Agomelatine: An astounding sui-generis antidepressant?

: Major depressive disorder (MDD) is one of the foremost causes of disability and premature death worldwide. Although the available antidepressants are effective and well tolerated, they also have many limitations. Therapeutic advances in developing a new drug's ultimate relation between MDD and chronobiology, which targets the circadian rhythm, have led to a renewed focus on psychiatric disorders. In order to provide a critical analysis about antidepressant properties of agomelatine, a detailed PubMed (Medline), Scopus (Embase), Web of Science (Web of Knowledge), Cochrane Library, Google Scholar, and PsycInfo search was performed using the following keywords: melatonin analog, agomelatine, safety, efficacy, adverse effects, pharmacokinetics, pharmacodynamics, circadian rhythm, sleep disorders, neuroplasticity, MDD, bipolar disorder, anhedonia, anxiety, generalized anxiety disorder (GAD), and mood disorders. Agomelatine is a unique melatonin analog with antidepressant properties and a large therapeutic index that improves clinical safety. It is a melatonin receptor agonist (MT1 and MT2) and a 5-HT2C receptor antagonist. The effects on melatonin receptors enable the resynchronization of irregular circadian rhythms with beneficial effects on sleep architectures. In this way, agomelatine is accredited for its unique mode of action, which helps to exert antidepressant effects and resynchronize the sleep-wake cycle. To sum up, an agomelatine has not only antidepressant properties but also has anxiolytic effects.

New and Emerging Approaches to Better Define Sleep Disruption and Its Consequences

Current approaches to quantify and diagnose sleep disorders and circadian rhythm disruption are imprecise, laborious, and often do not relate well to key clinical and health outcomes. Newer emerging approaches that aim to overcome the practical and technical constraints of current sleep metrics have considerable potential to better explain sleep disorder pathophysiology and thus to more precisely align diagnostic, treatment and management approaches to underlying pathology. These include more fine-grained and continuous EEG signal feature detection and novel oxygenation metrics to better encapsulate hypoxia duration, frequency, and magnitude readily possible via more advanced data acquisition and scoring algorithm approaches. Recent technological advances may also soon facilitate simple assessment of circadian rhythm physiology at home to enable sleep disorder diagnostics even for “non-circadian rhythm” sleep disorders, such as chronic insomnia and sleep apnea, which in many cases also include a circadian disruption component. Bringing these novel approaches into the clinic and the home settings should be a priority for the field. Modern sleep tracking technology can also further facilitate the transition of sleep diagnostics from the laboratory to the home, where environmental factors such as noise and light could usefully inform clinical decision-making. The “endpoint” of these new and emerging assessments will be better targeted therapies that directly address underlying sleep disorder pathophysiology via an individualized, precision medicine approach. This review outlines the current state-of-the-art in sleep and circadian monitoring and diagnostics and covers several new and emerging approaches to better define sleep disruption and its consequences.

Current and Future Perspectives on Light Therapy Using Wearable Devices

Circadian rhythm is the internal clock that regulates physiological functions, including the sleep-wake cycle. Advancements in technology and lifestyle have negatively impacted the circadian rhythm, resulting in numerous sleep disorders. Because light is the most important “zeigeber” for synchronizing the circadian system, light therapy is effective for circadian rhythm sleep disorders. We compared light therapy glasses with a traditional light therapy box, summarized the characteristics of various light therapy glasses, and proposed future applications of wearable sleep technologies in light therapy.

Sleep disorders

In populations with serious chronic illness, sleep disturbances represent frequent distressing symptoms. The more common disorders include insomnia, excessive daytime sleepiness, and circadian rhythm sleep disorders. Primary sleep disturbances are thought to be a disorder of hyperarousal. Hypothalamic–pituitary–adrenal axis dysfunction has also been confirmed. Secondary sleep disorders may occur as a result of the advanced disease or its treatments. It has been associated with a large number of potential causes, both physical and psychological. Chronic medication use, neurological or psychiatric disorders, and environmental factors can also contribute. This chapter discusses the diagnosis of sleep disturbances, and both pharmacological and non-pharmacological treatments.

INSOMNIA, AS A PREDICTOR OF MENTAL DISORDERS IN HUMANITY. (LITERATURE REVIEW)

