Treatment Of Insomnia Disorders Research Articles

Paradoxical intention as a treatment for insomnia disorder: study protocol for a mixed-methods pilot trial

IntroductionParadoxical intention (PI) is an insomnia treatment developed in the 1970s, which instructs patients to gently attempt to remain awake while in bed at night with the lights off. Previous...

Toxicity of benzodiazepines in the treatment of insomnia disorders in older adults: a systematic literature review

Toxicity of benzodiazepines in the treatment of insomnia disorders in older adults: a systematic literature review

Penerapan Senam Lansia Pada Lansia Insomnia Di Desa Pilangsari Kabupaten Sragen

Background: feeling sleepy every day is the impact of sleep disturbance at night (insomnia), and can interfere with daily activities. Insomnia can cause other effects such as anxiety, stress, and ending with depression. In the elderly, sleep disturbances can cause various kinds of degenerative diseases that have been suffered and become uncontrolled. Treatment of insomnia disorder is carried out with non-pharmacological treatment, one of the non-pharmacological therapies that can be done is Elderly Exercise. Objective: To determine changes in the level of insomnia in the elderly before and after doing Elderly Exercise. Method: This application uses a descriptive method on 2 respondents, carried out 6 times in 2 weeks. The instrument used was KSPBJ-IRS (Jakarta Biological Psychiatric Study Group-Insomnia Rating Scale). Results: Treatment of insomnia disorder with Elderly Gymnastics given 6 times for 2 weeks in 30-45 minutes can affect the level of the respondent's sleep quality What specific exercises were included in the Elderly Gymnastics therapy?y so that there is a change in the elderly insomnia scale. Conclusion: the application shows that after the Elderly Seam was carried out 6 times in 2 weeks within 30-45 minutes there was a decrease in the insomnia scale in both respondents.

Interactions between insomnia, sleep duration and emotional processes: An ecological momentary assessment of longitudinal influences combining self-report and physiological measures.

Previous studies indicated that further investigation is needed to understand how insomnia disorder interacts with emotional processes. The present study is an ecological momentary assessment evaluating the link between emotional and sleep alterations in patients with insomnia. Physiological (heart rate and heart rate variability) and subjective (sleep and emotions) indices were observed for 5 days in patients with insomnia disorder (n = 97), good sleepers under self-imposed sleep restriction (n = 41), and good sleepers with usual amount of sleep (n = 45). We evaluated differences in emotion regulation strategies and in valence and variability of emotional experiences. Over 5 days, patients with insomnia showed increased sleep and emotional difficulties compared with both control groups. Independent from group allocation, days with more negative emotions were associated with higher sleep alterations. Longer wake episodes at night and higher diurnal heart rate were associated with increased variations in emotion experienced during the day. Only in patients with insomnia, use of adaptive emotion regulation strategies was associated with higher sleep efficiency. Our data showed that alterations in sleep and emotional processes are closely linked. A combination of strategies targeting both sleep and emotional processes appears promising in the prevention and treatment of insomnia disorder.

Real, misreported, and backfilled adherence with paper sleep diaries

ObjectivePaper-based sleep diaries play an important role in the diagnosis and treatment of insomnia disorder. Accurate self-report data help to guide therapy and track progress, both in the clinic and during research trials. Previous research with paper diaries suggests that timely adherence with self-report diaries may be an issue, which can result in biased event recall. Patients/methodsUniversity students (N = 31) were asked to track their bedtime and wake time within 30 min of these events on paper-based sleep diaries. Specially designed binders covertly timestamped when participants actually wrote on their sleep diary. We assessed adherence by comparing timestamped diary usage with what participants documented in their sleep diary. ResultsParticipants self-reported they were adherent with sleep diary instructions 97.9% of the time. However, timestamped data revealed that only 37.1% of diary entries were completed within the instructed timeframe. More than half of participants backfilled diary data, and three participants (9.7%) provided data that completely did not match their actual time of completion. ConclusionsWhen naïve to the objective tracking of their sleep diary usage, participants greatly over-reported the extent of their adherence. Non-adherence with sleep diary protocols poses a challenge for researchers utilizing this tool as a study outcome in clinical trials and for clinicians attempting to implement behavioral therapies for insomnia.

