[Clinical efficacy of shallow-needle therapy combined with estazolam on insomnia of liver stagnation transforming into fire pattern: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of shallow-needle therapy combined with estazolam on insomnia differentiated as liver stagnation transforming into fire and its effect on adrenocorticotropic hormone (ACTH) and cortisol (CORT), so as to explore the mechanism of this combined treatment. METHODS: A total of 119 patients with insomnia of liver stagnation transforming into fire pattern were randomly divided into shallow-needle therapy group (n=40), medication group (n=39), and shallow-needle therapy combined with medication group (combined therapy group,n=40). In the shallow-needle therapy group, the patients were treated with finger pressure and operation with shallow stimulating at Zhenjing (Dong's extra point, sedative point) and Taichong (LR3). In the medication group, the patients were administered with estazolam (1 mg) orally. In the combined therapy group, both shallow-needle therapy and medication were administered. The treatment was given once daily in each group, 10 days as one session of treatment and 2 sessions were required. Before and after the treatment, Pittsburgh sleep quality index scale (PSQI) and Self-rating anxiety scale (SAS) were used to assess sleep and anxiety status. ELISA was used to detect the contents of ACTH and CORT in plasma. The clinical efficacy was evaluated in each group. RESULTS: In within-group comparison, PSQI scores, SAS scores and the concentrations of ACTH and CORT in plasma were all decreased (P<0.05) after treatment for the patients of three groups. After treatment, the total PSQI score, the score for sleep latency, sleep duration and daytime dysfunction, as well as SAS score in the combined therapy group were all lower than those of the shallow-needle therapy group (P<0.05); the total PSQI score, the score for sleep duration and sleep efficiency, as well as SAS score were lower when compared with the medication group (P<0.05). The total effective rates were 87.50% (35/40), 82.05% (32/39) and 95.00% (38/40) in the shallow-needle therapy group, the medication group and the combined therapy group, respectively. The total effective rate in the combined therapy group was higher than those of the shallow-needle therapy group and the medication group separately (P<0.05). CONCLUSION: Shallow-needle therapy combined with estazolam is effective on insomnia of liver stagnation transforming into fire pattern, and its underlying effect mechanism is related to the reduction of plasma ACTH and CORT levels.

[Effect of acupuncture and estazolam on episodic memory and sleep structure in patients with chronic insomnia disorder: a randomized controlled trial].

OBJECTIVE: To compare the effect on chronic insomnia disorder (CID) and influences on episodic memory and sleep structure between acupuncture and estazolam tablets. METHODS: A total of 140 CID patients were randomized into a meridian-point group (46 cases, 1 case dropped off), a non-meridian-and-non-acupoint group (47 cases, 2 cases dropped off) and a medication group (47 cases, 2 cases dropped off). In the meridian-point group, Baihui (GV 20), Shenmen (HT 7), Sanyinjiao (SP 6), Zhaohai (KI 6) and Shenmai (BL 62) were selected and the routine acupuncture was applied. In the non-meridian-and-non-acupoint group, the needling technique was same as the meridian-point group. Acupuncture was given once daily for 4 weeks in the above two groups. In the medication group, estazolam tablets were administered orally, taken 1 to 2 mg per night, consecutively for 4 weeks. Before and after treatment, the changes in the following indexes were observed in each group, i.e. the score of insomnia severity index (ISI), the score of auditory verbal memory test (AVMT) and the relevant indexes of sleep structure [total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), sleep efficiency (SE) and the percentage of non rapid eye movement phase 1, 2 and 3 (N1, N2 and N3) and rapid eye movement time (REM) in TST]. RESULTS: After treatment, ISI scores were reduced in the meridian-point group and the medication group (P<0.01), the score in the meridian-point group was lower than the medication group and the non-meridian-and-non- acupoint group respectively (P<0.01) and that in the medication group was lower than the non-meridian-and-non-acupoint group (P<0.01). After treatment, the score of each of immediate recall, short-term delayed recall, long-term delayed recall and delayed recognition of AVMT was increased in the meridian-point group and the medication group respectively (P<0.01, P<0.05) and the score of each item of AVMT in the meridian-point group was higher than the medication group and the non-meridian-and-non-acupoint group respectively (P<0.01, P<0.05). The scores of immediate memory and delayed recognition in the medication group were higher than the non-meridian-and-non-acupoint group respectively (P<0.01). After treatment, SOL, WASO and N1% were all reduced (P<0.01) and TST, SE, N3% and REM% were all increased (P<0.01, P<0.05) in the meridian-point group and the medication group, N2% in the meridian-point group was reduced (P<0.01). After treatment, N1% and N2% in the meridian-point group were lower than the medication group (P<0.01) and N3% and REM% were higher than the medication group (P<0.01). After treatment, TST, SE and N3% in the meridian-point group and the medication group were all higher than the non-meridian-and-non-acupoint group respectively (P<0.01, P<0.05) and SOL, WASO and N1% were lower than the non-meridian-and-non-acupoint group respectively (P<0.01). REM% in the meridian-point group was also higher than the non-meridion-and-non-acupoint group (P<0.01), and N2% in the meridian-point group was also lower than the non-meridian-and-non-acupoint group (P<0.01). CONCLUSION: Compared with estazolam, acupuncture much better improves sleep quality and episodic memory in patients with chronic insomnia disorder, which is possibly related to the regulation of sleep structure of patients in treatment with acupuncture.

