Sleep-promoting Medications Research Articles

Melatonin Aids in Treating Mood and Sleep Problems Resulting from Hormonal Therapy in Breast Cancer Patients: A Randomized, Double-Blinded, Placebo-Controlled Trial

Background: Hormone therapy is commonly used to treat breast cancer but can cause mood disorders and sleep disturbances, negatively impacting patients' well-being. Objectives: This trial aimed to evaluate the effects of melatonin on sleep problems and mood changes in breast cancer patients undergoing hormone therapy. Methods: The study was conducted at Omid Hospital in Isfahan, Iran, using a randomized, double-blinded, placebo-controlled design. Participants were assessed using the Hospital Anxiety and Depression Scale (HADS) and were randomly assigned to receive either 6 mg of melatonin or a placebo daily for 4 weeks. Sleep quality, depression levels, and mood states were measured using the Pittsburgh Sleep Quality Index (PSQI), the Center for Epidemiological Studies-Depression Scale (CES-D), and the Profile of Mood States (POMS) Questionnaires at the beginning and end of the 4-week follow-ups. Results: Sixty participants (34 in the melatonin group and 26 in the placebo group) completed the study. Melatonin administration significantly improved sleep quality, latency, duration, and reduced the use of sleep-promoting medication, according to the PSQI scores. However, there were no significant improvements in depression severity or mood disorders, as assessed by the CES-D and POMS questionnaires, in either group following the 4-week melatonin supplementation period. Conclusions: Melatonin supplementation effectively alleviated sleep disturbances caused by hormone therapy in breast cancer patients. However, the study did not find substantial evidence supporting the use of melatonin for improving mood disorders or depression in this specific context.

O030 Impact of lemborexant on daytime sleepiness/alertness in participants with comorbid insomnia and mild obstructive sleep apnea

Abstract Introduction Comorbid insomnia with obstructive sleep apnea (COMISA) is associated with daytime functioning and cognitive impairments. Some sleep-promoting medications cause residual morning sleepiness, potentially exacerbating daytime impairment. This post-hoc analysis assessed the impact of lemborexant (LEM), a competitive dual orexin-receptor antagonist approved to treat insomnia in adults, on morning sleepiness/alertness in participants with COMISA. Methods Data from a subgroup of adults (≥55 years) with comorbid insomnia and mild OSA (apnea-hypopnea-index, 5 to ≤15 events/h) from Study E2006-G000-304 (NCT02783729), a 1-month, randomized study, were analyzed (N=410). Participants received placebo (PBO), LEM 5mg (LEM5), LEM 10mg (LEM10), or zolpidem tartrate 6.25mg (not reported). A daily sleep diary assessed morning sleepiness/alertness rated from 1 (extremely sleepy) to 9 (extremely alert). The percentage of participants shifting from baseline mild/moderate sleepiness (≤3) towards greater alertness (4, 5, or >5) during the first and last 7 mornings of the study was analyzed. Results At baseline, 17/75 (22.7%), 36/112 (32.1%), and 28/104 (26.9%) participants with COMISA receiving PBO, LEM5, or LEM10, respectively, reported mild/moderate sleepiness. Of these participants, a greater percentage shifted from mild/moderate sleepiness towards alertness with LEM5 (66.7%, 82.9%) and LEM10 (64.3%, 75.0%) versus PBO (47.1%, 64.7%) across the first and last 7 mornings, respectively. Discussion The sample size was too small to detect statistical differences; however, a greater percentage of participants with COMISA experienced improvements in morning sleepiness across the treatment period with LEM versus PBO. These data align with previous findings that LEM does not affect tasks requiring morning alertness.

Mechanisms of sleep disturbances in long-term cancer survivors: a childhood cancer survivor study report.

