Search

Chronic insomnia has the potential to significantly impact physical well-being, occupational performance, and overall quality of life. This review summarizes the clinical and basic research on the central regulatory mechanism of acupuncture in treating primary insomnia (PI), aiming to explore the clinical effectiveness and possible mechanism of acupuncture in treating PI. The currently available drugs for insomnia exhibit notable adverse effects and tend to induce dependence. Empirical evidence from clinical investigations has demonstrated that acupuncture has a favorable safety profile while substantially enhancing the sleep quality of individuals diagnosed with PI. The combination of acupuncture and medication has been shown to augment the therapeutic efficacy of medication while reducing the dosage and mitigating the occurrence of unwanted effects. A review of the current clinical and basic research on the effects of acupuncture on central alterations in PI patients revealed that acupuncture exerts a regulatory influence on the functional activity of brain regions implicated in cognitive and emotional processes. Additionally, acupuncture has been found to impact metabolite levels and circadian clock gene expression and enhance inflammatory responses and energy metabolism. Notably, a single acupuncture intervention had a modulatory effect on functional brain regions similar to that of cumulative acupuncture. The current clinical trials on acupuncture have been limited in scale, and basic research has focused on a single objective. With the continuous progress of brain research, extensive clinical randomized controlled trials of high quality can be combined with various neuroimaging technology modalities. Moreover, different targets and pathways can be explored through basic research. This may serve to enhance the understanding of the fundamental central nervous system mechanisms involved in the efficacy of acupuncture in treating PI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yao, Liu, Li, Zheng, Sun, He, Zhong, Ma, Huang and Wang.)

Objectives: Primary insomnia is a substantial public health burden, but current treatments for this disorder have limited effectiveness and adherence. Herein, we aimed to investigate the efficacy and safety of continuous theta burst stimulation (cTBS) for the treatment of primary insomnia., Methods: This two-armed, randomized, sham-controlled trial was conducted at Peking University Sixth Hospital and local community clinics. A total of 46 patients with primary insomnia were recruited and randomly allocated to either the cTBS group or sham group. Forty-one patients completed 10 sessions of cTBS or sham intervention and follow-up assessments., Results: After the intervention, the severity of insomnia was significantly lower in the cTBS group than in the sham group, with a large effect size (Cohen's d = -1.938). Additionally, 52.4 % of patients in the cTBS group achieved a response (Insomnia Severity Index score reduction ≥8), whereas only 4 % of patients in the sham group achieved a response. The duration of objective total sleep time and slow-wave sleep were higher in the cTBS group than in the sham group. The degree of anxiety was lower in the cTBS group than in the sham group. There were no significant differences in depression, sleepiness, or cognitive function between the cTBS and sham groups. During follow-up, the sleep quality of the cTBS group significantly improved and remained stable at the 6-month follow-up., Conclusion: In this randomized clinical trial, cTBS improved insomnia symptoms and was generally well tolerated, thus supporting the further development of cTBS for the treatment of primary insomnia., Competing Interests: Declaration of competing interest The authors report that they have no financial conflicts of interest with respect to the content of this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To assess efficacy of Chinese medicine (CM) on insomnia considering characteristics of treatment based on syndrome differentiation., Methods: A total of 116 participants aged 18 to 65 years with moderate and severe primary insomnia were randomized to the placebo (n=20) or the CM group (n=96) for a 4-week treatment and a 4-week follow-up. Three CM clinicians independently prescribed treatments for each patient based on syndromes differentiation. The primary outcome was change in total sleep time (TST) from baseline. Secondary endpoints included sleep onset latency (SOL), wake time after sleep onset (WASO), sleep efficiency, Pittsburgh Sleep Quality Index (PSQI) and CM symptoms., Results: The CM group had an average 0.6 h more (95% confidence interval (CI): 0.3-0.9, P<0.001) TST and 34.1% (10.3%-58.0%, P=0.005) more patients beyond 0.5 h TST increment than that of the placebo group. PSQI was changed -3.3 (-3.8 to -2.7) in the CM group, a -2.0 (-3.2 to -0.8, P<0.001) difference from the placebo group. The CM symptom score in the CM group decreased -2.0 (-3.3 to -0.7, P=0.003) more than the placebo group. SOL and WASO changes were not significantly different between groups. The analysis of prescriptions by these clinicians revealed blood deficiency and Liver stagnation as the most common syndromes. Prescriptions for these clinicians displayed relative stability, while the herbs varied. All adverse events were mild and were not related to study treatment., Conclusion: CM treatment based on syndrome differentiation can increase TST and improve sleep quality of primary insomnia. It is effective and safe for primary insomnia. In future studies, the long-term efficacy validation and the exploratory of eutherapeutic clinicians' fixed herb formulas should be addressed (Registration No. NCT01613183)., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The neuropathologic mechanism of primary insomnia (PI) of females remains unclear. This study aims to investigate the features of amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) in females with PI using functional magnetic resonance imaging (fMRI), and then explore the abnormalities of functional connectivity (FC)., Materials and Methods: A total of 39 female PI patients and 31 female healthy controls (HC) were enrolled in the study. The sleep condition was assessed using the Pittsburgh Sleep Quality Index (PSQI), and Insomnia Severity Index (ISI), and their depressive symptom was evaluated using the Hamilton Depression Scale (HAMD-24). The rs-fMRI was once conducted for every subject. ReHo, ALFF, and ROI-based FC were used to analyze the changes of brain function., Results: ALFF values were increased in the Cerebelum&#95;4&#95;5&#95;L, as well as decreased ALFF in the bilateral Frontal&#95;Sup&#95;Medial (SFGmed), Angular&#95;L (ANG.L), Parietal&#95;Inf&#95;R (IPL.R), SupraMarginal&#95;R (SMG.R), and Postcentral&#95;R (PoCG.R). ReHo values were increased in the Temporal&#95;Pole&#95;Mid&#95;R (TPOsup.R), as well as decreased ReHo in the Insula&#95;R (INS.R), Frontal&#95;Inf&#95;Oper&#95;R (ORBinf.R), Putamen&#95;R (PUT.R), Rolandic&#95;Oper&#95;R (ROL.R), bilateral Cingulum&#95;Post (PCG), bilateral Frontal&#95;Sup&#95;Medial (SFGmed), bilateral anterior cingulate and paracingulate gyri (ACG), and the bilateral precuneus (PCUN). Across the entire brain, there was a decline in the FC between Angular&#95;R and Frontal&#95;Sup&#95;Medial&#95;L., Conclusion: Alterations in brain regions of female patients with PI involved multiple functional networks, including the default mode network, the salience network, the central executive network, and the limbic network. Reduced coordination between functional networks may be an important mechanism for insomnia and may lead to reduced cognitive function and decision-making ability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Jie, Liu, Wu, Wang, Zhang, Fang, Wang, Zhao and Liu.)