[Yinyang Ruyin acupuncture on refractory insomnia: a randomized controlled trial].

OBJECTIVE: To compare the therapeutic effect of Yinyang Ruyin acupuncture, conventional acupuncture and oral estazolam tablet on refractory insomnia. METHODS: A total of 180 patients with refractory insomnia were randomized into a Yinyang Ruyin acupuncture group, a conventional acupuncture group and a medication group, 60 cases in each group. In the Yinyang Ruyin acupuncture group, Yinyang Ruyin acupuncture was applied at Baihui (GV 20), Waiguan (TE 5), Neiguan (PC 6), Weishu (BL 21), Zhongwan (CV 12) and Taixi (KI 3); in the conventional acupuncture group, conventional acupuncture was applied at Baihui (GV 20), Shenmen (HT 7), Sanyinjiao (SP 6), Zhaohai (KI 6), Shenmai (BL 62) and Anmian (Extra). Supplementary acupoints were added according to different patterns in the two acupuncture groups, and the treatment was given once a day, 7 times as one course and 4 courses were required. In the medication groups, estazolam was taken orally 1 h before sleep, 1 mg each time, once a day for 4 weeks. The Pittsburgh sleep quality index (PSQI) score was observed before and after treatment and the therapeutic effect was evaluated in the 3 groups. RESULTS: The total effective rates in the Yinyang Ruyin acupuncture group and the conventional acupuncture group were 90.0% (54/60) and 83.3% (50/60), which were superior to 30.0% (18/60) in the medication group (both P<0.05). Compared before treatment, the PSQI scores were significantly reduced in the two acupuncture groups (all P<0.05), the sleep efficiency and the total score of PSQI were reduced in the medication group (both P<0.05). After treatment, the changes of sleep latency, sleep efficiency, sleep disorder, daytime function and total score of PSQI in the Yinyang Ruyin acupuncture group were significantly larger than those in the conventional acupuncture group (all P<0.05). The changes of PSQI scores in the Yinyang Ruyin acupuncture group were significantly larger than the medication group (all P<0.05). The changes of sleep quality, sleep latency, sleep time, sleep disorder, daytime function and total score of PSQI in the conventional acupuncture group were significantly larger than the medication group (all P<0.05). CONCLUSION: The therapeutic effect of Yinyang Ruyin acupuncture on refractory insomnia is superior to estazolam and conventional acupuncture.

