The Acceptability of a Non-Benzodiazepine Hypnotic (Zopiclone) in General Practice

The hypnotic effects of Zopiclone, a novel cyclopyrrolone derivative, were compared with placebo in a double-blind randomized crossover study in insomniac patients. Subjective morning assessments by the patients showed that Zopiclone 7·5 mg improved the quality of sleep, with a reduction in the sleep onset latency and the number of nocturnal awakenings. Zopiclone was judged by the physicians to be superior to placebo and was preferred by the patients. Subjective residual effects and adverse reactions were minimal.

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0484 How Much Improvement in Subject-Reported Sleep Onset Latency is Needed for Patients to Report a Positive Impact of Their Insomnia Medication?

SLEEP ◽

10.1093/sleep/zsaa056.481 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A185-A186

Author(s):

C Drake ◽

J Yardley ◽

K Pinner ◽

C Perdomo ◽

D Kumar ◽

...

Keyword(s):

Positive Impact ◽

Sleep Onset ◽

Sleep Diary ◽

Sleep Onset Latency ◽

Onset Latency ◽

Double Blind ◽

Meaningful Improvement ◽

Treatment Groups ◽

Medication Effect ◽

Full Analysis

Abstract Introduction How much improvement would be considered meaningful from the patient perspective is not well defined. In SUNRISE-2 (NCT02952820; E2006-G000-303), using the Patient Global Impression-Insomnia version (PGI-I), subjects rated how treatment impacted subjective (sleep diary-based) sleep onset latency (sSOL; Question2; positive, neutral, and negative) relative to before starting treatment. Meaningful change can thus be determined based on the change from baseline (CFB) in subjects with a positive score. Methods SUNRISE-2 (n=949, full analysis set) was a Phase 3, 12-month, double-blind, global study in subjects age ≥18y with insomnia disorder. Subjects received PBO (N=318), LEM 5mg (LEM5, N=316) or LEM 10mg (LEM10, N=315) for 6 months. At the end of Month 6, PBO subjects were rerandomized to LEM5 or LEM10; LEM5 and LEM10 subjects continued at the same dose for 6 more months. The ranges of median CFB in sSOL (minutes) at 6 months were examined in response to PGI-I Item 2. Results At 6 months, subjects reporting positive medication effect (PBO, n=110; LEM5, n=178; LEM10, n=159) showed median CFB in sSOL from -17.5 to -32.1 minutes across treatment groups. In subjects reporting neutral effect (PBO, n=49; LEM5, n=28; LEM10, n=27), median CFB in sSOL ranged from -10.4 to -25.6 minutes across treatment groups. In subjects reporting negative medication effect (PBO, n=82; LEM5, n=34; LEM10, n=32), median CFB in sSOL ranged from -8.6 to -10.4 minutes across treatment groups. The PBO group provided the smallest numbers for each response category range. Conclusion Subjects reporting positive medication effect on PGI-I Item 2, i.e. decreased time to fall asleep, had corresponding changes from baseline in sSOL ranging from -17.5 to -32.1 minutes. Thus, this range may represent a clinically meaningful improvement as perceived by patient-subjects, and may be useful to clinicians in determining whether a treatment regimen is working for their patients. Support Eisai Inc.

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385 Subjective-objective sleep discrepancy and quality of life in self-reported insomnia and sleep apnea

SLEEP ◽

10.1093/sleep/zsab072.384 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A152-A153

Author(s):

Yan Ma ◽

Michael Goldstein ◽

Roger Davis ◽

Gloria Yeh

Keyword(s):

