Effects of Bedtime Dosing With Suvorexant and Zolpidem on Balance and Psychomotor Performance in Healthy Elderly Participants During the Night and in the Morning.

PURPOSE/BACKGROUND: This study was designed as an early assessment of the safety of the orexin receptor antagonist suvorexant, but also included exploratory assessments of balance and psychomotor performance that are the focus of this report. METHODS/PROCEDURES: This was a double-blind, randomized, 3-period, crossover, phase 1 study. Balance and psychomotor performance were evaluated during the night in 12 healthy elderly participants after bedtime administration of suvorexant 30 mg (a supratherapeutic dose), the GABAergic agonist zolpidem 5 mg (the recommended dose in the elderly), or placebo. Balance (body sway measured by platform stability) and psychomotor performance (measured by choice reaction time) were assessed predose and at 1.5, 4, and 8 hours postdose in each period. Memory (measured by word recall) was assessed predose and at 4 hours postdose. FINDINGS/RESULTS: At 1.5 hours after nighttime administration of each drug (the approximate time of their anticipated maximal plasma concentrations), both zolpidem and suvorexant increased body sway versus placebo, with a greater increase for zolpidem than suvorexant. Suvorexant increased choice reaction time compared with placebo or zolpidem at 1.5 hours. There were no treatment differences on body sway or choice reaction time at 4 or 8 hours, or on word recall at 4 hours. IMPLICATIONS/CONCLUSIONS: These exploratory data suggest that a 30-mg dose of suvorexant (supratherapeutic) and a 5-mg dose of zolpidem (recommended dose in the elderly) impaired balance at 1.5 hours in healthy elderly people, with potentially less impairment for suvorexant relative to zolpidem, but no treatment differences on body sway or psychomotor performance at 4 and 8 hours. Because of their exploratory nature, these findings and their clinical relevance, if any, require confirmation in a prospective study.

Efficacy and safety of herbal medicine (Bailemian capsule) for treating insomnia: Protocol for a systematic review and meta-analysis.

BACKGROUND: Insomnia has become a universal subhealth disease, affecting more and more modern people's health and quality of life. At present, western medicine is only symptomatic treatment for insomnia. Bailemian Capsule (BLMC) is a proprietary Chinese medicine for treating insomnia. It has been widely used in China, but lacks evidence for evidence-based medicine. At the same time, the clinical efficacy and safety of BLMC are controversial. Therefore, the effectiveness and safety of BLMC in the treatment of insomnia are studied and systematically evaluated in this study. It provides reliable theoretical support for the treatment of insomnia with Traditional Chinese Medicine and the combination of traditional Chinese and Western medicine. METHODS: The information was retrieved from electronic databases, Cochrane, PubMed, EMBASE, SinoMed, China National Knowledge Infrastructure, VIP Data, and WangFang Data. Randomized controlled trials on the BLMC in the treatment of insomnia were conducted. There was no limitation on the literature language. RevMan 5.3 software and STATA 12.0 software were used to perform the meta-analysis. RESULTS: This review will be to assess the efficacy and safety of BLMC for insomnia. CONCLUSION: Our systematic evaluation will provide evidence for the clinical efficacy and safety of BLMC in the treatment of insomnia, and will be published in the form of academic papers in the future to provide new ideas for clinicians in the treatment of insomnia.

Evaluation of the Sleep-Prolonging Effect of Lagenaria vulgaris and Cucurbita pepo Extracts on Pentobarbital-Induced Sleep and Possible Mechanisms of Action.

Introduction: Sleeplessness is the most common sleep disorder. In this study, the hypnotic effect of macerated (HAME) and soxhlet (HASE) extract of Lagenaria vulgaris (fruit and seed) and Cucurbita pepo (fruit) were studied in mice. Methods: Extracts and fractions were administered intra-peritoneally (i.p.) in mice 30 min before the sodium pentobarbital (30 mg/kg, i.p.). Moreover, the influence of flumazenil or naloxone on the hypnotic effects of the extract and its toxic effects were evaluated. Results: The HAME and HASE of C. pepo prolonged the pentobarbital-induced sleep duration at dose of 200 mg/kg. The HAME of L. vulgaris (fruit) at dose of 200 mg/kg increased the sleeping time. The HAME and HASE of L. vulgaris (seed) increased sleep duration at doses of 50 and 100 mg/kg. Besides, flumazenil (2 mg/kg) reversed the effects of both diazepam (P < 0.001 vs. diazepam group), 200 mg/kg of HAME of C. pepo and 50 mg/kg of HAME and HASE of L. vulgaris (seed). All fractions especially ethyl-acetate fraction (EAF) of L. vulgaris (seed) increased the sleep duration. Naloxone reversed the hypnotic effect of HAME and HASE of L. vulgaris (seed). The extracts showed no neurotoxic effects on PC12 and L929 cell lines. Conclusion: The results showed that L. vulgaris (seed and fruit) and C. pepo potentiated pentobarbital hypnosis without toxic influence. The hypnotic effects of L. vulgaris seed was greater than its fruit and C. pepo. The GABA and opioid receptors may play role in the sleep-induction of L. vulgaris seed.

Chronopathophysiological implications of orexin in sleep disturbances and lifestyle-related disorders.

