Herbal medicines for insomnia through regulating 5-hydroxytryptamine receptors: a systematic review / 中国天然药物

Insomnia is a common sleep disorder without effective therapy and can affect a person's life. The mechanism of the disease is not completely understood. Hence, there is a need to understand the targets related to insomnia, in order to develop innovative therapies and new compounds. Recently, increasing interest has been focused on complementary and alternative medicines for treating or preventing insomnia. Research into their molecular components has revealed that their sedative and sleep-promoting properties rely on the interactions with various neurotransmitter systems in the brain. In this review, the role of 5-hydroxytryptamine (5-HT) in insomnia development is summarized, while a systematic analysis of studies is conducted to assess the mechanisms of herbal medicines on different 5-HT receptors subtypes, in order to provide reference for subsequent research.

Clinical application of Chaihu Jia Longgu Muli Decoction based on modern pathophysiology mechanism / 中国中药杂志

Chaihu Jia Longgu Muli Decoction was firstly recorded in Treatise on Cold Damage(ZHANG Zhong-jing, Eastern Han dynasty). According to this medical classic, it is originally used in the treatment of the Shaoyang and Yangming syndrome. Based on the modern pathophysiological mechanism, this study interpreted the classic provisions of Chaihu Jia Longgu Muli Decoction. Original records of "chest fullness" "annoyance" "shock" "difficult urination" "delirium" "heavy body and failing to turn over" all have profound pathophysiological basis, involving disorders in cardiovascular, respiratory, nervous, and mental systems. This formula is widely used, which can be applied to treat epilepsy, cerebral arteriosclerosis, cerebral infarction, and other cerebrovascular diseases, hypertension, arrhythmia, and other cardiovascular diseases, insomnia, constipation, anxiety, depression, cardiac neurosis and other acute and chronic diseases as well as diseases in psychosomatic medicine. The clinical indications include Bupleuri Radix-targeted syndrome such as fullness and discomfort in chest and hypochondrium, bitter taste mouth, dry throat, and dizziness, the insomnia, anxiety, depression, susceptibility to fright, upset, dreamfulness and other psychiatric symptoms, red tongue, thick and yellow tongue coating, and wiry hard and powerful pulse. This formula was found to be used in combination with other formulas, such as Gualou Xiebai Decoction, Wendan Decoction, Zhizhu Pills, Juzhijiang Decoction, Suanzaoren Decoction, and Banxia Baizhu Tianma Decoction.

Produção de fumo e insônia: relato de caso sobre os determinantes socioeconômicos para o uso contínuo de benzodiazepínicos em uma zona rural no Sul do Brasil / Tobacco production and insomnia: case report on socioeconomic determinants of the continuous use of benzodiazepines in a rural area in southern Brazil / Producción de tabaco e insomnio: Reporte de caso sobre determinantes socioeconómicos del uso continuo de benzodiacepinas en una zona rural del sur de Brasil

Introdução: A fumicultura concentra-se sobretudo em áreas rurais do Sul do país. Reconhecidamente, as áreas rurais apresentam disparidades socioeconômicas, desigualdades no acesso geográfico, bem como dificuldade de retenção de profissionais na Atenção Primária à Saúde (APS). Apresentação do caso: Descrevem-se, neste artigo, as intersecções de determinantes socioeconômicos de saúde ao se abordar um paciente masculino, de 57 anos, em uso crônico de benzodiazepínicos para o tratamento de insônia. Ao se aprofundar a anamnese, os determinantes socioeconômicos que levaram ao desenvolvimento da insônia foram identificados como: dificuldades financeiras na produção de tabaco, preocupações excessivas com o trabalho e presença de depressão como comorbidade. Nesse sentido, ser produtor de tabaco e a relação com a empresa podem ser considerados determinantes socioeconômicos da saúde para o desenvolvimento de insônia. Conclusões: No contexto deste caso, a rotatividade de profissionais e a falta de criação de vínculo fez com que o paciente permanecesse cronicamente a tratar a insônia como benzodiazepínico, o que é proscrito. Assim, revelam-se a fragmentação do cuidado e a alta rotatividade de profissionais como determinantes socioeconômicos da saúde.

Introduction: Tobacco production is mainly concentrated in rural areas of the southern region of the country. Rural areas present socioeconomic disparities, inequalities in geographic access, and difficulties in retaining professionals in primary care. Mental health problems, such as insomnia, are common in clinical practice. Case presentation: This article describes the intersections of the social determinants of health when approaching a patient with chronic use of benzodiazepines for treatment of insomnia. By delving deep into anamnesis, the socioeconomic determinants that led to the development of insomnia were identified as: financial trouble with tobacco production, excessive concern about work and presence of depression as comorbidity. Conclusions: In this context, the turnover of health professionals and lack of doctor-patient relationship meant that the patient continued using benzodiazepines, which are not recommended for long-term treatment. Therefore, fragmented care and high professional turnover stand out as socioeconomic determinants of health.

