Treatment Of Chronic Insomnia Research Articles

Effect of combined treatment with transcranial direct current stimulation and repetitive transcranial magnetic stimulation compared to monotherapy for the treatment of chronic insomnia: a randomised, double-blind, parallel-group, controlled trial

Effect of combined treatment with transcranial direct current stimulation and repetitive transcranial magnetic stimulation compared to monotherapy for the treatment of chronic insomnia: a randomised, double-blind, parallel-group, controlled trial

Napping during cognitive behavioural therapy for insomnia: Friends or foes?

SummaryCognitive and Behavioural Therapy for Insomnia (CBT‐I) is the gold standard treatment for chronic insomnia, with one crucial step being the restriction of time spent in bed. This restriction often intensifies early afternoon sleepiness, leading to a natural gateway for a short recuperative nap, which might foster adherence to CBT‐I over time. In practice, mental health professionals providing CBT‐I lack consensus on whether or not to tolerate short naps during the CBT‐I period for requesting patients. In this pilot study, we examined the effects of authorised napping on CBT‐I efficiency in patients with insomnia (a napping group was compared with a matched non‐napping group, n = 108). We report that napping enhanced early afternoon alertness and importantly did not affect CBT‐I‐mediated improvements in the Insomnia Severity Index and Beck Depression Inventory‐2 and in self‐reported sleep efficiency, latency, and wake after sleep onset (assessed by the sleep diaries). Further investigations using objective methods of sleep assessments are now needed to confirm that napping behaviour does not compromise the improvements enabled by CBT‐I and may even strengthen adherence to the treatment.

Effects of a Triage Checklist to Optimize Insomnia Treatment Outcomes and Reduce Hypnotic Use: The RESTING Study.

Evaluate a triaged stepped-care strategy among adults 50 and older with insomnia disorder. Participants (N=245) were classified at baseline by a Triage-Checklist. Those projected to do better if they start treatment with therapist versus digitally delivered CBT-I (tCBT-I versus dCBT-I) constituted the YES stratum (n=137); the rest constituted the NO stratum (n=108). Participants were randomized within stratum to a strategy that utilized only dCBT-I (ONLN) or to a strategy that prospectively allocated the first step of care to dCBT-I or tCBT-I based on the Triage-Checklist and switched dCBT-I non-responders at 2-months to tCBT-I (STEP). Co-primary outcomes were the insomnia severity index (ISI) and the average nightly amount of prescription hypnotic medications used (MEDS), assessed at 2,4,6,9, and 12 months post-randomization. Mixed effects models revealed that, compared to ONLN, participants in STEP had greater reductions in ISI (p=0.001; η2=0.01) and MEDS (p=0.019, η2=0.01). Within the YES stratum, compared to ONLN, those in STEP had greater reductions in ISI (p=0.0001, η2=0.023) and MEDS (p=0.018, η2=0.01). Within the ONLN arm, compared to the YES stratum, those in the NO stratum had greater reductions in ISI (p=0.015, η2=0.01) but not in MEDS. Results did not change with treatment-dose covariate adjustment. Triaged-stepped care can help guide allocation of limited CBT-I treatment resources to promote effective and safe treatment of chronic insomnia among middle age and older adults. Further refinement of the Triage-Checklist and optimization of the timing and switching criteria may improve the balance between effectiveness and use of resources.

Modern approach to pharmacotherapy of chronic insomnia in childhood

Insomnia is a widespread problem in the pediatric population. The prevalence of insomnia in childhood varies from 5% to 50%. The lack of adequate therapy can lead to chronicity, impairment of cognitive and motor functions, and eventually development of cardiovascular and metabolic diseases, diabetes, and gastrointestinal and mental disorders. Thus, timely identification and treatment of childhood insomnia is important. This study aimed to summarize and systematize current information about the modern approach to pharmacotherapy of chronic insomnia in childhood. Modern and foreign randomized controlled trials over the past 10 years were analyzed. Treatment of chronic insomnia includes non-pharmacological and pharmacological approaches. Behavioral strategies are recommended as first-line treatment for childhood insomnia. The availability of different pharmacological drug groups allows for a personalized approach to treatment. However, the use of off-label drugs requires a justified prescription. The lack of large-scale clinical studies on the effectiveness, tolerability, dosing, and safety profile of drugs implies the need for further research to better understand the risks (negative side effects) and benefits of using such drugs for treating sleep disorders in children.