Background: Insomnia is very common in psychiatric disorders, but the polysomnographic (PSG) characteristics of insomnia in various psychiatric disorders are still not agreed upon. This study aimed to investigate the characteristics of PSG and its relationship with metabolic indicators in insomnia patients with affective disorders and primary insomnia (PI) patients., Methods: A total of 38 patients with PI, 44 major depressive disorder patients with insomnia (DI), 49 generalized anxiety disorder patients with insomnia (GI), and 19 bipolar mania patients with insomnia (BI) were included. PSG was used to detect sleep problems in subjects, and biochemical indicators were also collected., Results: The results of this study found that subjects with BI were lower on REM sleep latency (RL), awakenings number (AN), number of microarousals (NM), and apnea-hypopnea index (AHI) than those with DI and GI, and lower on RL and AN than those with PI. Subjects with PI had lower NM and AHI than those with DI and GI. Patients with DI had a higher RL than those with GI. All results passed Bonferroni correction (p < 0.00078). No differences in biochemical indices were found among the four groups of subjects. Also, AHI was found to be positively correlated with free triiodothyronine (FT3) and fasting blood glucose in subjects., Conclusion: This study suggests that various psychiatric disorders may have their characteristics in terms of PSG parameters, which prompted us to focus on the PSG characteristics of these disorders when assessing them, as well as to focus on their biochemical indicators., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Primary insomnia (PI) refers to syndromes of difficulty falling asleep, poor sleep quality, early awakening, and difficulty falling asleep after waking up. Although there have been numerous studies, the specific etiology and pathogenesis of PI are still misunderstanding. In recent years, the gut microbiota has been proved to be involved in the metabolism of many mental disorders. But the specific mechanisms of its involvement in PI have not been fully elucidated. This study aims to explore the relationship between the gut microbiota and the symptoms, cognitive function changes in PI., Methods: In this study, the gut microbiota of PI patients and healthy controls was profiled by performing stool 16s rRNA gene sequencing. The co-occurrence network was constructed by using Weight Gene Co-expression Network Analysis (WGCNA) algorithm. The correlation between gut microbiota associated pathways and traits in PI were predicted., Results: WGCNA results demonstrated several Operational Taxonomic Units (OTU) modules are correlated to symptoms. By using PICRUSt2 software, we predicted the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of microbiota in modules. For instance, sleep efficiency may be correlated with the presence of Insulin signaling pathway, Flavonoid biosynthesis, Ascorbate and aldarate metabolism, Nitrotoluene degradation, Biotin metabolism, RNA polymerase and Chlorocyclohexane and chlorobenzene degradation. Total sleep time may be correlated with the presence of Tyrosine metabolism, Propanoate metabolism, Carbon fixation pathways in prokaryotes, Carotenoid biosynthesis, Systemic lupus erythematosus, Nitrotoluene degradation and Biosynthesis of unsaturated fatty acids. The severity of insomnia may be correlated with Insulin signaling pathway, Flavonoid biosynthesis, Ascorbate and aldarate metabolism, Nitrotoluene degradation, Biotin metabolism and RNA polymerase. Change of name score in Montreal Cognitive Assessment (MoCA) may be correlated with Tyrosine metabolism, Propanoate metabolism, Carbon fixation pathways in prokaryotes, Carotenoid biosynthesis, Systemic lupus erythematosus, Nitrotoluene degradation, Biosynthesis of unsaturated fatty acids, Apoptosis, Steroid hormone biosynthesis, Geraniol degradation, Protein digestion and absorption and Bisphenol degradation in Gut Microbiota (GM)., Conclusion: This study revealed the potential relationships between gut microbiota and PI. By using pathway prediction and enrichment analysis, we concluded many metabolic pathways may associated with some important traits of insomnia patients, including sleep efficiency, severe insomnia, total sleep time and change of name score in MoCA. The metabolic pathways include Insulin signaling pathway, Flavonoid biosynthesis, Ascorbate and aldarate metabolism, Nitrotoluene degradation, Biotin metabolism, RNA polymerase and Chlorocyclohexane, chlorobenzene degradation, Tyrosine metabolism, Propanoate metabolism, Carbon fixation pathways in prokaryotes, Carotenoid biosynthesis, Systemic lupus erythematosus, Biosynthesis of unsaturated fatty acids, Apoptosis, Steroid hormone biosynthesis, Geraniol degradation, Protein digestion and absorption and Bisphenol degradation.Our study demonstrated that PI patients demonstrate significant changes in gut microbiota, which will help delineate the relationship between gut microbiota and syndromes of PI., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Benzodiazepines, such as flunitrazepam, may be at risk of disinhibition, leading to aggressiveness, impulsivity, self-harm, and possibly suicide attempts, whereas ramelteon may be far from disinhibition., Case Presentation: In a 43-year-old female with primary insomnia, flunitrazepam alone did not induce any type of disinhibition, but the addition of ramelteon to flunitrazepam brought about disinhibition, leading to aggressiveness and finally to her suicide attempt. Her disinhibition rapidly subsided as soon as ramelteon alone was discontinued., Conclusion: These findings suggest that a suicide attempt may occur during ramelteon and flunitrazepam combination in a susceptible patient., Competing Interests: The author declares no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Background: Insomnia is the second most commonly presenting symptom, after pain, in clinics. Insomnia prevalence in India is 28.1 %., Objective: This study explores the effect of Mamsyadi Kwatha in the management of primary insomnia., Materials and Methods: Fifty patients attending KLE Ayurveda hospital meeting the diagnostic criteria of primary insomnia (DSM IV TR) were enrolled. Patients were randomly divided into two groups: group MK and TK. Intervention in group MK was 24 ml of Mamsyadi Kwatha twice a day and in group TK was 24 ml of Tagaradi Kwatha twice a day for 30 days. Assessment was done through primary outcome measures like Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), insomnia severity index (ISI). Secondary outcome measures were sleep diary recordings of past 15 days and depression anxiety and stress scale (DASS). Follow ups were at base line, 15th and 30th day of interventions. Laboratory assessments of liver function test, haemoglobin, and serum creatinine levels were carried at base line and 30th day of intervention., Results: Effect on primary and secondary outcomes showed that both the drugs were comparable. = Within group comparison of both the drugs showed that they produced significant improvement in PSQI, ESS, ISI, sleep diary variables, and DASS. However, Mamsyadi kwath has additional benefit of early recovery in total sleep. Both the drugs showed good safety profile evaluated through serum creatinine and liver function tests., Conclusion: The effects of Mamsyadi Kwatha is comparable to Tagaradi Kwatha. Both drugs produced significant improvement in clinical assessments of insomnia, anxiety, depression, and stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

This study examined the integrity of white matter tracts in 25 participants with primary insomnia (PI), 50 participants with major depressive disorder (MDD), and 25 healthy controls. Seven white matter tracts, selected based on prior research, were quantified by fractional anisotropy (FA) as well as by related measures of diffusivity using diffusion tensor imaging (DTI) on a 3-T scanner. All 100 participants were free of significant medical, psychiatric (excluding the MDD group) and sleep disorders (excluding the PI group), were free of central nervous system medications, and completed an extensive clinical assessment. Subjective and objective sleep measures revealed significant sleep disruption in both the PI and MDD groups. Relative to the controls, both the PI and MDD groups demonstrated impaired integrity in three of the seven white matter tracts: the genu of the corpus callosum (GenuCC), the superior longitudinal fasciculus (SLF), and the inferior longitudinal fasciculus (ILF). We demonstrated reduced FA in the GenuCC, reduced FA and reduced axial diffusivity (AD) in the SLF, as well as reduced AD and radial diffusivity in the ILF. Finally, in an exploratory analysis of the combined cohorts, FA in the GenuCC and FA in the SLF were negatively correlated with depression severity and positively correlated with total sleep time. Abnormalities documented in the GenuCC, SLF and ILF, and present in both the PI and MDD groups may suggest some shared neurobiology., (© 2023 European Sleep Research Society.)

This pilot study examines the therapeutic effects of bifrontal low frequency (LF) TMS on primary insomnia. In this prospective, open-label study 20 patients with primary insomnia and without major depressive disorder received 15 sequential bifrontal LF rTMS stimulation sessions. By week 3, PSQI scores declined from baseline score of 12.57(sd 2.74) to 9.50 (sd 4.27), a large effects size (0.80 (CI 0.29, 1.36)), and CGI-I scores improved for 52.6% of participants. Results of this pilot indicate that the novel bifrontal LF rTMS benefitted this group of patients suffering from primary insomnia, with absence of sham control a significant study limitation., Competing Interests: Declaration of Competing Interest None of the authors have a conflict of interest to declare in regards to this research. Research reported in this publication was supported through an internal Department of Psychiatry seed funding award and through statistical analysis support provided by the University of Florida Clinical and Translational Science Institute, which is supported in part by the NIH National Center for Advancing Translational Sciences under award number UL1TR001427. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: The brain waves pattern in primary insomniacs is different from healthy subjects. Studies have shown that binaural beats can alter the pattern of brain waves in healthy individuals; however, the efficacy of binaural beats in altering the pattern of brain waves in primary insomniacs has not yet been investigated. This study aims to evaluate the efficacy of theta binaural beat on the absolute power of theta activity in primary insomniacs., Methods: This study was a randomized clinical trial with experimental and control groups. The primary insomniacs received theta binaural beats in the experimental group while the control group received white noise. Their brain waves were recorded by electroencephalogram for 25 min; the first 5 min was without stimulus (first block), the next was followed by 15 min of receiving stimulus (binaural beat or white noise), and the last 5 min without stimulus (fifth block). The Matlab software, version R2019a, EEGLAB toolbox, and SPSS software, version 24 were used to analyze the data., Results: The absolute power of theta activity in the experimental group was significantly higher in the last block compared to the first block in all brain lobes (P<0.05). The largest changes in theta activity were in the temporal and parietal lobes, and the last one was in the prefrontal lobe. In the control group, none of the brain lobes showed significant differences in the last block compared to the first block., Conclusion: Theta binaural beat can alter the absolute power of theta activity in primary insomniacs. The implications of the study are discussed., Highlights: Theta binaural beat can be effective in changing the brain wave pattern of primary insomniacs.The amount of changes in the absolute power of theta wave activity in different brain regions of primary insomniacs under the influence of theta binaural beat was not the same.The effect of theta binaural beat on temporal and parietal was higher than other brain areas, whereas the prefrontal and occipital had the least significant changes in the absolute power of theta activity., Plain Language Summary: Different people experience different brain waves based on the type of activity they do in their life at the same time. This brain wave pattern can change especially after a person decides to go to bed and experience an ideal sleep. Theta brain wave, which plays a role in important activities such as memory, deep relaxation, and day-dreaming, helps a person to change from wakefulness to sleep faster. Research literature has shown that people with insomnia have different brain waves than healthy people, especially in the theta brain wave. Accordingly, many interventions have been carried out to improve the sleep quality of these people and change their brain waves. It has been shown that binaural beat as a low-cost method based on sound waves, can change the brain waves of healthy people, but so far, no study has been done to investigate the effect of these sound waves (especially theta waves) on the brain waves of people with insomnia. The current study was conducted with the aim of investigating a non-invasive method (theta binaural beat) to improve the brain wave pattern of people suffering from insomnia. The findings of this study showed that theta binaural beat can be effective in changing the brain wave pattern of people suffering from insomnia., Competing Interests: The authors declared no conflict of interest., (Copyright© 2023 Iranian Neuroscience Society.)

