0781 Impact Of Suvorexant On Total Daytime Sleep Hours In Shift Workers: A Randomized, Double-blind, Placebo-controlled Clinical Field Trial

Abstract Introduction Many shift workers have an inability to sleep during the daytime following a night shift not due to insomnia or lack of sleep pressure, but because a circadian signal promoting wakefulness is hampering their ability to maintain sleep. We have previously hypothesized that the neuropeptide hypocretin-1 is, in part, responsible for the physiologic expression of this circadian wake signal. As such, it was our intent to determine whether a pharmacologic blockade of hypocretin would enable shift workers to obtain more daytime sleep. Methods Nineteen shift workers took part in a placebo-controlled, double-blind field study of suvorexant. Following two weeks of baseline, participants received 10 mg suvorexant/placebo for one week and were titrated upward to 20 mg suvorexant/placebo for an additional two weeks. Subjective (diaries) and objective (actigraphy) sleep were monitored throughout. No restrictions were placed on participants’ schedules. Results Both subjective and objective measures of total sleep time significantly improved in the active vs. the placebo condition, increasing by 2.08 ± 0.47 hours (diary) or 1.04 ± 0.53 hours (actigraphy) by the end of the 10 mg condition, and increasing by 2.97 ± 0.56 hours (diary) or 2.16 ± 0.75 hours (actigraphy) by the end of the 20 mg condition. Physician ratings of change in the severity of symptoms similarly improved in the active group. There were no adverse events reported in the active condition. Conclusion Robust changes in total sleep time were observed after administration of suvorexant, a dual-hypocretin antagonist, prior to daytime sleep in a field study of shift workers. The very large changes in total sleep time, coupled with the permissive nature of the therapeutic mechanism (i.e., suppressing wake rather than inducing sleep) indicate that this could be a viable and important therapy for shift workers. Support Merck Sharpe and Dohme investigator-initiated study #53236

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Effects of Light on Daytime Sleep in 12 Hours Night Shift Workers: A Field Study

Journal of Sleep Medicine ◽

10.13078/jsm.19026 ◽

2019 ◽

Vol 16 (1) ◽

pp. 26-35

Author(s):

Su Jung Choi ◽

Hea Ree Park ◽

Eun Yeon Joo

Keyword(s):

Field Study ◽

Night Shift ◽

Shift Workers ◽

Daytime Sleep

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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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Personality Traits and Insomnia Symptoms in Shift Workers

Frontiers in Psychology ◽

10.3389/fpsyg.2021.689741 ◽

2021 ◽

Vol 12 ◽

Author(s):

Brigitte Holzinger ◽

Lucille Mayer ◽

Gerhard Klösch

Keyword(s):

Sleep Quality ◽

Personality Traits ◽

Sleep Duration ◽

Total Sleep Time ◽

Sleep Time ◽

Work Schedule ◽

Shift Workers ◽

Time In Bed ◽

Shift Schedules ◽

Insomnia Symptoms

The discrepancy between natural sleep-wake rhythm and actual sleep times in shift workers can cause sleep loss and negative daytime consequences. Irregular shift schedules do not follow a fixed structure and change frequently, which makes them particularly harmful and makes affected individuals more susceptible to insomnia. The present study compares insomnia symptoms of non-shift workers, regular shift workers, and irregular shift workers and takes into account the moderating role of the Big Five personality traits and levels of perfectionism. Employees of an Austrian railway company completed an online survey assessing shift schedules, sleep quality and duration, daytime sleepiness, and personality traits. A total of 305 participants, of whom 111 were non-shift workers, 60 regular shift workers, and 134 irregular shift workers, made up the final sample. Irregular shift workers achieved significantly worse scores than one or both of the other groups in time in bed, total sleep time, sleep efficiency, sleep duration, sleep quality, sleep latency, and the number of awakenings. However, the values of the irregular shifts workers are still in the average range and do not indicate clinical insomnia. Participants working regular shifts reported the best sleep quality and longest sleep duration and showed the least nocturnal awakenings, possibly due to higher conscientiousness- and lower neuroticism scores in this group. Agreeableness increased the effect of work schedule on total sleep time while decreasing its effect on the amount of sleep medication taken. Perfectionism increased the effect of work schedule on time in bed and total sleep time. Generalization of results is limited due to the high percentage of males in the sample and using self-report measures only.

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0487 Effects of Suvorexant on Sleep Architecture in Patients with Alzheimer’s Disease and Insomnia

SLEEP ◽

10.1093/sleep/zsaa056.484 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A187-A187

Author(s):

V Svetnik ◽

T Wang ◽

P Ceesay ◽

O Ceren ◽

E Snyder ◽

...