Introducción: La producción de tabaco se concentra principalmente en las zonas rurales del sur del país. Se reconoce que las zonas rurales presentan desigualdades socioeconómicas, desigualdades en el acceso geográfico, así como dificultad para retener profesionales en Atención Primaria de Salud (APS). Los problemas de salud mental como el insomnio son comunes en la práctica clínica. Presentación de caso: Este artículo describe las intersecciones de los determinantes socioeconómicos de la salud al abordar a un paciente uso crónico de benzodiazepinas para el tratamiento del insomnio. Al profundizar la anamnesis, se identificaron los determinantes socioeconómicos que llevaron al desarrollo del insomnio como: dificultades económicas en la producción de tabaco, excesiva preocupación por el trabajo y la presencia de depresión como comorbilidad. En este sentido, ser productor de tabaco y la relación con la empresa pueden considerarse determinantes socioeconómicos de la salud para el desarrollo del insomnio. Conclusiones: En el contexto de este caso, la rotación de profesionales y la falta de vinculación hicieron que el paciente continuara crónicamente tratando el insomnio como una benzodiazepina, lo que no es recomendable. Así, la fragmentación de la atención y la alta rotación profesional se evidencia como un determinante socioeconómico de la salud.

Insomnio en tiempos de pandemia / Insomnia in pandemic times

El sueño es una función biológica de importancia para los seres vivos y su alteración más frecuente es el insomnio. Se define como la dificultad para conciliar o mantener el sueño, acompañada de una sensación de descanso no reparadora, a pesar de que las condiciones ambientales para ello son adecuadas, y que suele asociarse a fatiga y somnolencia durante el día. En los tiempos prepandemia ya se sabía que existía una alta prevalencia, pero durante la pandemia las cifras han aumentado y probablemente seguirán aumentando postpandemia, lo que conlleva a un incremento de las consultas en la atención primaria. Las medidas no farmacológicas son esenciales para incrementar la eficacia de las medidas terapéuticas. Las benzodiacepinas y los compuestos Z tienen bastantes efectos adversos y no son la primera opción, especialmente en los adultos mayores. La melatonina es mejor tolerada pero su eficacia no está comprobada.

Sleep is an important biological function for living beings and its most frequent alteration is insomnia. It is defined as difficulty in falling or staying asleep, accompanied by a feeling of non-restorative rest, despite adequate environmental conditions, and is usually associated with fatigue and sleepiness during the day. In pre-pandemic times, it was already known that there was a high prevalence, but during the pandemic, the figures have increased and will probably continue to increase post-pandemic, leading to an increase in consultations in primary care. Non-pharmacological measures are essential to increase the efficacy of therapeutic measures. Benzodiazepines and Z-compounds have quite a few adverse effects and are not the first choice, especially in older adults. Melatonin is better tolerated but its efficacy is not verified.

Sleep-improving mechanism of Chaiqin Ningshen Granules in insomnia rats: based on hippocampal metabonomics / 中国中药杂志

With the ultra high performance liquid chromatography-quadruple-electrostatic field orbitrap high resolution mass spectrometry(UHPLC-Q Exactive Orbitrap-MS)-based metabonomics technology, this study aims to analyze the effect of Chaiqin Ningshen Granules(CNG) on endogenous metabolites in insomnia rats of liver depression syndrome and explore the sleep-improving mechanism of this prescription. Parachlorophenylalanine(PCPA, ip) and chronic stimulation were combined to induce insomnia of liver depression pattern in rats, and the effect of CNG on the macroscopic signs, hemorheology, and neurotransmitters in the hippocampus of insomnia rats of liver depression syndrome was observed. After the administration, rat hippocampus was collected for liquid chromatography-mass spectrometry(LC-MS) analysis of the metabolomics. Principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed for analyzing the metabolites in rat hippocampus and screening potential biomarkers. MetPA was used to yield the related metabolic pathways and metabolic networks. The results show that the drugs can significantly improve the mental state, liver depression, and blood stasis of rats, significantly increase the content of 5-hydroxytryptamine(5-HT) and gamma aminobutyric acid(GABA) in hippocampus(except low-dose CNG), and significantly reduce the content of glucose(Glu)(except low-dose CNG). Among them, estazolam and high-dose CNG had better effect than others. Metabolomics analysis yielded 27 potential biomarkers related to insomnia. MetPA analysis showed 4 metabolic pathways of estazolam in intervening insomnia and 3 metabolic pathways of high-dose CNG in intervening insomnia, involving purine metabolism, glycerophospholipid metabolism, histidine metabolism, and caffeine metabolism. CNG can alleviate insomnia by regulating endogenous differential metabolites and further related metabolic pathways. The result lays a basis for further elucidating the mechanism of CNG in improving sleep.

