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In humans, sleep is divided into nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. (1) The non-REM sleep consists of 3 stages (N1-N3), with N1 and N2 [...]

Sunobinop is a novel, potent, selective partial agonist at nociceptin/orphanin FQ peptide (NOP) receptors. The primary objective of this randomized, double-blind, placebo-controlled study was to assess the next-day residual effects of an evening dose of sunobinop in healthy participants. Participants were randomized into 1 of 5 treatment sequences. Treatment consisted of 1 dose each of sunobinop 0.2, 0.6, 2, and 6mg suspension and placebo suspension. Key pharmacodynamic (PD) measures included the digit symbol substitution test (DSST), Karolinska sleepiness scale (KSS), and body sway. The randomized safety population consisted of 25 participants. The DSST, KSS, and body sway showed dose-dependent effects following the administration of sunobinop, with no significant differences versus placebo at sunobinop doses <2 mg. At sunobinop 2 mg, PD effects were relatively small in magnitude and inconsistent. The last timepoint where significant differences between sunobinop 2 mg and placebo on the DSST, KSS, and body sway were observed was at 12 h, 16.5 h, and 13.5 h postdose, respectively. Sunobinop 6 mg resulted in larger and consistent PD effects, with significant differences from placebo at all timepoints up to 16.5-18 h postdose. Somnolence was the most frequently reported adverse event (AE), and all AEs were mild-to-moderate. No deaths occurred during the study or discontinuations due to an AE. Overall, a nighttime oral dose of sunobinop up to 2mg was safe and generally well tolerated in healthy participants with limited next-day residual effects that were consistent with other sedative/hypnotic drugs. [ABSTRACT FROM AUTHOR]

Poor sleep quality is a widespread concern. While the influence of particle exposure on sleep disturbances has received considerable attention, research exploring other dimensions of sleep quality and the chemical components of the particles remains limited. We employed a marginal structural model to explore the association of long-term exposure to PM 2.5 and its chemical components with poor sleep quality. The odds ratio (95 % CI) for poor sleep quality was 1.335 (1.292–1.378), 1.097 (1.080–1.113), 1.137 (1.100–1.174), 1.197 (1.156–1.240), and 1.124 (1.107–1.140) per IQR increase in the concentration of PM 2.5 , SO 4 2−, NO 3 −, NH 4 +, and BC, respectively. The score (and 95 % CI) of sleep latency, use of sleep medication, habitual sleep efficiency, subjective sleep quality, and daytime dysfunction were affected by PM 2.5 , with an increase of 0.059 (0.050–0.069), 0.054 (0.049–0.059), 0.011 (0.008–0.014), 0.011 (0.005–0.018), and 0.026 (0.018–0.034) per IQR increase in PM 2.5 concentrations, respectively. This study supports the association of long-term exposure to PM 2.5 and its chemical components with poor sleep quality. • PM 2.5 and its chemical components are associated with poor sleep quality. • NH 4 + has the most significant impact among PM 2.5 chemical components. • PM 2.5 has a significant impact on sleep latency and use of sleep medication. [ABSTRACT FROM AUTHOR]

Background: Chronic progressive external ophthalmoplegia (CPEO) belongs to the group of mitochondrial encephalomyopathies. Anaesthesia for patients with CPEO may be associated with an increased risk due to known drug effects on mitochondrial metabolism. Therefore, the aim of this analysis was to evaluate anaesthesiological concepts in patients with CPEO requiring ophthalmic surgery. Methods: This is a retrospective, monocentric cohort analysis of eleven patients with CPEO undergoing ophthalmic surgery either with general anaesthesia or local anaesthesia in a German university hospital from January 2012 to February 2022. Results: A total of twelve ophthalmic surgery procedures were performed in eleven adult patients with CPEO. Six patients underwent surgery after receiving local anaesthesia (LA cohort). Five patients underwent six surgical procedures under general anaesthesia (GA cohort). In five cases within the GA cohort, propofol and remifentanil were used for the maintenance of anaesthesia. In one case, balanced anaesthesia with desflurane and remifentanil was used. The median duration of general anaesthesia was 37.5 min (range, 25–65 min). Patients stayed in the recovery room for a median of 48.5 min (range, 35–70 min). All patients were discharged on the first postoperative day. No relevant complications occurred in either the LA or GA cohort. Conclusion: Both local and general anaesthesia are feasible concepts for patients with CPEO undergoing ophthalmic surgery. Propofol, at least with a short duration (less than one hour) of use, appears to be a feasible hypnotic drug in CPEO patients. [ABSTRACT FROM AUTHOR]

Background: When considering changing hypnotic pharmacotherapy, lemborexant has attracted attention as a candidate due to its effectiveness and safety profile. However, few studies have investigated switching patterns in clinical practice. Research design and methods: We conducted a retrospective cohort study using a nationwide claims database. Patients prescribed a single hypnotic who either subsequently switched to (switching cohort) or were additionally prescribed (add-on cohort) lemborexant between July 2020 and December 2021 were identified. Proportion of successful switching was defined as remaining on lemborexant alone or without any hypnotic at 6 months after lemborexant initiation. Results: The success proportion was 70.1% in the switching cohort (n = 4,861) and 38.6% in the add-on cohort (n = 9,423). In the add-on cohort, the success proportion was lower in patients with a hypnotic history of ≥180 days (31.4%) and in patients whose prescribed hypnotic was a benzodiazepine or non-benzodiazepine (31.5% and 37.6%, respectively). Conclusion: The proportion of successful switching was higher in patients who switched to lemborexant than in those who added lemborexant as a concomitant treatment. The lower success proportion in the add-on cohort might be related to clinically more severe insomnia, and/or a concomitant prescription of benzodiazepine or non-benzodiazepine, from which discontinuation may be challenging. [ABSTRACT FROM AUTHOR]

Introduction: The HGSHS:A is one of the most commonly used measures of hypnotic suggestibility. However, this test suffers from low feasibility due to a time requirement exceeding 1 h, and from a questionable representation of the normal population. Recently, a short version of HGSHS-5:G was developed and published, and now the first results are available. The scope of this investigation was to verify the assumption of equally positioned and normally distributed scores, resulting in equally sized suggestibility groups in a number of different studies with full or short versions of HGSHS, and to compare the results of the 11-item score with the 5-item score, the latter being calculated from either the full version or the short version test. Methods: Data from 21 studies with testing for HGSHS were analyzed, 15 using the HGSHS:A full version and six using the HGSHS-5:G short version, for a total of 2,529 data sets. Position and distribution of both the 11-item score and the 5-item score were tested. Linear regression analysis was used to compare the two scores, as well as cross-table and weighted Cohen's kappa to determine the match of grouping into low and high suggestibility. To evaluate contributing factors to the observed differences in the study results, a multifactorial analysis of variance was performed. Results: In the different studies, position and distribution of scores, as well as group sizes for low and high suggestibles, varied. All score distributions were found to be non-normal and shifted to the right from the middle score; the shift was more extensive with the 11-item score. The correlation between both scores calculated from full version tests was moderate (R² = 0.69), as was the match of suggestibility grouping (κ = 0.58). Studies using the short version involving less student-dominated populations showed sufficient agreement with the full version, but lower scores were caused by an increase in the zero score. Conclusion: A normal population is not represented in most applications of HGSHS, and grouping into low and high suggestibles varies, mainly due to different positions of score distributions. A direct comparison of full and short versions of HGSHS tested in the same subjects is still missing. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic has affected children and adolescents in several ways, including worsened mental health, improvement of asthma, and increases in diabetes ketoacidosis. Less is known about how medication use in children and adolescents has been affected by the pandemic. Objectives: To explore how the COVID‐19 pandemic affected drug utilisation in children and adolescents in Norway, Sweden, and Italy, by child age. Methods: We conducted a longitudinal drug utilisation study among all children and adolescents (<18 years old) in Norway and Sweden and a nationwide paediatric database covering 3% of the paediatric population in Italy. We conducted an interrupted time‐series analysis from January 2018 to December 2021, with March 2020 as the interruption point. Dispensing or prescription rates of antidepressants, anxiolytics, sleep medications, attention‐deficit/hyperactivity disorder (ADHD) medications, insulin, and asthma medications were examined. Results: The study population in January 2018 consisted of 3,455,521 children and adolescents (136,188 from Italy, 1,160,431 from Norway, and 2,158,902 from Sweden). For sleep medications and insulin, there were only minor changes in level or trend in some age groups after March 2020. For asthma medications, the pandemic was associated with an immediate decrease in dispensing in Norway and Sweden (range of change in level: −19.2 to −3.7 dispensings per 1000 person‐months), and an increasing trend in all countries afterward (range of change in trend: 0.3–6.4 dispensings per 1000 person‐months), especially for the youngest age groups. Among adolescents, the pandemic was associated with an increased trend for ADHD medications, antidepressants, and anxiolytics in Norway and Sweden, but not in Italy. Conclusions: The increasing trend of psychotropic medication dispensing, especially among adolescents after the start of the pandemic, is concerning and should be investigated further. Aside from a temporary effect on asthma medication dispensing, the pandemic did not greatly affect the dispensing of the medications investigated. [ABSTRACT FROM AUTHOR]

