia is one of the major challenges in medical science nowadays as it leads to the great socio-economic burden by impairing daytime function as well as the development of exhaustion, depression and memory disturbance in affected individuals. Several important classes of drugs have been tried including the BZDs and Non-BZD hypnotics. Available drugs to combat this disease have the limitations of abuse potential, tolerance and cognitive impairments. In some instances, withdrawal symptoms have been observed on abrupt cessation of those drugs. The Orexin system has been very recently targeted as a therapeutic option to overcome those limitations. Daridorexant as a Dual Orexin Receptor Antagonists (DORA) in the treatment of insomnia has been evaluated in several preclinical and clinical studies. Available information obtained from those studies has shown promising future for this drug in the management of insomnia. Beyond its effectiveness in insomnia, it has been successfully used in patients suffering from Obstructive sleep apnoea, Chronic Obstructive Airway Disease (COAD), Alzheimer's Disease (AD), hypertension and cardiovascular disorders. Larger studies need to address the safety issues as well as obtain robust pharmacovigilance information to safeguard the risk-benefit aspect of this drug in insomniac adults.