Treatment of Circadian Rhythm Sleep–Wake Disorders

: Circadian rhythm sleep–wake disorders (CRSWDs) are a distinct class of sleep disorders caused by alterations to the circadian time-keeping system, its entrainment mechanisms, or a mismatch between the endogenous circadian rhythm and the external environment. The main clinical manifestations are insomnia and excessive daytime sleepiness that often lead to clinically meaningful distress or cause mental, physical, social, occupational, educational, or other functional impairment. CRSWDs are easily mistaken for insomnia or early waking up, resulting in inappropriate treatment. CRSWDs can be roughly divided into two categories, namely, intrinsic CRSWDs, in which sleep disturbances are caused by alterations to the endogenous circadian rhythm system due to chronic changes in the regulation or capture mechanism of the biological clock; and extrinsic circadian rhythm sleep–wake disorders, in which sleep disorders, such as jet lag or shift-work disorder, result from environmental changes that cause a mismatch between sleep–wakefulness times and internal circadian rhythms. Sleep diaries, actigraphy, and determination of day and night phase markers (dim light melatonin onset and core body temperature minimum) have all become routine diagnostic methods for CRSWDs. Common treatments for CRSWD currently include sleep health education, time therapy, light therapy, melatonin, and hypnotic drug therapy. Here, we review the progress in the epidemiology, etiology, diagnostic evaluation, diagnostic criteria, and treatment of intrinsic CRSWD, with emphasis on the latter, in the hope of bolstering the clinical diagnosis and treatment of CRSWDs.

Therapeutic aspects of melatonin applications

The results of multicenter clinical trials show the broad potential of melatonin since discovery of this adaptogen to the present day. Melatonin is a neuropeptide that is synthesized mainly in the small brain gland, the pineal gland, and has a unique effect in humans and animals. Using melatonin, the pineal gland participates in the organization of circadian periodism and regulation of cyclic processes, acting as an intermediary between the pacemaker mechanism of the suprachiasmatic nuclei (SCN) and peripheral organs. The pineal gland and the SCN of the hypothalamus form part of the system of the so-called biological clock of the body, which plays a key role in the mechanisms of regulation of the biological clock via circadian rhythms and ageing. Initially, melatonin was only considered a hormone involved in the synchronization of the mechanisms of the circadian rhythm, but later it was found that, in addition to this hormonal function, it takes part in the regulation of the seasonal cycle in animals and humans.At present, melatonin drugs have shown high efficacy and safety in various sleep-wake disorders regardless of their genesis, disorganization of circadian rhythms, stress adjustment disorders, rapid change of time zones, shift work and in complex therapy of patients with cerebrovascular diseases.The article considers the multimodal capabilities of melatonin, including adaptogenic, biorhythmogenic, hypnotic, immunostimu-lating, antioxidant effects. The role of melatonin in the treatment of various central nervous system disorders, including neurodegenerative diseases, has been determined.The review emphasizes the wide-ranging effects of melatonin and offers great opportunities for measuring melatonin as a biomarker for early detection and follow-up of various diseases.

Melatonin as a Potential Adjuvant Treatment for COVID-19 beyond Sleep Disorders

Melatonin is registered to treat circadian rhythm sleep–wake disorders and insomnia in patients aged 55 years and over. The essential role of the circadian sleep rhythm in the deterioration of sleep quality during COVID-19 confinement and the lack of an adverse effect of melatonin on respiratory drive indicate that melatonin has the potential to be a recommended treatment for sleep disturbances related to COVID-19. This review article describes the effects of melatonin additional to its sleep-related effects, which make this drug an attractive therapeutic option for treating patients with COVID-19. The preclinical data suggest that melatonin may inhibit COVID-19 progression. It may lower the risk of the entrance of the SARS-CoV-2 virus into cells, reduce uncontrolled hyper-inflammation and the activation of immune cells, limit the damage of tissues and multiorgan failure due to the action of free radicals, and reduce ventilator-induced lung injury and the risk of disability resulting from fibrotic changes within the lungs. Melatonin may also increase the efficacy of COVID-19 vaccination. The high safety profile of melatonin and its potential anti-SARS-CoV-2 effects make this molecule a preferable drug for treating sleep disturbances in COVID-19 patients. However, randomized clinical trials are needed to verify the clinical usefulness of melatonin in the treatment of COVID-19.