Sleep, a mysterious behavior, has recently been recognized as a crucial factor for health and longevity. The daily sleep/wake cycle provides the basis of biorhythms controlling whole-body homeostasis and homeodynamics; therefore, disruption of sleep causes several physical and psychological disorders, including cardiovascular disease, obesity, diabetes, cancer, anxiety, depression, and cognitive dysfunction. However, the mechanism linking sleep disturbances and sleep-related disorders remains unknown. Orexin (also known as hypocretin) is a neuropeptide produced in the hypothalamus. Central levels of orexin oscillate with the daily rhythm and peak at the awake phase. Orexin plays a major role in stabilizing the wakefulness state. Orexin deficiency causes sleep/wake-state instability, resulting in narcolepsy. Hyper-activation of the orexin system also causes sleep disturbances, such as insomnia, and hence, suvorexant, an orexin receptor antagonist, has been clinically used to treat insomnia. Importantly, central actions of orexin regulate motivated behaviors, stress response, and energy/glucose metabolism by coordinating the central-autonomic nervous systems and endocrine systems. These multiple actions of orexin maintain survival. However, it remains unknown whether chronopharmacological interventions targeting the orexin system ameliorate sleep-related disorders as well as sleep in humans. To understand the significance of adequate orexin action for prevention of these disorders, this review summarizes the physiological functions of daily orexin action and pathological implications of its mistimed or reduced action in sleep disturbances and sleep-related disorders (lifestyle-related physical and neurological disorders in particular). Timed administration of drugs targeting the orexin system may prevent lifestyle-related diseases by improving the quality of life in patients with sleep disturbances.

Efficacy of Violet oil, a traditional Iranian formula, in patients with chronic insomnia: A randomized, double-blind, placebo-controlled study.

ETHNOPHARMACOLOGICAL RELEVANCE: Violet oil is an ancient herbal drug which has been extensively used to treat insomnia in traditional Iranian Medicine clinics. Violet oil is an almond or sesame oil-based extract of Viola odorata, which is administered as nasal drops. This study aimed to evaluate the efficacy of Violet oil in the treatment of insomnia. METHODS AND MATERIALS: This study was conducted as a 3-arm double-blind randomized trial. A total of 75 patients with chronic insomnia were enrolled and randomly assigned to three groups in Traditional Iranian Medicine Clinic of Mashhad University of Medical Sciences, Mashhad, Iran. The treatment consisted of intranasal dropping of Violet oil, Almond oil or placebo (1% solution of Carboxymethyl cellulose) in each nostril every night before sleep for 30 days, i.e. three drops of the drug (including either Violet oil or Almond oil) or the placebo was used every night before the sleep. All the patients were asked to complete Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) questionnaires before and after the intervention. RESULTS: There were no significant differences between patients in the three groups before the intervention (P > 0.05). However, there were significant differences between the three groups after the intervention in ISI scores (P<0.002) and PSQI scores (p<0.001). When comparing the pre- and post-treatment data, the ISI and PSQI scores improved significantly in all the three groups as follows: Violet oil (P<0.001), Almond oil (P<0.001) and placebo (P<0.001). The results also showed that the Violet oil had the most effect among the three groups. In addition, it was more effective on sleep quality than sleep quantity. CONCLUSION: Considering the effects of natural nasal drug on the improvement of sleep quality in insomniac patients, this study has proposed the use of Violet oil as a natural and herbal drug in a non-oral method without serious side effects for treatment of insomnia.

Dietary Zinc Acts as a Sleep Modulator.

While zinc is known to be important for many biological processes in animals at a molecular and physiological level, new evidence indicates that it may also be involved in the regulation of sleep. Recent research has concluded that zinc serum concentration varies with the amount of sleep, while orally administered zinc increases the amount and the quality of sleep in mice and humans. In this review, we provide an exhaustive study of the literature connecting zinc and sleep, and try to evaluate which molecular mechanism is likely to be involved in this phenomenon. A better understanding should provide critical information not only about the way zinc is related to sleep but also about how sleep itself works and what its real function is.

Efficacy of orally administered Silexan in patients with anxiety-related restlessness and disturbed sleep--A randomized, placebo-controlled trial.

The anxiolytic effect of Silexan, a patented active substance with an essential oil produced from Lavandula angustifolia flowers, was investigated in patients with anxiety-related restlessness and disturbed sleep. 170 out-patients with a diagnosis of restlessness (ICD-10 R45.1), a Hamilton Anxiety Scale (HAMA) total score ≥18 points and ≥2 points for HAMA items 'Tension' and 'Insomnia' participated in this randomized, double-blind trial and received 80mg Silexan or placebo once daily for 10 weeks. Patients with clinically important other psychiatric or neurological disorders potentially interfering with the assessment of treatment efficacy were excluded. Outcome variables were the HAMA as well as the Pittsburgh Sleep Quality Index (PSQI), the Zung Self-rating Anxiety Scale, a State Check inventory and the Clinical Global Impressions questionnaire. In the Silexan group the HAMA total score decreased from an average of 25.5±6.0 points at baseline to 13.7±7.0 points at treatment end, compared to a decrease from 26.5±6.1 to 16.9±9.8 for placebo, corresponding to decreases of 12.0 and 9.3 points (marginal means), respectively (group difference: p=0.03, ANCOVA with factor treatment and baseline value as covariate). In all outcome measures the treatment effect of Silexan was more pronounced than with placebo. According to the HAMA, 48.8% and 33.3% of the patients were responders (Silexan, placebo; reduction ≥50%; p=0.04) and 31.4% and 22.6% achieved remission (HAMA<10; p=0.20). 33.7% (Silexan) and 35.7% (placebo) of the participants reported adverse events. The study confirms the calming and anxiolytic efficacy of Silexan.