Sleep problems following childhood cancer treatment may persist into adulthood, exacerbating cancer-related late effects and putting survivors at risk for poor physical and psychosocial functioning. This study examines sleep in long-term survivors and their siblings to identify risk factors and disease correlates. Childhood cancer survivors (≥5 years from diagnosis; n = 12 340; 51.5% female; mean [SD] age = 39.4 [9.6] years) and siblings (n = 2395; 57.1% female; age = 44.6 [10.5] years) participating in the Childhood Cancer Survivor Study completed the Pittsburgh Sleep Quality Index (PSQI). Multivariable Poisson-error generalized estimating equation compared prevalence of binary sleep outcomes between survivors and siblings and evaluated cancer history and chronic health conditions (CHC) for associations with sleep outcomes, adjusting for age (at diagnosis and current), sex, race/ethnicity, and body mass index. Survivors were more likely to report clinically elevated composite PSQI scores (>5; 45.1% vs 40.0%, adjusted prevalence ratio [PR] = 1.20, 95% CI = 1.13 to 1.27), symptoms of insomnia (38.8% vs 32.0%, PR = 1.26, 95% CI = 1.18 to 1.35), snoring (18.0% vs 17.4%, PR = 1.11, 95% CI = 1.01 to 1.23), and sleep medication use (13.2% vs 11.5%, PR = 1.28, 95% CI = 1.12 to 1.45) compared with siblings. Within cancer survivors, PSQI scores were similar across diagnoses. Anthracycline exposure (PR = 1.13, 95% CI = 1.03 to 1.25), abdominal radiation (PR = 1.16, 95% CI = 1.04 to 1.29), and increasing CHC burden were associated with elevated PSQI scores (PRs = 1.21-1.48). Among survivors, sleep problems were more closely related to CHC than diagnosis or treatment history, although longitudinal research is needed to determine the direction of this association. Frequent sleep-promoting medication use suggests interest in managing sleep problems; behavioral sleep intervention is advised for long-term management.

Comparative short-term safety and efficacy of hypnotics: A quantitative risk-benefit analysis.

Several professional societies have provided recommendations for prescribing medications for insomnia. None has provided an integrative analysis that concurrently quantifies safety and efficacy (e.g., risk-benefit ratios). This represents an important gap for informing clinician decision-making. Accordingly, the aim of the present review is to provide such an analysis for five classes of sleep-promoting medications. Adverse event data values were extracted from the most recent FDA-approved package inserts and converted to an integer before being placebo-adjusted and standardized as a rate per 1000 (AEr). Efficacy data, pre-to-post self-reported data for active and placebo conditions were acquired from pivotal trials identified in "white papers" and systematic reviews/meta-analyses. Weighted effect sizes were calculated for subjective sleep latency, wake time after sleep onset and total sleep time, and then were averaged by medication class for each sleep continuity variable. Overall efficacy was represented by a single variable, SWT (sleep latency + wake time after sleep onset + total sleep time). Risk-benefit was represented using a simple ratio value. For safety, it was found that melatonin receptor agonists had the lowest adverse event rate (AEr = 43.1), and non-benzodiazepine benzodiazepine receptor agonists had the highest rate (AEr = 255.0). For efficacy, it was found that the pre-to-post placebo adjusted effect sizes were largest for benzodiazepines (effect size = 1.94) and smallest for melatonin receptor agonists (effect size = 0.109). For risk-benefit, histamine antagonist had the most favourable profile (risk-benefit = 69.5), while melatonin receptor agonist had the least favourable profile (risk-benefit = 395.7). Overall, the combined metric for risk-benefit suggests that treatment with a histamine antagonist is optimal and potentially represents the best first-line therapy for the medical management of insomnia.

P.051 Effect of lemborexant on cognition in patients with comorbid insomnia disorder and mild obstructive sleep apnea

Background: Some sleep-promoting medications are associated with cognitive impairment, making treatment of comorbid obstructive-sleep-apnea (OSA) and insomnia (COMISA) challenging. Lemborexant is a dual-orexin-receptor-antagonist approved for insomnia treatment. This post-hoc analysis evaluated cognition in the subgroup of subjects with mild-OSA (apnea-hypopnea-index ≥5–<15 events/h-of-sleep). Methods: Study E2006-G000-304 was a 1-month, randomized, double-blind, placebo (PBO)- and active-comparator (zolpidem-ER 6.25mg [ZOL])-controlled study of lemborexant 5/10mg (LEM5/LEM10). Subjects ≥55y with insomnia disorder/sleep maintenance problems were enrolled (N=1006). A cognitive-performance assessment battery (CPAB) was performed at morning waketime of Days(D)2/3 and D30/31. Change-from-baseline (CFB) for mean power-of-attention (PoA), continuity-of-attention (CoA), quality-of-memory (QoM), and speed-of-memory-retrieval (SoMR) for CPAB tasks was analyzed. Results: The mild-OSA subgroup comprised 410 (40.8%) subjects. On D2/3 and D30/31, CFB for PoA, CoA, QoM, and SoMR for LEM5/LEM10 were not significantly different than PBO. On D2/3, PoA and QoM were significantly worse with ZOL vs PBO; QoM was significantly better with LEM5/LEM10 vs ZOL. On D30/31, SoMR was significantly worse with ZOL vs PBO and significantly better with LEM5/LEM10 vs ZOL. LEM safety in the subgroup was consistent with the overall study population. Conclusions: Memory and attention domains in subjects with COMISA characterized by mild-OSA were not impacted by LEM, unlike ZOL.Support: Eisai Inc.