Clinical effectiveness of Tui Na for insomnia compared with estazolam: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The purpose of this systematic review (SR) is to evaluate the effectiveness and safety of Tui Na therapy for insomnia. METHODS: Two authors separately searched PubMed, the Cochrane Library, EMBASE, SinoMed Database, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science Technology Journal Database, related SR and published protocols at the same time to find randomized controlled trials (RCTs), which compared Tui Na therapy with estazolam therapy for insomnia, from their inception to January1st 2019. Screening documents, data extraction, quality assessment of methodology and quality assessment of evidence were also conducted by two authors separately at the same time. We used Cochrane Risk of Bias tool to assess the methodological quality of included RCTs. The results of meta-analysis were made via RevMan software (5.3). The quality of evidence was assessed by on-line GRADEpro. The primary outcome: Pittsburgh Sleep Quality Index (PSQI) score, the secondary outcome: clinical effectiveness rate and the safety index: adverse events. The clinical effectiveness of these included RCTs all focused on the improvement of patients' satisfaction with sleep time and sleep quality. RESULTS: We included 22 RCTs(1,999 participants), meeting the inclusion and exclusion criteria. The assessment of methodological quality was not satisfied, in which "high risk", "unclear risk" and "low risk" all existed. The results of meta-analysis demonstrated that (1)for primary outcome, the PSQI score of Tui Na therapy was lower than that of estazolam therapy after treatment in subgroup1(Head)(MD-2.39,95%CI[-3.79,-0.98],I2 = 82%,n = 291,3 trials) and subgroup4(Abdomen)(MD-1.7,95%CI[-2.53,-0.87],I2 = 0%,n = 120,2 trials);while there was no significant difference between Tui Na therapy and estazolam therapy in subgroup2(Head and trunk)(MD-1.39,95%CI[-3.03,0.24],I2 = 90%,n = 200, 2 trials) and subgroup3(Head, trunk and extremities)(MD-0.51,95%CI[-1.53,0.5],I2 = 30%,n = 126,2 trials).(2) for secondary outcomes(the clinical effectiveness rate and safety index),the clinical effectiveness rate of Tui Na therapy was higher than that of estazolam therapy after treatment in subgroup1(Head)(RR1.21,95%CI[1.05,1.39],I2 = 26%,n = 239,3 trials), subgroup2(Head and trunk)(RR1.15,95%CI[1.08,1.23],I2 = 33%,n = 1024,10 trials) and subgroup4(Abdomen)(RR1.12,95%CI[1.01,1.23],I2 = 0%,n = 180,3 trials); while there was no significant difference between Tui Na therapy and estazolam therapy in subgroup3(Head, trunk and extremities)(RR1.03,95%CI[0.94,1.13],I2 = 28%,n = 346,4 trials).Safety index, 5 RCTs reported adverse events. Among them, only 1 RCT reported adverse event in Tui Na therapy, which was daytime drowsiness; all 5 RCTs reported adverse events in estazolam therapy, which were dry mouth, dizziness, daytime drowsiness etc. The evidence quality was generally low to very low. CONCLUSION: Tui Na therapy appeared to be superior to estazolam therapy in treating areas(head; abdomen), while there was no significant difference between Tui Na therapy and estazolam therapy in treating areas(head and trunk; head, trunk and extremities). No serious adverse event was reported in Tui Na therapy. However the methodological quality and evidence quality were not satisfied. Therefore we could not make a convincing conclusion on the effectiveness and safety of Tui Na therapy for insomnia. Practitioners should combine their experience, evidence of our review and patients' preferences to make a proper treatment. And more high quality RCTs and well-designed protocols of Tui Na therapy for insomnia are needed in the future.

The anxiolytic-like effects of estazolam on a PTSD animal model.

Post-traumatic stress disorder (PTSD) is a serious psychiatric disorder. Estazolam has been shown to produce anxiolytic-, hypnotic-, amnestic-, and sedative-like effects. However, few studies are concerned about its anti-PTSD-like effects. The anti-PTSD-like effects of estazolam were evaluated by single prolonged stress animal model. After exposure to single prolonged stress, rats (Sprague-Dawley, male, 8 weeks) were administered by estazolam (0.5, 1 and 2 mg/kg, i.p.) from day 2 to 13 once daily. The behavioral assessments were performed during treatment with drugs. After the behavioral evaluation, the role of allopregnanolone in the anti-PTSD-like effects of estazolam was also evaluated via astrocyte cells and brain tissues (e.g. prefrontal cortex, hippocampus, and amygdala). The PTSD-like behavioral deficits were significantly blocked by estazolam (1 and 2 mg/kg, i.p.) without affecting locomotor activity. Consistently, the levels on allopregnanolone were increased by estazolam (1 and 2 mg/kg, i.p.) in prefrontal cortex, hippocampus, and amygdala. The levels of allopregnanolone were increased by sertraline (1 µmoL/L) and estazolam (4 µmoL/L), while the effects were antagonized by trilostane (1 µmoL/L) and finasteride (1 µmoL/L) in astrocyte cells, respectively. Collectively, the anxiety-like behavior deficits were ameliorated by estazolam in the single prolonged stress animal model that was associated with biosynthesis of allopregnanolone.