Anxiolytic impact of cognitive behavioural therapy for insomnia in patients with co-morbid insomnia and generalized anxiety disorder.

Cognitive behavioural therapy for insomnia (CBT-I) is an effective treatment for chronic insomnia that also improves non-sleep symptoms, such as mood and anxiety. Identifying sleep-specific variables that predict anxiety change after CBT-I treatment may support alternative strategies when people with generalized anxiety disorder (GAD) do not improve from standard GAD treatment. To investigate CBT-I on changes in anxiety and evaluate whether changes in sleep-specific variables predict anxiety outcomes. Seventy-two participants presenting with insomnia and GAD (GAD-I) completed four sessions of CBT-I. Participants completed daily diaries and self-report measures at baseline and post-treatment. CBT-I in a co-morbid GAD-I sample was associated with medium reductions in anxiety, and large reductions in insomnia severity. Subjective insomnia severity and tendencies to ruminate in response to fatigue predicted post-treatment anxiety change, in addition to younger age and lower baseline anxiety. The findings suggest that younger GAD-I participants with moderate anxiety symptoms may benefit most from the anxiety-relieving impact of CBT-I. Reducing perceived insomnia severity and the tendency to ruminate in response to fatigue may support reductions in anxiety in those with GAD-I.

Improving sleep outcomes in patients with cancer with chronic insomnia using cognitive behavioral therapy: A retrospective study.

e13555 Background: Cancer patients experience a threefold higher rate of insomnia (23-54%) than the general population. Cognitive behavioral therapy for Insomnia (CBT- i) is the gold standard treatment of chronic insomnia. Few studies, however, have demonstrated CBT- i efficacy for chronic insomnia in cancer patients. To address the needs of cancer patients with insomnia, a psycho-oncology physician trained to provide CBT- i therapy established an insomnia clinic in an ambulatory oncology center tailored for oncology patients. The objective of this study is to assess the efficacy of CBT- i for chronic insomnia among cancer patients. Methods: A retrospective review of electronic medical records was performed on consecutive referrals to an insomnia clinic in an ambulatory oncology center. All patients with ICD-10 confirmed chronic insomnia diagnosis who received at least 2 sessions up to a maximum of 7 sessions of CBT- i were included in the analysis. Demographic variables, cancer-related disease and treatment variables, and sleep parameters at initial session (T1) and last session (T2) were collected. Sleep parameters included sleep efficiency, total sleep time, sleep onset latency, number of nightly awakenings, and sleep quality. Semi-structured psychiatric clinical interviews, past medical and sleep history, and patient-rated Pittsburgh Sleep Quality Index (PSQI) scores at T1 were collected. Data analysis utilized SPSS descriptive statistics and T-test to compare differences between the baseline (T1) and post-CBT- i treatment (T2) sleep variable outcome measures. Results: The sample included 18 cancer patients (mean age 59 years; 12 Hispanics, 6 non-Hispanics; 16 females, 2 males) with ICD-10-confirmed chronic insomnia treated with CBT- i. Cancer-related variables among the sample included a mean duration of 18 months since cancer diagnosis, disease staging ranging from 0-IV, and 16 patients completed curative treatment. The sample included 13 breast cancer patients. Mean duration of insomnia was 6 years. PSQI score was 14 (PSQI score ranges from 0 to 21, scores above 5 are indicative of poor sleep quality). The mean number of sessions delivered was 5. Sleep parameters at T2 showed a significant improvement compared to those at T1 (Table). The number of nightly awakenings decreased from 3 at T1 to 2 at T2 (p=0.01), and 78% (14/18) of patients reported an improvement in their sleep quality at T2. Conclusions: Cognitive Behavioral Therapy for Insomnia demonstrates efficacy in the treatment of chronic insomnia in cancer patients and is easily administered within an ambulatory oncology center. [Table: see text]

Knowledge mapping of chronic insomnia: a bibliometric analysis (2000-2023).