Analgesic efficacy of sleep-promoting pharmacotherapy in patients with chronic pain: a systematic review and meta-analysis

Dysregulation of sleep heightens pain sensitivity and may contribute to pain chronification. Interventions which consolidate and lengthen sleep have the potential to improve pain control. The main objective of this systematic review was to examine the effects of sleep-promoting pharmacotherapy on pain intensity in patients with chronic pain. Multiple electronic databases were searched from inception to January 2022 to identify relevant randomized controlled trials (RCTs). Two independent reviewers screened titles, abstracts, and full-text articles; extracted data; and assessed risk of bias for each included study. The GRADE approach was used to determine the strength of evidence. The search identified 624 articles. After full-text screening, 10 RCTs (n = 574 randomized participants) involving 3 pharmacologic interventions (melatonin, zopiclone, and eszopiclone) and 7 different chronic pain populations were included. Minimum clinically significant pain reduction ≥30% was reported in 4 studies. There is low-quality evidence (downgraded due to inconsistency and imprecision) that 2 to 8 weeks treatment with a sleep-promoting medication alone or in combination with an analgesic (6 trials, n = 397) decreases pain intensity compared with placebo or the same analgesic treatment alone (SMD -0.58 [95% confidence interval -1.00, -0.17], P = 0.006). Analyses of associations between changes in sleep and pain outcomes were only provided in 2 articles, with inconsistent findings. Notably, pain-relieving effects were most consistent in melatonin trials. Only 3 studies implemented polysomnography to obtain objective sleep measures. Low-quality evidence indicates that pharmacologic sleep promotion may decrease pain intensity in chronic pain populations. More research is needed to fully understand the influence of sleep-targeting interventions on pain control.

Sleep Problems, Social Anxiety and Stuttering Severity in Adults Who Do and Adults Who Do Not Stutter

Background: While there is sufficient evidence that children and adolescents who stutter reported more impaired sleep compared to children and adolescents who did not stutter, findings among adults who stutter (AWS) were scarce. Furthermore, stuttering is associated with issues related to verbal communication in a social context. As such, it was conceivable that AWS reported higher scores for social anxiety, compared to adults who do not stutter (AWNS). In the present study, we tested whether AWS reported higher sleep complaints compared to AWNS. We further tested whether scores for social anxiety and stuttering independently predicted sleep disturbances. Methods: A total of 110 AWS (mean age; 28.25 years, 27.30% females) and 162 AWNS (mean age; 29.40 years, 51.20% females) completed a series of self-rating questionnaires covering sociodemographic information, sleep disturbances and social anxiety. Adults with stuttering further completed a questionnaire on stuttering. Results: Compared to AWNS, AWS reported a shorter sleep duration, a lower sleep efficiency, higher scores for drug use in terms of sleep-promoting medications (significant p-values and medium effect sizes), and an overall higher PSQI score (significant p-values and large effect size), when controlling for age and social anxiety. Next, while p-values were always significant for subjective sleep quality, sleep disturbances, and daytime functioning, when controlling for age and social anxiety, their effect sizes were trivial or small. For sleep latency, the p-value was not significant and the effect size was trivial. Among AWS, higher scores for stuttering and older age, but not social anxiety, predicted higher sleep disturbances. The association between higher sleep disturbances and higher stuttering severity was greatest among those AWS with highest scores for social anxiety. Conclusions: When compared to AWNS, AWS self-reported higher sleep disturbances, which were associated with older age, and higher scores for stuttering severity, but not with social anxiety. Adults who stutter might be routinely asked for their sleep quality.