Real-world evidence on the association between natural medicinal products and the recurrence of sleep disorders is currently limited, particularly when compared to the evidence reported for prescription hypnotics. In a retrospective cohort analysis, we investigated patients with sleep disorders prescribed either the natural medicinal product Neurexan (Nx4), benzodiazepines, or nonbenzodiazepines (Z-drugs) using the IQVIA Disease Analyzer database, which encompasses electronic medical records nationwide in Germany. A 1:1 matching procedure based on age, sex, prevalent depression, anxiety or adjustment disorder, and the number of medical consultations in the past 12 months resulted in four cohorts: patients prescribed Nx4 were matched with those prescribed Z-drugs (two cohorts with 8594 matched patients each), and another cohort of patients prescribed Nx4 were matched with those prescribed benzodiazepines (7779 matched pairs). Results from multivariable-adjusted Cox regression models demonstrated that Nx4 was associated with a significantly lower risk of recurrent sleep disorder diagnosis within 30–365 days after prescription compared to both Z-drugs (HR = 0.65, 95%CI = 0.60–0.70, p < 0.001) and benzodiazepines (HR = 0.85, 95%CI = 0.79–0.93, p < 0.001). Additionally, Nx4 was associated with a lower prevalence of depression compared to Z-drugs (HR = 0.90, 95%CI = 0.83–0.98, p = 0.020) and benzodiazepines (HR = 0.89, 95%CI = 0.82–0.97, p = 0.009). These findings suggest an association between Nx4 and improved sleep and mental health outcomes. However, due to inherent limitations in the study design, the causality of this relationship cannot be stated. [ABSTRACT FROM AUTHOR]

5-Alkylated barbituric acids are an important class of compounds that constitute the basic moiety of several clinically used hypnotic drugs. Here we report a catalyst-free domino Knoevenagel-Michael addition involving barbituric acid, aldehyde, and N,N-disubstituted aniline in solvent acetonitrile to synthesize 5-alkylated barbituric acid derivatives (72–94% yield) without using any chromatographic separation techniques. The C-4 position of aniline acts as the Michael donor. All the reactions are successfully performed without catalysts, providing an environment-friendly and economical route for the synthesis. Moreover, catalyst-free reactions are less sensitive to air and moisture unlike many metal catalysts, with easy separation of products, and simple operating procedures as there is no need for catalyst weighing, recovery, and removal. A plausible mechanism is also proposed based on control experiments. [ABSTRACT FROM AUTHOR]

Introduction Whether psychiatric symptoms after recovery from coronavirus disease 2019 (COVID-19) are specific to this illness remains unclear. Methods In this retrospective study, the Diagnosis Procedure Combination data and outpatient clinic data were used for patients who received inpatient treatment in Saiseikai-affiliated hospitals for COVID-19 or other respiratory tract infections (non-COVID) from 2020 to 2022. The primary outcome was new prescriptions of psychotropic drugs after discharge (i. e., prescriptions of psychotropics to patients who had not received them before or during their hospitalization). Values of interest were compared between groups using the chi-square test or Fisher's exact test. A COX proportional-hazards model was used to examine factors associated with psychotropic prescriptions after discharge in age- and sex-matched COVID-19 and non-COVID patients. Results Of 31,993 chart records, 19,613 were excluded due to a positive history with psychiatric disorders (n=2,445), prescriptions of psychotropics (n=744), and no follow-ups (n=16,424). Thus, 3,648 COVID-19 and 8,732 non-COVID patients were included (mean [range] duration of follow-up, days: 146.9 [1–727] and 239.2 [1–729], respectively). Two hundred and four (5.6%) of the 3,648 patients with COVID-19 received psychotropic prescriptions after discharge. No statistically significant differences were observed in the prescription rates of any psychotropic category between the COVID-19 and non-COVID groups. An increase in severity during hospitalization was significantly associated with more frequent psychotropic prescriptions (hazard ratio 1.83, p<0.001). Discussion The development of psychiatric symptoms should be closely observed, especially in patients who experienced increased severity during hospitalization, regardless of whether they suffered from COVID-19. [ABSTRACT FROM AUTHOR]

Insomnia symptoms are common among medical students. This study explored the perspectives of medical students about which sleep management strategies to use. Medical students responded to an online survey on their thoughts about the use of various sleep management strategies. Of the 828 respondents, 568 (69%) provided responses to questions about the most preferred strategies and 450 (54%) provided responses about their least preferred strategies. About 48.5% felt their insomnia symptoms were too mild to see a clinician and 23.9% did not think their symptoms warranted sleep medication. Over 40% of students could not avoid work before sleep, have consistent sleep/wake times, or engage in regular exercise because of their busy and inconsistent schedules. Approximately 40–60% could not improve their sleep environment (e.g. better heating and bed) because of the associated costs. Over 80% reported an inability to change their pre-sleep habits (e.g. using electronics close to bedtime, using bed for activities other than sleep or sex). Half of the students disliked relaxation techniques or felt they would not help. Around 30–50% did not believe that changing caffeine and/or alcohol intake would affect their sleep. Medical students may benefit from additional sleep education. Clinicians may need to discuss which strategies individual students prefer and modify their recommendations accordingly. [ABSTRACT FROM AUTHOR]

Objectives: The failure rate and risk factors of upper airway surgery with drug induced sleep endoscopy (DISE) remain unknown in the treatment of obstructive sleep apnea (OSA). This review aims to analyze the failure rate of upper airway surgery with DISE and identify obstruction sites for surgical failure. Methods: A systematic review was conducted using PubMed, Embase, Web of Science, and Google Scholar until May 20th, 2023. We included studies that used DISE to assess obstructive sites before upper airway surgery and reported surgical failure rates and outcomes in patients with OSA. Results: 25 studies with a total of 1522 patients were included in the systematic review and meta-analysis. Upper airway surgery guided by DISE had a relatively low failure rate of 37% (95% CI 0.31–0.44) in the random effects model (I2 = 85.97%, P < 0.001). According to the velum, oropharynx, tongue base, and epiglottis (VOTE) scoring system, major risk factors for surgical failure included circumferential collapse at the velum, lateral wall collapse and small tonsils at the oropharynx, anterior–posterior lingual collapse and complete collapse at the tongue base. High body mass index and large preoperative apnea hypopnea index were also risk factors for OSA surgical failure. Conclusions: Upper airway surgery guided by DISE in patients with OSA had a low failure rate of 37%. DISE can identify obstruction sites associated with surgical failure and guide single-level and multi-level surgeries. [ABSTRACT FROM AUTHOR]