Metabonomic study of biochemical changes in serum of PCPA-induced insomnia rats after treatment with Suanzaoren Decoction / 中国中药杂志

Suanzaoren Decoction(SZRD) is a classical formula for the clinical treatment of insomnia. This study analyzed the effect of SZRD on endogenous metabolites in insomnia rats based on metabonomics and thereby explored the anti-insomnia mechanism of SZRD. To be specific, DL-4-chlorophenylalanine(PCPA) was used to induce insomnia in rats. Then pathological changes of the liver and brain were observed and biochemical indexes such as 5-hydroxytryptamine(5-HT), dopamine(DA), glutamate(Glu), γ-aminobutyric acid(GABA), and norepinephrine(NE) in the hippocampus and prostaglandin D2(PGD2), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and IL-6 in the serum of rats were detected. On this basis, the effect of SZRD on PCPA-induced insomnia rats was preliminarily assessed. The metabolic profile of rat serum samples was further analyzed by ultra-performance liquid chromatography-quadrupole-time of flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were combined with t-test and variable importance in projection(VIP) to identify differential metabolites, and MetaboAnalyst 5.0 was employed for pathway analysis. The results showed that SZRD could improve the pathological changes of brain and liver tissues, increase the levels of neurotransmitters 5-HT, DA, and GABA in hippocampus and the level of PGD2 in hypothalamic-pituitary-adrenal axis(HPA axis), and reduce the levels of IL-1β and TNF-α in serum of insomnia rats. Metabonomics analysis yielded 12 significantly changed potential metabolites: 5-aminovaleric acid, N-acetylvaline, L-proline, L-glutamate, L-valine, DL-norvaline, D(-)-arginine, pyroglutamic acid, 1-methylguanine, L-isoleucine, 7-ethoxy-4-methylcoumarin, and phthalic acid mono-2-ethylhexyl ester(MEHP), which were related with multiple biochemical processes including metabolism of D-glutamine and D-glutamate, metabolism of alanine, aspartate, and glutamate, metabolism of arginine and proline, arginine biosynthesis, glutathione metabolism. These metabolic changes indicated that SZRD can improve the metabolism in insomnia rats by regulating amino acid metabolism.

Effective substance and mechanism of Ziziphi Spinosae Semen extract in treatment of insomnia based on serum metabolomics and network pharmacology / 中国中药杂志

This study aims to study the effective substance and mechanism of Ziziphi Spinosae Semen extract in the treatment of insomnia based on serum metabolomics and network pharmacology. The rat insomnia model induced by p-chlorophenylalanine(PCPA) was established. After oral administration of Ziziphi Spinosae Semen extract, the general morphological observation, pentobarbital sodium-induced sleep test, and histopathological evaluation were carried out. The potential biomarkers of the extract in the treatment of insomnia were screened by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS) combined with multivariate analysis, and the related metabolic pathways were further analyzed. The "component-target-pathway" network was constructed by ultra-high performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry(UHPLC-Q-Exactive-MS/MS) combined with network pharmacology to explore the effective substances and mechanism of Ziziphi Spinosae Semen in the treatment of insomnia. The results of pentobarbital sodium-induced sleep test and histopathological evaluation(hematoxylin and eosin staining) showed that Ziziphi Spinosae Semen extract had good theraputic effect on insomnia. A total of 21 endogenous biomarkers of Ziziphi Spinosae Semen extract in the treatment of insomnia were screened out by serum metabolomics, and the metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and nicotinate and nicotinamide metabolism were obtained. A total of 34 chemical constituents were identified by UHPLC-Q-Exactive-MS/MS, including 24 flavonoids, 2 triterpenoid saponins, 4 alkaloids, 2 triterpenoid acids, and 2 fatty acids. The network pharmacological analysis showed that Ziziphi Spinosae Semen mainly acted on target proteins such as dopamine D2 receptor(DRD2), 5-hydroxytryptamine receptor 1 A(HTR1 A), and alpha-2 A adrenergic receptor(ADRA2 A) in the treatment of insomnia. It was closely related to neuroactive ligand-receptor interaction, serotonergic synapse, and calcium signaling pathway. Magnoflorine, N-nornuciferine, caaverine, oleic acid, palmitic acid, coclaurine, betulinic acid, and ceanothic acid in Ziziphi Spinosae Semen may be potential effective compounds in the treatment of insomnia. This study revealed that Ziziphi Spinosae Semen extract treated insomnia through multiple metabolic pathways and the overall correction of metabolic disorder profile in a multi-component, multi-target, and multi-channel manner. Briefly, this study lays a foundation for further research on the mechanism of Ziziphi Spinosae Semen in treating insomnia and provides support for the development of innovative Chinese drugs for the treatment of insomnia.