Recently, significant scientific research breakthroughs have been witnessed in the treatment of chronic insomnia. However, it seems that there is currently no bibliometric analysis of this. Therefore, we hope to comprehensively review and analyze the scholarly system and research focus in the field of chronic insomnia treatment through bibliometric methods. Between 2000 and 2023, we explored various papers in relation to the treatment of chronic insomnia in the Web of Science Core Collection(WOSCC) database. Subsequently, the collected papers were subjected to bibliometric analysis utilizing CiteSpace, VOSviewer, and the "bibliometric" package in R language. With China and the United States(USA) among them, a total of 2937 papers were published across 49 countries. Publications related to the treatment of chronic insomnia were increasing year by year. The Laval University, Washington University, Pittsburgh University, and Stanford University were key research institutions. The journal Sleep was widely popular in the field and was also one of the most cited journals. These papers came from 148 authors, with Morin, Charles M., Roth, Thomas, Espie, Colin A., Harvey, Allison G., and Buysse, Daniel J. publishing the most papers and Morin, cm being co-cited the most. The treatment process of chronic insomnia can be divided into three main stages: drug intervention, diseases related to chronic insomnia, and cognitive behavioral therapy and mental health. Keywords such as "children and adolescents", "novel coronavirus pneumonia" (COVID-19), "mental health" and "heart failure" have become the focus of current research. We carried out a detailed bibliometric review of the development trends and research results of chronic insomnia research through this study for the first time. The information it provides reveals recent research hotspots and cutting-edge issues, providing valuable reference materials for researchers focusing on the treatment of chronic insomnia.

0415 Real-world Data and Health-related Quality of Life in Treatment of Chronic Insomnia with Daridorexant

0415 Real-world Data and Health-related Quality of Life in Treatment of Chronic Insomnia with Daridorexant

The Orexin system as a new approach for the improvement of sleep and daytime activity: an innovative therapy option for the treatment of chronic insomnia

ZusammenfassungDie chronische Insomnie ist eine der häufigsten Störungen des Schlafes. Ihre pharmakologische Therapie ist auf einige wenige zugelassene Hypnotika beschränkt.Der duale Orexin-Rezeptorblocker Daridorexant ist ein vom Wirkmechanismus und den Wirkeffekten her neuartiges schlafförderndes Medikament, welches in Studien mit Betroffenen mit einer moderaten bis schweren Insomnie seine Effektivität nachweisen konnte. Sowohl in der Gesamtpopulation und auch bei den über 65-Jährigen verkürzte Daridorexant objektiv die Einschlaflatenz und die Wachzeit im Schlaf und verlängerte die subjektive Schlafdauer. Letzteres ist insbesondere bei älteren Insomniepatienten besonders ausgeprägt. Für Schlafgestörte zusätzlich relevant ist die positive Wirkung von Daridorexant auf die Tagesbefindlichkeit, die anhand eines Fragebogens zu Schläfrigkeit, Wachheit, Kognition und Stimmung nachgewiesen werden konnte. Besserungen zeigten sich auch in verschiedenen Analogskalen zum Schlaf. Die Verträglichkeit war im Untersuchungszeitraum von 3 Monaten sehr gut, Zeichen einer Toleranz- oder Abhängigkeitsentwicklung fanden sich nicht.Aufgrund der Besserung von Schlaf und Tagesbefindlichkeit sowie des günstigen Nebenwirkungsprofils empfiehlt sich Daridorexant als ein innovatives Hypnotikum, welches die Differentialtherapie der chronischen Insomnie bereichert.