The relationship between sleep problems and gaming addiction in adults

IntroductionProlonged exposure to Video games may have several negative cognitive and emotional consequences.However, a few investigations have explored the effects of video games addiction on sleep.ObjectivesTo study the effects of gaming addiction on sleep patterns in young adultsMethods We conducted a cross-sectional, descriptive and analytical study.Data were collected using a self-administered questionnaire on social networks targeting young adults between 18–40 years. We used the gaming addiction scale (GAS) in its validated Arabic short version. We also used the validated Arabic version of the Pittsburgh Sleep Quality Index (PSQI) to assess the sleep quality of our participants.ResultsOne hundred and nine participants were included. The mean age was 29.6 ± 10.3. Males accounted for 60.6% of the study population. The mean Gas score was 13.11± 6.08.According to the GAS,25.7% were addicted gamers. The mean PSQI score was 7.25± 3.15. A poor sleep quality pattern (score > 6) was found in 59.6% of the participants. We found that the GAS score was significantly correlated to the total score of PSQI( P=0.003). We also found that the group with poor sleep quality had higher GAS scores (p= 0.014). We found a correlation between the GAS score and the following components of the PSQI: subjective sleep quality ( p= 0.01), sleep disturbances (p=0.024) and the use of sleep-promoting medication ( p=0.046)ConclusionsOur study showed that video gaming behavior had a significant effect on sleep quality. This can have negative consequences on life quality, together with an impaired performance at awakening.DisclosureNo significant relationships.

Valerian and postoperative sleep: a retrospective cohort analysis of gynecological, urologic, and general surgical patients.

Postoperative sleep disturbances appear to be a common complication after surgery being treated with sleep-promoting medication such as valerian, but robust data and evidence of medicinal approaches are lacking. We performed a retrospective cohort analysis of all 21 168 urological, gynecological, and general surgical patients of the University Medical Center Freiburg, Germany, who underwent surgery between 2015 and 2020. Target parameters were the usage of sleep-promoting medication to estimate the occurrence of postoperative sleep disturbances as well as the kind of sleep medication with a special focus on herbal medication such as valerian. Drug-treated sleep disturbances occurred in 15% (n = 3083) of the patients. Valerian was the second most applied drug (n = 814, 26.4%) after classic benzodiazepines (n = 1 138, 36.9%). The majority of patients got valerian as monotherapy. Age, length of stay, and comorbidities were associated with demand for sleep medication in general (p < .001). Valerian monotherapy was more common in women (OR 1.53, 95% CI: 1.33-1.77, p < .001), elderly patients (OR 1.50, 95% CI: 1.29-1.75, p < .001), and patients with prolonged hospital stay (OR 2.23, 95% CI: 1.91-2.61, p < .001). Valerian plays an important role in the treatment of postoperative sleep disturbances clinically, and it appears to be a promising therapeutic approach especially in women, older and sicker patients, and those with prolonged hospital stay. Further research has to clarify the efficacy of valerian postoperatively. DRKS00027903, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00027903.

Crew endurance training in the united states navy: Lessons learned from senior leadership, prospective commanding/executive officers, and department heads

The Crew Endurance Team at the Naval Postgraduate School led a 3-year project to develop and deliver crew endurance and sleep hygiene training to support the US Navy’s implementation of circadian-based watchbills. As part of this effort, 16 training sessions were delivered to 362 active-duty service members (ADSMs) of the USN, including senior Navy leaders (n=249), prospective commandingIexecutive officers (PCOIPXOs) (n=30) at the Surface Warfare Officers School (SWOS) and students (n=83) attending SWOS Department Head School. Overall, responses from all audiences were positive indicating a high level of satisfaction with the training. We identified the need to expand two parts of the training: stimulants and sleep-promoting medications, and tips for sleeping in military environments. We will continue to tailor the training to the specific needs of ADSMs. We continue to train military audiences to increase awareness of the critical importance of sleep for operational performance and resilience.

Eight-week high-intensity interval training is associated with improved sleep quality and cardiorespiratory fitness in patients with depressive disorders.