Efficacy and safety of Wuling capsule for insomnia disorder: a systematic review and meta-analysis of randomized controlled trials

ObjectivesWuling capsule has been used in treatment of insomnia disorder in China for decades, but the reported treatment efficacy of different studies was not consistent. This study intended to evaluate the efficacy and safety of Wuling capsule for insomnia disorder, so as to provide evidence for clinical application. MethodsEight databases (MEDLINE, EMBASE, Ovid, Cochrane Library, Chinese National Knowledge Infrastructure, VIP information database, Chinese Biomedical Database and Wanfang) were searched from inception to September 14, 2021. Randomized controlled trials (RCTs) comparing Wuling capsule with controls in adults with insomnia disorder were eligible. The primary outcome was sleep quality assessed by Pittsburgh Sleep Quality Index (PSQI), and the secondary outcomes were severity of insomnia disorder measured by Sleep Dysfunction Rating Scale (SDRS) and adverse events. This study was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0. ResultsNineteen RCTs with a total of 1850 participants were included. In terms of sleep quality assessed by PSQI, Wuling capsule significantly lowered PSQI score (MD: −1.92, 95% CI: [−2.34, −1.50], P < 0.00001, I2 = 95%) compared to controls, and the effect of Wuling capsule was significantly better than control no matter when Wuling capsule as monotherapy (MD: −1.71, 95% CI: [−2.33, −1.09], P < 0.00001, I2 = 97%) or as adjunctive therapy (MD: −2.10, 95% CI: [−2.66, −1.55], P < 0.00001, I2 = 90%). Wuling capsule was more effective for the treatment duration lasted 8 weeks (MD: −2.57, 95% CI: [−3.52, −1.62], P < 0.00001, I2 = 93%) than 4 weeks (MD: −1.68, 95% CI: [−2.13, −1.22], P < 0.00001, I2 = 95%). In terms of severity of insomnia disorder measured by SDRS, Wuling capsule significantly reduced SDRS score (MD: −4.21, 95% CI: [−4.95, −3.46], P < 0.00001, I2 = 0%) compared to benzodiazepines. Wuling capsule significantly reduced adverse events compared to controls (RR: 0.47, 95% CI: [0.34, 0.65], P < 0.00001, I2 = 43%). ConclusionWuling capsule can safely and effectively improve sleep quality in patients with insomnia disorder. However, these findings require careful recommendation due to the high heterogeneity and high risk of bias in the included trials. Clinical trials with higher quality designs are needed.

Web-based provider training of cognitive behavioral therapy of insomnia: engagement rates, knowledge acquisition, and provider acceptability

ABSTRACT Insomnia is common but severely underreported and undertreated. One possible reason for this problem is the lack of providers in cognitive behavioral therapy for insomnia (CBT-I). To address this we created CBTIweb.org, an online training platform for providers to learn the basics of sleep, assessing insomnia, and CBT-I. The present study assessed the reach of CBTIweb by examining engagement, knowledge acquisition, and perceived acceptability. Participants who registered for CBTIweb self-reported their practice setting and personal characteristics (i.e. degree, profession, licensure status). Knowledge acquisition was assessed with pre- and post-tests, and provider acceptability was assessed via a survey. In the first three months after launching CBTIweb, 2586 providers registered and 624 of these completed the training within three months of registering. Chi-square tests of independence revealed no differences in completion rates by education or profession, though trainees were more likely to initiate and complete treatment than licensed providers. Paired t tests revealed significant knowledge acquisition, and most providers positively rated the website navigation, content, aesthetics, and understanding of core CBT-I skills. This study demonstrated CBTIweb is an effective platform for training health professionals to be minimally proficient in the gold standard treatment for insomnia disorder.