Objectives: To quantitatively measure the T1 value, T2 value, proton density (PD) value, and cerebral blood flow (CBF) in young and middle-aged primary insomnia (PI) patients, and analyze the correlations between relaxation times, PD, and CBF to explore potential brain changes., Methods: Cranial magnetic resonance (MR) images of 44 PI patients and 30 healthy subjects were prospectively collected for analysis. The T1, T2, PD, and CBF values of the frontal lobe, parietal lobe, temporal lobe, and occipital lobe were independently measured using three-dimensional arterial spin labeling (3D-ASL), synthetic magnetic resonance imaging (syMRI) and a whole-brain automatic segmentation method. The differences of these imaging indices were compared between PI patients and healthy subjects. Follow-up MR images were obtained from PI patients after 6 months to compare with pre-treatment images. The Wilcoxon signed rank test and Spearman rank were used for statistical analysis., Results: Bilateral CBF asymmetry was observed in 38 patients, with significant differences in both the T2 value and CBF between the four lobes of the brain ( p  < 0.01). However, no significant difference was found in the T1 and PD values between the bilateral lobes. A negative correlation was found between CBF and T2 values in the right four lobes of patients with primary insomnia (PI). During follow-up examinations, five PI patients showed a disappearance of insomnia symptoms and a decrease in CBF in both brain lobes., Conclusion: Insomnia symptoms may be associated with high CBF, and most PI patients have higher CBF and lower T2 values in the right cerebral hemispheres. The right hemisphere appears to play a critical role in the pathophysiology of PI. The 3D-ASL and syMRI technologies can provide a quantitative imaging basis for investigating the brain conditions and changes in young and middle-aged PI patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Luo, Li, Shen, Zhou, Zou, Tang and Guo.)

(1) Background: The purpose of this study was to investigate the efficacy and safety of transcutaneous vagus nerve stimulation (t-VNS) in the treatment of primary insomnia. (2) Methods: This is a single center, randomized, double-blind study. A total of 30 patients diagnosed with primary insomnia were randomly divided into two groups to receive 20 Hz t-VNS in either the auricular concha area (treatment group) or periauricular area (control group), twice a day for 20 min during a one-month study period. The effective rate of treatment, defined as a ≥50% reduction of the Pittsburgh Sleep Index Scale (PSQI) after treatment, was compared between the two groups as the primary outcome. Response rate (defined as ≥10% change in the PSQI score), and changes in the Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores were also assessed. (3) Results: After one month of treatment, the PSQI score of the treatment group decreased significantly ( p = 0.001). The effective rate of the treatment group (73% vs. 27%, p = 0.027) was significantly higher than that of the control group. No statistical differences in changes of HAMA and HAMD scores were detected between the two groups. There were no complications in all patients. (4) Conclusion: T-VNS appeared to be a safe and effective treatment for primary insomnia.

Melatonin is the main hormone involved in the control of the sleep-wake cycle. It is easily synthesisable and can be administered orally, which has led to interest in its use as a treatment for insomnia. Moreover, as production of the hormone decreases with age, in inverse correlation with the frequency of poor sleep quality, it has been suggested that melatonin deficit is at least partly responsible for sleep disorders. Treating this age-related deficit would therefore appear to be a natural way of restoring sleep quality, which is lost as patients age. However, despite the undeniable theoretical appeal of this approach to insomnia, little scientific evidence is available that supports any benefit of this substitutive therapy. Furthermore, the most suitable dose ranges and pharmaceutical preparations for melatonin administration are yet to be clearly defined. This review addresses the physiology of melatonin, the different pharmaceutical preparations, and data on its clinical usefulness., (Copyright © 2018 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Melatonin is the main hormone involved in the control of the sleep-wake cycle. It is easily synthesisable and can be administered orally, which has led to interest in its use as a treatment for insomnia. Moreover, as production of the hormone decreases with age, in inverse correlation with the frequency of poor sleep quality, it has been suggested that melatonin deficit is at least partly responsible for sleep disorders. Treating this age-related deficit would therefore appear to be a natural way of restoring sleep quality, which is lost as patients age. However, despite the undeniable theoretical appeal of this approach to insomnia, little scientific evidence is available that supports any benefit of this substitutive therapy. Furthermore, the most suitable dose ranges and pharmaceutical preparations for melatonin administration are yet to be clearly defined. This review addresses the physiology of melatonin, the different pharmaceutical preparations, and data on its clinical usefulness., (Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: To observe the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on the sleep quality and nocturnal heart rate variability (HRV) in patients with primary insomnia., Methods: Twenty-one patients with primary insomnia were included. Using SDZ-ⅡB electric acupuncture apparatus, Xin (CO 15 ) and Shen (CO 10 ) were stimulated with disperse-dense wave, 4 Hz/ 20 Hz in frequency, (0.2±30%) ms of pulse width and tolerable intensity. Electric stimulation was given once every morning and evening of a day, 30 min each time, for 4 weeks totally. Before and after treatment, the score of Pittsburgh sleep quality index (PSQI), objective sleep structure (total sleep time [TST], sleep latency [SL], wake after sleep onset [WASO], sleep efficiency [SE], the percentages of non-rapid eye movement period 1, 2, 3, and the percentage of rapid eye movement period to TST [N1%, N2%, N3%, REM%] ) and nocturnal HRV (high frequency [HF], low frequency [LF], the ratio of LF to HF [LF/HF], standard deviation for the normal RR intervals [SDNN], squared root of the mean sum of squares of differences between adjacent intervals RR [RMSSD], the percentage of adjacent RR intervals with differences larger than 50 ms in the entire recording [PNN50%], the mean of sinus RR intervals [NNMean] ) were compared in the patients separately., Results: After treatment, the score of each item and the total score of PSQI and SL were all reduced as compared with those before treatment ( P <0.01, P <0.001); SE, N3%, LF, HF, LF/HF, SDNN, NNMean and RMSSD were all increased compared with those before treatment ( P <0.001, P <0.01)., Conclusion: The taVNS improves the sleep quality and objective sleep structure in patients with primary insomnia, which is probably related to the regulation of autonomic nervous functions.

Cognitive behavioral therapy for insomnia (CBT-I) is effective for not only primary insomnia (PI) but also comorbid insomnia (CI; insomnia associated with psychiatric/physical diseases or other types of sleep disorders). This study aimed to compare the outcomes of CBT-I implemented in the same manner between patients with PI and CI. In total, 41 adult patients who had completed CBT-I were enrolled in this retrospective analysis and divided into a PI group and a CI group. The authors then examined and compared the significance of changes after therapy between the two groups. The magnitude of improvement on the Japanese version of the Insomnia Severity Index (ISI-J) was analyzed as the primary endpoint. In the PI group ( n  = 24), both the ISI-J score and the dose of hypnotics decreased significantly following CBT-I. On the other hand, in the CI group ( n  = 17), only the dose of hypnotics decreased significantly; no statistically significant improvement was seen in the ISI-J score. Sleep onset latency and sleep quality rating in recorded sleep diaries were significantly correlated with improved ISI-J scores in the CI group only. CBT-I was shown to be effective for CI, but its efficacy for CI was inferior to that for PI in terms of impact on sleep and mental condition. These results suggest that in addition to the basic components of CBT-I, treatment for CI, especially when accompanied by severe insomnia symptoms, should include approaches targeting the comorbid disease., Competing Interests: Conflict of interestMasayuki Iwashita, Wataru Yamadera, Ayana Hotchi, Tomohiro Utsumi, Misato Amagai, Junpei Ishii, Takako Suzuki, Hiroshi Itoh and Masahiro Shigeta declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Japanese Society of Sleep Research 2022.)

Background: Acupuncture has been widely practiced for primary insomnia (PI). However, the relative benefit and harm among acupuncture therapies remain uncertain., Objectives: To compare and evaluate the effect differences of multiple acupuncture therapies for patients with PI., Methods: Systematic literature search for randomized controlled trials (RCTs). Pairs of reviewers independently conducted literature screening, data extraction, and risk of bias assessment. Meta-analysis was conducted using R and Stata software. The Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) was used to assess certainty of evidence and interpret results., Results: Fifty-seven RCTs with 4678 patients were included. Compared with usual treatment, multiple acupuncture therapies showed a better effect for Pittsburgh sleep quality index score. And acupoints catgut embedding (ACE) was proved to be the most effective with a moderate certainty of evidence; auricular acupressure or auricular acupuncture plus manual acupuncture (AP + MA), electroacupuncture plus acupoint application (EA + APA), and intradermal needle (IN) might be also the most effective with low certainty of evidence. ACE, ACE + MA, AP + MA, EA, EA + APA, HPN, MA and PBN + MA showed significantly improvement in effective rate when compared with usual treatment. Insufficient evidence reported on Epworth Sleepiness Scale, Athens Insomnia Scale, and recurrence rate. The most common slight adverse events mainly included hematoma, pain, headache, and bleeding., Conclusions: With moderate to low certainty of evidence, multiple acupuncture therapies showed impressive insomnia improvement, especially ACE, AP + MA, and EA + APA. Differences between therapies were small or insignificant and based-on low or very low certainty of evidence., Competing Interests: Conflict of interest None of the authors have any conflict of interest to declare in this study. The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: https://doi.org/10.1016/j.sleep.2022.03.012., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To explore the modulation of transcutaneous auricular vagus nerve stimulation (taVNS) on default mode network (DMN) in patients with primary insomnia (PI)., Methods: A total of 22 PI patients (one patient dropped off and two patients were excluded) were included and treated with taVNS. The bilateral auricular points of Xin (CO 15 ) and Shen (CO 10 ) were selected and treated with disperse-dense wave at frequency of 4 Hz/20 Hz, the intensity was based on the patient's tolerance. taVNS was given once in the morning and once in the evening for 30 minutes each time. The treatment lasted for at least 5 days a week for 4 weeks. At the same time, 16 healthy subjects matched with gender and age were recruited. The Pittsburgh sleep quality index (PSQI) score was evaluated before and after treatment in PI patients. The resting-state functional magnetic resonance imaging (rs-fMRI) data of PI patients before and after treatment and healthy subjects at baseline period were collected to observe the effect of taVNS on the functional connection (FC) between posterior cingulate cortex (PCC) and whole brain., Results: After treatment, the total score of PSQI in PI patients was lower than that before treatment ( P <0.01). Compared with healthy subjects, the FC of the left PCC was increased either with the left orbital superior frontal gyrus or with left middle frontal gyrus ( P <0.001), and the FC between right PCC and left middle frontal gyrus was increased in PI patients before treatment ( P <0.001). Compared before treatment, the FC between left PCC and left middle frontal gyrus was decreased ( P <0.05), and the FC of the right PCC was decreased either with the right medial prefrontal cortex or with the left middle frontal gyrus in PI patients after treatment ( P <0.001, P <0.01)., Conclusion: taVNS can modulate the FC between anterior and posterior DMN, and between DMN and cognitive control network of PI patients, which may be one of the brain effect mechanisms of taVNS in the treatment of PI patients.