Effect of Suanzaoren Decoction on molecular levels of bile acids in serum, liver, and ileum of insomnia mice / 中国中药杂志

To explore the mechanism of Suanzaoren Decoction in the treatment of insomnia from endogenous bile acid regulation, the present study investigated the hepatoprotective effect of Suanzaoren Decoction and the molecular changes of bile acids in the serum, liver, and ileum of insomnia model mice and Suanzaoren Decoction treated mice. The insomnia model in mice was established by the sleep deprivation method. After Suanzaoren Decoction(48.96 mg·kg~(-1)·d~(-1)) intervention by gavage for 7 days, the related indicators, such as water consumption, food intake, body weight, aspartate aminotransferase(AST), alanine transaminase(ALT), and total bile acid(TBA) were detected, and the pathological changes of the liver and ileum were observed. The molecular levels and distribution of 23 bile acids in the serum, liver, and ileum were analyzed by UPLC-MS/MS combined with principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA). The results showed that Suanzaoren Decoction could improve the decreased water consumption and food intake, weight loss, and increased AST and ALT in the model group, and effectively reverse the injury and inflammation in the liver and ileum. The bile acids in the liver of the insomnia model mice were in the stage of decompensation, and the bile acids in the serum, liver, and ileum of the mice decreased or increased. Suanzaoren Decoction could regulate the anomaly of some bile acids back to normal. Seven bile acids including glycoursodeoxycholic acid(GUDCA), glycodesoxycholic acid(GDCA), tauro-α-MCA(T-α-MCA), α-MCA, taurodeoxycholate(TDCA), T-β-MCA, and LCA were screened out as the main discriminant components by PLS-DA. It is concluded that Suanzaoren Decoction possesses the hepatoprotective effect and bile acids could serve as the biochemical indicators to evaluate the drug efficacy in the treatment of abnormal liver functions caused by insomnia. The mechanism of Suanzao-ren Decoction in soothing the liver, resolving depression, tranquilizing the mind, and improving sleep may be related to the molecular regulation of bile acid signals.

Regulatory aspects and evidences of melatonin use for sleep disorders and insomnia: an integrative review / Aspectos regulatórios e evidências do uso de melatonina em distúrbio do sono e insônia: uma revisão integrativa

ABSTRACT Background: Insomnia is a sleep disorder characterized by difficulty of falling asleep or maintaining sleep, which affects different age groups. Currently, melatonin is used as a therapeutic treatment in cases of insomnia in children, adults, and elderly people. Objective: To evaluate the effectiveness of melatonin in sleep disorders, its dosage, potential adverse effects, as well as labeling laws and regulations in Brazil. Methods: This integrative review was carried out using the Cochrane Library, Medline (Pubmed), and Science Direct databases. Twenty-five articles and three documents available on the Brazilian Society of Endocrinology and Metabology (SBEM) and National Health Surveillance Agency (ANVISA) websites published between 2015 and 2020 were selected to be evaluated in full. Results: It was found that in most of the selected articles the use of melatonin reduces sleep latency. The effective melatonin doses varied according to each age group, from 0.5 to 3 mg in children, 3 to 5 mg in adolescents, 1 to 5 mg in adults, and 1 to 6 mg in elderly people. Side effects are mild when taking usual doses. In Brazil, no registered drug and current regulation on the use and marketing of melatonin has been identified. Conclusion: The use of melatonin is an alternative therapy that can be used for sleeping disorders. According to the evidences found, it did not demonstrate toxicity or severe side effects, nor dependence even when administered at high doses, suggesting that it is a safe medication to treat patients of different ages suffering from sleeping disorders.

RESUMO Antecedentes: Insônia é um distúrbio do sono caracterizado por dificuldade de iniciar e manter o sono, afetando diferentes faixas etárias. Atualmente, a melatonina é utilizada no tratamento de insônia em crianças, adultos e idosos. Objetivo: Avaliar a eficácia da melatonina nos distúrbios do sono, posologia e potenciais efeitos adversos, bem como a regulamentação vigente no Brasil. Métodos: Trata-se de uma revisão integrativa, os artigos foram identificados nas bases de dados Cochrane Library, Medline (Pubmed) e Science Direct, totalizando 25 artigos, e foram selecionados três materiais disponíveis no site da Sociedade Brasileira de Endocrinologia e Metabologia e Agência Nacional de Vigilância Sanitária, publicados entre 2015 e 2020. Resultados: Verificou-se na maioria dos artigos selecionados que a melatonina reduz a latência do sono. Quanto as dosagens de melatonina identificou-se variação em cada faixa etária, para crianças de 0,5 a 3mg; adolescentes de 3 a 5mg; adultos de 1 a 5mg e idosos 1 mg a 6 mg demostraram serem eficazes. Em doses habituais os efeitos colaterais são leves. No Brasil, não foi identificado medicamento registrado e regulamentação vigente sobre o uso e comercialização de melatonina. Conclusão: A utilização da melatonina é uma alternativa que pode ser utilizada em distúrbios do sono. De acordo com as evidências encontradas, não demonstrou toxicidade ou efeitos colaterais severos, nem dependência mesmo em doses elevadas, sendo, portanto, segura para tratamento de pacientes desde crianças a idosos que sofrem de distúrbios do sono.