The impact of insomnia disorder on adult attention-deficit/hyperactivity disorder severity: A six-month follow-up study

Background and objectivesThe longitudinal relationship between insomnia disorder and adult attention-deficit/hyperactivity disorder (ADHD) has been scarcely investigated. This study aimed to evaluate the relationship between the remission of insomnia disorder and adult ADHD clinical severity, psychiatric and medical comorbidities, and the health-related quality of life (HRQoL) in a 6-month follow-up. MethodsNinety-two adult patients with ADHD and insomnia disorder (52.2% males; mean age 39.5 ± 11.0 years) were comprehensively assessed at baseline, 3 months, and 6 months of a follow-up period. The evaluation included semi-structured interviews (for ADHD and comorbidity assessment), the Pittsburgh Sleep Quality Index, Insomnia Severity Index, and Epworth Sleepiness Scale. The diagnosis of ADHD and insomnia disorder was performed according to DSM-5 criteria. At baseline and follow-up, psychoeducation/sleep hygiene and, if necessary, pharmacological were prescribed for insomnia. ResultsEighty-seven patients completed the 6-month follow-up. Insomnia disorder remission was reported in 72.4% of cases and was related to a greater improvement in ADHD symptoms and severity throughout the follow-up period. Additionally, an improvement in psychiatric comorbidities and better HRQoL were associated with insomnia disorder remission. ConclusionThe current study highlights that the treatment of insomnia disorder in ADHD adult patients may have an important role in the outcome of ADHD therapeutic approaches by reducing their severity.

Prevention of Incident and Recurrent Major Depression in Older Adults With Insomnia

Older adults with insomnia have a high risk of incident and recurrent depression. Depression prevention is urgently needed, and such efforts have been neglected for older adults. To examine whether treatment of insomnia disorder with cognitive behavioral therapy for insomnia (CBT-I) compared with an active comparator condition, sleep education therapy (SET), prevents major depressive disorder in older adults. This assessor-blinded, parallel-group, single-site randomized clinical trial assessed a community-based sample of 431 people and enrolled 291 adults 60 years or older with insomnia disorder who had no major depression or major health events in past year. Study recruitment was performed from July 1, 2012, to April 30, 2015. The trial protocol was modified to extend follow-up from 24 to 36 months, with follow-up completion in July 2018. Data analysis was performed from March 1, 2019, to March 30, 2020. Participants were randomized to 2 months of CBT-I (n = 156) or SET (n = 135). The primary outcome was time to incident major depressive disorder as diagnosed by interview and Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria. Secondary outcome was sustained remission of insomnia disorder before depression event or duration of follow-up. Among 291 randomized participants (mean [SD] age, 70.1 [6.7] years; 168 [57.7%] female; 7 [2.4%] Asian, 32 [11.0%] Black, 3 [1.0%] Pacific Islander, 241 [82.8%] White, 6 [2.1%] multiracial, and 2 [0.7%] unknown), 156 were randomized to CBT-I and 135 to SET. A total of 140 participants (89.7%) completed CBT-I and 130 (96.3%) participants completed SET (χ2 = 4.9, P = .03), with 114 (73.1%) completing 24 months of follow-up in the CBT-I group and 117 (86.7%) in the SET group (χ2 = 8.4, P = .004). After protocol modification, 92 (59.0%) of the CBT-I participants and 86 (63.7%) of the SET participants agreed to extended follow-up (χ2 = 0.7, P = .41), with 81 (51.9%) of the CBT-I participants and 77 (57.0%) of the SET group completing 36 months of follow-up (χ2 = 0.8; P = .39). Incident or recurrent major depression occurred in 19 participants (12.2%) in the CBT-I group and in 35 participants (25.9%) in the SET group, with an overall benefit (hazard ratio, 0.51; 95%, CI 0.29-0.88; P = .02) consistent across subgroups. Remission of insomnia disorder continuously sustained before depression event or during follow-up was more likely in CBT-I participants (41 [26.3%]) compared with the SET participants (26 [19.3%], P = .03). Those in the CBT-I group with sustained remission of insomnia disorder had an 82.6% decreased likelihood of depression (hazard ratio, 0.17; 95%, CI 0.04-0.73; P = .02) compared with those in the SET group without sustained remission of insomnia disorder. The findings of this randomized clinical trial indicate that treatment of insomnia with CBT-I has an overall benefit in the prevention of incident and recurrent major depression in older adults with insomnia disorder. Community-level screening for insomnia concerns in older adults and wide delivery of CBT-I-based treatment for insomnia could substantially advance public health efforts to treat insomnia and prevent depression in this vulnerable older adult population. ClinicalTrials.gov Identifier: NCT01641263.

Poor Sleep in Inflammatory Bowel Disease Is Reflective of Distinct Sleep Disorders.