Primary insomnia (PI) is among the most prevalent sleep-related disorders and has a far-reaching impact on daytime functioning. Repetitive transcranial magnetic stimulation (rTMS) has drawn attention because of its effectiveness and safety. The purpose of the current study was to detect changes in the topological organization of whole-brain functional networks and to determine their associations with the clinical treatment effects of rTMS. Resting-state functional magnetic resonance imaging (rsfMRI) data from 32 patients with PI were collected and compared with findings from 32 age- and gender-matched healthy controls (HCs). The patients were treated with Stanford accelerated intelligent neuromodulation therapy, which is a recently validated neuroscience-informed accelerated intermittent theta-burst stimulation protocol. Graph theoretical analysis was used to construct functional connectivity matrices and to extract the attribute features of small-world networks in insomnia. Scores on the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and the associations between these clinical characteristics and functional metrics, were the primary outcomes. At baseline, the patients with PI showed inefficient small-world property and aberrant functional segregation and functional integration compared with the HCs. These properties showed renormalization after individualized rTMS treatment. Furthermore, low functional connectivity between the right insula and left medial frontal gyrus correlated with improvement in ISI scores. We highlight functional network dysfunctions in PI patients and provide evidence into the pathophysiological mechanisms involved and the possible mode of action of rTMS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qi, Zhang, Li, Sun, Ma, Li, Li, Ren, Xi and Huang.)

Insomnia is a common problem, affecting individuals' health and quality of life. Among several therapies used to treat this condition, spiritual interventions are suggested to have beneficial outcomes on sleep disturbances. Nevertheless, a systematic compilation of the evidence available is still needed in the literature in order to scientifically investigate the topic. To examine the most common spiritual interventions proposed to treat sleep disorders and to assess the scientific evidence of these interventions. This is a scoping literature review conducted by independent researchers on the following databases: PubMed, SCOPUS, Web of Science, Cochrane Library and OpenGrey. A boolean expression was used, and all studies published in the last 5 years investigating the role of spiritual or religious interventions on insomnia were included. From a total of 3257 articles retrieved in our search, ten studies were included in the final analysis. There is a wide array of techniques used to treat insomnia or the mental disorders associated with insomnia, such as mantra, yoga, mindfulness, praying/meditation, daily spiritual experiences, psycho-religious training and intervention. The included studies showed a positive influence of spiritual/religious interventions on insomnia directly and indirectly. However, there is a scarcity of clinical trials and most studies have small sample sizes and used only subjective measures, resulting in a low evidence. The results of the present review point to a promising role of spirituality and religion on better sleep outcomes, particularly in the improvement in insomnia. However, the heterogeneity and the quality of these studies suggest caution while interpreting these findings. More clinical trials are needed in this area to provide a recommendation of these methods in clinical practice., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

The efficacy and safety of dual orexin receptor antagonists (DORAs) for primary insomnia have been well verified in several large randomized controlled trials (RCTs) over the past several decades. However, there have been few systematic comparisons of different DORAs, and the best DORA for insomniacs has remained unclear. Here, Medline, Embase, Cochrane library, and clinicaltrials.gov were searched for RCTs (through December 31, 2020) to evaluate different DORAs versus a placebo. We pooled data from 13 RCTs. DORAs were superior to the placebo in all efficacy outcomes except the subjective number of awakenings (P = 0.90), but also showed higher risks of somnolence, abnormal dreams, fatigue, and dry mouth (somnolence: P < 0.00001; abnormal dreams: P = 0.03; fatigue: P = 0.001; dry mouth: P = 0.007). No statistical differences were found between any two of the DORAs in terms of primary efficacy outcomes. However, lemborexant yielded the three-highest surfaces under the curve ranking area (SUCRA) values (78.25%, 96.25% and 89.13%). Taken together, we conclude that DORAs are superior to the placebo in terms of efficacy and safety measures., Competing Interests: Conflicts of interest The authors do not have any conflicts of interest to disclose., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: It is unclear whether the patterns of functional connectivity density (FCD) differ between patients with primary insomnia (PI) and healthy subjects. In the present study, we investigated the features of FCD in patients with PI using resting-state functional MRI (rsfMRI)., Methods: rsfMRI datasets of 32 patients with PI and 34 healthy controls (HCs) were obtained using a 3-Tesla scanner. FCD analysis was performed to compare voxels with abnormal whole-brain functional connectivity with other voxels among patients with PI and HCs. Abnormal brain regions were then used as seed points for FC analysis., Results: Compared with HCs, patients with PI exhibited significantly decreased FCD in the left medial frontal gyrus and increased FCD in the left supplementary motor area (SMA). With the left medial frontal gyrus as the seed point, patients with PI showed decreased FC between the left medial frontal gyrus and the left fusiform gyrus compared with HCs. With the left SMA as the seed point, patients with PI exhibited increased FC between the left SMA and the right anterior cingulate gyrus. Correlation analysis revealed that the increased FCD values in the left SMA were positively correlated with sleep latency in patients with PI., Conclusion: Default-mode network and SMA dysfunctions may be related to the pathophysiology of PI., Competing Interests: The authors declare that they have no conflicts of interest., (© 2022 Ji et al.)

Background: Cognitive behavioral therapy for insomnia (CBT-I) is a first-line therapy for insomnia disorders. We assessed changes in discrepancies between subjective and objective sleep measures and correlations between discrepancy changes and clinical insomnia severity for CBT-I in patients with primary insomnia METHODS: Fifty-two outpatients (mean age, 60.3 years; 26 women) with primary insomnia were treated by individual CBT-I (50 min, maximum six sessions, once every 1-2 weeks). One week before and after CBT-I, patients recorded a sleep log and wore an actigraphy device. Subjective and objective time in bed (TIB), total sleep time (TST), sleep-onset latency (SOL), wake time after sleep onset (WASO), and sleep efficiency (SE) were evaluated by averaging 1-week records. Relative values of sleep discrepancy in TIB, TST, SOL, WASO, and SE were calculated for estimating effects of CBT-I. The therapeutic effects were also evaluated using psychological scales before and after CBT-I., Results: Subjective and objective discrepancies in sleep measures decreased by 36, 25, and 37 min in TST, SOL, and WASO, respectively, and 7% in SE (all P < 0.001) after CBT-I. Seven patients transitioned from underestimating SE before CBT-I to overestimating SE after CBT-I. Although CBT-I improved relative values of discrepancy in WASO and SE, alongside ISI, the improvement in insomnia severity only correlated with SOL discrepancy., Conclusions: CBT-I may reduce the discrepancy between subjective and objective sleep measures in patients with primary insomnia. However, a greater therapeutic effect of CBT-I was observed in reducing the ISI, which was slightly influenced by improvements in sleep discrepancies., (© 2021. International Society of Behavioral Medicine.)

As a representative of acupuncture and nonpharmaceutical therapy, auricular acupuncture has been widely for the treatment of insomnia. Transcutaneous auricular vagus nerve stimulation (taVNS) is a combination of auricular point stimulation and vagus nerve stimulation. It can not only treat primary insomnia effectively, but also is noninvasive, painless, portable and economical. The medial prefrontal cortex (mPFC) is a core region of default mode network (DMN), which is important for maintenance of sleep. However, the mechanism of taVNS in alleviating primary insomnia (PI) remains to be clarified. In this study, we found that taVNS could not only effectively reduce the score of Pittsburgh Sleep Quality Index, but also decreased functional connection (FC) between the left mPFC and bilateral dorsal anterior cingulate gyrus as well as FC between the right mPFC and the occipital cortex in patients with PI. Furthermore, the decrease in FC was positively correlated with the decline of sleep index score. Therefore, we proposed that treatment with taVNS can improve sleep quality and prolong sleep duration in patients with PI by reducing FC within DMN, FC between DMN and salience network, as well as FC between DMN and the occipital cortex. This may be one of mechanisms of taVNS in treating PI., (© 2021 American Association for Anatomy.)