Keyword(s):

Receptor Antagonist ◽

Clinical Response ◽

Total Sleep Time ◽

Sleep Time ◽

Sleep Architecture ◽

Sleep Laboratory ◽

Double Blind ◽

Moderate Severity ◽

Competitive Antagonism ◽

Significant Difference

Abstract Introduction Suvorexant, an orexin receptor antagonist that enables sleep to occur via competitive antagonism of wake-promoting orexins, improved total sleep time (TST) in a sleep laboratory polysomnography (PSG) study of patients with AD and insomnia. Here we report on the effects of suvorexant on sleep architecture in the study. Methods This was a randomized, double-blind, 4-week trial (ClinicalTrials.gov NCT02750306). Participants who met diagnostic criteria for both probable AD dementia (of mild to moderate severity) and insomnia were randomized to suvorexant 10mg (could be increased to 20mg based on clinical response) or matching placebo. Overnight sleep laboratory PSG was performed on 3 nights: screening, baseline, and Night-29 (last night of dosing). Suvorexant differences from placebo in changes-from-baseline at Night-29 for sleep architecture were analyzed as exploratory endpoints. Results A total of 274 participants were included in the analysis (suvorexant N=135, placebo N=139). At Night-29, suvorexant improved TST by 28 minutes versus placebo (p=0.001). There were no significant differences between suvorexant and placebo in the % of TST spent in REM (1.3%, 95% CI: -0.5, 3.0), N1 (0.6%, 95% CI: -1.2, 2.5), N2 (-1.0%, 95% CI: -3.2, 1.2), or N3 (-0.6%, 95% CI: -1.8, 0.6). There was no significant difference between suvorexant and placebo in latency to REM (-5.4 minutes, 95% CI: -23.4, 12.7). Conclusion Suvorexant improves TST without altering the underlying sleep architecture in AD patients with insomnia. Support Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA

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Sleep Time Duration Does Not Affect Oral Inflammation and Periodontal Health Status in Night-Shift Workers: A Cross-Sectional Study

Nature and Science of Sleep ◽

10.2147/nss.s279088 ◽

2020 ◽

Vol Volume 12 ◽

pp. 1083-1090

Author(s):

Retno Indrawati Roestamadji ◽

Muhammad Luthfi ◽

Meircurius Dwi Condro Surboyo ◽

Rauhansen Bosafino Rumokoi ◽

Fridaniyanti Khusnul Khotimah

Keyword(s):

Health Status ◽

Night Shift ◽

Sleep Time ◽

Cross Sectional Study ◽

Sectional Study ◽

Time Duration ◽

Periodontal Health ◽

Cross Sectional ◽

Shift Workers ◽

Oral Inflammation

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0488 Pilot Evaluation of an Actigraphy Watch Compared to Polysomnography in a Clinical Trial of Suvorexant for Treating Insomnia in Patients with Alzheimer’s Disease

SLEEP ◽

10.1093/sleep/zsaa056.485 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A187-A187

Author(s):

V Svetnik ◽

T Wang ◽

P Ceesay ◽

E Snyder ◽

O Ceren ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Gold Standard ◽

Treatment Effects ◽

Total Sleep Time ◽

Sleep Time ◽

Sleep Laboratory ◽

Double Blind ◽

Recording Time ◽

Daytime Activity

Abstract Introduction Suvorexant, an orexin receptor antagonist, improved total sleep time (TST) in a sleep laboratory polysomnography (PSG) study of patients with Alzheimer’s disease (AD) and insomnia. The study included a pilot evaluation of an actigraphy watch for continuously recording patient’s sleep and daytime activity. We report on the utility of the watch for assessing sleep in relation to gold-standard PSG. Methods This was a randomized, double-blind, 4-week trial (ClinicalTrials.gov NCT02750306). Participants who met diagnostic criteria for both probable AD dementia and insomnia were randomized to suvorexant 10-20mg or placebo. Overnight sleep laboratory PSG was performed on 3 nights: screening, baseline, and Night-29 (last dose). An actigraphy watch (Garmin vívosmart® HR) was worn continuously by the patient. Separate analyses were performed for PSG and watch. We compared treatment effects on change-from-baseline in PSG-TST at Night-29 and WATCH-TST at Week-4 (average TST per night over Week-4). We also analyzed Night-29 data only with watch data restricted to the PSG recording time. Results A total of 274 participants were included in the Night-29 PSG analysis (suvorexant=135, placebo=139) and 223 in the Week-4 watch analysis (suvorexant=113, placebo=110). Suvorexant improved Night-29 PSG-TST by 28 minutes versus placebo (p=0.001) and Week-4 WATCH-TST by 17 minutes versus placebo (p=0.144). In the subgroup who had usable data for both assessments at Night-29 (suvorexant=57, placebo=50), the watch overestimated TST compared to PSG (e.g. placebo baseline scores = 412 minutes for WATCH-TST and 265 minutes for PSG-TST) and underestimated change-from-baseline treatment effects: the suvorexant versus placebo difference was 35 minutes for PSG-TST (p=0.057) and 20 minutes for WATCH-TST (p=0.405). Conclusion The watch was less sensitive than PSG for evaluating treatment effects on TST. However, results obtained with the watch were directionally similar to PSG in indicating a benefit of suvorexant versus placebo for improving TST in AD patients with insomnia. Support Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA

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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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