Insomnia disorder is a subjective complaint of sleep dissatisfaction including both night-time and daytime symptoms. Currently there are three commonly used diagnostic manuals each with their own set of criteria, which is often credited for the wide range in insomnia prevalence reported by population-based studies, especially those with self-reported insomnia. However, there are limited studies directly comparing different criteria and little is known about associations with health outcomes. Thus, the aim of this study was to compare the most commonly used diagnostic criteria for insomnia from the literature and to explore the associations with a range of physical and mental health outcomes. We used data from 21,083 women and men from the seventh survey of the population-based Tromsø Study which included adults aged 40–99 years. A revised version of the Bergen Insomnia Scale was used to define insomnia based on the 4th (revised) and 5th edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR and DSM5), the 10th edition of the International Classification of Diseases (ICD-10), and the 3rd edition of the International Classification of Sleep Disorders (ICSD-3). We found the following prevalence of insomnia: DSM-IV-TR 23.6 %, DSM5 8.5 %, ICD-10 9.9 % and ICSD-3 20.0 %. When looking at each symptom, we found over half the participants classified as having insomnia using the DSM-IV-TR and ICSD-3 criteria did not report having impaired daytime functioning at least three days per week. Overall, participants with DSM5 and ICD-10 insomnia appeared to have worse health profiles, based on a higher percentage meeting the cut-off for possible anxiety or depression, reporting a psychological problem or chronic pain, and using antidepressants, painkillers or sleeping pills. However logistic regression models showed largely the same health factors had the same association with the odds for being classified as having insomnia disorder from each set of criteria. Overall, this study suggests that insomnia prevalence may be overestimated if daytime symptoms are not adequately included in accordance with current guidelines. • Insomnia prevalence range widely likely due to different diagnostic criteria. • Criteria were compared in over 20,000 individuals from a general population sample. • Insomnia prevalence ranged from 8.5 % to 23.6 % from the same population. • The lowest prevalence's were associated with worse health profiles. [ABSTRACT FROM AUTHOR]

Dynamic balance assessments such as walking adaptability may yield a more realistic prediction of drug‐induced falls compared with postural stability measurements, as falls often result from limited gait adjustments when walking. The Interactive Walkway (IWW) measures walking adaptability but sensitivity to medication effects is unknown. If proven sensitive and specific, IWW could serve as a biomarker for targeted fall‐risk assessments in early clinical drug development. In this three‐way crossover study, 18 healthy elderly (age: 65–80 years) subjects received 5 mg zolpidem, 10 mg suvorexant, or placebo in the morning. Assessments were performed pre‐dose and approximately hourly until 9 h post‐dose. IWW assessments included an 8‐meter walking test, goal‐directed stepping, obstacle‐avoidance, and tandem‐walking. Other pharmacodynamic measurements were the Timed‐Up‐and‐Go (TUG) test at a comfortable and fast pace, adaptive tracking, and body sway. A decline in performance was observed for zolpidem compared with placebo for 3 h post‐dose in IWW walking adaptability outcome measures, TUG, adaptive tracking, and body sway. For the IWW tasks, a decrease in walking speed (among others) was observed. IWW parameters were not affected by suvorexant compared with placebo at any timepoint. However, an increase of 9.8% (95%CI: 1.8%, 18.5%) in body sway was observed for suvorexant compared with placebo up to 3 h post‐dose. The IWW successfully quantified drug effects of two hypnotic drugs and distinguished between zolpidem and suvorexant regarding their effects on walking. As a biomarker, the IWW demonstrated sensitivity in assessing dynamic balance and potential fall risk in early phase clinical drug development. [ABSTRACT FROM AUTHOR]

Barbiturates are a class of sedative and hypnotic drugs. These are commonly used as antiepileptics and anesthetic agents now. Current usage of sedatives in India is about 1.08%, and the abuse is about 0.11%. Barbiturate overdose or poisonings can lead to severe central nervous system depression, potentially life-threatening respiratory depression, and may lead to respiratory arrest. Treatment in the majority of cases of barbiturate poisoning is artificial ventilation and other supportive therapies. Extracorporeal treatments (ECTRs) are required in only 0.1% of cases of poisoning. There is a lack of prospective intervention studies for obvious ethical reasons; however, the ECTR in poisoning (EXTRIP) workgroup recommends the use of ECTRs in severe barbiturate overdose/poisoning. [ABSTRACT FROM AUTHOR]

Background A compelling hypothesis about attention-deficit/hyperactivity disorder (ADHD) etiopathogenesis is that the ADHD phenotype reflects a delay in cortical maturation. Slow-wave activity (SWA) of non-rapid eye movement (NREM) sleep electroencephalogram (EEG) is an electrophysiological index of sleep intensity reflecting cortical maturation. Available data on ADHD and SWA are conflicting, and developmental differences, or the effect of pharmacological treatment, are relatively unknown. Methods We examined, in samples (M age = 16.4, SD  = 1.2), of ever-medicated adolescents at risk for ADHD (n = 18; 72% boys), medication-naïve adolescents at risk for ADHD (n = 15, 67% boys), and adolescents not at risk for ADHD (n = 31, 61% boys) matched for chronological age and controlling for non-ADHD pharmacotherapy, whether ADHD pharmacotherapy modulates the association between NREM SWA and ADHD risk in home sleep. Results Findings indicated medication-naïve adolescents at risk for ADHD exhibited greater first sleep cycle and entire night NREM SWA than both ever-medicated adolescents at risk for ADHD and adolescents not at risk for ADHD and no difference between ever-medicated, at-risk adolescents, and not at-risk adolescents. Conclusions Results support atypical cortical maturation in medication-naïve adolescents at risk for ADHD that appears to be normalized by ADHD pharmacotherapy in ever-medicated adolescents at risk for ADHD. Greater NREM SWA may reflect a compensatory mechanism in middle-later adolescents at risk for ADHD that normalizes an earlier occurring developmental delay. [ABSTRACT FROM AUTHOR]

Insomnia disorder is a global public health issue, commonly treated with hypnotics. However, long-term use of benzodiazepine derivatives (BZDs), especially polypharmacy with this kind of drug, carries risks for dependence and abuse. This study using large-scale medical insurance records investigated the causes of polypharmacy through the treatment of insomnia disorder. A cross-sectional study analyzed anonymized medical record data from July 2014 to March 2018 provided by a nationwide Japanese health insurance association covering 405,952 individuals. Outpatients prescribed at least one sleep medication were included. Demographic data, pharmacological classification of the drugs, and comorbidities were assessed using hierarchical logistic regression analysis to explore their associations with polypharmacy. Of the 33,212 outpatients who were prescribed sleep medications, 32.5 % were prescribed multiple types. After adjusting for demographics and type of sleep medications as covariates, hypnotic polypharmacy was significantly associated with younger age, the presence of certain kinds of comorbidities, and using BZD anxiolytics before bedtime with the highest adjusted odds ratios (8.01–9.39) when referenced with BZD hypnotics. On the other hand, usage of orexin receptor antagonists, melatonin receptor agonists, and Z-drugs indicated lower odds ratios (0.74–0.87). Hypnotic polypharmacy is relatively common in the Japanese general population. With the introduction of non-pharmacological therapy in mind, assessing patients' comorbidities and avoiding the use of benzodiazepines, especially BZD anxiolytics, before bedtime would be recommended to prevent polypharmacy. • Among hypnotic users, 32.5 % received hypnotic polypharmacy. • Younger age and presence of certain comorbidities increased the odds of polypharmacy. • Using benzodiazepines was significantly associated with hypnotic polypharmacy. • Using benzodiazepine anxiolytics before bedtime showed the highest polypharmacy odds. • Orexin antagonists and melatonin agonists showed lower odds for polypharmacy. [ABSTRACT FROM AUTHOR]

