Effects of melatonin on sleep disturbances in multiple sclerosis: A randomized, controlled pilot study

Background Sleep disturbances are commonly reported by people with multiple sclerosis (PwMS). However, optimal management of sleep disturbances is uncertain, and objective studies of sleep quality in PwMS are scarce. Objectives To determine the effect of exogenous melatonin on sleep quality and sleep disturbances in PwMS. Methods Thirty adult PwMS reporting sleep difficulties were recruited in a randomized, controlled, double-blind cross-over study. They took either melatonin or placebo for 2 weeks, and the opposite for the following 2 weeks. During weeks 2 and 4, an actigraph was used to capture mean total sleep time and sleep efficiency. Patient-reported outcomes (PROs) were collected at weeks 0, 2 and 4. Results Melatonin use significantly improved mean total sleep time ( p = 0.03), with a trend towards higher sleep efficiency ( p = 0.06). No PROs were significantly different; there was a trend for melatonin use to decrease mean Insomnia Severity Index score ( p = 0.07), improve Pittsburgh Sleep Quality Index sleep quality component ( p = 0.07), and improve NeuroQoL-Fatigue ( p = 0.06). No other PROs showed differences between melatonin and placebo; nor did step count measured by actigraphy (all p > 0.45). Conclusion These results provide preliminary evidence that melatonin, a low-cost, over-the-counter supplement, could improve objective measures of sleep quality in PwMS.

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Self-report sleep quality combined with sleep time variability distinguishes differences in fatigue, anxiety, and depression in individuals with multiple sclerosis: A secondary analysis

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217318815924 ◽

2018 ◽

Vol 4 (4) ◽

pp. 205521731881592 ◽

Cited By ~ 1

Author(s):

Catherine F Siengsukon ◽

Mohammed Alshehri ◽

Mayis Aldughmi

Keyword(s):

Multiple Sclerosis ◽

Sleep Quality ◽

Sleep Disturbances ◽

Total Sleep Time ◽

Secondary Analysis ◽

Sleep Time ◽

Anxiety And Depression ◽

Time Variability ◽

Poor Sleep ◽

Poor Sleep Quality

Background Nearly 70% of individuals with multiple sclerosis report sleep disturbances or poor sleep quality. Sleep disturbances may exacerbate or complicate the management of multiple sclerosis-related symptoms. While sleep variability has been associated with several health outcomes, it is unclear how sleep variability is associated with multiple sclerosis-related symptoms. Objective The purpose of this study was to determine how total sleep time variability combined with self-reported sleep quality is associated with fatigue, depression, and anxiety in individuals with multiple sclerosis. Methods This study involved a secondary analysis of actigraphy data and questionnaires to assess sleep quality, fatigue, anxiety, and depression. Results There were significant differences between the Good Sleepers (good sleep quality/low sleep time variability; n=14) and Bad Sleepers (poor sleep quality/high sleep time variability; n=23) in overall fatigue ( p=0.003), cognitive ( p=0.002) and psychosocial fatigue ( p=0.01) subscales, and in trait anxiety ( p=0.007). There were significant differences in state ( p=0.004) and trait ( p=0.001) anxiety and depression ( p=0.002) between the Good Sleepers and Poor Reported Sleepers (poor sleep quality/low sleep time variability; n=24). Conclusion These results indicate different factors are associated with poor sleep quality in individuals with low versus high total sleep time variability. Considering the factors that are associated with sleep quality and variability may allow for better tailoring of interventions aimed at improving sleep issues or comorbid conditions.

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Differential Effects of DHA- and EPA-Rich Oils on Sleep in Healthy Young Adults: A Randomized Controlled Trial

Nutrients ◽

10.3390/nu13010248 ◽

2021 ◽

Vol 13 (1) ◽

pp. 248

Author(s):

Michael J. Patan ◽

David O. Kennedy ◽

Cathrine Husberg ◽

Svein Olaf Hustvedt ◽

Philip C. Calder ◽

...