A timed activity protocol to address sleep-wake disorders in home dwelling persons living with dementia: the healthy patterns clinical trial

Background Sleep-wake disorders occur in most persons living with dementia and include late afternoon or evening agitation, irregular sleep-wake rhythms such as daytime hypersomnia, frequent night awakenings, and poor sleep efficiency. Sleep-wake disorders pose a great burden to family caregivers, and are the principal causes of distress, poor quality of life, and institutionalization. Regulating the sleep-wake cycle through the use of light and activity has been shown to alter core clock processes and suggests that a combination of cognitive, physical, and sensory-based activities, delivered at strategic times, may be an effective mechanism through which to reduce sleep-wake disorders. Methods A definitive Phase III efficacy trial of the Healthy Patterns intervention, a home-based activity intervention designed to improve sleep-wake disorders and quality of life, is being conducted using a randomized two-group parallel design of 200 people living with dementia and their caregivers (dyads). Specific components of this one-month, home-based intervention involve 4 in-home visits and includes: 1) assessing individuals’ functional status and interests; 2) educating caregivers on environmental cues to promote activity and sleep; and 3) training caregivers in using timed morning, afternoon, and evening activities based on circadian needs across the day. The patient focused outcomes of interest are quality of life, measures of sleep assessed by objective and subjective indicators including actigraphy, subjective sleep quality, and the presence of neuropsychiatric symptoms. Caregiver outcomes of interest are quality of life, burden, confidence using activities, and sleep disruption. Salivary measures of cortisol and melatonin are collected to assess potential intervention mechanisms. Discussion The results from the ongoing study will provide fundamental new knowledge regarding the effects of timing activity participation based on diurnal needs and the mechanisms underlying timed interventions which can lead to a structured, replicable treatment protocol for use with this growing population of persons living with dementia. Clinical trial registration Clinicaltrials.gov # NCT03682185 at https://clinicaltrials.gov/; Date of clinical trial registration: 24 September 2018.

The Role of Sleep Quality and Mental Health in Cardiovascular Disease

Objectives: Cardiovascular diseases (CVDs) may accompany other diseases. Of which can name sleep disorders and also other psychiatric disorders. Aim: In current study we evaluate the concomitant mental health disorders and the sleep quality among the acute myocardial infarction (AMI) and acute coronary syndrome (ACS) patients. Method:180 cases were selected through random sampling. 90 of the cases were hospitalized because of acute myocardial AMI and 90 patients were admitted with the diagnosis of ACS. Demographic, GHQ 28 and PSQI questionnaire was applied to evaluate the demographic features, psychological wellbeing and sleep quality subsequently. Results: 57.8% of cases were women 42.2% were men. The age range was 27 75 years old and the mean age was 49.93+11.73years old. 87.8% of the patients were married and rest were single. The mean score for the GHQ 28 questionnaire was22.43+10.99in patients with angina and in AMI patients.38.8% of ACS patients and 50% of AMI patients didn’t feel well psychologically. The mean score for sleep quality in ACS patients was 3.08+3.6 and 4.06+3.8 in AMI patients. 32.3% of ACS cases and 24.4% of AMI cases had troubles in sleeping. Conclusion: The mental health disorders prevail in AMI and ACS patients. Furthermore, the poor sleep quality was correlated with mental health disorders. Keywords: Sleep Wake Disorders, Mental Health, Acute Coronary Syndrome, Myocardial Infarction

Differences in Psychiatric Comorbidities and Gender Distribution among Three Clusters of Personality Disorders: A Nationwide Population-Based Study

Personality disorders (PDs) are grouped into clusters A, B, and C. However, whether the three clusters of PDs have differences in comorbid mental disorders or gender distribution is still lacking sufficient evidence. We aim to investigate the distribution pattern across the three clusters of PDs with a population-based cohort study. This study used the Taiwan national database between 1995 and 2013 to examine the data of patients with cluster A PDs, cluster B PDs, or cluster C PDs. We compared the differences of psychiatric comorbidities classified in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition across the three clusters of PDs. Moreover, we formed gender subgroups of the three PDs to observe the discrepancy between male and female. Among the 9845 patients, those with cluster A PDs had the highest proportion of neurodevelopmental disorders, schizophrenia and neurocognitive disorders, those with cluster B PDs demonstrated the largest percentage of bipolar disorders, trauma and stressor disorders, feeding and eating disorders, and substance and addictive disorders, and those with cluster C PDs had the greatest proportion of depressive disorders, anxiety disorders, obsessive–compulsive disorders, somatic symptom disorders, and sleep–wake disorders. The gender subgroups revealed significant male predominance in neurodevelopmental disorders and female predominance in sleep–wake disorders across all three clusters of PDs. Our findings support that some psychiatric comorbidities are more prevalent in specified cluster PDs and that gender differences exist across the three clusters of PDs. These results are an important reference for clinicians who are developing services that target real-world patients with PDs.