Sleep disorders and changes in the profile of the cortisol awakening response (CAR) are potential predictive factors for the incidence of major depressive disorder (MDD). However, these parameters usually are evaluated separately, lacking information regarding the simultaneous association of sleep disorders and CAR, mainly throughout the MDD severity. This study addressed the relationship between sleep quality and CAR in patients with initial/mild depression (MD, n = 30) versus advanced/treatment-resistant (TRD, n = 28), compared with a group of healthy controls (CG, n = 49), aiming to point out in a clinical perspective which alterations in sleep and CAR have been observed along major depression severity stages. TRD patients presented a blunted CAR and poorer sleep quality comparing MD and CG groups. Additionally, MD patients showed worse sleep quality and larger CAR than CG. Taken together, both sleep quality and CAR were correlated with MDD symptoms and predictors of MDD severity, with a greater classification power for sleep quality. From sleep quality, specifically, the use of sleep medication and sleep efficiency predicted depression severity, discriminating mild and treatment-resistant depression. These results show the importance of assessing sleep quality and CAR in patients with major depression when there is a need for evaluation of the disorder's severity in a clinical context. CAR and sleep quality can be useful complementary tools to help in the clinical identification of major depression severity and the understanding of their impact on MDD may support further studies that aim to improve intervention strategies to increase the effectiveness of treatments. [ABSTRACT FROM AUTHOR]

Research supports the efficacy of therapeutic hypnosis for reducing acute and chronic pain. However, little is known about the mechanisms underlying these effects. This paper provides a review of the evidence regarding the role that electroencephalogram-assessed bandwidth power has in identifying who might benefit the most from hypnotic analgesia and how these effects occur. Findings are discussed in terms of the slow wave hypothesis, which posits that brain activity in slower bandwidths (e.g., theta and alpha) can facilitate hypnosis responsivity. Although the extant research is limited by small sample sizes, the findings from this research are generally consistent with the slow wave hypothesis. More research, including and especially studies with larger sample sizes, is needed to confirm these preliminary positive findings. [ABSTRACT FROM AUTHOR]

For athletes, sleep is essential for recovery and performance. Yet, up to two-thirds of athletes report poor sleep quality. Comprehensive data across all sports disciplines on the underlying causes of sleep problems are missing. We reanalyzed a data set of N = 1004 Swiss top athletes across an extensive array of 88 sports to gain knowledge on the specific deficits in sleep health with respect to gender, sport classes, sport-related factors, and well-being. We found that 18% of athletes were affected by at least two out of five high-risk sleep factors: 9% of athletes slept less than 6 h per day, 30% were dissatisfied with their sleep, 17% showed problems falling asleep within 30 min, 18% of athletes reported difficulty maintaining sleep more than three times a week, and 6% of athletes used sleeping pills more than once a week. We found sleep health strongly linked to overall well-being and mental health (22% showed at least moderate symptoms of either depression or anxiety). Therefore, screening and treating sleep disorders might effectively improve mental health and general well-being as well as performance among athletes around the globe. [ABSTRACT FROM AUTHOR]

Red hair has been linked to altered sensitivity to pain, analgesics, and hypnotics. This alteration may be impacted by variants in the melanocortin-1 receptor (MC1R) gene, which are mainly found in redheads. The aim of this narrative review was to explore and present the current state of knowledge on red hair and its plausible associations with altered responsiveness to pain, analgesics, and hypnotics. Structured searches in the PubMed, CINAHL Complete, and Scopus electronic databases were conducted. Evidence suggests that women with red hair have an increased sensitivity to pain. Conversely, data also indicate a higher pain tolerance in homozygous carriers of MC1R variant alleles. Varied responses to analgesia have been reported, with both increased analgesic responsiveness in homozygous carriers of MC1R variant alleles and less analgesia in redheads. Data indicate an increased need for hypnotics in redheads. However, failed attempts to find statistical associations between red hair and altered responsiveness to hypnotics are also evident. Even though there seems to be an association between red hair and an altered responsiveness to pain, analgesics, and/or hypnotics, the results of this narrative review are inconclusive. Further research studies with larger populations and MC1R testing are needed. [ABSTRACT FROM AUTHOR]

The use of z-drugs has increased worldwide since its introduction. Although the prescribing patterns of hypnotics differ among countries, zolpidem is the most widely used z-drug in the world. Zolpidem may be involved in poisoning and deaths. A simple and fast HPLC-PDA method was developed and validated. Zolpidem and the internal standard chloramphenicol were extracted from plasma using a sonication-assisted dispersive liquid–liquid microextraction procedure. The method was validated including selectivity, linearity, precision, accuracy, and recovery. The calibration range (0.15–0.6 µg/mL) covers therapeutic and toxic levels of zolpidem in plasma. The limit of quantification was set at 0.15 µg/mL. Intra- and interday accuracy and precision values were lower than 15% at the concentration levels studied. Excellent recovery results were obtained for all concentrations. The proposed method was successfully applied to ten real postmortem plasma samples. In our series, multiple substances (alcohol and/or other drugs) were detected in most cases of death involving zolpidem. Our analytical method is suitable for routine toxicological analysis. [ABSTRACT FROM AUTHOR]

Six decades ago the world learned that thalidomide, a seemingly non-toxic sedative and hypnotic, caused severe birth defects including the flipper-like deformity of the arms known as phocomelia. When thalidomide was tested against placebo by the trialist Louis Lasagna in 1960 (while the drug was banned from the U.S. marketplace), he found the 100-mg dosage equivalent to placebo, as well as greatly inferior to the 200-mg dosage, in producing sleep. Even as these findings were made known, a 100-mg dose of thalidomide was in general use as a sleep aid for pregnant women. It appears that unbeknownst to themselves, an untold number of pregnant women around the world who were prescribed thalidomide incurred the risks of a teratogen in return for the benefits of a sugar pill. [ABSTRACT FROM AUTHOR]

Background: The use of opioid medicines is common in developed countries, particularly among older adults and those with mental health disorders. It is unclear if the association between mental disorders and opioid medicines is causal, or is due to reverse causality or confounding. Methods: We used a 10% random sample of the Australian Pharmaceutical Benefits Scheme (years 2012–2022) to examine the cross‐sectional, case–control and longitudinal association between the dispensing of antidepressants, anxiolytics, hypnotics, antipsychotics and lithium, and opioid medicines. We used logistic regression, structural equation models (SEM), and Cox regression to analyze the data. Analyses were adjusted for age (years), sex, and number of non‐psychotropic medicines dispensed during the year. Results: The 2022 file contained 804 334 individuals aged 50 years or over (53.1% women), of whom 181 690 (22.6%) received an opioid medicine. The adjusted odds ratio of being dispensed opioid medicines was 1.44 (99% CI = 1.42–1.46) for antidepressants, 1.97 (99% CI = 1.92–2.03) for anxiolytics, 1.55 (99% CI = 1.51–1.60) for hypnotics, 1.32 (99% CI = 1.27–1.38) for antipsychotics, and 0.60 (99% CI = 0.53–0.69) for lithium. Similar associations were noticed when we compared participants who were or not dispensed opioid medicines in 2022 for exposure to psychotropic agents between 2012 and 2021. SEM confirmed that this association was not due to reverse causality. The dispensing of antidepressants was associated with increased adjusted hazard (HR) of subsequent dispensing of opioid medicines (HR = 1.29, 99% CI = 1.27–1.30). Similar associations were observed for anxiolytics, hypnotics and antipsychotics, but not lithium. Conclusions: The dispensing of opioid medicines is higher among older individuals exposed to antidepressants, anxiolytics, hypnotics and antipsychotics than those who are not. These associations are not due to reverse causality or study design. Preventive strategies seeking to minimise the risk of inappropriate use of opioid medicines in later life should consider targeting this high‐risk population. [ABSTRACT FROM AUTHOR]