This study aimed to examine the effect of high-intensity interval training (HIIT) on both sleep and cardiorespiratory fitness in patients with depression. Using a single pre- and post-test study design with no control group, 82 patients diagnosed with depressive disorders underwent HIIT comprising a total of 24 15-min sessions, three times per week for 8weeks. Depressive symptoms, sleep quality, and cardiorespiratory fitness were evaluated using the Beck depression inventory-II, the Pittsburgh sleep quality index (PSQI), and cardiopulmonary exercise testing (CPET) in the form of maximum oxygen uptake (VO2 max), respectively. All 82 patients completed the intervention. HIIT training was associated with significant improvements in BDI-II score (diff = - 1.57 [95% CI - 2.40 to - 0.73], P = 0.001), PSQI score (diff = - 1.20 [95% CI - 2.10 to - 0.32], P = 0.008), and CPET VO2 max (diff = 0.95 [95% CI 0.62-1.28], P = 0.001). Effect size calculations revealed that the greatest improvement occurred in CPET VO2 max (Cohen's d = 0.64) and that improvements in the BDI-II and PSQI scores were somewhat smaller in magnitude (Cohen's d = - 0.41 and - 0.30, respectively). Sleep quality improvements were observed in sleep latency, habitual sleep efficiency, and the use of sleep-promoting medications (Cohen's d = 0.18, 0.19, and 0.25, respectively). Change in cardiorespiratory fitness successfully predicted change in sleep quality but not in depressive symptoms. Adverse effects were limited to minor injuries which did not interfere with completion of training. HIIT training delivered over 8weeks was associated with improvements in depression symptoms, sleep quality, and cardiorespiratory fitness in patients with depressive disorders.

341 Acute effects of seltorexant, a selective orexin-2 antagonist (JNJ- 42847922), on driving after bedtime administration

Abstract Introduction Seltorexant (JNJ-42847922), a potent and selective antagonist of the human orexin-2 receptor, is being developed for the treatment of major depressive disorder. Seltorexant also has sleep-promoting properties. Investigating the effects of sleep-promoting medications on driving is important because some of these agents (e.g. GABAA receptor agonists) may be associated with increased risk of motor vehicle accidents. We evaluated the effect of seltorexant on driving after forced awakening at night, using a validated driving simulator. Methods This double-blind, placebo and active-controlled, randomized, 3-way cross-over study was conducted in 18 male and 18 female healthy subjects. All subjects received seltorexant 40 mg, zolpidem 10 mg, or placebo 15 minutes before bedtime. Eighteen subjects were awakened at 2- and 6-hours post-dose, and the other 18 at 4- and 8-hours post-dose. At those timepoints, pharmacokinetics, objective (standard deviation of the lateral position [SDLP]) and subjective effects (using Perceived Driving Quality and Effort Scales) on driving ability, postural stability and subjective sleepiness were assessed. Results For seltorexant, the SDLP difference from placebo (95% confidence interval) at 2-, 4-, 6- and 8-hours post-dose was 3.9 cm (1.26, 6.60), 0.9 cm (-1.08, 2.92), 1.1 cm (-0.42, 2.63), and 0.6 cm (-2.75, 1.55), respectively vs. 9.6 cm (6.97, 12.38), 6.6 cm (3.53, 9.60), 4.7 cm (1.46, 7.85), and 1.3cm (-1.16, 3.80), respectively for zolpidem. The difference from placebo was significant at 2-hours after taking seltorexant, while the difference from placebo was significant at 2, 4 and 6-hours after zolpidem. Subjective driving quality was decreased for both drugs at all time points and driving effort was increased up to 4-hours post-dose for both medications. Subjective sleepiness showed a significant increase compared to placebo 2- and 4-hours after administration of either drug. Postural stability was decreased up to 2-hours after administration of seltorexant, and up to 4-hours after administration of zolpidem. Conclusion Compared to zolpidem, objective effects on driving performance were more transient after seltorexant administration and largely normalized by 4–6 hours post-dose. Support (if any) This work was sponsored by Janssen R&amp;D.