Dysfunction of the sleep-wake transition is considered to be associated with the pathology of patients with primary insomnia (PI). Previous animal study had reported that brain circuits between the striatum and cortex can regulate sleep-wake transitions. So far, few studies have systematically explored the structural connectivity of the striatum-centered circuits and their potential roles in patients with PI. In this study, we chosen the striatum as the seed and 10 priori target regions as masks to assess the structural connectivity by using seed-based classification with a diffusion tensor imaging (DTI) probabilistic tractography method. Track strengths of the striatum-centered circuits were compared between 22 patients with PI (41.27 ± 9.21 years) and 30 healthy controls (HC) (35.2 ± 8.14 years). Pittsburgh Sleep Quality Index (PSQI) was used to measure the sleep quality in all participants. Lower track strengths (left striatum- anterior cingulate cortex (ACC), left striatum- dorsal anterior cingulate cortex (dACC), left striatum-Hippocampus, and right striatum-Hippocampus) were observed in patients with PI compared to HC. Additionally, the lower track strengths of brain circuits mentioned above were negatively correlated with PSQI. Taken together, our findings revealed the lower tract strength of frontostriatal circuits in patients with PI and HC, which provided the implications of the system-level structural connections of frontostriatal circuits in the pathology of PI. We suggested that the track strengths of the frontostriatal circuits calculated from DTI can be the potential neuroimaging biomarkers of the sleep quality in patients with PI., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

While it has been reported that both foods and nutrients for individuals are connected with sleep, there is no evidence regarding the association of dietary patterns, identified by factor analysis, with primary insomnia. The present study sought to evaluate the association between major dietary patterns and the chance of having primary insomnia. Objective: The present case-control study was performed using 444 people (111 cases and 333 control), aged 18 to 60 years, referred to Isfahan health centers. Dietary intake was assessed via a food frequency questionnaire in a case-control study in Isfahan, Iran. Principal component analysis was used to determine major dietary patterns. The presence of primary insomnia was measured via the insomnia severity index questionnaire, and the subjects were grouped as healthy or insomniac. Methods: Three major dietary patterns were recognized, and named; Western, Iranian Traditional and Healthy, respectively. The cumulative percentage of variance explained by three dietary patterns was 48.2%. Those in second (OR = 0.30; 95%CI: 0.2-0.46) and third (OR = 0.22; 95%CI: 0.15-0.35) tertiles of healthy dietary pattern were less likely suffer with insomnia. This association remained significant only in the highest tertile after adjusting potential confounders (OR = 0.45; 95%CI: 0.32-0.95). We found no significant association between greater adherence to Western or Iranian traditional dietary patterns and primary insomnia. Results: The findings showed that although no statistically significant association was observed between both Western and Iranian traditional dietary patterns with primary insomnia, people with greater adherence to the healthy dietary pattern are less likely to have primary insomnia.Conclusions: The findings showed that although no statistically significant association was observed between both Western and Iranian traditional dietary patterns with primary insomnia, people with greater adherence to the healthy dietary pattern are less likely to have primary insomnia.

Background: The neural mechanisms of sleep beliefs and attitudes in primary insomnia (PI) patients at resting state remain unclear. The aim of this study was to investigate the features of regional homogeneity (ReHo) in PI using resting-state functional magnetic resonance imaging (rsfMRI)., Methods: Thirty-two PI patients and 34 normal controls (NC) underwent rsfMRI using a 3 T scanner at Tongde Hospital of Zhejiang Province. Participants were assessed with the Dysfunctional Beliefs and Attitudes about Sleep scale (DBAS-16) and Pittsburgh Sleep Quality Index (PSQI). Statistical analyses were performed to determine the regions in which ReHo differed between the two groups. Correlation analyses were performed between the ReHo index of each of these regions and DBAS-16 in PI patients., Results: PI patients showed increased ReHo values in the right superior frontal gyrus, and decreased ReHo values in the left cerebellar gyrus, left inferior occipital gyrus (IOG) and left amygdala compared with those of NC. ReHo values in the left IOG were negatively correlated with total DBAS-16 scores, and scores for "consequences of insomnia" and"worry/helplessness about sleep"in PI patients., Conclusions: These results suggest that ReHo alterations in the left IOG may play an important role in the dysfunctional beliefs and attitudes about sleep in PI., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Primary insomnia is a worldwide problem and it has a considerable negative impact on one's physical and mental health. Studies have shown that non-synonymous Single-nucleotide polymorphisms in 5-hydroxytryptamine (serotonin or 5-HT) are related to primary insomnia. Previous studies have shown that 5-HT polymorphism (rs140700) is related to depression, and insomnia is often accompanied by depression and anxiety. The relationship between this site and primary insomnia is unknown. We speculated that this site may be related to primary insomnia, so we investigated the relationship between rs140700 and primary insomnia., Aims: To explore the relationship between the 5-HT gene polymorphism rs140700 and primary insomnia., Methods: In this study, we included 57 patients with primary insomnia and 54 age- and gender-matched normal controls. The subjects who belonged to the Chinese population were subjected to polysomnography for three consecutive nights. Their sleep quality was assessed, and the genotypes of the 5-hydroxytryptamine (5-HT) gene polymorphism rs140700 were determined by the flight mass spectrometry., Results: The genotype distributions of the 5-HT gene polymorphism rs140700 were in Hardy-Weinberg equilibrium in both patients and controls (P > 0.05). The allele and genotype distributions of this variant were comparable between the patients and controls in all subjects and between genders (all P > 0.05). The influence of rs140700 on percentage of stage 1 (P = 0.015) change and arousal index (P = 0.028) of primary insomnia was statistically significant. The logistic multi-factor regression analysis results revealed that 5-HT gene polymorphism rs140700 was not a risk factor for primary insomnia in the Chinese population (P = 0.589)., Conclusions: The 5-HT gene polymorphism rs140700 may not be a susceptibility locus for primary insomnia in the Chinese population., (© 2020 Royal Australasian College of Physicians.)

Background: The efficacy of acupuncture for treating primary insomnia (PI) has been explored in several meta-analyses where the outcomes measures were based on subjective self-reported sleep rating scales. Sleep state misperception is common in PI and self-reports underestimate sleep duration and quality. No systematic reviews or meta-analyses have investigated the efficacy of acupuncture in improving objective sleep measures in PI., Objective: To perform a systematic review to determine whether objective sleep parameters are improved by acupuncture in patients with PI., Methods: Randomized controlled trials treating PI via verum-acupuncture versus sham-/placebo-acupuncture or waitlist control were searched for in English [MEDLINE (via PubMed), Sciverse ScienceDirect, Cochrane Central Register of Controlled Trials (CENTRAL), AMED, Springer, EMBASE (Elsevier), Ebsco Medline, and PsycINFO (ProQuest)] and Chinese (SinoMed, CNKI, Wanfang and CQVIP) databases, from the dates of the databases' inception to January 2020. The parameters of polysomnography (PSG), actigraphy, or micromovement sensitive mattress/pillow sleep monitoring systems were considered as the primary outcome measures. Revman 5.3 and Stata 16.0 software were used to conduct the meta-analysis. Heterogeneity was examined by using I 2 statistics and publication bias was assessed via Egger's test., Results: Eleven studies involving 775 patients met the inclusion criteria. The results of meta-analysis suggested that acupuncture can increase total sleep time [MD = 55.29, 95%CI (29.16, 81.42), p < 0.01], increase sleep efficiency [MD = 8.96, 95%CI (3.97, 13.95), p < 0.01], decrease wake after sleep onset [MD = -49.54, 95%CI (-82.98, -16.09), p < 0.01], and reduce number of awakening times [MD = -6.29, 95%CI (-10.75, -1.82), p < 0.01] compared with either sham-/placebo-acupuncture or waitlist control. Subsequent analysis indicated a superior effect for verum-acupuncture in comparison with sham-/placebo-acupuncture or waitlist-control when the recommended lowest threshold dosage (12 sessions) was met. Despite positive outcomes, most studies reviewed were heterogeneous and at risk of bias due to methodological issues., Conclusions: Despite limited evidence, acupuncture was significantly associated with improvements in several objective sleep parameters (increases in total sleep time and sleep efficiency, and reductions in wake after sleep onset and number of awakening times) as well as subjective sleep quantity and quality in patients with PI. A minimum therapeutic threshold dosage (≥12 sessions) is recommended. Well-designed RCTs using PSG are required to clarify the influence of acupuncture on sleep architecture/structure and to promote better application of acupuncture as a treatment for PI., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To explore the changes of small-world network properties in patients with primary insomnia based on resting-state functional magnetic resonance imaging (rs-fMRI)., Objective: The rs-MRI data and neurological scale data of 65 patients and 60 matched healthy controls were collected. The brain network was constructed using GRENTA software. SPSS software and network-based statistical analysis methods were used for statistical analysis., Objective: There was no significant difference between the two groups in terms of age, gender or education level ( P > 0.05), but PSQI, HAMA and HAMD scale scores differed significantly between the two groups ( P < 0.05). Both of the groups showed attributes of the small-world network. Compared with the control group, the patients with insomnia showed lower Cp, γ, Eloc, λ, connectivity, and σ of the small world network ( P < 0.05)., Objective: Patients with primary insomnia have lower global and local efficiencies than healthy individuals, and their ability to transmit information on the surface topology is impaired. Our data provide objective imaging evidences for the neuropathological mechanism of patients with primary insomnia.