Getting a good night's sleep was of great importance to early modern people because it was central to healthy routine and the practice of piety. Re-examining printed regimens and herbals reveals that lust was thought to interrupt slumber and that managing sexual impulse and activity is a hitherto unexplored aspect of sleep care. Aspects of routine had to be repeated moderately and in succession in order to prevent disease and imbalance. Feeling sleepy and feeling lustful were, this article finds, connected in complicated and often conflicting ways in bedtime routine. Printed herbals and domestic recipe books shows that soporific materials were also useful in lessening lust. Such findings point to a shared culture of herbal knowledge that centred around bedtime and beds. Early modern people grappled with social, practical, moral and medical concerns when deciding how and when to use their beds, revealing the ways in which sleep care, sexuality and the pursuit of a healthy body and soul intersected. [ABSTRACT FROM AUTHOR]

Objectives of the study were to determine the prevalence of thyroid disorders and evaluate the relationship between them and sleep quality in the Saudi Arabian population. Patients and Methods: The study employed an observational cross-sectional design and included a representative Saudi Arabian cohort. The Pittsburgh Sleep Quality Index (PSQI) was included in a digital self-administered survey that participants were asked to complete. Results: There were 1044 responders in the study, most of whom (54%) were between the ages of 21 and 30. Female respondents made up 62% of the sample. Thyroid disorders were diagnosed in 9.2% of cases. A significant correlation was found (p=0.001 and p< 0.001, respectively) between thyroid disorders and sleep disturbances as well as the use of sleep medications. Conclusion: The study revealed a significant prevalence of poor sleep quality in the Saudi population as a whole, with thyroid disorder diagnosis and female gender emerging as independent risk factors. More extensive longitudinal studies in the area are desperately needed. [ABSTRACT FROM AUTHOR]

Objective: The purpose of the study is to assess if daily use of hypnotics increases mortality, aspiration pneumonia and hip fracture among relatively healthy individuals aged 75 years or older who lead independent lives in the community. Method and Patients: Of the adults aged 75 years or older residing in Hokkaido prefecture of Japan (n = 705,538), those who did not meet several exclusion criteria were eligible for generating propensity score‐matched cohorts (n = 214,723). Exclusion criteria included co‐prescribed medications acting on the central nervous system, diagnoses of malignant neoplasm, dementia, depression, etc. We compared 33,095 participants who were prescribed hypnotics for daily use (hypnotic group) with a propensity score‐matched cohort without a prescription (control group). Participants were followed for more than 42 months. Results: During the 42‐month follow‐up period, the incidence of the three outcome measures in the hypnotics group was significantly higher than that in the control group (aspiration pneumonia p < 0.001, hip fracture p = 0.007, and all‐cause mortality p < 0.001). Sensitivity analyses utilizing inverse probability weighting demonstrated hazard ratios of 1.083 [1.023–1.146] for mortality, 1.117 [1.014–1.230] for aspiration pneumonia, and 1.720 [1.559–1.897] for hip fracture. Meanwhile, the attribute risk differences were 2.7, 1.5, and 1.0 per 1000 patient‐years, respectively. Conclusions: Although daily use of hypnotics increased the risk of three events, their attribute risk differences were fewer than 3.0 per 1000 patient‐years. The results will help provide guidance on whether it is reasonable to prescribe hypnotics to geriatric population aged 75 or older leading independent lives in the community. Clinical trial registration: UMIN‐CTR UMIN000048398. Key points: It is controversial if daily use of hypnotics increases mortality, aspiration pneumonia and hip fracture in individuals aged 75 years or older leading independent lives in the community.We compared 33,095 participants who were prescribed hypnotics for daily use (hypnotic group) with a propensity score‐matched cohort without a prescription (control group).The incidence of the three adverse events in the hypnotics group was significantly higher than that in the control group, although the attribute risk differences were 2.7, 1.5, and 1.0 per 1000 patient‐years, respectively.The results will help provide guidance on whether it is reasonable to prescribe hypnotics to geriatric population aged 75 or older leading independent lives in the community. [ABSTRACT FROM AUTHOR]

• Sleep medications often carry residual effects potentially affecting driving safety. • Considering the vehicle's standard deviation of lateral position, most molecules paralleled the placebo, outperforming zopiclone. • Repeated administration caused fewer residual effects compared to acute one, except for flurazepam. • Repeated administration reduced residual effects. Sleep medications often carry residual effects potentially affecting driving safety, warranting network meta-analysis (NMA). PubMed/EMBASE/TRID/Clinicaltrials.gov/WHO-ICTRP/WebOfScience were inquired for randomized controlled trials of hypnotic driving studies in persons with insomnia and healthy subjects up to 05/28/2023, considering the vehicle's standard deviation of lateral position - SDLP (Standardized Mean Difference/SMD) and driving impairment rates on the first morning (co-primary outcomes) and endpoint. Risk-of-bias, global/local inconsistencies were measured, and CINeMA was used to assess the confidence in the evidence. Of 4,805 identified records, 26 cross-over RCTs were included in the systematic review, of which 22 entered the NMA, focusing on healthy subjects only. After a single administration, most molecules paralleled the placebo, outperforming zopiclone regarding SDLP. In contrast, ramelteon 8 mg, daridorexant 100 mg, zolpidem 10 mg bedtime, zolpidem middle-of-the-night 10 mg and 20 mg, mirtazapine 15–30 mg, and triazolam 0.5 mg performed significantly worse than placebo. Lemborexant 2.5–5 mg, suvorexant 15–20 mg, and zolpidem 3.5 mg middle-of-the-night associated with lower impairment than zopiclone. Repeated administration (maximum follow-up time of ten days) caused fewer residual effects than acute ones, except for flurazepam. Heterogeneity and inconsistency were negligible. Confidence in the evidence was low/very low. Sensitivity analyses confirmed the main analyses. Most FDA-approved hypnotics overlapped placebo at in-label doses, outperforming zopiclone. Repeated administration for 15 days or less reduced residual effects, warranting further research on the matter. [ABSTRACT FROM AUTHOR]

In this paper, we present the development and the validation of a novel index of nociception/anti-nociception (N/AN) based on skin impedance measurement in time and frequency domain with our prototype AnspecPro device. The primary objective of the study was to compare the Anspec-PRO device with two other commercial devices (Medasense, Medstorm). This comparison was designed to be conducted under the same conditions for the three devices. This was carried out during total intravenous anesthesia (TIVA) by investigating its outcomes related to noxious stimulus. In a carefully designed clinical protocol during general anesthesia from induction until emergence, we extract data for estimating individualized causal dynamic models between drug infusion and their monitored effect variables. Specifically, these are Propofol hypnotic drug to Bispectral index of hypnosis level and Remifentanil opioid drug to each of the three aforementioned devices. When compared, statistical analysis of the regions before and during the standardized stimulus shows consistent difference between regions for all devices and for all indices. These results suggest that the proposed methodology for data extraction and processing for AnspecPro delivers the same information as the two commercial devices. [ABSTRACT FROM AUTHOR]

We investigated the metabolism and disposition of vornorexant, a novel dual orexin receptor antagonist, in rats and dogs, and clarified in vitro metabolite profiles in humans. Furthermore, we investigated the pharmacokinetics of active metabolites in rats and dogs and their CNS distribution in rats to elucidate its contribution to drug efficacy. [14C]vornorexant was rapidly and mostly absorbed after the oral administration in rats and dogs. The drug‐derived radioactivity, including metabolites, was distributed to major organs such as the liver, kidneys in rats, and was almost eliminated within 24 h post‐dose in both species. Metabolite profiling revealed that main clearance mechanism of vornorexant was metabolism via multiple pathways by oxidation. The major circulating components were the cleaved metabolites (M10, M12) in rats, and the unchanged form in dogs, followed by M1, and then M3. Incubation with human hepatocytes resulted in formation of metabolites, including M1, M3, M10, and M12. The metabolic pathways were similar in all tested species. Resulting from the PK and CNS distribution of active metabolites (M1 and M3) with weaker pharmacological activity, the concentration of the unchanged form was higher than that of active metabolites in rat CSF and dog plasma, suggesting that the unchanged form mainly contributed to the drug efficacy. These findings demonstrate that vornorexant is absorbed immediately after administration, and vornorexant and its metabolites are rapidly and completely eliminated in rats and dogs. Thus, vornorexant may have favorable pharmacokinetic profiles as a hypnotic drug to provide rapid onset of action and minimal next‐day residual effects in humans. [ABSTRACT FROM AUTHOR]