Poor sleep is common in inflammatory bowel disease (IBD), predicting increased risk of flares, surgery, and/or hospitalization and reducing quality of life. To profile specific sleep disorder symptoms in IBD, informing intervention efforts. 312 adults with Crohn's disease or ulcerative colitis were recruited from an academic medical center in New Hampshire, USA. Participants completed online surveys about sleep including well-validated measures of sleep quality, insomnia, restless leg syndrome, sleep apnea, and circadian rhythms. Participants also answered questions about IBD-related problems that could interfere with sleep. 69.4% of participants reported experiencing poor sleep and 50% reported clinically significant insomnia. Participants with active IBD symptoms were more likely to have poor sleep and insomnia. Of those with poor sleep, 67.8% met the clinical threshold for insomnia disorder and 31.3% met criteria for two or more sleep disorders. IBD-related sleep disruptions (e.g., nighttime awakenings due to bowel movements) were not significantly related to poor sleep quality, but significantly related to insomnia severity for participants with active Crohn's disease. While poor sleep in IBD is reflective of a number of different sleep problems, it is most frequently related to insomnia. IBD symptom severity contributes to insomnia, but insomnia is also distinct from IBD-related sleep disruptions. Future research on the treatment of insomnia disorder in particular in individuals with IBD is warranted.

Review of the Efficacy and Safety of Lemborexant, a Dual Receptor Orexin Antagonist (DORA), in the Treatment of Adults With Insomnia Disorder.

To provide an overview of the efficacy and safety of lemborexant in the treatment of insomnia disorder by assessing the currently available literature. A literature search of PubMed was performed (2010 to March 2021) using the following search terms: lemborexant, sleep, orexin. All relevant English-language studies were reviewed and considered, with a focus on phase 3 trials. The efficacy and safety of lemborexant in the treatment of insomnia disorder in adults was demonstrated in 2 phase 3 trials. Lemborexant significantly reduced latency to persistent sleep compared with placebo. The first study also demonstrated a significant reduction compared with the active control zolpidem ER. Somnolence and headache were relatively common, but the marked adverse effects associated with other medications commonly used to treat insomnia, such as cognitive and psychomotor impairment and complex sleep-related behaviors, were not observed. Although nonpharmacological therapy is considered first-line treatment for insomnia disorder, pharmacological treatment is most commonly utilized. Lemborexant is a viable pharmacological treatment option for patients who are unable to tolerate the adverse effects associated with the most commonly prescribed medications for insomnia, such as benzodiazepines and sedative-hypnotics (Z drugs). This is especially true for geriatric patients, who may be more sensitive to these adverse effects. Lemborexant can be recommended to treat insomnia disorder when pharmacological treatment is warranted. It has demonstrated efficacy in clinical trials and is likely better tolerated than most currently available treatment options.

Cannabinoids in the Treatment of Insomnia Disorder: A Systematic Review and Meta-Analysis.