Chronic insomnia and ways to overcome it

Relevance. Chronic insomnia is one of the most common forms of nighttime sleep disorders. It leads to a decrease in human performance, the development of social maladjustment, and even changes in the personal sphere. Chronic insomnia can become a trigger for decompensation of somatic, neurological and mental diseases, which determines the need to find ways to overcome it. Objective. To determine the efficacy and safety of the dietary supplement Alpha-Melatonin Relax in the treatment of chronic insomnia in patients with chronic cerebral ischemia. Materials and methods. The study involved 30 patients (18 women and 12 men) with chronic cerebral ischemia of stage I and II, the average age of which was 46.12 ± 4.98 years. The course of treatment consisted of 30 days of taking Alpha-Melatonin Relax, 1–2 tablets 30–60 minutes before bedtime. Clinical and neurological symptoms were assessed and tested using the Pittsburgh Sleep Quality Index (PSQI) questionnaire, Epworth Daytime Sleepiness Scale, and the Hospital Anxiety and Depression Scale (HADS) in dynamics. Results and their discussion. The study results showed that 30-day administration of Alpha-Melatonin Relax provided a significant p≤0.05 improvement in the subjective assessment of the quality of night sleep, a decrease in the time to fall asleep, an increase in sleep duration, a decrease in the severity of emotional disorders and daytime dysfunction. Clinical and neurological follow-up of patients during the treatment course revealed a significant reduction in the severity of chronic insomnia, asthenia, and anxiety-depressive symptoms, which allows us to recommend the use of the dietary supplement Alpha-Melatonin Relax in clinical practice. Conclusions. Based on the data of a clinical-neurological and psychodiagnostic study, the statistically significant effectiveness of the dietary supplement AlphaMelatonin Relax in correcting the symptoms of chronic insomnia in patients with the initial stages of chronic brain ischemia has been proven.

Daridorexant treatment for chronic insomnia: a real-world retrospective single-center study

IntroductionChronic insomnia disorder (CID) significantly impacts well-being and daily functioning. Daridorexant, a double orexin receptor blocker, has shown efficacy in randomized clinical trials and has been recently approved for the treatment of CID in adult patients. This retrospective observational study aimed to describe real-world data on daridorexant effectiveness and safety in adult patients with CID.MethodsConsecutive patients initiating on-label daridorexant at the Sleep Medicine Centre, University Hospital of Rome Tor Vergata were enrolled. Baseline and 30-day follow-up (FU) evaluations included patients’ and CID characteristics, comorbidities, and clinicians’ and patients’ subjective ratings of changes with the Clinical and Patient Global Impression-Improvement scores (CGI-Is and PGI-Is), as well as Insomnia Severity Index (ISI) scores in a subgroup of patients.ResultsSixty-nine patients initiated 50-mg daily dosage. At FU, 58% of both patients and clinicians rated CID as improved on CGI-Is and PGI-Is, with no differences based on comorbidities, sex, or number of previous medications. No significant predictors of CGI-Is and PGI-Is improvement were identified. At FU, ISI scores (n = 24) significantly decreased from 18.25 ± 3.21 to 12.08 ± 6.12 (Z = 8.000; p < 0.001). Of these, eight patients (33.3%) had absence of insomnia symptoms, and no patients reported a worsening in ISI score categories.ConclusionsThis study suggests daridorexant to be effective and safe in real-world CID treatment whether used as a first-ever treatment, switch, or add-on, as reflected by subjective and objective measures and the absence of serious treatment-related adverse events. Future research on larger cohorts should explore daridorexant potential across diverse patient characteristics.

Prevalence and associations of multiple hypnotic prescriptions in a clinical sample.