A method of injecting ferromagnetic implants based on barium hexaferrite into the brain of an animal was proposed. Behavioral responses of mice to the external magnetic influence after the introduction of non-toxic nanomagnetic particles of barium hexaferrite were studied. A decrease in the BOLD signal at the nitric oxide "outflow" was shown in the framework of the proposed kinetic model. [ABSTRACT FROM AUTHOR]

Background: To determine the patterns of irrational use of medications among a sample of adult patients with insomnia. Methods: We included 89 adult patients diagnosed with chronic insomnia who had consumed medications for this disorder during the 12 months prior to admission to a specialized Sleep Disorders Clinic (SDC) in Mexico City. With a 13-item survey, information was gathered on patterns of medication use and irrational use, considering therapeutic indications, dose, route of administration, and duration of treatment. Results: The participants had taken hypnotics (65%), antidepressants (21%), anticonvulsants (8%), and antipsychotics (6%), and 92% had irrational use of their medication. Irrational use was greatest with benzodiazepines and antipsychotics. There were two main types of irrational use: (1) 47% of participants had consumed a drug unsuitable for their condition, although it was almost always prescribed by a doctor, and (2) 43% had consumed a drug for longer than the maximum time recommended. Conclusion: It is worrisome to find that the irrational use of medications to treat insomnia, especially benzodiazepines and antipsychotics is widespread. Although most participants had acquired their medication by prescription, for many the drug was inappropriate to treat their condition. It should be mandatory that patients with insomnia receive specialized medical attention in primary clinical care. [ABSTRACT FROM AUTHOR]

Background: As interventional procedures become more common in clinical practice, sedatives are being increasingly used to enhance patient experience, overall safety, and procedural efficacy. An appropriate sedation depth, which is crucial for patient safety, is determined according to sedative dosage, procedural stimuli, and patient status. Thus, it is important that clinicians understand the continuous nature of sedation levels. Current Concepts: Although sedation offers benefits, it also carries risks. Thus, vigilant monitoring during and after a procedure is important for preventing excessive sedation depth and related complications. Combining sedatives with analgesics, including opioids, often has a synergistic effect that necessitates a dosage reduction. Interdisciplinary guidelines for moderate sedation were recently developed to address expanding procedural scopes and patient population diversity. Discussion and Conclusion: To ensure sedation safety and success in new procedures, healthcare providers should refer to relevant studies. In cases with limited evidence, sedative dosages should be determined based on their pharmacological characteristics. [ABSTRACT FROM AUTHOR]

Determining the most effective insomnia medication for patients may require therapeutic trials of different medications. In addition, medication side effects, interactions with co-administered medications, and declining therapeutic efficacy can necessitate switching between different insomnia medications or deprescribing altogether. Currently, little guidance exists regarding the safest and most effective way to transition from one medication to another. Thus, we developed evidence-based guidelines to inform clinicians regarding best practices when deprescribing or transitioning between insomnia medications. Five U.S.-based sleep experts reviewed the literature involving insomnia medication deprescribing, tapering, and switching and rated the quality of evidence. They used this evidence to generate recommendations through discussion and consensus. When switching or discontinuing insomnia medications, we recommend benzodiazepine hypnotic drugs be tapered while additional CBT-I is provided. For Z-drugs zolpidem and eszopiclone (and not zaleplon), especially when prescribed at supratherapeutic doses, tapering is recommended with a 1-2-day delay in administration of the next insomnia therapy when applicable. There is no need to taper DORAs, doxepin, and ramelteon. Lastly, off-label antidepressants and antipsychotics used to treat insomnia should be gradually reduced when discontinuing. In general, offering individuals a rationale for deprescribing or switching and involving them in the decision-making process can facilitate the change and enhance treatment success.

Risa Hirata,1 Naoko E Katsuki,1 Hitomi Shimada,2 Eiji Nakatani,3 Kiyoshi Shikino,4,5 Chihiro Saito,6 Kaori Amari,7 Yoshimasa Oda,8 Midori Tokushima,1 Masaki Tago1 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Shimada Hospital of Medical Corporation Chouseikai, Saga, Japan; 3Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan; 4Department of General Medicine, Chiba University Hospital, Chiba, Japan; 5Department of Community-Oriented Medical Education, Chiba University Graduate School of Medicine, Chiba, Japan; 6Shizuoka General Hospital, Shizuoka, Japan; 7Department of Emergency Medicine, Saga-Ken Medical Centre Koseikan, Saga, Japan; 8Department of General Medicine, Yuai-Kai Foundation and Oda Hospital, Saga, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81 952 34 3238, Fax +81 952 34 2029, Email tagomas@cc.saga-u.ac.jpPurpose: There has been no large-scale investigation into the association between the use of lemborexant, suvorexant, and ramelteon and falls in a large population. This study, serving as a pilot investigation, was aimed at examining the relationship between inpatient falls and various prescribed hypnotic medications at admission.Patients and Methods: This study was a sub-analysis of a multicenter retrospective observational study conducted over a period of 3 years. The target population comprised patients aged 20 years or above admitted to eight hospitals, including chronic care, acute care, and tertiary hospitals. We extracted data on the types of hypnotic medications prescribed at admission, including lemborexant, suvorexant, ramelteon, benzodiazepines, Z-drugs, and other hypnotics; the occurrence of inpatient falls during the hospital stay; and patients’ background information. To determine the outcome of inpatient falls, items with low collinearity were selected and included as covariates in a forced-entry binary logistic regression analysis.Results: Overall, 150,278 patients were included in the analysis, among whom 3,458 experienced falls. The median age of the entire cohort was 70 years, with men constituting 53.1%. Binary logistic regression analysis revealed that the prescription of lemborexant, suvorexant, and ramelteon at admission was not significantly associated with inpatient falls.Conclusion: The administration of lemborexant, suvorexant, and ramelteon at admission may not be associated with inpatient falls.Keywords: lemborexant, hypnotics, in-hospital falls, risk factor

Abstract Aims In Japan, the daily dosage of hypnotic drugs for insomnia treatment is increasing year by year, and over‐dependence on treatment with hypnotic drugs is a major problem. This study aimed to examine the factors related to the elimination of prescriptions of three or more hypnotic drugs within 1 year in our clinic. Methods We conducted two surveys. Survey ① assessed the frequency of prescriptions of three or more hypnotic drugs by retrospectively reviewing the medical records of all patients who visited general and psychiatric outpatient clinics from January 2013 to March 2019. Survey ② assessed changes in prescriptions of hypnotic and psychotropic drugs within the subsequent year by retrospectively reviewing the medical records of all patients prescribed three or more hypnotic drugs who visited neuropsychiatric outpatient clinics multiple times between April 2013 and March 2019. Results The frequency of prescribing three or more hypnotic drugs was six to nine times higher in psychiatry than in other departments. Flunitrazepam and brotizolam were the most common drugs prescribed and had the second lowest discontinuation rate after zolpidem. Conversely, eszopiclone, zopiclone, and suvorexant had the highest discontinuation rates. The success factors for drug reduction were age (odds ratio [OR]: 0.97, p

Study objectivesRecent initiatives to discourage overprescription of sleep medications have increased awareness of their potential adverse effects; however, it is unknown whether these efforts translated into a decline in use of these medications in the United States. We assessed recent national trends in the use of medications used for sleep disturbance.MethodsWe used data from n = 29,400 participants in the 2013-2018 National Health and Nutrition Examination Survey. At each of three waves of in-person assessments, participants presented prescription bottles for all medications used in the prior month. Interviewers recorded each medication and participants self-reported duration and reasons for use. We identified all medications used for sleep disturbance and categorized medications into two categories: Food and Drug Administration-approved sleep medications and those used off-label for sleep disturbance. We examined changes in the prevalence in use of these medications across the study period.ResultsThe odds of using medications for sleep disturbance decreased 31% between 2013 and 2018 (odds ratio = 0.69, 95% confidence interval = 0.51-0.93, P = .015). This trend was driven by declines in use of Food and Drug Administration-approved medications for sleep disturbance, especially for medium- and long-term duration of use. Notably, among those age 80+ years, we observed an 86% decline (odds ratio = 0.14, 95% confidence interval = 0.05-0.36, P < .001) in use of Food and Drug Administration-approved sleep medications over the study period.ConclusionsUse of prescription medications for sleep disturbance declined nationally, suggesting a possible effect of efforts to curb overprescription and encourage judicious use of these agents. Future research needs to examine whether these changes have coincided with improved population sleep health.CitationKaufmann CN, Spira AP, Wickwire EM, et al. Declining trend in use of medications for sleep disturbance in the United States from 2013 to 2018. J Clin Sleep Med. 2022;18(10):2459-2465.