Keyword(s):

Sleep Quality ◽

Controlled Trial ◽

Sleep Time ◽

Sleep Efficiency ◽

Omega 3 ◽

Double Blind ◽

Differential Effects ◽

Positive Effects ◽

Time In Bed ◽

Oily Fish

Emerging evidence suggests that adequate intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs), which include docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), might be associated with better sleep quality. N-3 PUFAs, which must be acquired from dietary sources, are typically consumed at suboptimal levels in Western diets. Therefore, the current placebo-controlled, double-blind, randomized trial, investigated the effects of an oil rich in either DHA or EPA on sleep quality in healthy adults who habitually consumed low amounts of oily fish. Eighty-four participants aged 25–49 years completed the 26-week intervention trial. Compared to placebo, improvements in actigraphy sleep efficiency (p = 0.030) and latency (p = 0.026) were observed following the DHA-rich oil. However, these participants also reported feeling less energetic compared to the placebo (p = 0.041), and less rested (p = 0.017), and there was a trend towards feeling less ready to perform (p = 0.075) than those given EPA-rich oil. A trend towards improved sleep efficiency was identified in the EPA-rich group compared to placebo (p = 0.087), along with a significant decrease in both total time in bed (p = 0.032) and total sleep time (p = 0.019) compared to the DHA-rich oil. No significant effects of either treatment were identified for urinary excretion of the major melatonin metabolite 6-sulfatoxymelatonin. This study was the first to demonstrate some positive effects of dietary supplementation with n-3 PUFAs in healthy adult normal sleepers, and provides novel evidence showing the differential effects of n-3 PUFA supplements rich in either DHA or EPA. Further investigation into the mechanisms underpinning these observations including the effects of n-3 PUFAs on sleep architecture are required.

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Tasimelteon safely and effectively improves sleep in Smith–Magenis syndrome: a double-blind randomized trial followed by an open-label extension

Genetics in Medicine ◽

10.1038/s41436-021-01282-y ◽

2021 ◽

Author(s):

Christos M. Polymeropoulos ◽

Justin Brooks ◽

Emily L. Czeisler ◽

Michaela A. Fisher ◽

Mary M. Gibson ◽

...

Keyword(s):

Sleep Quality ◽

Crossover Study ◽

Total Sleep Time ◽

Sleep Time ◽

Open Label ◽

Double Blind ◽

Open Label Study ◽

Label Study ◽

Sleep Complaints ◽

Open Label Extension

Abstract Purpose To assess the efficacy of tasimelteon to improve sleep in Smith–Magenis syndrome (SMS). Methods A 9-week, double-blind, randomized, two-period crossover study was conducted at four US clinical centers. Genetically confirmed patients with SMS, aged 3 to 39, with sleep complaints participated in the study. Patients were assigned to treatment with tasimelteon or placebo in a 4-week crossover study with a 1-week washout between treatments. Eligible patients participated in an open-label study and were followed for >3 months. Results Improvement of sleep quality (DDSQ50) and total sleep time (DDTST50) on the worst 50% of nights were primary endpoints. Secondary measures included actigraphy and behavioral parameters. Over three years, 52 patients were screened, and 25 patients completed the randomized portion of the study. DDSQ50 significantly improved over placebo (0.4, p = 0.0139), and DDTST50 also improved (18.5 minutes, p = 0.0556). Average sleep quality (0.3, p = 0.0155) and actigraphy-based total sleep time (21.1 minutes, p = 0.0134) improved significantly, consistent with the primary outcomes. Patients treated for ≥90 days in the open-label study showed persistent efficacy. Adverse events were similar between placebo and tasimelteon. Conclusion Tasimelteon safely and effectively improved sleep in SMS.

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Study of correlation between perceived sleep disturbances in depressed patients with objective changes in sleep architecture using polysomnography before and after antidepressant therapy

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20202894 ◽

2020 ◽

Vol 8 (7) ◽

pp. 2551

Author(s):

Ganesh Ingole ◽

Harpreet S. Dhillon ◽

Bhupendra Yadav

Keyword(s):