Insomnia is associated with significant comorbidity, disability and impact on quality of life and, despite advances in pharmacotherapy and psychotherapy, remains a significant burden to society. Cannabinoids are gaining acceptance for use as medicines in the treatment of insomnia disorder. We conducted a systematic review and meta-analysis to evaluate the efficacy of cannabinoids in the treatment of insomnia disorder. We performed a systematic review of the PubMed, Cochrane Library, MEDLINE, and Cumulative Index to Nursing and Allied Health Literature Complete databases from inception to 5 December 2019, and again prior to data abstraction, for studies of cannabis-based products for the treatment of insomnia disorder in adults. Inclusion criteria were (1) clinical studies, (2) participants aged ≥18years, (3) insomnia disorder either formally diagnosed against contemporaneous diagnostic criteria or quantified with validated instruments and (4) compared cannabis-based products with the standard of care, placebo or a sedative. No language restrictions were imposed. Non-primary research, animal studies and studies of cannabis-induced insomnia were excluded. Risk of bias was assessed using the RoB 2 tool for randomised controlled trials (RCTs) and Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) tool for non-randomized trials. Heterogeneity was assessed with the I2 statistic. A total of five studies (two RCTs and three non-randomised studies) with 219 study participants were included, of which three could be combined. The three non-randomised studies contributed data on the Pittsburgh Sleep Quality Index Questionnaire score, showing a favourable effect of cannabinoids at ≤4weeks of follow-up (mean difference -1.89 [95% confidence interval {CI} -2.68 to -1.10]; n=176) and at 8 weeks of follow-up (mean difference -2.41 [95% CI -3.36 to -1.46]; n=166). One double-blind crossover RCT (n=32) reported that, compared with amitriptyline, nabilone-a synthetic analogue to tetrahydrocannabinol (THC)-improved Insomnia Severity Index scores after 2 weeks of treatment (adjusted difference -3.25 [95% CI -5.26 to -1.24]) and resulted in a more restful sleep as a sub-measure of the Leeds Sleep Evaluation Questionnaire (LSEQ) (difference 0.48 [95% CI 0.01-0.95]) but with no effect on overall sleep quality as measured by the LSEQ. In a single ascending-dose RCT (n=9), THC reduced sleep-onset latency compared with placebo at 10mg, 20mg and 30mg doses (mean difference -43.00min [95% CI -82.76 to -3.24], -62.00 [95% CI -103.60 to -20.40] and -54.00 [95% CI -103.93 to -4.07], respectively). All the included studies were assessed as poor quality, mainly due to small sample sizes, short treatment periods, uncertain clinical significance and high risk of bias. Few studies have examined the efficacy of cannabinoids in the treatment of insomnia disorder. Despite some possible signals for efficacy, the heterogeneity of participants, interventions, efficacy outcomes and results, and the high risk of bias across included trials, do not reliably inform evidence-based practice. This review highlights shortcomings in the existing literature, including lack of diagnostic clarity, poorly defined participant groups, non-standardised interventions and studies of inappropriate design, duration and power to detect clinically meaningful outcomes. Further research in the form of high-quality RCTs are required before drawing any conclusions about the efficacy of cannabinoids in the treatment of insomnia disorder. PROSPERO registration number, CRD42020161043.

0504 Efficacy and Safety of Seltorexant in Insomnia Disorder

Abstract Introduction Insomnia disorder affects 3-6% of the population and includes functional impairing symptoms for ≥3 months. Current hypnotics have limitations (eg fall risk, dependency, parasomnia, cognitive impairment). In a previous proof-of-concept study, seltorexant, a selective orexin-2 receptor antagonist, dosed at 40mg nightly improved sleep efficiency, latency to persistent sleep (LPS), and wake after sleep onset (WASO) versus placebo. Methods A multicenter, double-blind, randomized, parallel-group, active- and placebo-controlled, 14-day, dose-finding study (NCT03375203) assessed the efficacy and safety of seltorexant in adult and elderly subjects meeting DSM-5 insomnia disorder criteria. Subjects were randomized (1:1:1:1:1 ratio) to: placebo, seltorexant 5mg, 10mg, 20mg, or zolpidem. Primary endpoint: Based on PSG, dose response in LPS change on Night 1 relative to baseline. Secondary endpoints included change from baseline in: WASO over the first 6 hours (WASO-6) on Night 1, and LPS and WASO-6 on Night 13. Multiple Comparison Procedure-Modeling, ANCOVA and MMRM were used for data analyses. Results 365 patients were randomized and 347 (95%) completed the double-blind phase with 68% women and median age of 59yr (22 to 84yr). Statistically significant dose-response relationship (p-value &amp;lt;0.001) was observed for LPS at Night 1 (5mg=12%, 10mg=36%, 20mg=49% improvement compared with placebo). Similar findings were observed for WASO-6 and benefits sustained from Night 1 to 13. The 20 mg dose showed greater improvement than zolpidem on LPS at Nights 1 and 13 and on WASO-6 at Night 13. Overall treatment-emergent adverse events rates were comparable in the seltorexant, placebo, and zolpidem treatment groups. Conclusion Statistically significant and clinically meaningful improvements on LPS &amp; WASO-6 were observed for seltorexant 10 and 20mg dose groups versus placebo. No safety concerns were observed. Seltorexant with its novel mechanism holds potential as a new treatment for insomnia disorder. Support