We examined the prevalence of multiple hypnotic prescriptions and its association with clinical and demographic characteristics from the electronic health record (EHR) in the Mayo Clinic Biobank. Adult participants enrolled in the Mayo Clinic Biobank with an EHR number of ≥ 1 year were included (n = 52,940). Clinical and demographic characteristics were compared between participants who were and were not prescribed any hypnotic approved for insomnia by the US Food and Drug Administration and/or trazodone and in those prescribed a single vs multiple (≥ 2) hypnotics. A phenotype-based, phenome-wide association study (PheWAS) examining associations between hypnotic prescriptions and diagnoses across the EHR was performed adjusting for demographic and other confounders. A total of 17,662 (33%) participants were prescribed at least 1 hypnotic and 5,331 (10%) received ≥ 2 hypnotics. Participants who were prescribed a hypnotic were more likely to be older, female, White, with a longer EHR, and a greater number of diagnostic codes (all P < .001). Those with multiple hypnotic prescriptions were more likely to be younger, female, with a longer EHR, and a greater number of diagnostic codes (all P < .001) compared with those prescribed a single hypnotic. The PheWAS revealed that participants with multiple hypnotic prescriptions had higher rates of mood disorders, anxiety disorders, suicidal ideation, restless legs syndrome, and chronic pain (all P < 1 e-10). Receiving multiple hypnotic prescriptions is common and associated with a greater prevalence of psychiatric, chronic pain, and sleep-related movement disorders. Future studies should examine potential genetic associations with multiple hypnotic prescriptions to personalize treatments for chronic insomnia. Kolla BP, Mansukhani MP, Chakravorty S, Frank JA, Coombes BJ. Prevalence and associations of multiple hypnotic prescriptions in a clinical sample. J Clin Sleep Med. 2024;20(5):793-800.

Dynamic meditation as an intervention for treatment of chronic insomnia

Dynamic meditation as an intervention for treatment of chronic insomnia

The European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023.

Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B).

Protocol for a randomized controlled trial exploring the brain mechanism and therapeutic effect of electroacupuncture on cognitive function and sleep quality in chronic insomnia

BackgroundInsomnia is a prevalent sleep disorder that affects up to 15% of the population worldwide and is the second most common mental health issue. There is increasing interest in the effects of long-term insomnia on cognitive function. Electroacupuncture can effectively improve cognitive function and sleep quality, yet the underlying brain network mechanisms remain unclear. This study aims to explore the network regulatory mechanisms associated with enhanced cognitive function and sleep quality, providing theoretical support for the use of electroacupuncture in the clinical treatment of chronic insomnia.MethodsThis study is divided into two parts. Sixteen individuals with chronic insomnia and 16 healthy controls of similar age and gender will be recruited in Study 1 to examine the brain network topology of individuals with chronic insomnia. Study 2 will be a randomized controlled trial with 120 chronic insomnia patients divided into three groups: Group A (electroacupuncture plus placebo drug), Group B (drug plus placebo electroacupuncture), and Group C (placebo electroacupuncture plus placebo drug). Participants will be exposed to 24 treatments over an 8-week period (3 times per week) and monitored for 12 additional weeks. The primary outcome measure will be changes in brainwave data from before to after the treatment. In addition, the Wisconsin Card Sorting Test and the Pittsburgh Sleep Quality Index will be utilized as secondary outcomes to measure from before to after treatment and during the follow-up. A correlation analysis will be conducted to explore links among modifications in brainwave patterns, Wisconsin Card Sorting Test scores, and Pittsburgh Sleep Quality Index scores. Additionally, any adverse events will be strictly monitored.DiscussionElectroacupuncture may represent an alternative treatment for chronic insomnia, and this trial is expected to reveal the brain mechanism by which electroacupuncture improves cognitive function and sleep quality in chronic insomnia patients.Trial registrationChiCTR2200060150 (Chinese Clinical Trial Registry, http://www.chictr.org.cn, registered on 20 May 2022).