Transcutaneous auricular vagus nerve stimulation (taVNS) has been reported to be effective in the treatment of primary insomnia (PI); however, its efficacy varies considerably across individuals for reasons that are unclear. In order to clarify the underlying mechanisms, this study investigated the effects of taVNS on spontaneous neuronal activity and autonomic nervous system function by functional magnetic resonance imaging (fMRI) and measurement of heart rate variability (HRV), respectively, in patients with PI. Forty patients with PI were divided into effective (group A) and ineffective (group B) groups based on their response to taVNS as determined by Pittsburgh Sleep Quality Index score reduction rate (group A ≥ 25% and group B < 25%). Spontaneous neuronal activity was measured by fractional amplitude of low-frequency fluctuations (fALFF) and HRV values and was compared between the two groups as well as before vs after taVNS. We then analyzed the correlations among efficacy of taVNS for 4 weeks, the fALFF and HRV values during continuous taVNS state. The results showed that the HRV parameter values (i.e., root mean square of successive differences, percentage of adjacent NN intervals differing by >50 ms, and high frequency) of group A were higher than those of group B during continuous taVNS state. In the fMRI scan, the fALFF values of the right cerebellum, right medial superior frontal gyrus, and bilateral supplementary motor area-which belong to the sensorimotor network (SMN)-were lower in group A than in group B during continuous taVNS state. The correlation analysis revealed that the efficacy of continuous taVNS and HRV and fALFF values were interrelated. These findings demonstrate that differential regulation of the SMN by the autonomic nervous system may be responsible for inter-individual variations in the efficacy of taVNS and suggest that HRV and fALFF are potential biomarkers for predicting PI patients' response to taVNS treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Zhang, Luo, Mai, Hou, Xia, Xu and Liu.)

Primary insomnia (PI), the most common sleep disorder, is primarily characterized by difficulties in initiating and maintaining sleep and deficits in daytime functioning. Study of white matter (WM) connections of the brain might provide valuable information regarding the underlying neural mechanism of PI. Diffusion tensor imaging (DTI) provides non-invasive access to the microstructural and network properties of brain WM, and thus, a great opportunity to quantitatively and sensitively study the human brain. The current literature of PI does not provide a consistent explanation of the etiology and pathology of the disorder; thus, we searched PubMed, EMBASE, and SCOPUS for DTI studies that compared WM integrity or network organization between PI patients and healthy controls to integrate all existing literature as an insight for further studies, and, hopefully, effective prevention and management of the disorder. English peer-reviewed full-text publications that investigated the diffusion indices of PI patients or those with insomnia symptoms compared with a group of healthy controls were included. We included 11 studies and extracted the data for qualitative synthesis. Except for one study, all studies were rated as high-quality, based on quality assessment. In aggregation, a total of 541 patients with PI and 679 healthy controls were included in this study. Our review of DTI studies suggests that WM disruptions in PI are better characterized in the context of neural networks. Frontostriatal, frontothalamic, and corticocortiscal networks, as well as the limbic system, seem to be the main neural networks with microstructural and network alterations in patients with PI. To illustrate, different parts of corona radiate and internal capsule within the corticosubcortical networks and superior longitudinal fasciculus within the corticocortical networks showed altered microstructural properties in PI patients. In view of the fact that the findings from individual studies are heterogeneous, it is difficult to derive consistent findings from the results, and the divergence of the findings must not be disregarded. Thus, this study is a starting point for future studies, and its implications for etiology and pathogenesis of insomnia should be regarded cautiously., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: According to the cognitive processing perspectives, patients with insomnia have insufficient neural management of expressional information. In this study, we compared the pre-attentive processing function of task-irrelevant facial expressions in patients with primary insomnia (PI) and matched healthy controls, with expression-related mismatch negativity (EMMN) elicited by emotional faces as the indicator., Methods: Using three schematic facial expressions (neutral, happy, and sad) as task-irrelevant stimuli, we investigated the visual processing of PI patients (n = 22) and healthy subjects (n = 22) in an expression-related oddball paradigm designed to elicit the visual N170 and EMMN component. After recording and analyzing the electroencephalogram of all participants, amplitude analysis of N170 and EMMN was eventually conducted under corresponding time window., Results: Compared with control group, the amplitude of sad-EMMN component was significantly attenuated in patients with PI, while no remarkable difference was observed under the happy condition. In addition, negative cognitive bias was further validated in the control group, but not presented in the PI group., Conclusion: The current data suggest dysfunctional expressional information processing in PI patients, accompanied by the disorganization of high level perceptual strategy of processing facial emotional expression.

Background: Primary insomnia (PI) is defined as a sleep disorder with no definite cause or inducement. Electroacupuncture, a treatment of inserting needles into specific points on the body surface and applying electrical stimulation, has been proved effective in treating PI with minimal adverse effects. However, the influence of gender difference on the clinical treatment efficacy of electroacupuncture for PI patients remains unclear. Therefore, we designed a clinical trial to compare the clinical treatment efficacy of electroacupuncture for PI patients with different genders. The research on the mechanism of electroacupuncture suggested it could modulate the sleep and wakefulness by activating or deactivating brain regions via a needling/tactile somatosensory specific stimulus. Therefore, we also designed a resting-state functional magnetic resonance imaging (rs-fMRI) study to detect the spontaneous brain activity of PI patients before and after the electroacupuncture treatment., Method: Thirty PI patients were recruited to accept 5-week electroacupuncture treatment on HT-7. Athens Insomnia Scale (AIS) and Pittsburgh sleep quality index (PSQI) questionnaires were used to evaluate the clinical treatment efficacy. Rs-fMRI was employed to observe the spontaneous brain activity in the resting state at the baseline and after 5 weeks of electroacupuncture treatment, which was measured by the fractional amplitude of low-frequency fluctuations (fALFF)., Result: The AIS and PSQI scores were significantly decreased both in the female PI group and the male PI group after treatment. The decreased PSQI of female patients was significantly more than that of male patients (p < .05). The gender-related difference in the cerebral response to electroacupuncture was mainly in posterior cingulate and supramarginal gyrus., Conclusion: There is a gender-related difference in the clinical treatment efficacy of electroacupuncture for PI patients, and female patients may benefit more from electroacupuncture. Gender-related differences in the cerebral response to electroacupuncture may be one of the factors affecting clinical treatment efficacy., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: The aim of this study was to determine the efficacy of exogenous melatonin supplementation for sleep disturbances in patients with middle-aged primary insomnia., Methods: This is a randomized double-blind, placebo-controlled parallel study. Participants were recruited from Tianlin community, Xuhui district, Shanghai. Ninety-seven consecutive middle-aged patients with primary insomnia were randomized to receive 3 mg fast-release melatonin (n = 51) or placebo (n = 46) for four-weeks. Objective sleep parameters tested by overnight polysomnography, subjective sleep performance and daytime somnolence obtained from the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI) and Epworth Sleepiness Scale (ESS) were obtained at baseline and after treatment. Treatment was taken daily 1 h before bedtime. Serious adverse events and side-effects were monitored., Results: Melatonin supplementation significantly decreased early wake time [-30.63min (95% CI, -53.92 to -7.34); P = 0.001] and percentage of N2 sleep [-7.07% (95% CI, -13.47% to -0.68%); P = 0.031]. However, melatonin had no significant effect on other objective sleep parameters including sleep latency, sleep efficiency, wake during the sleep and percent of N1, N3 and REM sleep. Melatonin had no effect on insomnia symptoms and severity on the PSQI [1.53(95% CI, -0.55 to 3.61); p = 0.504]; ISI [0.81 (95% CI, -2.27 to 3.88); p = 0.165] and ESS [-0.83 (95% CI, -3.53 to 1.88); p = 0.147]. No serious adverse events were reported., Conclusions: Melatonin supplementation over a four-week period is effective and safe in improving some aspects of objective sleep quality such as total sleep time, percentage of rapid eye movement and early morning wake time in middle-aged patients with insomnia., Trial Registration: Identifier: ChiCTR-TRC-13003997; Prospectively registered on 2 December 2013., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Studies have explored brain structural abnormalities in patients with primary insomnia (PI). However, most of them are based on volumetric measures, in a specific region of interest, and have small sample sizes. Here, we investigated changes in cortical morphology (thickness and volume) in PI using an advanced surface-based morphometric method. Sixty-seven patients with PI and 55 matched healthy controls were recruited for this study and underwent a structural magnetic resonance imaging scan. The reconstructed cortical surface was processed by Freesurfer 6.0. A general linear model was used to explore group differences in surface-based morphometric features. Furthermore, the association between these cortical features and clinical characteristics were assessed in the PI group. Compared to controls, PI patients showed cortical thickening in the left orbital frontal cortex (OFC), right rostral anterior cingulate cortex (rACC), left middle cingulate cortex (MCC), bilateral insula, left superior parietal lobule (SPL), and right fusiform area (FFA), and showed increased cortical volume in the left OFC, right rACC, bilateral rostral middle frontal gyrus, and right FFA. Cortical thickness in the right OFC and FFA was positively correlated with the severity of insomnia in the PI group, suggesting a right-lateralized relationship. This study was the first to explore multiple-scale cortical morphometric changes in a relatively large sample of PI patients. Our results suggest that hypertrophic cortical morphology may underlie the neuropathology of primary insomnia.