Quality Of Life ◽

Sleep Apnea ◽

Sleep Onset ◽

Sleep Time ◽

Sleep Onset Latency ◽

Onset Latency ◽

Falling Asleep ◽

Objectively Measured ◽

Sleep Difficulties

Abstract Introduction Current diagnostic classifications define insomnia based on self-reported sleep difficulties. However, differences between self-reported and objectively measured sleep parameters (subjective-objective sleep discrepancy or sleep misperception) are very common. Insomnia and sleep apnea cause common impairments that overlap and have negative impacts on overall health. Previous studies have encouraged an in-depth understanding of subjective-objective sleep discrepancy to inform a role for behavioral, mind-body approaches to insomnia. In this study, utilizing patients with insomnia and comorbid sleep apnea, we aimed to understand associations between self-reported insomnia, sleep difficulties, sleep misperception and quality-of-life. Methods We conducted a secondary analysis using data from the Sleep Heart Health Study (a multi-site nationally representative sample) to examine the profile of subjective and objective sleep measures in people with insomnia (IS, n=73) and comorbid sleep apnea (IS+SA, n=143), compared to individuals with sleep apnea only (SA, n=296) and normal sleep controls (NSC, n=126). We also compared the magnitude of sleep misperception between these four groups and examined the corresponding impact of subjective insomnia complaints on quality-of-life. Results Sleep discrepancy was found in all four groups. After controlling for age, sex, mental health conditions, sleep apnea severity, and objectively measured sleep time, the presence of self-reported insomnia had the strongest association with sleep discrepancy on total sleep time (TST, β=-34.4, p<0.001) and sleep onset latency (SOL, β=14.7, p<0.001). Subjects who reported no difficulty falling asleep slightly underestimated their sleep onset latency, while those who reported difficulty substantially overestimated sleep latency. Self-reported insomnia had a significantly negative impact on the quality of life in both physical and mental components (p<0.001). Conclusion Sleep discrepancy exists in normal controls, insomnia, and sleep apnea. Subjects with self-reported insomnia have a higher degree of sleep misperception. Both sleep apnea and self-reported insomnia are associated with negative QOL. Those with comorbid sleep apnea report the greatest sleep discrepancy and lowest QOL. Further research is needed to better understand individual profiles of misperception and insomnia phenotypes, apnea comorbidity and quality-of-life. Behavioral, mind-body interventions may offer strategies to address mental stress, sleep misperception, and insomnia. Support (if any) NCCIH T32AT000051 and NHLBI 5T32HL007901-22

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Effects of the selective orexin-2 receptor antagonist JNJ-48816274 on sleep initiated in the circadian wake maintenance zone: a randomised trial

Neuropsychopharmacology ◽

10.1038/s41386-021-01175-3 ◽

2021 ◽

Author(s):

Victoria L. Revell ◽

Ciro della Monica ◽

Jeewaka Mendis ◽

Hana Hassanin ◽

Robin J. Halter ◽

...

Keyword(s):

Receptor Antagonist ◽

Rem Sleep ◽

Spectral Power ◽

Randomised Trial ◽

Sleep Onset ◽

Residual Effects ◽

Phase Advance ◽

Sleep Onset Latency ◽

Placebo Condition ◽

Double Blind

AbstractThe effects of orexinergic peptides are diverse and are mediated by orexin-1 and orexin-2 receptors. Antagonists that target both receptors have been shown to promote sleep initiation and maintenance. Here, we investigated the role of the orexin-2 receptor in sleep regulation in a randomised, double-blind, placebo-controlled, three-period crossover clinical trial using two doses (20 and 50 mg) of a highly selective orexin-2 receptor antagonist (2-SORA) (JNJ-48816274). We used a phase advance model of sleep disruption where sleep initiation is scheduled in the circadian wake maintenance zone. We assessed objective and subjective sleep parameters, pharmacokinetic profiles and residual effects on cognitive performance in 18 healthy male participants without sleep disorders. The phase advance model alone (placebo condition) resulted in disruption of sleep at the beginning of the sleep period compared to baseline sleep (scheduled at habitual time). Compared to placebo, both doses of JNJ-48816274 significantly increased total sleep time, REM sleep duration and sleep efficiency, and reduced latency to persistent sleep, sleep onset latency, and REM latency. All night EEG spectral power density for both NREM and REM sleep were unaffected by either dose. Participants reported significantly better quality of sleep and feeling more refreshed upon awakening following JNJ-48816274 compared to placebo. No significant residual effects on objective performance measures were observed and the compound was well tolerated. In conclusion, the selective orexin-2 receptor antagonist JNJ-48816274 rapidly induced sleep when sleep was scheduled earlier in the circadian cycle and improved self-reported sleep quality without impact on waking performance.