Literature research of Passiflora incarnata and discussion of its traditional Chinese medicine properties / 中国中药杂志

Based on the research literatures of Passiflora incarnata and the theory of traditional Chinese medicine, the paper discussed the traditional Chinese medicinal properties of P. incarnate, so as to provide a theoretical basis for the compatibility and application of P. incarnata. The literature databases of CNKI, Wanfang, VIP, Web of Science, PubMed and Scopus were selected, and the literatures relating to P. incarnata were reviewed to screen out the scientific research literatures with a high credibility, rational design and reliable conclusions. Foreign pharmacopoeia was consulted, and the listed products were summarized. The traditional Chinese medicine properties of P. incarnata were studied based on 32 clinical trials, 66 pharmacological researches, 64 chemical constituents researches as well as the theory of traditional Chinese medicine. It was preliminarily concluded that the medicinal properties of P. incarnata are sweet, cool, and enter heart, liver channels. The function is mainly to calm the heart and tranquilizing the mind, and calm the liver wind. It is used for hyperactivity of liver-Yang, stagnation of liver-Qi, restlessness of mind, depression, nervousness, insomnia. This paper summarized the source, characteristics of natures, tastes and channel tropism, usage and dosage, function indications of P. incarnata, and defined its clear traditional Chinese medicine property, which lays a theoretical foundation for the compatibility and clinical application of P. incarnata and Chinese medicine.

Network Meta-analysis of Chinese patent medicines of Ziziphi Spinosae Semen in treatment of primary insomnia / 中国中药杂志

To systematically evaluate the efficacy of oral Chinese patent medicines of Ziziphi Spinosae Semen in the treatment of primary insomnia by using network Meta-analysis. Nine databases(CNKI, Wanfang, VIP, CBM, PubMed, EMbase, Web of Science, Medline and Cochrane Library) were systematically and comprehensively undertaken to identify the literatures published from the establishment of each database to August, 2020. Randomized controlled trials(RCTs) on oral Chinese patent medicine of Ziziphi Spinosae Semen in the treatment of primary insomnia, either alone or in combination with conventional sedative hypnotics, were screened out according to inclusion criteria and exclusion criteria. Literature screening, data extraction and the evaluation of the risk of bias for the included studies were conducted independently by 2 researchers. Traditional Meta-analysis and Bayesian network Meta-analysis were then conducted with use of Stata 15.0 and R software. Finally, a total of 42 RCTs were included, involving 9 kinds of oral Chinese patent medicines and 4 196 patients. The results of Meta-analysis showed that(1) in terms of improving Pittsburgh sleep quality index scale score, the efficacy of the combination of drugs was significantly superior to that of sedative-hypnotics or most of Chinese patent medicines used alone, and Bailemian Capsules combined with sedative-hypnotics had the best effect; both the efficacy of Shenqi Wuweizi Tablets and Compound Zaoren Anshen Capsules alone were significantly superior to that of conventional sedative-hypnotics treatment, and Shenqi Wuweizi Tablets had the best effect.(2)In terms of safety, single use or combined use of Chinese patent medicine had a certain improvement as compared with conventional sedative-hypnotics treatment. Due to the large clinical heterogeneity, the studies could not be combined quantitatively, and no serious adverse reactions occurred in all patients enrolled in the study. The results showed that Chinese patent medicine of Ziziphi Spinosae Semen combined with conventional sedative-hypnotics could significantly improve the short-term sleep quality of patients with primary insomnia. In the comparison among single use of drugs, Shenqi Wuweizi Tablets had the largest possibility for best effect. However, the lack of evidences for international promotion, the influence of different types of sedative-hypnotics treatment and intervention time on the curative effect, and the patients' different acceptance of combined treatment should be considered before clinical application. Limited by the number and quality of the included studies, the above conclusions need to be further verified by more large sample-size and high-quality studies.