Factors influencing the effectiveness of digital cognitive behavioural therapy for chronic insomnia in clinical practice.

Digital cognitive behavioural therapy for chronic insomnia (D-CBT-I) has been shown to be as efficacious as traditional CBT-I. However, not all patients achieve insomnia remission after treatment. We explored the factors influencing the effectiveness of D-CBT-I in a clinical practice. A total of 414 Asian chronic insomniacs were studied during a 6 week D-CBT-I intervention. All patients were assessed at baseline and posttreatment and were determined to be remitters or non-remitters, responders or non-responders by posttreatment criteria; Insomnia Severity Index (ISI <8) or ISI reduction ≥8, to examine whether remission and response status were associated with patient baseline characteristics. The average baseline ISI score in all subjects was 16.29 points. At posttreatment, 192 (46.4%) patients achieved ISI remission and 218 (52.7%) patients demonstrated an ISI response. An increased baseline early morning awakening time and ISI score were independently associated with a lower odds for remission (OR, 0.995 and 0.991, respectively). Increased baseline Patients Health Questionnaire-9 score was independently associated with higher odds for response (OR, 1.114). Our results suggest that D-CBT-I can be recommended as the first-line treatment for chronic insomnia, particularly in insomniacs with milder insomnia symptoms and more severe depressive symptoms. Meanwhile, the effectiveness of D-CBT-I was adversely affected by longer early morning awakening time and higher insomnia severity at pretreatment, which may be improved by more intense intervention and greater therapeutic support or by traditional CBT-I.

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.

Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.

Chronic insomnia affects 5% to 10% of the US population, increasing the demand for treatment options and the corresponding research to prove their validity.1 This review compares recommendations from 3 clinical guidelines and summarizes hypnotic medications, including their newly reported side effects not mentioned in the guidelines. In addition, we aim to provide an overview of what pharmacotherapies are available for prescribers and patients. A literature search was conducted for articles published prior to January 10, 2022, and case reports and clinical studies were retrieved from PubMed and Google Scholar. Definitive conclusions cannot be drawn regarding the safety and efficacy of medications reviewed; however, trends are apparent. All 3 guidelines included in this review remarked most treatment recommendations as weak except for cognitive behavioral therapy for insomnia, which is effective but not readily available. Furthermore, based on the 15 case reports and 13 clinical studies presented in this review, many of the medications used for treatment of insomnia present safety concerns. Benzodiazepines and benzodiazepine receptor agonists are commonly used hypnotic agents with the "Z-drugs" having robust data establishing their efficacy for the short-term treatment of chronic insomnia. However, significant adverse effects related to the central nervous system (CNS), including developing tolerance, addiction, CNS depression, and amnesia, remain barriers to their long-term use. In comparison, newer agents present more favorable side-effect profiles although with less established efficacy. Additionally, off-label agents, including antidepressants, antihistamines, and natural supplements, are discussed due to their prominent use.

Development and Initial Evaluation of Web-Based Cognitive Behavioral Therapy for Insomnia in Rural Family Caregivers of People With Dementia (NiteCAPP): Mixed Methods Study.