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Comparative Efficacy of Triazolam, Flurazepam and Placebo in Out-Patients Insomniacs

Journal of International Medical Research ◽

10.1177/030006057800600412 ◽

1978 ◽

Vol 6 (4) ◽

pp. 337-342 ◽

Cited By ~ 10

Author(s):

Angela J Bowen

Keyword(s):

Crossover Trial ◽

Sleep Onset ◽

Quality Of Sleep ◽

Comparative Efficacy ◽

Short Term ◽

Night Time ◽

Double Blind ◽

Hypnotic Efficacy ◽

Better Than

The short-term hypnotic efficacy of triazolam was compared to that of flurazepam and placebo in 120 out-patient insomniacs. Each patient was studied with a two-night, double-blind crossover trial. Triazolam (0.5 mg) was compared to placebo and flurazepam (30 mg). Triazolam (0.25 mg) was compared to flurazepam (15 mg and 30 mg). Triazolam (0.5 mg) was preferred to both placebo and flurazepam (30 mg). Triazolam (0.5 mg) was superior to placebo in improving quality of sleep, shortening sleep onset, increasing sleep duration, and reducing the number of night-time awakenings. Triazolam (0.5 mg) was superior to flurazepam (30 mg) in speeding sleep onset and increasing the quality of sleep. Triazolam (0.25 mg) was preferred to flurazepam (15 mg) and was significantly better than flurazepam on all sleep questions. Triazolam (0.25 mg) was preferred by more patients than flurazepam (30 mg) and was judged equally efficacious on indivdual sleep questions. Reports of side-effects were minimal for both drugs.

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Melatonin in pediatric neurology

ORL ro ◽

10.26416/orl.33.4.2016.168 ◽

2016 ◽

Vol 4 (1) ◽

pp. 56-59

Author(s):

Raluca Ioana Teleanu ◽

Magdalena Sandu ◽

Eugenia Roza

Keyword(s):

European Union ◽

Food Safety ◽

Sleep Onset ◽

Sleep Onset Latency ◽

The European Union ◽

Onset Latency ◽

Entire Life ◽

Light Darkness ◽

Efficacy Studies ◽

Endogenous Melatonin

Melatonin is a hormone produced by the pineal gland during the night, as a response to the light-darkness variation. The endogenous melatonin levels have a cyclic evolution throughout the entire life. Various roles have been cited such as the in utero developement of the fetus through its action on the placenta, neurons and glial cells, a major role in the regulation of the cyrcadian rhythm, antioxidative, antiinflammatory roles, as well as celullar and umoral immunity modulation. In the European Union, exogenous melatonin has been evaluated by the European Food Safety Authority (EFSA) for reducing sleep onset latency and the conclusion was that it has efficacy studies in this regard.

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The Monday Effect Revisited: A Diary and Sleep Actigraphy Study

Sleep and Vigilance ◽

10.1007/s41782-020-00105-5 ◽

2020 ◽

Vol 4 (2) ◽

pp. 167-176

Author(s):

Achim Elfering ◽

Christin Gerhardt ◽

Diana Pereira ◽

Anna Schenker ◽

Maria U. Kottwitz

Keyword(s):

Sleep Duration ◽

Sleep Onset ◽

Monday Morning ◽

Sleep Onset Latency ◽

Onset Latency ◽

Social Stressors ◽

Monday Effect ◽

Work Related ◽

Cognitive Failure ◽

Delayed Sleep

Abstract Purpose Accidents are more likely to occur during the morning hours of Mondays (Monday effect). This might be due to a higher level of cognitive failure on Monday morning at work. Methods In a pilot actigraphy study across one working week, we explored this Monday effect and regressed daily self-reported workplace cognitive failure on weekdays (Monday versus other days), background social stressors at work, delayed sleep onset and sleep duration. Diary data were gathered from 40 full-time employees. Results Confirming our assumptions, results revealed work-related cognitive failure and sleep-onset latency on the previous night to be higher on Mondays compared to other workdays. Work-related cognitive failure correlated positively with delayed sleep-onset latency and background social stressors. In multilevel regression analysis, Monday significantly explained variations in workplace cognitive failure. The addition of background social stressors at work and sleep-onset latency to the regression model showed unique contributions to the prediction of workplace cognitive failure. No significant two-way or three-way interactions between working days, sleep-onset latency or sleep duration, and background social stressors were found. Conclusion Peak levels of cognitive failure on Monday morning and the association of cognitive failure with social stressors at work contribute to understanding the mechanisms involved in the increased prevalence of occupational accidents on Monday morning. Occupational safety interventions should address both social stressors at work and individual sleep hygiene.

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193 Sleep Variability and Affect Dynamics Among College Students during COVID-19 Pandemic

SLEEP ◽

10.1093/sleep/zsab072.192 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A78-A78

Author(s):

Zahra Mousavi ◽

Jocelyn Lai ◽

Asal Yunusova ◽

Alexander Rivera ◽

Sirui Hu ◽

...