906: Prevalence of Sleep-Promoting Medication Continuation at Transition out of the Intensive Care Unit

Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Cognitive behavioural therapy interventions for insomnia among shift workers: RCT in an occupational health setting

IntroductionThe aim of the study was to compare the effectiveness of cognitive behavioural therapy interventions for insomnia (CBT-I) to that of a sleep hygiene intervention in a randomized controlled design among shift workers. We also studied whether the features of shift work disorder (SWD) affected the results.MethodsA total of 83 shift workers with insomnia disorder were partially randomized into a group-based CBT-I, self-help CBT-I, or sleep hygiene control intervention. The outcomes were assessed before and after the interventions and at 6-month follow-up using questionnaires, a sleep diary, and actigraphy.ResultsPerceived severity of insomnia, sleep-related dysfunctional beliefs, burnout symptoms, restedness, recovery after a shift, and actigraphy-based total sleep time improved after the interventions, but we found no significant differences between the interventions. Mood symptoms improved only among the group-based CBT-I intervention participants. Non-SWD participants had more mental diseases and symptoms, used more sleep-promoting medication, and had pronounced insomnia severity and more dysfunctional beliefs than those with SWD. After the interventions, non-SWD participants showed more prominent improvements than those with SWD.ConclusionsOur results showed no significant differences between the sleep improvements of the shift workers in the CBT-I interventions and of those in the sleep hygiene control intervention. Alleviation of mood symptoms seemed to be the main added value of the group-based CBT-I intervention compared to the control intervention. The clinical condition of the non-SWD participants was more severe and these participants benefitted more from the interventions than the SWD participants did.Trial registrationClinicalTrials.gov, NCT02523079.

The Prevalence of Sleep Disturbances and Sleep Quality in Older Chinese Adults: A Comprehensive Meta-Analysis

ABSTRACTObjective: This is a meta-analysis of the pooled prevalence of insomnia-specific sleep disturbances (sleep disturbances thereafter) and sleep quality in older Chinese adults. Method: Both English (PubMed, Embase and PsycINFO) and Chinese (Chinese National Knowledge Infrastructure [CNKI], WanFang and SinoMed) databases were systematically searched. Data extraction and quality assessment were independently performed by two investigators. Random-effects model was performed to pool the prevalence of sleep disturbances and sleep quality. Subgroup and meta-regression analyses were performed to explore the source of heterogeneity. Funnel plots, Egger’s regression model, and Begg’s test were used to assess publication bias. Results: A total of 47 studies were included. The pooled prevalence of sleep disturbances was 35.9% (95% CI: 30.6%–41.2%). Older adults in rural areas had higher prevalence of sleep disturbances than their counterparts in urban areas. Sleep quality was measured by the Pittsburgh Sleep Quality Assessment (PSQI) in all studies with available data. In the 27 studies with available data, the pooled mean PSQI total score was 6.64 (95% CI: 6.14–7.13). There was no significant difference between genders and between rural and urban areas. Compared to men, women had higher mean scores in sleep latency (Q = 23.62, p < 0.001), sleep efficiency (Q = 12.08, p = 0.001), and use of sleep-promoting medications (Q = 4.07, p = 0.044). Conclusion: Sleep disturbances are common in older Chinese adults, particularly in older women.

Payer Perspective of the American Academy of Sleep Medicine Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia

Payer Perspective of the American Academy of Sleep Medicine Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia

GABA Receptors and the Pharmacology of Sleep.

Current GABAergic sleep-promoting medications were developed pragmatically, without making use of the immense diversity of GABAA receptors. Pharmacogenetic experiments are leading to an understanding of the circuit mechanisms in the hypothalamus by which zolpidem and similar compounds induce sleep at α2βγ2-type GABAA receptors. Drugs acting at more selective receptor types, for example, at receptors containing the α2 and/or α3 subunits expressed in hypothalamic and brain stem areas, could in principle be useful as hypnotics/anxiolytics. A highly promising sleep-promoting drug, gaboxadol, which activates αβδ-type receptors failed in clinical trials. Thus, for the time being, drugs such as zolpidem, which work as positive allosteric modulators at GABAA receptors, continue to be some of the most effective compounds to treat primary insomnia.

Circadian misalignment affects sleep and medication use before and during spaceflight.