Sleep Disturbances ◽

Total Sleep Time ◽

Antidepressant Treatment ◽

Sleep Onset ◽

Sleep Time ◽

Sleep Efficiency ◽

Sleep Architecture ◽

Wake Time ◽

Depressed Patients ◽

Before And After

Background: A prospective cohort study to correlate perceived sleep disturbances in depressed patients with objective changes in sleep architecture using polysomnography (PSG) before and after antidepressant therapy.Methods: Patients were recruited into the study after applying strict inclusion and exclusion criterion to rule out other comorbidities which could influence sleep. A diagnosis of Depressive episode was made based on ICD-10 DCR. Psychometry, in the form of Beck Depressive inventory (BDI) and HAMD (Hamilton depression rating scale) insomnia subscale was applied on Day 1 of admission. Patients were subjected to sleep study on Day 03 of admission with Polysomnography. Patients were started on antidepressant treatment post Polysomnography. An adequate trial of antidepressants for 08 weeks was administered and BDI score ≤09 was taken as remission. Polysomnography was repeated post remission. Statistical analysis was performed using Kruskal Wallis test and Pearson correlation coefficient.Results: The results showed positive (improvement) polysomnographic findings in terms of total sleep time, sleep efficiency, wake after sleep onset, percentage wake time and these findings were statistically significant. HAM-D Insomnia subscale was found to correlate with total sleep time, sleep efficiency, wake after sleep onset, total wake time and N2 Stage percentage.Conclusions: Antidepressant treatment effectively improves sleep architecture in Depressive disorder and HAM-D Insomnia subscale correlates with objective findings of total sleep time, sleep efficiency, wake after sleep onset, total wake time and duration of N2 stage of NREM.

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Randomized Double-Blind Controlled Trial on the Effect of Proteins with Different Tryptophan/Large Neutral Amino Acid Ratios on Sleep in Adolescents: The PROTMORPHEUS Study

Nutrients ◽

10.3390/nu12061885 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1885 ◽

Cited By ~ 1

Author(s):

Oussama Saidi ◽

Emmanuelle Rochette ◽

Éric Doré ◽

Freddy Maso ◽

Julien Raoux ◽

...

Keyword(s):

Sleep Quality ◽

Dietary Intake ◽

Sleep Disturbances ◽

Controlled Trial ◽

Internal Clock ◽

Sleep Efficiency ◽

Large Neutral Amino Acid ◽

Double Blind ◽

Circadian Phase ◽

Two Samples

Disturbed sleep is common in adolescents. Ingested nutrients help regulate the internal clock and influence sleep quality. The purpose of this clinical trial is to assess the effect of protein tryptophan (Trp)/large neutral amino acids (LNAAs) ratio on sleep and circadian rhythm. Ingested Trp is involved in the regulation of the sleep/wake cycle and improvement of sleep quality. Since Trp transport through the blood–brain barrier is competing with LNAAs, protein with higher Trp/LNAAs were expected to increase sleep efficiency. This randomized double-blind controlled trial will enroll two samples of male adolescents predisposed to sleep disturbances: elite rugby players (n = 24) and youths with obesity (n = 24). They will take part randomly in three sessions each held over a week. They will undergo a washout period, when dietary intake will be calibrated (three days), followed by an intervention period (three days), when their diet will be supplemented with three proteins with different Trp/LNAAs ratios. Physical, cognitive, dietary intake, appetite, and sleepiness evaluations will be made on the last day of each session. The primary outcome is sleep efficiency measured through in-home electroencephalogram recordings. Secondary outcomes include sleep staging, circadian phase, and sleep-, food intake-, metabolism-, and inflammation-related biochemical markers. A fuller understanding of the effect of protein Trp/LNAAs ratio on sleep could help in developing nutritional strategies addressing sleep disturbances.

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The selective orexin-2 receptor antagonist seltorexant improves sleep: An exploratory double-blind, placebo controlled, crossover study in antidepressant-treated major depressive disorder patients with persistent insomnia

Journal of Psychopharmacology ◽

10.1177/0269881118822258 ◽

2019 ◽

Vol 33 (2) ◽

pp. 202-209 ◽

Cited By ~ 9

Author(s):

Sander Brooks ◽

Gabriël E Jacobs ◽

Peter de Boer ◽

Justine M Kent ◽

Luc Van Nueten ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Depressive Symptomatology ◽

