Burden of Insomnia and Sleep Disturbances and the Impact of Sleep Treatments in Patients with Probable or Possible Alzheimer’s Disease: A Structured Literature Review

Background: Sleep disturbances are frequent in Alzheimer’s disease (AD). This review summarizes the impact of sleep disturbances on AD patients and their caregivers and the effects of currently available sleep therapies. Methods: Published studies (January 1985–March 2020) assessing the burden associated with insomnia/sleep disturbances in the AD population and insomnia treatment effects were identified by searching PubMed, Embase and Cochrane Library and screened against inclusion criteria. Findings: This review included 58 studies which assessed patient and caregiver burden, institutionalization, and insomnia treatments in AD patients with sleep disturbances. Sleep disturbances were associated with worse cognition, functional ability, and behavioral and neuropsychological functioning, including increased depression and anxiety. Health status and quality of life of both patients and caregivers were reduced in the presence of sleep disturbances, with caregiver burden driven largely by disruptive nocturnal behaviors including nighttime awakenings and wanderings. Sleep disturbances were also associated with institutionalization. Although significant associations between sleep problems and clinical outcomes were apparent, there was generally no control for other influencing factors (e.g. cognitive status). With respect to insomnia treatments, bright light, and behavioral therapies as well as drugs such as trazodone, risperidone and suvorexant showed some promise in AD patients, but studies were primarily small and limited data were available, particularly in regard to insomnia treatment effects on associated clinical burden. Interpretation: Sleep disturbances are a significant problem for AD patients and caregivers. They are associated with behavioral and psychological problems and cognitive decline and impose a burden on caregivers, but remain poorly characterized and under-researched. As the global population is aging and AD is on the rise, data from larger, prospective trials are required to fully understand the clinical correlates of sleep disturbances and the impact of insomnia treatments on AD patients and their caregivers.

Efficacy of Prolonged-Release Melatonin 2 mg (PRM 2 mg) Prescribed for Insomnia in Hospitalized Patients for COVID-19: A Retrospective Observational Study

Background: we have observed the effect of insomnia treatment in clinical and prognostic differences of patients admitted for COVID-19 pneumonia in respiratory sub-intensive units that were administered a prolonged-release melatonin 2 mg (PRM 2 mg) therapy versus a group of patients out of therapy. Materials and Methods: We evaluated 40 patients on prolonged-release melatonin 2 mg (PRM 2 mg) therapy versus a control group of 40 patients out of therapy. Results: patients in the PRM 2 mg group had a shorter duration of therapy with non-invasive ventilation (5.2 ± 3.0 vs. 12.5 ± 4.2; p < 0.001), with a shorter stay in sub-intensive care (12.3 ± 3.2 vs. 20.1 ± 6.1; p < 0.001), and, therefore, a shorter overall duration of hospitalization (31.3 ± 6.8 vs. 34.3 ± 6.9 p = 0.03). In addition, a lower incidence of delirium was found (2.2 ± 1.1 vs. 3.3 ± 1.3; p < 0.001). Conclusions: A significant increase in sleep hours and a reduction in delirium episodes occurs in hospitalized insomniac patients treated with PRM 2 mg, compared to untreated patients. Based on these preliminary results, we can assume that there are benefits of prolonged-release melatonin 2 mg in COVID-19 therapy.

Traditional Herbal Remedies Used for Managing Anxiety and Insomnia in Italy: An Ethnopharmacological Overview

Anxiety and insomnia are among the most common mental health disorders and are a major cause of disability around the world. Traditional herbal medicines are receiving significant attention in global health debates. Several Italian regions maintain rural traditions and are among the most extensively studied areas of Europe regarding medicinal plant uses. The present overview aims to highlight the use of wild and cultivated plants, specifically as sedatives and for insomnia treatment in Italy, and to collect, analyze, and summarize the available literature about their pharmacological activity as well as clinical and pre-clinical studies concerning the most cited plants. In total, 106 wild taxa are used in Italy for sedative purposes. The plant species belong to 76 genera and 32 families, of which the most cited are Asteraceae (24.2%) and Lamiaceae (21.1%). Leaves (29%) and flowers (27%) are the plant parts mostly used as infusion (70%) and decoction (25%). Out of 106 taxa documented, only the most cited are analyzed in this overview (A. arvensis L., C. nepeta L., C. monogyna Jacq., H. lupulus L., L. nobilis L., L. angustifolia Mill., M. sylvestris L., M. chamomilla L., M. officinalis L., O. basilicum L., P. rhoeas L., P. somniferum L., R. officinalis L., T. platyphyllus Scop., and V. officinalis L.). Among the fifteen species selected, only seven have been studied for their pharmacological activity as hypnotic-sedatives. Future pre-clinical and clinical studies are needed to better clarify the mechanism of action of bioactive compounds and confirm the potential of these alternative therapies.