Prospective memory (PM) is essential in everyday life because it concerns the ability to remember to perform an intended action in the future. This ability could be influenced by poor sleep quality, the role of which, however, is still being debated. To examine the role of sleep quality in PM in depth, we decided to perform a retrospective naturalistic study examining different clinical populations with a primary sleep disorder or comorbid low sleep quality. If sleep is important for PM function, we could expect poor sleep to affect PM performance tasks both directly and indirectly. We examined a total of 3600 nights, recorded using actigraphy in participants belonging to the following groups: primary insomnia (731 nights); narcolepsy type 1 (1069 nights); attention deficit hyperactivity disorder (152 nights in children and 239 in adults); severe obesity (232 nights); essential hypertension (226 nights); menopause (143 nights); healthy controls (808 nights). In a naturalistic activity-based PM task, each participant originally wore an actigraph around the non-dominant wrist and was requested to push the event-marker button at two specific times of day: bedtime (activity 1) and get-up time (activity 2). Each clinical group showed significantly lower sleep quality in comparison to the control group. However, only narcolepsy type 1 patients presented a significantly impaired PM performance at get-up time, remembering to push the event-marker button around half the time compared not only to healthy controls but also to the other clinical groups. Overall, the present results seem to point to sleep quality having no effect on the efficiency of a naturalistic activity-based PM task. Moreover, the data indicated that narcolepsy type 1 patients may show a disease-specific cognitive deficit of PM.

Background: Primary insomnia (PI) is characterized by difficulties in initiating sleep or maintaining sleep, which lead to many serious diseases. Acupuncture for PI has drawn attention with its effectiveness and safety. However, the operation of choosing acupoints lacks scientific suggestion. Our trial aims to provide reference and scientific basis for the selection of acupoints and to explore its possible mechanism., Methods: A patient-assessor-blinded, randomized and sham controlled trial was designed to compare the efficacy of 5-weeks acupuncture at a single acupoint, the combination of multi-acupoints, and a sham point. The Pittsburgh sleep quality index and Athens Insomnia Scale questionnaire were used for the primary clinical outcomes, while polysomnography was performed for the secondary clinical outcomes. The resting state functional MRI was employed to detect the cerebral responses to acupuncture. The brain activity in resting state was measured by calculating the fractional amplitude of low-frequency fluctuations (fALFF), which reflected the idiopathic activity level of neurons in the resting state. These results were analyzed by two factorial ANOVA test and post-hoc t-tests., Results: The clinical outcomes suggest that acupuncture could improve clinical symptoms, and the combination of multi-acupoints might lead to a better clinical efficacy. The rs-fMRI results suggested that the brain activity of certain regions was related to the sleep experience, and acupuncture could regulate the activity of these regions. Furthermore, the combination of multi-acupoints could impact more regions which were influenced by the sleep experience., Conclusions: Acupuncture has been proven to be beneficial for PI patients, and the combination of multi-acupoints might improve its efficacy., Trial Registration: This trial has been registered on the U.S. National Library of Medicine (https://clinicaltrials.gov) ClinicalTrials.gov Identifier: NCT02448602 . Registered date: 14/04/2015.

Background: We aimed at evaluating the amplitude changes of the motor evoked potentials (MEPs) induced by of low-frequency (LF) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) in10 patients with primary insomnia (PI) and in 10 age-matched healthy controls., Methods: Median peak-to-peak MEP amplitudes were assessed in all subjects at three times: at baseline (T 0 ), after the first train of a single rTMS session (T 1 ), and after the whole rTMS procedure (T 2 ). This consists of 20 trains of 1 Hz stimulation with 50 stimuli per train and an intertrain interval of 30 s., Results: Resting motor threshold (RMT) and MEPs amplitude did not differ between the two groups at T 0 . A reduction of MEP size was observed at both T 1 and T 2 in all subjects, but this was significantly less pronounced in patients than in control subjects., Conclusions: The lack of MEP inhibition reflects an altered response to LF rTMS in patients with PI. These rTMS findings are indicative of an altered cortical plasticity in inhibitory circuits within M1 in PI. Subjects with PI exhibited an impairment of the LTD-like mechanisms induced by inhibitory rTMS, thus providing further support to the involvement of GABA neurotransmission in the pathophysiology of PI., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The physiological mechanism underlying primary insomnia (PI) is poorly understood. Resting-state functional magnetic resonance imaging (fMRI) has emerged as a powerful tool to explore PI. However, previous studies ignore the dynamics of the brain activity. In the current study, we aimed to explore altered dynamic intrinsic brain activity in PI. Fifty-nine patients with PI and 47 matched healthy controls (HCs) were recruited and underwent resting-state fMRI. The variance of dynamic amplitude of low frequency fluctuation (dALFF) maps across time was calculated to measure the temporal variability of intrinsic brain activity and then compared between patients with PI and HCs. As a result, patients with PI presented increased variance of dALFF in the bilateral hippocampus extending to the parahippocampus, the right putamen and the right anterior insula cortex. In addition, the variance of dALFF in the right putamen was positively correlated with Self-rating Anxiety Scale (SAS) score in PI. Our results revealed increased instability of intrinsic activity in PI., (Copyright © 2020 Meng, Zheng, Liu, Yin, Hua, Fu, Wu and Jiang.)

Objectives: The present study examined the abnormal resting state functional connections (RSFCs) in structural deficit brain regions of primary insomnia (PI) patients., Methods: Thirty-three PI patients and 38 well-matched healthy controls participated in our study. We used voxel-based morphometry and RSFC to study functional connectivity abnormalities of brain regions with structural deficits in PI patients., Results: PI patients showed decreased gray matter (GM) volume in the left dorsolateral prefrontal cortex, left orbitofrontal cortex (OFC), bilateral middle frontal gyrus (MFC), right inferior frontal gyrus (IFG), and left inferior temporal gyrus. Gray matter volume in the right MFC negatively correlated with Self-Rating Scale of Sleep (SRSS) scores, and GM volume in the right IFG negatively correlated with SRSS and Insomnia Severity Index (ISI) scores. Therefore, the right MFC and right IFG were selected as regions of interest for RSFC analysis. PI patients had weakened RSFC between the right inferior parietal gyrus (IPC) and the right MFC compared to the healthy controls and between the left OFC and right IFG. The RSFC between the right MFC and right IPC negatively correlated with SRSS scores. The RSFC between the right IFG and left OFC negatively correlated with SRSS, ISI, SAS, and SDS scores., Conclusions: The present study found structural changes in the right MFC and right IFG accompanied by RSFC changes. This finding may provide novel insights into the neural mechanisms of PI via combining structural and functional modality information., (Copyright © 2020 Xie, Qin, Dong, Wang, Liu, Xue, Hao, Liu, Yuan and Yu.)

Objective: To compare the clinical effect differences among different acupoint selection methods for primary insomnia., Methods: A total of 333 patients with primary insomnia were recruited from 3 study centers and randomly divided into a group A (111 cases, 7 cases dropped off), a group B (111 cases, 5 cases dropped off) and a group C (111 cases, 2 cases dropped off). The patients in the group A were treated with acupuncture at Shenmen (HT 7) and Baihui (GV 20), the patients in the group B were treated with acupuncture at Sanyinjiao (SP 6) and Baihui (GV 20), and the patients in the group C were treated with acupuncture at non-acupoint and Baihui (GV 20). All the treatment was given once a day, 30 min each time; 5 treatments were taken as a course and 5 courses of treatment were given. The Pittsburgh sleep quality index (PSQI) and Athens insomnia scale (AIS) scores were evaluated before and after treatment as well as 4 weeks after treatment. The encephalofluctuograph technology (ET) was observed before and after treatment., Results: Compared before treatment, the PSQI scores after treatment and at follow-up were significantly decreased in three groups ( P <0.01), and the decrease in the group A and the group B was greater than that in the group C ( P <0.01). Compared before treatment, the AIS scores after treatment and at follow-up was significantly decreased in three groups ( P <0.01), and the decrease in the group A was greater than that in the group C ( P <0.05). The interclass and between-groups ET before and after treatment had no significant difference ( P >0.05)., Conclusion: The acupuncture at acupoints along the meridians could improve the sleep quality in patients with primary insomnia, and the therapeutic effect of acupoint along the meridians is better than that of non-acupoint.

Purpose: Insomnia is the most prevalent sleep complaint in the general population but is often intractable due to uncertainty regarding the underlying pathomechanisms. Sleep is regulated by a network of neural structures interconnected with the core nodes of the brain connectome referred to as the "rich club". We examined alterations in brain rich-club organization as revealed by diffusion tensor imaging (DTI) and the statistical relationships between abnormalities in rich-club metrics and the clinical features of primary insomnia (PI)., Methods: This study recruited 43 primary insomnia (PI) patients and 42 age-, sex-, and education level-matched healthy controls (HCs). Differences in global and regional network parameters between PI and healthy control groups were compared by nonparametric tests, and Spearman's correlations were calculated to assess associations of these network metrics with PI-related clinical features, including disease duration and scores on the Pittsburgh Sleep Quality Index, Insomnia Severity Index, Self-Rating Anxiety Scale, and Self-Rating Depression Scale., Results: Weighted white matter networks exhibited weaker rich-club organization in PI patients than HCs across different thresholds (50%, 75%, and 90%) and parcellation schemes [automated anatomical labeling (AAL)-90 and AAL-1024]. Aberrant rich-club organization was found mainly in limbic-cortical-basal ganglia circuits and the default-mode network., Conclusions: Abnormal rich-club metrics are a characteristic feature of PI-related to disease severity. These metrics provide potential clues to PI pathogenesis and may be useful as diagnostic markers and for assessment of treatment response., (Copyright © 2020 Wu, Zhou, Fu, Zeng, Ma, Fang, Yang, Li, Yin, Hua, Liu, Li, Yu and Jiang.)