Total Sleep Time ◽

Sleep Time ◽

Sleep Efficiency ◽

Least Square ◽

Self Report ◽

Major Depressive ◽

Double Blind

Background: Insomnia is common in patients with major depressive disorder. Although antidepressants improve mood, insomnia often persists as a result of physiological hyperarousal. The orexin-2 receptor is increasingly being recognized as a new target for the treatment of persistent insomnia in major depressive disorder . Aim: This exploratory study investigated the effects of seltorexant on objective sleep parameters and subjective depressive symptoms in antidepressant treated major depressive disorder patients with persistent insomnia. Methods: Twenty male and female patients received a single dose of 10, 20, 40 mg seltorexant and placebo with a washout period of seven days in a double-blind four-way crossover study. Effects on latency to persistent sleep, total sleep time and sleep efficiency were assessed with polysomnography. Subjective changes in mood were explored by the Quick Inventory of Depressive Symptomatology Self-Report. Safety was recorded and suicidal ideation and behavior were assessed with the Columbia Suicide Severity Rating Scale. Results: Latency to persistent sleep was significantly shorter for all doses of seltorexant compared to placebo. Placebo least square mean was 61.05 min with least square mean ratios treatment/placebo (80% confidence interval) of 0.32 (0.24–0.44), 0.15 (0.11–0.2) and 0.17 (0.12–0.23) 19.69, 9.2, 10.15 for 10, 20 and 40 mg seltorexant respectively, (all p<0.001). Total sleep time was significantly longer for all doses of seltorexant compared to placebo. Sleep efficiency was significantly improved. The Quick Inventory of Depressive Symptomatology Self-Report demonstrated a trend to mood-improvement for the 40 mg group. Conclusions: Seltorexant showed a statistically significant, dose-dependent decrease in latency to persistent sleep, and increase in total sleep time and sleep efficiency combined with a tendency toward subjectively improved mood.

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689 Objective Assessment of Inpatient Sleep Patterns and Quality: A Pilot Study

SLEEP ◽

10.1093/sleep/zsab072.687 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A269-A269

Author(s):

Sarah Sussman ◽

Ashwin Ananth ◽

Elie Fares ◽

Maurits Boon ◽

Colin Huntley ◽

...

Keyword(s):

Sleep Quality ◽

Slow Wave Sleep ◽

Total Sleep Time ◽

Objective Assessment ◽

General Medicine ◽

Sleep Time ◽

Sleep Medicine ◽

Inpatient Setting ◽

Wrist Actigraphy ◽

Patient Reported

Abstract Introduction Sleep disruption is common among hospitalized patients due to psychological, physiological, and environmental reasons including illness, pain, anxiety, invasive interventions, frequent monitoring, and stimuli, especially noise and light. The AASM has published guidelines for the use of actigraphy in the outpatient setting, but there is a paucity of literature evaluating the validity of actigraphy in inpatients. The aim of this study is to evaluate sleep in hospitalized general medicine patients undergoing sleep medicine consultation using actigraphy and qualitative surveys. Methods A single-site prospective study in hospitalized medicine patients. Patients were observed with a Fitbit® Charge3 wrist actigraphy device overnight, then administered 7 surveys: Richards-Campbell Sleep Questionnaire (RCSQ), qualitative questionnaires assessing sleep history, sleep hygiene, barriers to sleep, STOP-BANG, Epworth Sleepiness Scale (ESS), and Patient-Health Questionniare-2 (PHQ-2). Actigraphy data including total sleep time, slow wave sleep time, and number of awakenings was compared with patient-reported data. Results In preliminary analysis, six patients met inclusion criteria and underwent sleep medicine consultation, overnight actigraphy, and completed 7 surveys. Based on subjective sleep history questionnaires, average total sleep time was 437 + 215 minutes. Actigraphy revealed average total sleep time was 228 + 80 minutes with an average of 3.6 nocturnal awakenings. Increased number of awakenings on actigraphy was not correlated with increased number of awakenings by survey. The most frequently reported barriers to sleep on patient surveys were pain and being woken up for labs or vital signs. The average STOP-BANG score was 6 out of 8 and average ESS was 14 out of 24. Conclusion Restorative sleep warrants consideration alongside complex medical care during hospitalization. Patients experience decreased total sleep time and increased number of awakenings while in the hospital compared with their subjective estimates of sleep at home. Actigraphy provides a non-invasive and reliable way to monitor some sleep parameters in the inpatient setting. An elevated STOP-BANG score could represent sleep disordered breathing and impact perceptions of sleep quality. Patient-identified barriers to sleep are targets for quality improvement. Future studies should compare inpatient actigraphy data to polysomnographic data and the effect of sleep-directed interventions on sleep quality in the hospital. Support (if any):