0546 Sleep Science at Home - Delivering Sleep Assessment and Digital CBT-i at Scale

Abstract Introduction Cognitive-behavioral therapy for insomnia (CBT-I) is the current first-line treatment for insomnia disorder, recommended by the AASM and SRS. Digital versions of CBT-I have been developed and validated to address the need for implementation at scale but still suffer from poor accessibility and compliance. Therefore, the aim of this open-label, Real-World Study (RWS) was to assess the engagement and efficacy of a next-generation CBT-i 6-weeks program. Methods 1304 subjects were included in the analysis between Dec 23rd, 2018 and December, 14th 2019. The main inclusion criteria were having an Insomnia Severity Index ISI ≥ 15 and completion of one week of Dreem program. The variables have been measured by the Dreem headband (DH) for objective variables, and on subjects’ answers to questionnaires for subjective ones. Results The retention during this RWS was 70.4 % (Pre: n = 1304 and Week 4: n = 935). The program led to a clinically significant decrease of 7.42 points on the ISI (p &amp;lt; 0.001). The obj-WASO was reduced by 35% (n = 359, p &amp;lt; 0.001), obj-Awakenings were reduced by 37% (n = 359 p &amp;lt; 0.001), obj-SE was increased by 2.56 points (n = 305, p &amp;lt; 0.001) and obj-SOL was reduced by 22% (n = 359, p &amp;lt; 0.001). The subj-SOL was reduced by 41% (n = 176, p &amp;lt; 0.001), subj-SE was increased by 8.9 points (n =168, p &amp;lt; 0.001), subj-SD was increased by 16% (baseline: 307.50 ± 88.86 min; post 357.07 ± 91.24 min, subj-SD (n = 174, p &amp;lt; 0.001). Conclusion The results of this RWS suggest this insomnia program has a high engagement compared to other digital CBT-I programs and is as effective as traditional in-person CBT-I. This new generation of Insomnia therapy combining hardware, software and therapist serves as an efficient and engaging treatment implementable at scale. Support This study has been supported by Dreem sas.

Local sleep and wakefulness—the concept and its potential for the understanding and treatment of insomnia disorder

In ancient mythology, sleep was often regarded as an inactive state, close to death. Research in the past century has, however, demonstrated that the brain is highly active and oscillates through well-defined stages during sleep. Yet it is only over the past decade that accumulating evidence has shown that sleep and wake processes can occur simultaneously, localized in distinct areas of the brain. The aim of this article is to review relevant aspects of the shift from global to local concepts of sleep–wake regulation and to further translate this perspective to the clinical problem of insomnia. Animal and human studies show that local wake-like activations (‘islands of wakefulness’) can occur during both major sleep stages, i.e. non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Preliminary evidence suggests that higher levels of local wake-like activity, not captured in standard polysomnographic recordings, might underlie the perception of disrupted sleep or even wakefulness during polysomnographic epochs of sleep in patients with chronic insomnia. To further decipher the neural mechanisms, advanced techniques of high-density electroencephalography (hdEEG) and non-invasive brain stimulation techniques can be applied. Furthermore translating the concept of local sleep and wakefulness to the prevalent health problem of chronic insomnia might help to reduce the current mismatch between subjective sleep–wake perception and standard recordings, and might inform the development of new treatments.