Informal caregivers of people with dementia frequently experience chronic insomnia, contributing to stress and poor health outcomes. Rural caregivers are particularly vulnerable but have limited access to cognitive behavioral therapy for insomnia (CBT-I), a recommended frontline treatment for chronic insomnia. Web-based delivery promises to improve insomnia, particularly for rural caregivers who have limited access to traditional in-person treatments. Our team translated an efficacious 4-session standard CBT-I content protocol into digital format to create NiteCAPP. This study aimed to (1) adapt NiteCAPP for dementia caregivers to create NiteCAPP CARES, a tailored digital format with standard CBT-I content plus caregiver-focused modifications; (2) conduct usability testing and evaluate acceptability of NiteCAPP CARES' content and features; and (3) pilot-test the adapted intervention to evaluate feasibility and preliminary effects on sleep and related health outcomes. We followed Medical Research Council recommendations for evaluating complex medical interventions to explore user needs and adapt and validate content using a stepwise approach: (1) a rural dementia caregiver (n=5) and primary care provider (n=5) advisory panel gave feedback that was used to adapt NiteCAPP; (2) caregiver (n=5) and primary care provider (n=7) focus groups reviewed the newly adapted NiteCAPP CARES and provided feedback that guided further adaptations; and (3) NiteCAPP CARES was pilot-tested in caregivers (n=5) for feasibility and to establish preliminary effects. Self-report usability measures were collected following intervention. Before and after treatment, 14 daily electronic sleep diaries and questionnaires were collected to evaluate arousal, health, mood, burden, subjective cognition, and interpersonal processes. The stepped approach provided user and expert feedback on satisfaction, usefulness, and content, resulting in a new digital CBT-I tailored for rural dementia caregivers: NiteCAPP CARES. The advisory panel recommended streamlining content, eliminating jargon, and including caregiver-focused content. Focus groups gave NiteCAPP CARES high usefulness ratings (mean score 4.4, SD 0.79, scored from 1=least to 5=most favorable; score range 4.2-4.8). Multiple features were evaluated positively, including the intervention's comprehensive and engaging information, caregiver focus, good layout, easy-to-access intervention material, and easy-to-understand sleep graphs. Suggestions for improvement included the provision of day and night viewing options, collapsible text, font size options, tabbed access to videos, and a glossary of terms. Pilot-test users rated usefulness (mean score 4.3, SD 0.83; range 4.1-4.5) and satisfaction (mean score 8.4, SD 1.41, scored from 1=least to 10=most satisfied; range 7.4-9.0) highly. Preliminary effects on caregiver sleep, arousal, health, mood, burden, cognition, and interpersonal processes (all P<.05) were promising. Adaptations made to standard digital CBT-I created a feasible, tailored digital intervention for rural dementia caregivers. Important next steps include further examination of feasibility and efficacy in a randomized controlled trial with an active control condition, a multisite effectiveness trial, and eventual broad dissemination. ClinicalTrials.gov NCT04632628; https://clinicaltrials.gov/ct2/show/NCT04632628.

Natural Immunosuppressants as a Treatment for Chronic Insomnia Targeting the Inflammatory Response Induced by NLRP3/caspase-1/IL-1β Axis Activation: A Scooping Review.

Chronic insomnia is an inflammatory-related disease with an important pathological basis for various diseases which is a serious threat to a person's physical and mental health. So far, many hypotheses have been proposed to explain the pathogenesis of insomnia, among which inflammatory mechanisms have become the focus of scientific attention. In this regard, the aim of the present scooping review is to evaluate the potential benefits of natural compounds in treatment of chronic insomnia targeting nucleotide-binding oligomerization domain (NOD)-like receptor-pyrin-containing protein 3 (NLRP3)/caspase-1/IL-1β axis as one of the most important activators of inflammatory cascades. The data show that compounds that have the potential to cause inflammation induce sleep disorders, and that inflammatory mediators are key molecules in regulating the sleep-related activity of neurons. In the inflammatory process of insomnia, the role of NLRP3 in the pathogenesis of insomnia has been gradually considered by researchers. NLRP3 is an intracellular sensor that recognizes the widest range of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). After identification and binding to damage factors, NLRP3 inflammasome is assembled to activate the caspase-1 and IL-1β. Increased production and secretion of IL-1β may be involved in central nervous system dysregulation of physiological sleep. The current scooping review reports the potential benefits of natural compounds that target NLRP3 inflammasome pathway activity and highlights the hypothesis which NLRP3 /caspase-1/IL-1β may serve as a potential therapeutic target for managing inflammation and improving symptoms in chronic insomnia.