["Governor vessel daoqi method of acupuncture" combined with estazolam for insomnia: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy differences between "governor vessel daoqi method of acupuncture" combined with estazolam and estazolam alone for insomnia. METHODS: Seventy patients of insomnia were randomly divided into an observation group and a control group, 35 cases in each one. The patients in the control group were treated with oral administration of estazolam, 2 mg each time; the estazolam was taken 30 min before sleeping. The patients in the observation group were treated with "governor vessel daoqi method of acupuncture" combined with estazolam; the positive reaction points along governor vessel and Baihui (GV 20) were selected as the main points. The acupuncture was given for 30 min per treatment, once every two days. Both groups were treated for four weeks. Pittsburgh sleep quality index (PSQI) and polysomnography (PSG) were observed before and after treatment. Clinical efficacy was assessed between the two groups and adverse reactions were recorded. RESULTS: The total effective rate was 94.3% (33/35) in the observation group, which had no significant difference with 82.9% (29/35) in the control group (P>0.05). The cured and markedly effective rate was 71.4% (25/35) in the observation group, which was superior to 42.9% (15/35) in the control group (P<0.05). Each item score and total score of PSQI were decreased obviously after treatment in the observation group (all P<0.05), while the score of sleep latency, sleep duration and sleep efficiency as well as total score of PSQI were decreased obviously after treatment in the control group (all P<0.05). The scores of sleep duration, sleep disturbance and day dysfunction due to sleepiness as well as total score of PSQI in the observation group were lower than that in the control group (all P<0.05). After treatment, the PSG-related parameters of total sleeping duration, sleeping latency, sleeping arousal and sleeping efficiency were improved significantly in the observation group (all P<0.05); the total sleeping duration, sleeping arousal and sleeping efficiency were also improved in the control group (all P<0.05). The total sleeping duration, sleeping latency, sleeping arousal and sleeping efficiency in the observation group were superior to those in the control group (all P<0.05). 4 adverse reactions in the observation group and 3 adverse reactions in the control group were observed. CONCLUSION: "Governor vessel daoqi method of acupuncture" combined with estazolam could significantly improve insomnia, which are superior to estazolam alone.

[Regulation action and nerve electrophysiology mechanism of acupuncture on arousal state in patients of primary insomnia].

OBJECTIVE: To compare the difference between acupuncture and estazolam on arousal state in patients of primary insomnia, and to explore its nerve electrophysiology mechanism. METHODS: Sixty-four patients of primary insomnia were randomized into an acupuncture group (32 cases) and a medication group (32 cases). After 3 patients were excluded, 31 cases in the acupuncture group and 30 cases in the medication group were included. Patients in the acupuncture group were treated with acupuncture at Sishencong (EX-HN 1), Anmian (Extra), Shenmen (HT 7), Sanyinjiao (SP 6), Zhaohai (KI 6), Shenmai (BL 62) as main acupoints, combined with supporting acupoints, once a day, five times per week, continuously for 4 weeks. Patients in the medication group were treated with oral administration of estazolam, once a day, continuously for 4 weeks. The Pittsburgh sleep quality index (PSQI) and mean sleep latency (MSL) of multiple sleep latency test (MSLT) were compared before and after treatment in the two groups; the polysomnography (PSG) was applied to monitor the indices regarding sleep structure. RESULTS: Compared before treatment, PSQI score was reduced after treatment in the two groups (both P<0.01), which was more significant in the acupuncture group (P<0.05). Compared before treatment, sleep onset latency (SOL), number of awakenings (NWAK) and wake after sleep onset (WASO) were reduced, while total sleep time (TST) and sleep efficiency (SE) were significantly increased in the two groups after treatment (all P<0.01). Compared before treatment, the percentage of non-rapid eye movement period 1/2/3 (N1, N2, N3) and the percentage of rapid eye movement period (REM) to TST were not significantly changed after treatment in the medication group (all P>0.05). Compared before treatment, the percentage of N1, N2 to TST was reduced, while the percentage of N3 and REM to TST was increased after treatment in the acupuncture group (P<0.01). The SOL, NWAK, WASO, TST, SE were not statistically changed after treatment in each group (all P>0.05). Compared with the medication group, the percentage of N1 and N2 was reduced while that of N3 and REM was increased after treatment in the acupuncture group (all P<0.01). After treatment, MSL of MSLT were obviously decreased in the two groups (both P<0.01), which were more significant in the acupuncture group (P<0.05). CONCLUSIONS: Acupuncture can more effectively improve sleep quality of primary insomnia than estazolam, and is more beneficial for regulation of hyperarousal state.