Recent Advances in Diagnosis and Treatment of Insomnia Disorder

Recent Advances in Diagnosis and Treatment of Insomnia Disorder

150: Insomnia and obstetric outcomes

Insomnia is common during pregnancy and has been associated with poor maternal and infant outcomes. We evaluated the effect of cognitive behavioral therapy for insomnia (CBTI) during pregnancy on obstetric outcomes, and hypothesized that treatment would result in better obstetric outcomes. This is a pre-planned secondary analysis of obstetric outcomes from a randomized controlled trial (RCT) of CBTI during pregnancy where the primary outcome was the Insomnia Severity Index (ISI). Eligibility for the RCT were a diagnosis of Insomnia Disorder based on Diagnostic and Statistical Manual for Mental Disorders 5th edition criteria, and gestational age of 18-32 weeks at enrollment. Women with comorbid sleep disorders, psychiatric disorders including major depressive disorder, and concomitant treatments that could impact sleep were ineligible. Women were randomized to 5 individual therapy sessions of CBTI or a control treatment. ISI was measured at baseline, weekly during treatment, and monthly post treatment. Obstetric outcomes were extracted from charts and included birthweight, gestational age at delivery, mode of delivery, hypertensive disorders and gestational diabetes, and were compared with ISI scores. 154 women were analyzed. Women whose insomnia remitted (ISI< 8 post-treatment) had a later gestational age at delivery (39.51+1.23 vs. 38.79+2.18 weeks; p=.035); there were no differences in birthweight, operative vaginal delivery, hypertensive disorders or gestational diabetes. Although CBTI resulted in better insomnia outcome (Manber R. et al., Obstet Gynecol 2019), obstetric outcomes were similar between treatment arms (p-values >0.3). Women who underwent cesarean for any reason (29%) had a higher ISI at baseline (15.13+4.23 vs. 17.05+4.55; p=0.019). Lower ISI scores at baseline and insomnia remittance resulted in better obstetric outcomes. Assessment for and treatment of insomnia disorder during pregnancy is important. Future adequately powered studies of CBTI should identify moderators and mediators of its effects on obstetric outcomes.

Acupuncture for patients with insomnia disorder using resting-state functional magnetic resonance imaging: a protocol for a randomized controlled trial

BackgroundInsomnia is among the most prevalent of the sleep-related disorders. Insomnia disorder is associated with a brain hyperarousal state manifested by abnormal regional brain activity and resting state functional connectivity. Acupuncture improves sleep quality and modulates the hyperarousal state; however, the underlying neurobiological basis for improved sleep quality is poorly understood. The purpose of this clinical trial is to study the efficacy of acupuncture in the treatment of insomnia disorder. In addition, the neural mechanism by which acupuncture affects insomnia disorder will be explored using resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological parameters.Methods and designA randomized, patient- and assessor-blinded trial will be conducted. We will randomize (in a 1:1 ratio) 60 eligible patients with insomnia disorder into a real acupuncture group or a sham acupuncture group. Interventions will be administered three times per week over a 4-week period, with an 8-week follow-up period. The healthy control group will consist of 30 age- and sex-matched healthy individuals who sleep well without any treatment intervention.All participants will undergo neuropsychological and rs-fMRI evaluations. The change in Pittsburgh Sleep Quality Index (PSQI) scores is the primary outcome parameter. The secondary outcome parameters include the Hyperarousal scale (HAS), rs-fMRI measurements, the Fatigue scale-14 (FS-14), the Hamilton depression scale (HAMD), the Hamilton anxiety scale (HAMA), a sleep diary, and an actigraph.Assessment of all parameters will be performed at baseline, post-treatment, and during follow-up. Analyses will be implemented based on intention-to-treat.DiscussionThe study results will be used to clarify the effectiveness and elucidate the mechanism by which acupuncture improves sleep quality in patients with insomnia disorder.Trial registrationChinese Clinical Trials Register, ChiCTR1800015282. Registered on 20 March 2018.

Evaluation of an integrated approach to the treatment of sleep disorders in patients with occupational occupational chronic mercury intoxication

Introduction. The issues of studying the central nervous system (CNS) damage under the influence of mercury remain relevant at the present time.The aim of the study was to identify the relationship of dissomnic and psychological disorders in patients in the remote post-exposure period of chronic mercury intoxication (ChMI) and to substantiate the effectiveness of the proposed scheme of their therapy.Materials and methods. The study involved 30 patients in the long-term period with occupational chronic mercury intoxication (CHMI) and 30 patients in the control group (CG), with complaints of sleep disorders without chronic expressed diseases, not in contact with toxic production factors in professional activity, 84 men — residents of the Irkutsk region from the comparison group to assess the health-related quality of life comparable with patients in social and living conditions and not in contact with harmful production factors. A set of clinical, neurophysiological, psychological and statistical methods was used in study.Results. Based on the data of polysomnographic examination revealed differences in the nature and severity of insomnia in patients of these groups. Confirmed the mixed nature of insomniatic disorders in patients with chronic mercury intoxication. Patients CG revealed changes in the structure of night sleep has focused on intracomesa violations. It was found that patients with CHMI suffer from a more severe form of insomnia compared to patients with CG, which is confirmed by the data of medical and psychological testing. High rates of reactive and personal anxiety, moderate levels of depression and asthenic state, as well as low values of estimates on all scales of health-related quality of life (HRQL), including the total physical and mental components, were revealed in patients with CRMI. Research’s scales HRQL in patients CG with sleep disorders did not reveal any significant differences compared with those in the comparison group, indicating medium and high levels of overall quality of life.Conclusions. The adequacy of the use of a complex of therapeutic and preventive measures, including two main methods of treatment of insomnia disorders, is proved by improving the quality and quantity of sleep structure and emotional and personal sphere.