Сон является важным физиологическим состоянием необходимым для здоровья и благополучия человека. Разные виды нарушений сна отрицательно сказываются на психическом здоровье и качестве жизни человека, являются фактором риска для возникновения или усугубления течения существующих заболеваний. По данным международной классификации нарушений сна, принято выделять шесть основных категорий: бессонница, нарушение дыхания во сне, центральные расстройства гиперсонливости, парасомнии, двигательные расстройства во сне, расстройства циркадного ритма сна. [1]. Учитывая такое разнообразие нарушений сна, мы сталкиваемся с большим количеством нозологий и специальностей, которые вовлечены в процесс диагностики и лечения данных пациентов. Литературные данные указывают на прямую связь нарушений сна с проблемами сердечно-сосудистой, дыхательной, нейроэндокринной систем. Лечением данной группы пациентов занимаются специалисты разных областей медицины - от стоматологов и оториноларингологов до психиатров и неврологов. Актуальность данной тематики не вызывает сомнений, так как по литературным данным в современном обществе до 50 % населения планеты сталкиваются с проблемами, связанными с нарушениями сна. В последние 30 лет этой нозологии уделяется очень много внимания в развитых странах мира, тем не менее, нарушения сна по-прежнему остаются острой проблемой влияющей на качество жизни и здоровье человечества. Sleep is an important physiological condition necessary for human health and well-being. Various types of sleep disorders adversely affect mental health and quality of life of a person, and are a risk factor for the onset or aggravation of existing diseases. According to the international classification of sleep disorders, it is customary to distinguish six main categories: insomnia, breathing disorders during sleep, central disorders of hypersomnia, parasomnias, movement disorders during sleep, and circadian rhythm sleep disorders. [1]. Given such a variety of sleep disorders, we are faced with a large number of nosologies and specialties that are involved in the process of diagnosing and treating these patients. Literature data indicate a direct connection between sleep disorders and problems of the cardiovascular, respiratory, neuroendocrine systems. This group of patients is treated by specialists in various fields of medicine - from dentists and otorhinolaryngologists to psychiatrists and neurologists. The relevance of this topic is beyond doubt, since according to literature data in modern society up to 50% of the world's population face problems associated with sleep disorders. In the past 30 years, this nosology has received a lot of attention in the developed countries of the world, however, sleep disorders still remain an acute problem affecting the quality of life and health of mankind.

Photoplethysmography in Normal and Pathological Sleep

This article presents an overview of the advancements that have been made in the use of photoplethysmography (PPG) for unobtrusive sleep studies. PPG is included in the quickly evolving and very popular landscape of wearables but has specific interesting properties, particularly the ability to capture the modulation of the autonomic nervous system during sleep. Recent advances have been made in PPG signal acquisition and processing, including coupling it with accelerometry in order to construct hypnograms in normal and pathologic sleep and also to detect sleep-disordered breathing (SDB). The limitations of PPG (e.g., oxymetry signal failure, motion artefacts, signal processing) are reviewed as well as technical solutions to overcome these issues. The potential medical applications of PPG are numerous, including home-based detection of SDB (for triage purposes), and long-term monitoring of insomnia, circadian rhythm sleep disorders (to assess treatment effects), and treated SDB (to ensure disease control). New contact sensor combinations to improve future wearables seem promising, particularly tools that allow for the assessment of brain activity. In this way, in-ear EEG combined with PPG and actigraphy could be an interesting focus for future research.

The role of circadian rhythms in individuals with attention deficit hyperactivity disorder and obesity: A narrative review

Background. A relationship between attention deficit hyperactivity disorder (ADHD) and obesity has been consistently documented. Obesity and metabolic syndrome have been associated with misalignment between daily activities and circadian rhythm. ADHD patients have a high prevalence of delayed sleep phase syndrome, which is a circadian rhythm disorder. Understanding this relationship is important for the evaluation of obese population at risk. Objective. The aim of this narrative review was to summarize the information updated until 2019 about the role of circadian rhythms in obese ADHD individuals. Method. A search was performed in MEDLINE, EMBASE, and Google Scholar database. The terms ADHD, obesity, circadian rhythm, sleep disorders, adolescent, adult, Adolesc, circadian, attention deficit hyperactivity disorder, and child were combined with logical functions. Results. A total of 132 articles were reviewed. Evidence showed that ADHD subjects have an increased risk to present obesity and circadian rhythms disorders. Some possible pathways for this relationship have been hypothesized including obesity as a risk factor, an underpinned common biological dysfunction, and behavioral and cognitive features of individuals with ADHD. As most of the articles are methodologically cross-sectional, it is not possible to establish causative associations. Discussion and conclusion. This review points out the importance of early recognizing and treating circadian rhythms disorders and obesity in ADHD patients. Future studies must be carried out with a longitudinal design to establish the effect of each comorbidity in the treatment of individuals with ADHD.

Circadian Rhythm Sleep Disorders

Circadian rhythm sleep disorders (CRSDs) cause disturbances in sleep and wakefulness due to a misalignment between the timing of the body’s intrinsic circadian clock and environmental light and social activity cycles. This chapter reviews these disorders with an emphasis on their neural pathways, genetic mechanisms, and regulatory factors. The authors discuss the relationship of CSRDs to physical and mental health, the treatment of CRSDs with circadian rhythm adjustment techniques, and the relationship of CSRDs to psychiatric disorders, along with potential chronobiologic treatments of psychiatric disorders. The chapter specifically addresses delayed sleep phase disorder, advanced sleep phase disorder, non-24-hour sleep–wake rhythm disorder, irregular sleep–wake disorder, shift work disorder, and chronobiology and psychiatric disorders. Melatonin and bright light therapy are covered.