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INNV-15. COMPARISON OF READIBAND™ ACTIGRAPH AND ASSOCIATED SLEEP/WAKE CLASSIFICATION ALGORITHMS WITH PATIENT-REPORTED SLEEP QUALITY AND FATIGUE IN GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa215.498 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii119-ii119

Author(s):

Megan Tipps ◽

Meghan Tierney ◽

Caitlin Monson ◽

Kelsey Jackson ◽

Nilanjana Banerji ◽

...

Keyword(s):

Sleep Quality ◽

Disease Progression ◽

Sleep Disturbances ◽

Clinical Information ◽

Sleep Efficiency ◽

Sleep Patterns ◽

Subjective Sleep Quality ◽

Ongoing Research ◽

Efficiency Measures ◽

Patient Reported

Abstract INTRODUCTION Fatigue and sleep disturbances are among the most common side-effects reported by patients with glioblastoma and contribute significantly to the quality-of-life for this population. Non-invasive monitoring of long-term sleep patterns and fatigue levels in this population would allow for comparison between iatrogenic sleep disturbances, disease progression, treatment tolerance, and self-reported levels of fatigue. Here, we describe initial results from the implementation of the Readiband™ Sleep Tracker (Fatigue Science), a wearable actigraph device, for monitoring sleep patterns and fatigue in patients with newly diagnosed glioblastoma. PATIENTS AND METHODS Patients were prospectively enrolled and asked to wear the Readiband™ Sleep Tracker for a maximum of twelve months or until disease progression. Patients were also asked to report fatigue levels and sleep quality via the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Pittsburg Sleep Quality Index (PSQI) questionnaires. Demographic, pathologic, and clinical information was abstracted from electronic medical records. RESULTS When data across all participants was combined, FACIT-F and PSQI scores were negatively correlated (r= -0.78, p< 0.001). Significant correlations were also seen between the Readiband™ measures for alertness, sleep quality, and sleep efficiency (p< 0.05 for all). However, we did not observe any correlations between the Redaiband™ measures and subjective survey responses. Interestingly, when patients were sub-divided based on tumor recurrence, we did see significant correlations between both survey scores and sleep quality and sleep efficiency measures (p< 0.05 for all) in patients that recurred during the study period. CONCLUSION The Readiband™ Sleep Tracker is a convenient and viable approach for monitoring sleep and fatigue in glioblastoma patients. Our preliminary findings suggest that actigraph measures may be a better indicator of subjective sleep quality and fatigue levels in specific sub-sets of this population. Ongoing research is exploring other clinical factors that might impact the accuracy of Readiband™ measures.

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Does media use before bedtime affect the sleep of psychosomatic rehabilitation patients?

Somnologie - Schlafforschung und Schlafmedizin ◽

10.1007/s11818-020-00282-5 ◽

2020 ◽

Vol 24 (4) ◽

pp. 253-258

Author(s):

Jasmin Faber ◽

Indra Steinbrecher-Hocke ◽

Peter Bommersbach ◽

Angelika A. Schlarb

Keyword(s):