EFFICACY OF LEMBOREXANT COMPARED WITH ZOLPIDEM EXTENDED RELEASE AND PLACEBO IN ELDERLY SUBJECTS WITH INSOMNIA: RESULTS FROM A PHASE 3 STUDY (SUNRISE 1)

Introduction Difficulties initiating sleep and maintaining sleep throughout the night are reported by more than 50% of elderly individuals. Many treatments for insomnia are not indicated for the treatment of sleep maintenance insomnia, which can be an issue particularly for elderly individuals whose primary complaints tend to be sleep maintenance insomnia. Here we report results from the subgroup of elderly subjects (65+ years) enrolled in a Phase 3 study of the dual orexin receptor antagonist lemborexant. The study enrolled older individuals (55+ years) with sleep maintenance insomnia, in which the efficacy of lemborexant, measured by polysomnography (PSG), was compared with both placebo (PBO) and zolpidem tartrate extended release (ZOL), the formulation of zolpidem that has been approved to treat sleep maintenance problems. Methods SUNRISE 1 was a randomized, double-blind, placebo- and active-controlled, 1-month, global Phase 3 study. The overall study enrolled female subjects age 55 and older and males age 65 and older. Results of the current analysis include only those age 65 and older. Subjects met DSM-5 criteria for insomnia disorder, and had a primary complaint of sleep maintenance insomnia. Current insomnia symptoms were confirmed with both a sleep diary and PSG. Subjects with symptoms of other sleep disorders (e.g., moderate to severe sleep apnea, periodic limb movement disorder, restless legs syndrome) were excluded, but those with sufficiently-treated comorbid medical or psychiatric conditions could be included. After an approximately 2-week single-blind Run-in Period where all subjects received placebo (PBO), subjects were randomized to PBO, ZOL (6.25mg), or lemborexant (LEM; 5mg [LEM5] or 10mg [LEM10]) for 1 month. Study drug was taken within 5 min of the start of the sleep period, which was calculated based on the mean habitual bedtime from the sleep diary. Average values from paired PSGs from each subject at Baseline (during the placebo run-in), Nights 1/2, and Nights 29/30 were analyzed for latency to persistent sleep (LPS), wake after sleep onset (WASO), WASO in the second half of the night (WASO2H), and sleep efficiency (SE). SE is defined as total sleep time divided by the time in bed, which was standardized for all subjects at 8 hours. Results A total of 1006 were randomized into the study. Of these, 453 (45%) were 65 years or older (137 males, 316 females) and are included in the results presented below. Most subjects (433/453; 95.6%) completed the study. A total of 8 (1.8%) subjects discontinued due to an adverse event. Table 1 shows difference from placebo in change from baseline values for PSG variables by timepoint (Nights 1/2, Nights 29/30). All comparisons of LEM5 and LEM10 to both PBO and ZOL were statistically significant at p The most common AEs in elderly subjects (>2% of elderly subjects in any active treatment group and >PBO) were headache, with rates of 4.3% (PBO), 4.2% (ZOL), 5% (LEM5), and 5% (LEM10), and somnolence, with rates of 2.2% (PBO), 0.8% (ZOL), 3.4% (LEM5), and 7.4% (LEM10). Conclusions Lemborexant improved both sleep onset and sleep maintenance compared to both PBO and ZOL. Importantly, LEM was significantly better than ZOL at reducing the amount of time spent awake during the second half of the night, which is the time when elderly individuals have the most difficulty maintaining sleep. These subpopulation analyses are similar to the results from the overall study, which included older adults 55-64 years as well. In this study, lemborexant appeared to be well-tolerated. Results of this study support the efficacy and safety of lemborexant as a treatment for insomnia disorder in elderly individuals who suffer from sleep maintenance insomnia. This research was funded by Eisai Inc. and Purdue Pharma L.P.