Introduction: Hypnotizability is conceptualized as a stable personality trait describing the ability to respond to suggestions given under hypnosis. Hypnotizability is a key factor in explaining variance in the effects of hypnotic suggestions on behavior and neural correlates, revealing robust changes mostly in high hypnotizable participants. However, repeated experience and training have been discussed as possible ways to increase willingness, motivation, and ability to follow hypnotic suggestions, although their direct influence on hypnotizability are still unclear. Additionally, it is important whether hypnotizability can be assessed reliably online. Methods: We investigated the influence of the degree of experience with hypnosis and the presentation mode (online versus live) on the stability of hypnotizability in two groups of 77 and 102 young, healthy students, respectively. The first group was tested twice with the Harvard Group Scale of Hypnotic Susceptibility (HGSHS) after two weeks. During this period, participants either repeatedly listened to a hypnosis or trained on a progressive muscle relaxation or served as waitlist control group. In the secondgroup, participants performed both an online or offline version of the HGSHS, with varying time intervals (1-6 weeks). Results: Contrary to our expectations, hypnotizability declined from the first to second assessment in the first group. The reductionwas most prominent in initially highly hypnotizable subjects and independent of the experience intervention. We observed a similar reduction of hypnotizability in the second group, independent of presentation modality. The reduction was again driven by initially highly hypnotizable subjects, while the scores of low hypnotizable subjects remained stable. The presentation modality (online vs. offline) did not influence HGSHS scores, but the test-retest reliability was low to moderate (rtt = 0.44). Discussion: Our results favor the conclusion that generally, hypnotizability is a relatively stable personality trait which shows no major influence of preexperience or modality of assessment. However, particularly highly hypnotizable subjects are likely to experience a decline in hypnotizability in a retest. The role of the concrete assessment tool, psychological factors, and interval length are discussed. Future studies should replicate the experiments in a clinical sample which might have higher intrinsic motivation of increasing responsiveness toward hypnotic interventions or be more sensitive to presentation mode. [ABSTRACT FROM AUTHOR]

Pineapple weed (Matricaria discoidea DC.) is a widespread plant in Europe and North America. In ethnomedicine, it is well-known for its anti-inflammatory and spasmolytic activities. The aim of this research was to develop novel methods of M. discoidea processing to obtain essential oil and dry extracts and to investigate their phytochemical compositions. Moreover, the molecular docking of the main substances and the in vivo studies on their soporific and analgesic activities were conducted. The essential oil and two dry extracts from M. discoidea were prepared. A total of 16 phenolic compounds (seven flavonoids, seven hydroxycinnamic acids, and two phenolic acids) in the dry extracts were identified by means of UPLC-MS/MS. In the essential oil, nine main terpenoids were identified by gas chromatography (GC). It was shown that phenolic extraction from the herb was successful when using 70% ethanol in a triple extraction method and at a ratio of 1:14–1:16. The in vivo studies with rodents demonstrated the analgesic activity of the M. discoidea extracts and improvements in the sleep of animals. The dry extracts of M. discoidea did not show any toxicity. The molecular docking analysis showed a high probability of COX-1,2 inhibition and NMDA receptor antagonism by the extracts. [ABSTRACT FROM AUTHOR]

Summary: Global warming is a major public health concern. Volatile anaesthetics are greenhouse gases that increase the carbon footprint of healthcare. Modelling studies indicate that total intravenous anaesthesia is less carbon intensive than volatile anaesthesia, with equivalent quality of care. In this observational study, we aimed to apply the findings of previous modelling studies to compare the carbon footprint per general anaesthetic of an exclusive TIVA strategy vs. a mixed TIVA‐volatile strategy. This comparative retrospective study was conducted over 2 years in two French hospitals, one using total intravenous anaesthesia only and one using a mixed strategy including both intravenous and inhalation anaesthetic techniques. Based on pharmacy procurement records, the quantity of anaesthetic sedative drugs was converted to carbon dioxide equivalents. The primary outcome was the difference in carbon footprint of hypnotic drugs per intervention between the two strategies. From 1 January 2021 to 31 December 2022, 25,137 patients received general anaesthesia in the hospital using the total intravenous anaesthesia strategy and 22,020 in the hospital using the mixed strategy. The carbon dioxide equivalent footprint of hypnotic drugs per intervention in the hospital using the total intravenous anaesthesia strategy was 20 times lower than in the hospital using the mixed strategy (emissions of 2.42 kg vs. 48.85 kg carbon dioxide equivalent per intervention, respectively). The total intravenous anaesthesia strategy significantly reduces the carbon footprint of hypnotic drugs in general anaesthesia in adult patients compared with a mixed strategy. Further research is warranted to assess the risk–benefit ratio of the widespread adoption of total intravenous anaesthesia. [ABSTRACT FROM AUTHOR]

Melatonin, a pineal hormone that modulates circadian rhythms, sleep, and neurotransmitters, is widely used to treat sleep disorders. However, there are limited studies on the safety of melatonin. Therefore, we aimed to present the overall patterns of adverse events (AEs) following melatonin administration and identify potential safety signals associated with melatonin. Using VigiBase, a global individual case safety report (ICSRs) database managed by the World Health Organization (WHO), we conducted a retrospective, observational, pharmacovigilance study of melatonin between January 1996 and September 2022. Disproportionality analysis was conducted using two comparator settings: all other drugs and other sleep medications. We used multivariable logistic regression to estimate reporting odds ratios (RORs) with 95% confidence intervals (CIs) to compare the frequencies of AEs reporting between melatonin and each comparator setting. Furthermore, we assessed adverse events of special interests (AESIs) that could potentially be associated with melatonin. Signals were identified when the following criteria were met: cases ≥3, x2 ≥ 4, IC025 ≥ 0, and the lower end of the 95% CI of ROR > 2. These signals were then compared with the AE information on the drug labels provided by regulatory bodies. A total of 35 479 AE reports associated with melatonin were identified, with a higher proportion of reports from females (57.1%) and individuals aged 45–64 years (20.8%). We identified 21 AEs that were commonly detected as safety signals in the disproportionality analyses, including tic, educational problems, disturbance in social behavior, body temperature fluctuation, and growth retardation. In AESI analyses, accidents and injuries (adjusted ROR 2.97; 95% CI, 2.80–3.16), fall (2.24; 2.12–2.37), nightmare (4.90; 4.37–5.49), and abnormal dreams (3.68; 3.19–4.25) were detected as a signal of melatonin when compared to all other drugs, whereas those signals were not detected when compared to other sleep medications. In this pharmacovigilance study, exogenous melatonin showed safety profiles comparable to other sleep medications. However, several unexpected potential safety signals were identified, underscoring the need for further investigation at the population level. [ABSTRACT FROM AUTHOR]