Huanglian Ejiao Decoction formula syndrome and its application for refractory insomnia / 中国中药杂志

Huanglian Ejiao Decoction,firstly recorded in Treatise on Febrile Diseases,could be used to treat heat-conversion syndrome of Shaoyin. It has been identified that,the indications of Huanglian Ejiao Decoction include:(1)in modern medicine,it can be used to treat insomnia,arrhythmia,oral ulcer,Xiali,blood syndrome and other diseases;(2)in terms of symptoms and signs,it is mainly used for restlessness,ritability,insomnia,extremely difficult to fall asleep,palpitation,atrial premature beat,ventricular premature beat and other arrhythmias,stomach distension and stuffiness,stomach pain,vomiting,abdominal pain,cramps,lower edge,constipation,blush,red lips,easy bleeding,red tongue,thin or no coating,dry tongue surface,or light red tongue,or dark red,thin white tongue coating,and rapid pulse. It has been also identified that,(1)although the original statement of Huanglian Ejiao Decoction is very simple,it can not only be used according to irritability and insomnia;(2)tongue image is not the key to syndrome differentiation of this prescription;(3)the essence of Shaoyin syndrome is not completely heart kidney Yang deficiency,which is closest to shock in modern medicine,including septic shock,hypovolemic shock and cardiogenic shock;(4)the essential difference between Shaoyin cold and heat conversion syndrome of Shaoyin lies in the different types of shock,in which cardiogenic shock is the main cold type,while septic shock is the main heat shock;(5)heat-conversion syndrome of Shaoyin is more common in the late stage of septic shock,and part of it can be seen in the stage of heart failure combined with sympathetic activation;(6)Dioscoreae Rhizoma and Rehmanniae Radix are often used to replace egg yolk;(7)Huanglian Ejiao Decoction takes effect quickly and the course of treatment is short.

Network Meta-analysis of efficacy and safety of Chinese patent medicines in treatment of insomnia / 中国中药杂志

To evaluate the efficacy and safety of Chinese patent medicines in the treatment of insomnia by frequency network Meta-analysis. Randomized controlled trials of Chinese patent medicines for insomnia were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase and Cochrane Library databases from the time of database establishment to October 2020. The quality of the included RCTs was evaluated according to the Cochrane bias risk standard, and the data was analyzed by RevMan 5.3 and Stata/MP 15.1. A total of 11 kinds of Chinese patent medicines in 27 RCTs were included. According to Meta-analysis, in term of the effective rate, Tianmeng Liquid, Zaoren Anshen Capsules, Shumian Capsules, Shensong Yangxin Capsules, Shenqi Wuweizi Tablets, Shugan Jieyu Capsules, Anshen Bunao Liquid and Qiye Anshen Tablets combined with nonbenzodiazepine drugs(NBZDs) were superior to NBZDs alone. In term of the improvement of Pittsburg sleeping quality index(PSQI) score, Tianmeng Liquid, Shumian Capsules, Shensong Yangxin Capsules, Bailemian Capsules, Shenqi Wuweizi Tablets, Shugan Jieyu Capsules, Yangxue Qingnao Granules and Yindan Xinnaotong Capsules combined with NBZDs were superior to NBZDs alone. In terms of the safety, Shumian Capsules, Shensong Yangxin Capsules, Shenqi Wuweizi Tablets and Qiye Anshen Tablets combined with NBZDs were superior to NBZDs alone. In terms of the avoidance of dizziness and headache, Qiye Anshen Tablets combined with NBZDs were superior to NBZDs alone. The results of Network Meta-analysis indicated that in term of the effective rate, top three optimal medication regimens were NBZDs combined with Shugan Jieyu Capsules, combined with Zaoren Anshen Capsules and combined with Shensong Yangxin Capsules in the order from high to low. With the respect of improvement of PSQI score, top three optimal medication regimens were NBZDs combined with Yangxue Qingnao Granules, combined with Tianmeng Liquid and combined with Yindan Xinnaotong Capsules in the order from high to low. In terms of the safety, top three optimal medication regimens were NBZDs combined with Qiye Anshen Tablets, combined with Shensong Yangxin Capsules and combined with Shenqi Wuweizi Tablets in the order from high to low. In terms of the avoidance of dizziness and headache, top three optimal medication regimens were NBZDs combined with Qiye Anshen Tablets, combined with Zaoren Anshen Capsules and combined with Shumian Capsules in the order from high to low. In terms of the avoidance of fatigue, top three optimal medication regimens were NBZDs combined with Shensong Yangxin Capsules, combined with Shumian Capsules and combined with Qiye Anshen Tablets in the order from high to low. In conclusion, Chinese patent medicines combined with NBZDs can effectively alleviate the symptoms of insomnia with a high safety. However, the conclusion of this study needs to be verified by more high-quality studies because of the low methodological quality of the included studies.