Sleep Quality ◽

Media Use ◽

Total Sleep Time ◽

Sleep Time ◽

Sleep Efficiency ◽

Subjective Sleep Quality ◽

Psychosomatic Rehabilitation ◽

Sleep Parameters ◽

Rehabilitation Clinic ◽

The Relationship

Abstract Objective Media use can affect sleep. However, research regarding various populations is sparse. The objective of this study was to examine the relationship between media use directly before bedtime and various sleep parameters in patients of a psychosomatic rehabilitation clinic. Methods Patients from a German psychosomatic rehabilitation clinic were tested regarding subjective sleep quality and insomnia symptoms based on questionnaires such as the Pittsburgh Sleep Quality Index (PSQI). Eligible patients also completed an additional sleep log over a period of 1 week. A total of 347 insomnia patients were enrolled, with a mean age of 49.77 years (range 22–64 years; median = 52 years). 57.5% of the patients were 50 years or older. Results Analysis showed that media use and various sleep diary parameters such as total sleep time (r = −0.386, p = 0.042; rTST2 = 0.149) and sleep efficiency (r = −0.507, p = 0.006; rSE2 = 0.257) were significantly associated. In detail, more media consumption was associated with less total sleep time and a lower sleep efficiency. The same result was found for media use and sleep efficiency on weekdays (r = −0.544, p = 0.002; rSE2 = 0.296), but not for other sleep parameters. However, media use time and subjective sleep quality were not significantly correlated, r = −0.055, p = 0.768. Conclusion This study, which is the first to examine the relation between media use and sleep in patients of a psychosomatic rehabilitation clinic, suggests a significant association between media use and sleep duration as well as sleep efficiency. However, more research is needed to investigate the relationship between media use and sleep in more detail, to increase patients’ quality of life and to incorporate these findings into the daily life of clinicians and therapists as well as into sleep hygiene education and sleep trainings.

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Hospitalized COVID-19 Patients Were Five Times More Likely to Suffer From Total Sleep Deprivation Compared to Non-COVID-19 Patients; an Observational Comparative Study

Frontiers in Neuroscience ◽

10.3389/fnins.2021.680932 ◽

2021 ◽

Vol 15 ◽

Author(s):

Eva S. van den Ende ◽

Kim D. I. van Veldhuizen ◽

Belle Toussaint ◽

Hanneke Merten ◽

Peter M. van de Ven ◽

...

Keyword(s):

Sleep Quality ◽

Comparative Study ◽

Sleep Deprivation ◽

Total Sleep Time ◽

Short Form ◽

Sleep Time ◽

Hospital Environment ◽

Poor Sleep ◽

Total Sleep Deprivation ◽

Patient Reported

Objectives: Sleeping disorders are a common complaint in patients who suffer from an acute COVID-19 infection. Nonetheless, little is known about the severity of sleep disturbances in hospitalized COVID-19 patients, and whether these are caused by disease related symptoms, hospitalization, or the SARS-CoV-2 virus itself. Therefore, the aim of this study was to compare the quality and quantity of sleep in hospitalized patients with and without COVID-19, and to determine the main reasons for sleep disruption.Methods: This was an observational comparative study conducted between October 1, 2020 and February 1, 2021 at the pulmonary ward of an academic hospital in the Netherlands. This ward contained both COVID-19-positive and -negative tested patients. The sleep quality was assessed using the PROMIS-Sleep Disturbance Short Form and sleep quantity using the Consensus Sleep Diary. Patient-reported sleep disturbing factors were summarized.Results: A total of 79 COVID-19 patients (mean age 63.0, male 59.5%) and 50 non-COVID-19 patients (mean age 59.5, male 54.0%) participated in this study. A significantly larger proportion of patients with COVID-19 reported not to have slept at all (19% vs. 4% of non-COVID-19 patients, p = 0.011). The Sleep quality (PROMIS total score) and quantity (Total Sleep Time) did not significantly differ between both groups ((median PROMIS total score COVID-19; 26 [IQR 17-35], non-COVID-19; 23 [IQR 18-29], p = 0.104), (Mean Total Sleep Time COVID-19; 5 h 5 min, non-COVID-19 mean; 5 h 32 min, p = 0.405)). The most frequently reported disturbing factors by COVID-19 patients were; ‘dyspnea’, ‘concerns about the disease’, ‘anxiety’ and ‘noises of other patients, medical staff and medical devices’.Conclusion: This study showed that both patients with and without an acute COVID-19 infection experienced poor quality and quantity of sleep at the hospital. Although the mean scores did not significantly differ between groups, total sleep deprivation was reported five times more often by COVID-19 patients. With one in five COVID-19 patients reporting a complete absence of night sleep, poor sleep seems to be a serious problem. Sleep improving interventions should focus on physical and psychological comfort and noise reduction in the hospital environment.

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