P053 Management of insomnia by Australian psychologists

Introduction Insomnia is the most common sleep disorder, 10–30% of adults have regular difficulties falling and/or staying asleep that cause significant daytime impairments. General Practitioner (GP) clinical guidelines recommend Cognitive Behavioural Therapy for insomnia (CBTi) as the first-line treatment rather than medications. However, most GPs do not have the time or training to administer CBTi, and consequently, many patients are prescribed sedative-hypnotic medicines. Psychologists have training in CBT and may be well placed to deliver behavioural therapy for insomnia. However, the amount of sleep-specific training, and knowledge of CBTi among Australian psychologists remains unknown. Identifying key barriers and enablers in the management of insomnia within psychology provides a first step in engaging with psychologists about the delivery of evidence-based insomnia treatment. Methods This qualitative study used a pragmatic inductive approach. Semi-structured interviews were conducted with 26 Australian psychologists. Interviews included case study scenarios to provide an in-depth exploration of psychologists’ knowledge and skills in the management of insomnia, and attitudes towards further training in CBTi. Interview transcripts were analysed using thematic analysis to identify themes. Results Preliminary themes identified in the data include; psychologists believe sleep is important for general well-being, insomnia is usually seen as secondary to other co-morbid disorders such as depression and anxiety that are the focus of treatment, most psychologists surveyed lack training and knowledge in CBTi. Discussion Most Australian psychologists are not well prepared to manage insomnia effectively with CBTi. Along with other primary health care professionals, psychologists need training in the management of insomnia.

Agomelatine, A Potential Multi-Target Treatment Alternative for Insomnia, Depression, and Osteoporosis in Postmenopausal Women: A Hypothetical Model

Insomnia, which is associated with menopausal depression, is a common symptom of menopause. Both symptoms have a common etiology, and can affect each other significantly. Pharmacological interventions, including hypnotics and antidepressants, and non-pharmacological therapies are generally administered in clinical practice for insomnia treatment. As another menopausal disorder, osteoporosis is described as a disease of low bone mineral density (BMD), affecting nearly 200 million women worldwide. Postmenopausal osteoporosis is common among middle-aged women. Since postmenopausal osteoporosis mainly results from low estrogen levels, menopausal hormone therapy (HT) is considered the first-line option for the prevention of osteoporosis during the menopausal period. However, almost no study has evaluated novel treatments for the combined prevention of insomnia, depression, and osteoporosis. Hence, it is necessary to develop new multi-target strategies for the treatment of these disorders to improve the quality of life during this vulnerable period. Melatonin is the major regulator of sleep, and it has been suggested to be safe and effective for bone loss therapy by MT-2 receptor activity. As a result, we hypothesize that agomelatine, an MT-1 and MT-2 receptor agonist and 5-HT2C receptor antagonist, holds promise in the combined treatment of insomnia, depression, and osteoporosis in middle-aged women during menopause.

Sleep disorders in acute and chronic pain

Pain is one of the leading causes of decline in quality of life. When pain syndromes occur, a person may experience unpleasant sensory sensations and concomitant disorders, which can lead to pain aggravation and sleep disturbances. According to experimental studies, increased pain sensation with reduced sleep duration occurs due to opioid, serotonergic, noradrenergic, and dopaminergic antinociceptive systems dysfunction. In clinical practice, a reduction in sleep duration is usually associated with insomnia, which is the most common sleep disorder. In pain syndromes, insomnia occurs in 53–90% of patients (for comparison: in the general population – in 7.4%). Non-pharmacological (cognitive-behavioral therapy) and pharmacological approaches are used in insomnia treatment. Some medications (amitriptyline, mirtazapine, trazodone, gabapentin, pregabalin) have both hypnotic and analgesic effects, which allows to use them for pain syndromes with sleep disturbances. It has been shown that the correction of sleep disorders can reduce the severity and frequency of pain.