Sublingual and oral zolpidem for insomnia disorder: a 3-month randomized trial

Objective: To evaluate the safety and efficacy of a 5 mg sublingual dose of zolpidem, compared to a 10 mg oral dose, at bedtime and "as needed" following middle-of-the-night awakenings. Methods: Participants were randomized into an oral group (oral zolpidem 10 mg and sublingual placebo at bedtime and "as-needed") and a sublingual group (oral placebo and sublingual zolpidem 5 mg at bedtime and "as-needed"). Participants underwent medical evaluation, polysomnography, the psychomotor vigilance test, and completed questionnaires. Results: Of 85 patients, 67 met the criteria for insomnia (48±10 years; 79% women) and were randomized. Of these, 46 completed 92±5 days of treatment. Mild-to-moderate adverse events were reported by 25% of the participants, including headache, sleepiness, and dizziness. Both treatments decreased middle-of-the-night awakenings by an average of -3.1±2.3 days/week and increased total sleep time by 1.5 hours. Changes in sleep quality and insomnia severity scores were also favorable and comparable between groups: variation depended on continuation of treatment. Regarding PSG findings, sleep latency decreased more in the sublingual group than the oral group (-14±42 vs. 10±29 min; p = 0.03). The psychomotor vigilance test showed minor residual effects 30 minutes after awakening, which reversed after 2 hours. Conclusions: The safety and efficacy of both zolpidem formulations are comparable. The sublingual 5 mg dose induced sleep more rapidly. Clinical trial registration: NCT01896336

Trastorno de insomnio. Consideraciones actuales / Insomnia disorder. Current considerations

RESUMEN El insomnio es el trastorno del sueño más frecuente en la población, se acompaña de un nivel significativo de malestar o deterioro de áreas importantes del funcionamiento humano. Es importante realizar un diagnóstico correcto de este desorden con el objetivo de instaurar un tratamiento adecuado que permita mejorar la calidad de vida de los pacientes que lo padecen. El objetivo de este artículo es ofrecer una revisión actualizada que contribuya al incremento y actualización de la información sobre este tema. Se realizó una revisión en artículos, principalmente de los últimos cinco años y se sistematizan los resultados para de esta forma contribuir a la superación de los profesionales.

ABSTRACT Insomnia is the most frequently sleep disorder in the population. It is linked to a significant discomfort and an impairment of important areas of the human functioning. The correct diagnosis of this disorder is important with the objective of prescribing an adequate treatment for improving the life quality of the patients suffering it. The aim of this article is offering an up-dated review contributing to increase and update the information on this topic. The authors carried out a review of articles published mainly during the last five years, and the results were systematized for contributing to the professionals´ upgrading.

What do Cochrane systematic reviews say about interventions for insomnia?

ABSTRACT CONTEXT AND OBJECTIVE: Insomnia is a frequent complaint that generates more than five million visits to doctors per year in the United States. This study summarizes all Cochrane systematic reviews (SRs) that evaluated interventions to treat insomnia. DESIGN AND SETTING: Review of SRs, conducted in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP). METHODS: A sensitive search was carried out in the Cochrane Database of Systematic Reviews to identify Cochrane SRs that assessed the effects of any type of intervention for people with insomnia. The results, main characteristics of the SRs and the certainty of the evidence obtained from them were synthesized and discussed. RESULTS: Seven SRs were included. They addressed the benefits and harm of acupuncture (n = 1), behavioral interventions (n = 1), music (n = 1), pharmacotherapy (n = 2), phototherapy (n = 1) and physical exercise (n = 1). The certainty of the evidence ranged from moderate to very low. CONCLUSION: Acupuncture, music, physical exercise, paroxetine, doxepin, trimipramine and trazodone seem to present some benefit for patients with insomnia. However, the uncertainty around these results means that no robust and definitive recommendations for clinical practice can be made until the benefits and harms from each intervention for patients with insomnia have been confirmed through further studies.

TeleCondutas: avaliação e manejo da insônia / TeleGuides: evaluation and management of insomnia

A insônia é o mais prevalente dos transtornos do sono. É definida como a insatisfação com a qualidade ou a quantidade de sono, que ocorre a despeito de adequada oportunidade para dormir e que impõe ao indivíduo algum tipo de prejuízo durante o dia. A prevalência da insônia crônica em sociedades industrializadas é de 5 a 10%. Entre pessoas portadoras de doença crônica (psiquiátricas ou não) e idosos, a prevalência é significativamente maior. Trata-se de queixa frequente na Atenção Primária à Saúde (APS). Este material contempla as situações mais comumente associadas a insônia na APS, assim como o manejo inicial desta queixa. Está baseado em extensa revisão das evidências disponíveis na literatura, em boas práticas clínicas e adaptado à realidade brasileira, considerando as intervenções terapêuticas disponíveis. Esta guia apresenta informação que orienta a conduta para casos de avaliação e manejo da insônia no contexto da Atenção Primária à Saúde, incluindo: Avaliação Geral, Avaliação Objetiva, Avaliação e Manejo em situações específicas, Intervenções Não-Farmacológicas, Manejo Farmacológico na APS, Retirada de benzodiazepínico, Preocupações com uso de amitriptilina, Fármacos não recomendados na APS, Avaliação longitudinal da insônia, Fluxograma para avaliação e manejo da insônia.