Primary insomnia (PI) is associated with increased spontaneous neuronal activity. Transcutaneous auricular vagus nerve stimulation (taVNS) modulates brain function, and it is an effective treatment for primary insomnia. However, whether taVNS alleviates insomnia through modulating spontaneous neuronal activity is not fully clarified. This study aims to investigate the instant effect of taVNS in modulating spontaneous neuronal activity in PI patients using resting-state functional magnetic resonance imaging (rs-fMRI). Twenty-two PI subjects underwent rs-fMRI scanning prior and immediately after 30 min treatment of taVNS controlled by twenty healthy adults. Amplitude of low frequency fluctuations (ALFF) analysis was employed to assess the difference in spontaneous neuronal activity between PI patients and healthy adults, as well as between pre-treatment and post-treatment of taVNS. The taVNS-induced altered ALFF brain areas were then selected as regions of interest to perform the resting state functional connectivity (RSFC) analysis in PI patients. The right precuneus showed significantly increased ALFF in PI patients. After immediate taVNS treatment, the ALFF was significantly decreased in the right precuneus and increased in the left middle occipital gyrus. The RSFC in right precuneus with right angular, right superior frontal gyrus, and right middle frontal gyrus was significantly decreased. This study provides insights into the instant brain effects of taVNS on PI patients., (Copyright © 2020 Zhao, Bi, Li, Zhang, Hong, Zhang, He, Fang and Rong.)

Objectives: The placebo response to orexin receptor antagonists in primary insomnia is little-known. Our aim was, therefore, to conduct a systematic review of placebo-controlled randomized clinical trials to characterize placebo response., Methods: We performed a comprehensive literature search for randomized, placebo-controlled, double-blind clinical trials evaluating the efficacy of orexin receptor antagonists addressing primary insomnia. To pool effect size estimates (Cohen's d) of placebo and orexin receptor antagonists across trials for outcome measures, a meta-analysis was done according to the Cochrane guideline., Results: The placebo response was significant and robust to improve the symptoms of insomnia in terms of objective and subjective measures, and the effects (0.70 ± 0.51) in subjective measures were smaller than that (1.10 ± 1.14) in objective measures (p = 0.027). The biphasic feature of placebo response showed an initial short-term increase of placebo effect and subsequent changeless long-term effect., Conclusion: The biphasic feature of placebo response is clinically useful, and neuroimaging is essential to clarify the long-term mechanism in the future., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Objective: To investigate the immediate brain effect of auricular electroacupuncture (EA) in the treatment of primary insomnia (PI)., Methods: In this study, 15 subjects with PI who were diagnosed according to Pitsburgh Sleep Quality Index (PSQI), and other 15 age- and gender-matched subjects without insomnia were recruited in the present study. The PI patients received EA (4 Hz/20 Hz, a tolerable electrical current strength) of auricular concha for 30 min, and their resting state functional magnetic resonance imaging (fMRI) data before and after treatment were collected. The healthy subjects received no any treatment and their resting state fMRI data were collected. The diffe-rence of default mode network functional connectivity between the patients and healthy subjects, and changes of the patient's brain functional connectivity after EA treatment were estimated by using seed-point-based analysis (SPBA)., Results: Analysis by taking the posterior cingulate gyrus as the seed-point showed that compared with the healthy participants before treatment, the patient's brain functional connectivity between the posterior cingulate gyrus and the right insula, or the inferior frontal gyrus of the right opercularis region, or the right rolandic operculum was increased. After 30 minutes' EA treatment, the functional connectivity between the posterior cingulate gyrus and the precuneus, the left angular gyrus, the left frontal superior gyrus, the left frontal middle cortex, the right temporalis inferior gyrus, the right temporalis middle gyrus or the left medial orbitofrontal cortex was decreased, while the functional connectivity between the posterior cingulate gyrus and the right lingual gyrus, or the cortex surrounding the right calcarine fissure was increased., Conclusion: EA of auricular concha has an instant effect in modulating the brain default mode network in PI patients, which may be its brain mechanism underlying improvement of PI.

Purpose: Individuals with primary insomnia frequently report cognitive impairment as a next-day consequence of disrupted sleep. Studies attempting to quantify daytime impairment objectively in individuals with insomnia have yielded mixed results, with evidence suggesting impairments in aspects of executive functioning but not psychomotor vigilance. It has been suggested that persons with insomnia may have latent performance deficits for which they would be able to compensate effectively under normal daytime circumstances - suggesting that any such deficits may be exposed through perturbation. In this context, we used a laboratory-based total sleep deprivation (TSD) paradigm to investigate psychomotor vigilance performance in individuals with chronic sleep-onset insomnia as compared to healthy normal controls., Participants and Methods: Fourteen participants, seven individuals with chronic sleep-onset insomnia (ages 24-40y) and seven age-matched, healthy normal sleepers completed a highly controlled in-laboratory study involving 38 h of TSD. A 10 min and a 3 min version of the psychomotor vigilance test (PVT) were administered every 3 h during TSD., Results: In both the individuals with sleep-onset insomnia and the age-matched normal sleepers, lapses of attention and false starts on the PVT were relatively infrequent during the first 16 h of the TSD period, but increased significantly when wakefulness was extended beyond 16 h. However, the effects of TSD on PVT performance were considerably exacerbated in the sleep-onset insomnia group, which showed about twice as many lapses of attention, more than twice as many false starts, and approximately twice as big a time-on-task effect on the 10 min PVT as the age-matched normal sleepers group, with similar findings on the 3 min PVT., Conclusion: These findings indicate that daytime impairment reported by individuals with sleep-onset insomnia has an objective performance component that is exposed during TSD. Thus, persons with sleep-onset insomnia could be at increased risk of performance impairment in settings that involve extended wakefulness. This underscores the importance of treating insomnia and suggests that laboratory sleep deprivation studies could serve to document the effectiveness of treatment approaches., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Hansen et al.)

Purpose: This study aims to obtain consensus statements required for the development of clinical guidelines for the use of benzodiazepines (BZDs) and Z-drugs for the management of primary insomnia in adults in Saudi Arabia., Methods: Three rounds of the e-Delphi technique using a Bristol Online Survey (BOS) were conducted between May and August 2018. The Director of the Saudi Sleep Medicine Group helped recruit the country's sleep medicine experts. Snowballing was used to forward invitation emails, information sheets, and the survey to known sleep medicine experts and physicians deemed to be interested in the field. All participants' details were anonymised except to the researcher., Results: Fifteen experts from four different regions and specialities in Saudi Arabia participated in Round 1. Twenty-one statements originated from participants' responses. In Round 2, there were 17 respondents and 16 of the statements obtained the required consensus of 70% or higher. Eleven experts participated in Round 3 and eight statements received 100% agreement, two received 91%, and six received 82%. Having obtained the required consensus of 80% or higher in Round 3, these 16 statements fulfilled the criteria to be included in future guidelines. The five statements that failed to attain the required consensus were rejected as inappropriate for inclusion in Saudi Arabian clinical guidelines., Conclusions: The items that achieved the required consensus can be included in future guidelines for the use of BZDs and Z-drugs in the treatment of primary insomnia in adults to standardize best practices in sleep medicine in Saudi Arabia.

Objective: To observe the clinical effect of "Yinqi Guiyuan" needling in the treatment of primary insomnia., Methods: A total of 79 primary insomnia outpatients were randomly divided into treatment group ( n =40) and control group ( n =39). The patients in the control group were given oral Estazolam tablets once a day, for successive 4 weeks. For patients of the treatment group, Zhongwan (CV12), Xiawan (CV10), Qihai (CV6), Guanyuan (CV4), Baihui (GV20), etc., were punctured with filiform needles for 30 min. The treatment was conducted three times per week for 4 successive weeks. The sleep quality (sleeping quality, falling asleep time, sleep duration, sleep efficiency, sleep disorders, hypnotic and daytime dysfunction, 0 to 21 points) was evaluated by using Pittsburgh Sleep Quality Index (PSQI). The severity of insomnia (self-perception, sleep satisfaction, daytime function damage, sensibility change, and concern for sleep problems, 0 to 28 points) was assessed using insomnia severity index (ISI) score. The therapeutic effect was evaluated according to the PSQI score reduction rate = (pre-treatment PSQI score-post-treatment PSQI score)/pre-treatment PSQI score ×100%., Results: After treatment, the total score of PSQI, ISI and the score of each item were all significantly reduced in the two groups relevant to their own pre-treatment ( P <0.05). The total score, and scores of hypnotic and daytime dysfunction were significantly lower in the treatment group than in the control group ( P <0.05). Of the 40 and 39 cases in the treatment and control groups, 5 (12.50%) and 4 (10.25%) were cured, 20 (50.00%) and 18 (46.15%) experienced marked improvement, 12 (30.00%) and 13 (33.33%) were effective, and 3 (7.50%) and 4 (10.25%) ineffective, with the total effective rate being 92.50% and 89.74%, respectively. No significant difference was found between the two groups in the effective rate ( P >0.05)., Conclusion: "Yinqi Guiyuan" needling and Estazolam are comparable in treatment primary insomnia, and the former is superior to the latter in avoiding hypnotic drug use and in improving daytime function.