Sleep deficiency and the use of sleep-promoting medication are prevalent during spaceflight. Operations frequently dictate work during the biological night and sleep during the biological day, which contribute to circadian misalignment. We investigated whether circadian misalignment was associated with adverse sleep outcomes before (preflight) and during spaceflight missions aboard the International Space Station (ISS). Actigraphy and photometry data for 21 astronauts were collected over 3,248 days of long-duration spaceflight on the ISS and 11 days prior to launch (n=231 days). Sleep logs, collected one out of every 3 weeks in flight and daily on Earth, were used to determine medication use and subjective ratings of sleep quality. Actigraphy and photometry data were processed using Circadian Performance Simulation Software to calculate the estimated endogenous circadian temperature minimum. Sleep episodes were classified as aligned or misaligned relative to the estimated endogenous circadian temperature minimum. Mixed-effects regression models accounting for repeated measures were computed by data collection interval (preflight, flight) and circadian alignment status. The estimated endogenous circadian temperature minimum occurred outside sleep episodes on 13% of sleep episodes during preflight and on 19% of sleep episodes during spaceflight. The mean sleep duration in low-Earth orbit on the ISS was 6.4±1.2 h during aligned and 5.4±1.4 h (P<0.01) during misaligned sleep episodes. During aligned sleep episodes, astronauts rated their sleep quality as significantly better than during misaligned sleep episodes (66.8±17.7 vs. 60.2±21.0, P<0.01). Sleep-promoting medication use was significantly higher during misaligned (24%) compared with aligned (11%) sleep episodes (P<0.01). Use of any medication was significantly higher on days when sleep episodes were misaligned (63%) compared with when sleep episodes were aligned (49%; P<0.01). Circadian misalignment is associated with sleep deficiency and increased medication use during spaceflight. These findings suggest that there is an immediate need to deploy and assess effective countermeasures to minimize circadian misalignment and consequent adverse sleep outcomes both before and during spaceflight.

Sleep-promoting medications in children: physician prescribing habits in Southwestern Ontario, Canada

BackgroundResearch indicates that physicians may frequently use pharmacotherapy to treat pediatric insomnia despite minimal safety data and very limited indications. Canadian data on the subject are lacking. This study aimed to determine physicians' views on and prescribing habits for sleep-promoting over-the-counter medication (OTCM) and prescription (RXM) medications for children. MethodsA modified 26-item version of the ‘Pediatric Sleep Medication Survey’, originally developed by Judith Owens and colleagues, was sent to 100 pediatricians and a random sample of 421 family physicians in Southwestern Ontario, Canada. ResultsA total of 67 returned surveys were sufficiently complete for analysis. Sixty-one respondents indicated their specialty (28 pediatricians, 33 family physicians). In a typical 6-month period, 89% and 66% of respondents have recommended OTCM and RXM, respectively, for children with sleep problems. Only 20% have received any formal training on pediatric sleep disorders. The most common circumstances and sleep problems for which OTCM or RXM were recommended were mood disorders, developmental delay and attention deficit hyperactivity disorder (ADHD) (56, 40, and 39%, respectively), and insomnia, bedtime struggles/delayed sleep onset and circadian rhythm disorders (52, 48, and 28%, respectively). A total of 30% recommended OTCM or RXM to otherwise healthy children with sleep problems. Melatonin (73%), OTC antihistamines (41%), antidepressants (37%), and benzodiazepines (29%) were the most commonly recommended OTCM and RXM, respectively. ConclusionsRespondents in our sample frequently use pharmacotherapy to treat pediatric sleep problems; few have received any training in this area. Our findings indicate the need for evidence-based guidelines and regular physician training in the management of pediatric sleep disorders.

Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015

A systematic literature review and meta-analyses (where appropriate) were performed and the GRADE approach was used to update the previous American Academy of Sleep Medicine Practice Parameters on the treatment of intrinsic circadian rhythm sleep-wake disorders. Available data allowed for positive endorsement (at a second-tier degree of confidence) of strategically timed melatonin (for the treatment of DSWPD, blind adults with N24SWD, and children/ adolescents with ISWRD and comorbid neurological disorders), and light therapy with or without accompanying behavioral interventions (adults with ASWPD, children/adolescents with DSWPD, and elderly with dementia). Recommendations against the use of melatonin and discrete sleep-promoting medications are provided for demented elderly patients, at a second- and first-tier degree of confidence, respectively. No recommendations were provided for remaining treatments/ populations, due to either insufficient or absent data. Areas where further research is needed are discussed.