¿Constituyen los cannabinoides una alternativa terapéutica para insomnio? / Do cannabinoids constitute a therapeutic alternative for insomnia?

INTRODUCCIÓN: Se ha planteado que la estimulación del sueño con cannabinoides podría constituir una alternativa terapéutica en pacientes con insomnio. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos ocho revisiones sistemáticas que en conjunto incluyen tres estudios primarios, de los cuales dos corresponden a ensayos aleatorizados. Concluimos que no está claro si los cannabinoides tienen un efecto en la severidad del insomnio o en la calidad del sueño; que podrían no tener efecto en la conciliación del sueño, despertar del sueño ni comportamiento durante vigilia, y probablemente se asocian a efectos adversos frecuentes.

INTRODUCTION: It has been suggested that cannabinoids would constitute a therapeutic alternative for patients with insomnia. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified eight systematic reviews including three studies overall, of which two were randomized trials. We concluded it is not clear whether cannabinoids have an effect on insomnia severity or on sleep quality; that they might have no effect on sleep conciliation, sleep awakening or behavior during wakefulness, and are probably associated with frequent adverse effects.

Transtornos do sono: atualização (1/2) / Sleep disorders: up to date (1/2)

Esta é uma primeira parte (1/2) da abordagem de fundamentos do sono e transtornos do sono (TS) sobre aspectos: neurobiológicos (neuroanatômicos, neuroquímicos e fisiológicos); clínicos (anamnese e exame físico; exames subjetivos - questionários e escalas; exames objetivos - polissonografia, teste de latências múltiplas e actigrafia). É valorizada a terceira Classificação Internacional dos Transtornos do Sono (ICSD-3) para abordar aspectos clínicos, diagnósticos e terapêuticos, segundo as quatro queixas principais referentes dos TS: Insônia, Sonolência excessiva diurna, Movimentos e comportamentos anormais durante o sono e Incapacidade de dormir na hora desejada. Neste artigo abordamos apenas: 1-Insônia - dificuldade em adormecer ou manter-ser dormindo, acordar cedo, ou um distúrbio na qualidade do sono que faz com que o sono pareça inadequado ou não restaurador; duração: aguda ou crônica; 2- Sonolência excessiva diurna; consequente a distúrbios do sono, privação do sono; distúrbios centrais da hipersonia; distúrbios médicos ou psiquiátricos. (AU)

This is the first part (1/2) on this paper about sleep fundamentals and sleep disorders (TS) questions: neurobiological (neuroanatomical, neurochemical and physiological); clinical (anamnesis and physical examination; subjective exams - questionnaires and scales; objective examinations - polysomnography, multiple latency tests and actigraphy). The third International Classification of Sleep Disorders (ICSD-3) is valued to address clinical, diagnostic and therapeutic aspects, according to the four main complaints regarding TS: Insomnia, Excessive daytime drowsiness, Abnormal movements and behaviors during sleep, and Inability to sleep at the desired time. In this paper, it is discussed the only first two: 1-Insomnia: difficulty falling as-leep, staying asleep, early morning waking, non- restorative sleep, quality of sleep, and amount of sleep; duration: acute or chronic. (AU)

Eszopiclone versus zopiclone in the treatment of insomnia

OBJECTIVE: To determine the therapeutic effects of two selective GABA-A agonists, zopiclone and eszopiclone, in the treatment of insomnia. METHODS: This study comprised a phase III, single-center, randomized, double-blind, double-dummy, parallel-group, non-inferiority trial. Patients were randomized to receive zopiclone 7.5 mg or eszopiclone 3 mg, both orally, for four weeks. In total, 199 patients were evaluated during two visits and then followed for at least six weeks. The primary endpoint was the Insomnia Severity Index after four weeks of treatment. Secondary endpoints were obtained through polysomnography data, including total sleep time, sleep latency and sleep efficiency. The frequency of adverse events was also analyzed. ClinicalTrials.gov: NCT01100164. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of eszopiclone over zopiclone. Analysis of objective parameters assessed by polysomnography showed that eszopiclone increased total sleep time and also improved sleep efficiency. The safety profile of both study treatments was similar and the most common events reported in both groups were dysgeusia, headache, dizziness, irritability and nausea. Adverse events were observed in 223 patients, 109 (85.2%) in the eszopiclone group and 114 (87.7%) in the zopiclone group. CONCLUSION: Based on the Insomnia Severity Index at the end of four weeks of treatment, eszopiclone demonstrated efficacy comparable to that of zopiclone in the treatment of insomnia, increasing total sleep time as well as sleep efficiency according to polysomnography.