Aims: In Japan, the daily dosage of hypnotic drugs for insomnia treatment is increasing year by year, and over‐dependence on treatment with hypnotic drugs is a major problem. This study aimed to examine the factors related to the elimination of prescriptions of three or more hypnotic drugs within 1 year in our clinic. Methods: We conducted two surveys. Survey ① assessed the frequency of prescriptions of three or more hypnotic drugs by retrospectively reviewing the medical records of all patients who visited general and psychiatric outpatient clinics from January 2013 to March 2019. Survey ② assessed changes in prescriptions of hypnotic and psychotropic drugs within the subsequent year by retrospectively reviewing the medical records of all patients prescribed three or more hypnotic drugs who visited neuropsychiatric outpatient clinics multiple times between April 2013 and March 2019. Results: The frequency of prescribing three or more hypnotic drugs was six to nine times higher in psychiatry than in other departments. Flunitrazepam and brotizolam were the most common drugs prescribed and had the second lowest discontinuation rate after zolpidem. Conversely, eszopiclone, zopiclone, and suvorexant had the highest discontinuation rates. The success factors for drug reduction were age (odds ratio [OR]: 0.97, p < 0.0037), trazodone addition (OR: 12.86, p < 0.0194) and number of years of psychiatric experience. Conclusions: The characteristics and success factors in relation to drug reduction in patients with multiple prescriptions of hypnotic drugs identified in this study may contribute to solving the problem of multiple prescriptions of hypnotic drugs. [ABSTRACT FROM AUTHOR]

Insomnia, commonly treated with benzodiazepine (BZD) receptor agonists, presents challenges due to associated serious side effects such as abuse and dependence. To address these concerns, many researches have been conducted to develop and advance both pharmacological and non-pharmacological interventions. Dual orexin receptor antagonists (DORAs), which include suvorexant, daridorexant and lemborexant, have recently been approved by United States Food and Drug Administration (US FDA) as a novel pharmacotherapeutic alternative. Unlike BZD receptor agonists that act as positive allosteric modulators of the gamma-aminobutyric acid type A subunit alpha 1 receptor, DORAs function by binding to both orexin receptor types 1 and 2, and inhibiting the action of the wake-promoting orexin neuropeptide. These drugs induce normal sleep without sleep stage change, do not impair attention and memory performance, and facilitate easier awakening. However, more real-world safety information is needed. Selective orexin-2 receptor antagonists (2-SORAs) is under clinical developments. This review provides an overview of the mechanism of action in relation to insomnia, pharmacokinetics, efficacy and safety information of DORAs and SORA. According to insomnia management guidelines, the firstline treatment for chronic insomnia is cognitive behavioral therapy for insomnia (CBT-I). Although it has proven effective in improving sleep-related quality of life, it has several restrictions limitations due to a face-to-face format. Recently, prescription digital therapy such as Somryst® was approved by US FDA. Somryst®, a smartphone app-based CBT-I, demonstrated meaningful responses in patients. However, digital limitations may impact scalability. Overall, these developments offer promising alternatives for insomnia treatment, emphasizing safety, efficacy, and accessibility. [ABSTRACT FROM AUTHOR]

The last ten years have seen the development and publication of numerous national and international guidelines devoted to the diagnosis and treatment of insomnia. These include guidelines by the American College of Physicians (ACP), the American Academy of Sleep Medicine (AASM), the British Sleep Society (BSS), the German Sleep Society (GSS), and the European Sleep Research Society (ESRS). Though coming from very diverse authors and backgrounds, these guidelines by and large agree concerning the therapeutic recommendations: cognitive behavioral treatment of insomnia (CBT-I), a multicomponent psychotherapeutic intervention, is unequivocally recommended as a first-line treatment. In this report, we will focus on the most recent guideline update from the ESRS, which was published in November 2023. After suggesting a careful diagnostic procedure, CBT-I, both applied face to face (F2F) or digitally (dCBT-I), is again recommended as a first-line treatment based on the available evidence. Hypnotic medications like benzodiazepines (BZ), benzodiazepine receptor agonists (BZRA), sedating antidepressants, and others are approved for short-term-treatment of up to four weeks. Orexin receptor antagonists (i.e., daridorexant) and prolonged release melatonin are considered as options for longer-term treatment when carefully considering the advantages and disadvantages. Both light therapy and exercise regimens were viewed as promising; however, they still lack convincing evidence for the time being. Given the fact that not every patient responds satisfactorily or even remits following CBT-I or other treatment options, the research agenda calls for the development and evaluation of new therapeutic avenues and combination therapies. [ABSTRACT FROM AUTHOR]

Sleep-related eating disorder (SRED) is a relatively rare but probably underestimated disorder, where affected patients exhibit nocturnal eating episodes with impaired consciousness and subsequent amnesia. SRED has originally been classified as NREM (non-rapid eye movement) parasomnia, with an obviously high number of concomitant sleep disorders. We suggest that SRED may represent a heterogenous disease, based on accumulating data in recent studies. Some SRED patients may be better classified as sleep-related movement disorders with an underlying dopaminergic dysfunction. Hypnotic drugs may play a crucial role in triggering amnestic SRED in both parasomnic and sleep-related movement-disordered SRED. [ABSTRACT FROM AUTHOR]

We have previously shown that the use of hypnotic drugs increased among young Scandinavians during 2012–2018. This study aimed to explore psychiatric and somatic morbidity among adolescent hypnotic drug users in a cohort study of 13–17-year-old individuals during 2008–2018 in Norway. Data sources were (i) prescription data from the Norwegian Prescription Database linked to specialist health care diagnoses from the Norwegian Patient Registry and (ii) sleep disorder diagnoses from the Primary Health Care Database. Hypnotic drugs were defined as the sedative antihistamine alimemazine and the ATC group "Hypnotics and Sedatives" (N05C), excluding midazolam. In 2017, 2519 girls (16.5/1000) and 1718 boys (10.7/1000) were incident (new) users of hypnotic drugs. Most of these new users (82% of girls, 77% of boys) were referred to secondary health care, where the most frequent diagnoses were mental and behavioral disorders (51.8% of girls, 46.2% of boys), while only 3.2% received a specific sleep disorder diagnosis. The most common mental and behavioral disorders were "Neurotic stress-related disorders" among girls (27.4%) and "Behavioral and emotional disorders" among boys (23.6%). In conclusion, the trend of increasing hypnotic drug use among adolescents reflects the initiation of hypnotic drugs in a subgroup of the population with a higher disease burden, mainly due to psychiatric disorders, than the general population. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze drug-induced sleep endoscopy (DISE) findings performed in 64 patients and to evaluate the association of DISE findings with PSG parameters. This retrospective, single center, observational study included patients with obstructive sleep apnoea (OSA) who have undergone DISE as part of surgical planning. DISE was performed using dexmedetomidine infusion. The data were documented as per VOTE (velum, oropharynx, tongue base and epiglottis) classification. The patient characteristics and level 2 Polysomnography (PSG) findings were analyzed with DISE findings. Among 62 patients, mean AHI and lowest oxygen saturation levels were 39.68 ± 27.59 and 78.36 ± 9.38, respectively. Mean ESS, SSS and PSQI levels were 10.74 ± − 4.96, 7.73 ± − 1.52, and 8.92 +/− 4.99, respectively. A Single level of obstruction was observed in 4.8% patients, followed by 40.3%, 43.5%, and 11.3% were found to have 2, 3, and 4 levels of obstruction, respectively. All patients had palatal involvement, followed by the oropharyngeal (88.7%), the tongue base (59.7%), and the epiglottis (12.9%) obstruction. There was no significant correlation between partial collapse at velopharynx with AHI. However, complete collapse at the level of the oropharynx (p < 0.05) and the tongue base (p < 0.001) showed a statistically significant association with AHI. Also, a significant correlation was observed between the number of sites and AHI Grade (p < 0.0001). The study helps to understand the association of different patterns and degrees of anatomical obstruction in OSA with different PSG parameters. PSG and DISE findings are complimentary to each other in treatment planning and selection of surgical procedures. [ABSTRACT FROM AUTHOR]

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