Keyword(s):

Emerging Adults ◽

Sleep Duration ◽

Sleep Onset ◽

Positive And Negative Affect ◽

Sleep Onset Latency ◽

Deep Sleep ◽

Onset Latency ◽

Sleep Patterns ◽

Light Sleep ◽

Affect Dynamics

Abstract Introduction Sleep disturbance is a transdiagnostic risk factor that is so prevalent among emerging adults it is considered to be a public health epidemic. For emerging adults, who are already at greater risk for psychopathology, the COVID-19 pandemic has disrupted daily routines, potentially changing sleep patterns and heightening risk factors for the emergence of affective dysregulation, and consequently mood-related disturbances. This study aimed to determine whether variability in sleep patterns across a 3-month period was associated with next-day positive and negative affect, and affective dynamics, proximal affective predictors of depressive symptoms among young adults during the pandemic. Methods College student participants (N=20, 65% female, Mage=19.80, SDage=1.0) wore non-invasive wearable devices (the Oura ring https://ouraring.com/) continuously for a period of 3-months, measuring sleep onset latency, sleep efficiency, total sleep, and time spent in different stages of sleep (light, deep and rapid eye movement). Participants reported daily PA and NA using the Positive and Negative Affect Schedule on a 0-100 scale to report on their affective state. Results Multilevel models specifying a within-subject process of the relation between sleep and affect revealed that participants with higher sleep onset latency (b= -2.98, p<.01) and sleep duration on the prior day (b= -.35, p=.01) had lower PA the next day. Participants with longer light sleep duration had lower PA (b= -.28, p=.02), whereas participants with longer deep sleep duration had higher PA (b= .36, p=.02) the next day. On days with higher total sleep, participants experienced lower NA compared to their own average (b= -.01, p=.04). Follow-up exploratory bivariate correlations revealed significant associations between light sleep duration instability and higher instability in both PA and NA, whereas higher deep sleep duration was linked with lower instability in both PA and NA (all ps< .05). In the full-length paper these analyses will be probed using linear regressions controlling for relevant covariates (main effects of sleep, sex/age/ethnicity). Conclusion Sleep, an important transdiagnostic health outcome, may contribute to next-day PA and NA. Sleep patterns predict affect dynamics, which may be proximal predictors of mood disturbances. Affect dynamics may be one potential pathway through which sleep has implications for health disparities. Support (if any):

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1253 Multiple sleep onset REM episodes in middle age woman with excessive daytime sleepiness – Is this automatically assumed narcolepsy?

SLEEP ◽

10.1093/sleep/zsaa056.1247 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A477-A477

Author(s):

Kamal Patel ◽

Bianca J Lang

Keyword(s):

Daytime Sleepiness ◽

Sleep Latency ◽

Sleep Onset ◽

Sleep Time ◽

Multiple Sleep Latency Test ◽

Sleep Onset Latency ◽

Onset Latency ◽

Obstructive Sleep ◽

Falling Asleep ◽

Multiple Sleep Latency

Abstract Introduction Presence of sleep onset REM episodes often raises concerns of narcolepsy. However other conditions have shown to have presence of sleep on REM episodes which include but not limited to obstructive sleep apnea, sleep wake schedule disturbance, alcoholism, neurodegenerative disorders, depression and anxiety Report of Case Here we present a case of 30 year old female with history of asthma, patent foraman ovale, migraine headache, and anxiety who presented with daytime sleepiness, falling asleep while at work, occasional scheduled naps, non-restorative sleep, sleep paralysis, and hypnopompic hallucination. Pertinent physical exam included; mallampati score of 4/4, retrognathia, high arched hard palate, crowded posterior oropharynx. She had a score of 16 on Epworth sleepiness scale. Patient previously had multiple sleep latency test at outside facility which revealed 4/5 SOREM, with mean sleep onset latency of 11.5 minutes. She however was diagnosed with narcolepsy and tried on modafinil which she failed to tolerate. She was tried on sertraline as well which was discontinued due to lack of benefit. She had repeat multiple sleep latency test work up which revealed 2/5 SOREM, with mean sleep onset latency was 13.1 minutes. Her overnight polysomnogram prior to repeat MSLT showed SOREM with sleep onset latency of 10 minutes. Actigraphy showed consistent sleep pattern overall with sufficient sleep time but was taking hydroxyzine and herbal medication. Patient did not meet criteria for hypersomnolence disorder and sleep disordered breathing. Conclusion There is possibility her medication may have played pivotal role with her daytime symptoms. We also emphasize SOREMs can be present in other disorders such as anxiety in this case and not solely in narcolepsy

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