Chinese herbal medicine for menopausal symptoms.

BACKGROUND: Chinese herbal medicine (CHM) usage is expected to increase as women suffering from menopausal symptoms are seeking alternative therapy due to concerns from the adverse effects (AEs) associated with hormone therapy (HT). Scientific evidence for their effectiveness and safety is needed. OBJECTIVES: To evaluate the effectiveness and safety of CHM in the treatment of menopausal symptoms. SEARCH METHODS: We searched the Gynaecology and Fertility Group's Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), MEDLINE, Embase, CINAHL, AMED, and PsycINFO (from inception to March 2015). Others included Current Control Trials, Citation Indexes, conference abstracts in the ISI Web of Knowledge, LILACS database, PubMed, OpenSIGLE database, and China National Knowledge Infrastructure database (CNKI, 1999 to 2015). Other resources included reference lists of articles as well as direct contact with authors. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effectiveness of CHM with placebo, HT, pharmaceutical drugs, acupuncture, or another CHM formula in women over 18 years of age, and suffering from menopausal symptoms. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed 864 studies for eligibility. Data extractions were performed by them with disagreements resolved through group discussion and clarification of data or direct contact with the study authors. Data analyses were performed in accordance with Cochrane Collaboration guidelines. MAIN RESULTS: We included 22 RCTs (2902 women). Participants were from different ethnic backgrounds with the majority of Chinese origin.When CHM was compared with placebo (eight RCTs), there was little or no evidence of a difference between the groups for the following pooled outcomes: hot flushes per day (MD 0.00, 95% CI -0.88 to 0.89; 2 trials, 199 women; moderate quality evidence); hot flushes per day assessed by an overall hot flush score in which a difference of one point equates to one mild hot flush per day (MD -0.81 points, 95% CI -2.08 to 0.45; 3 RCTs, 263 women; low quality evidence); and overall vasomotor symptoms per month measured by the Menopause-Specific Quality of Life questionnaire (MENQOL, scale 0 to 6) (MD -0.42 points; 95% CI -1.52 to 0.68; 3 RCTs, 256 women; low quality evidence).In addition, results from individual studies suggested there was no evidence of a difference between the groups for daily hot flushes assessed by severity (MD -0.70 points, 95% CI -1.00, -0.40; 1 RCT, 108 women; moderate quality evidence); or overall monthly hot flushes scores (MD -2.80 points, 95% CI -8.93 to 3.33; 1 RCT, 84 women; very low quality evidence); or overall daily night sweats scores (MD 0.07 points, 95% CI -0.19 to 0.33, 1 RCT, 64 women; low quality evidence); or overall monthly night sweats scores (MD 1.30 points, 95% CI -1.76 to 4.36, 1 RCT, 84 women; very low quality evidence). However one study using the Kupperman Index reported that overall monthly vasomotor symptom scores were lower in the CHM group (MD -4.79 points, 95% CI -5.52 to -4.06; 1 RCT, 69 women; low quality evidence).When CHM was compared with hormone therapy (HT) (10 RCTs), only two RCTs reported monthly vasomotor symptoms using MENQOL. It was uncertain whether CHM reduces vasomotor symptoms (MD 0.47 points, 95% CI -0.50 to 1.44; 2 RCTs, 127 women; very low quality evidence).Adverse effects were not fully reported in the included studies. Adverse events reported by women taking CHM included mild diarrhoea, breast tenderness, gastric discomfort and an unpleasant taste. Effects were inconclusive because of imprecise estimates of effects: CHM versus placebo (RR 1.51; 95% CI 0.69 to 3.33; 7 trials, 705 women; I² = 40%); CHM versus HT (RR 0.96; 95% CI 0.66 to 1.39; 2 RCTs, 864 women; I² = 0%); and CHM versus specific conventional medications (such as Fluoxetine and Estazolam) (RR 0.20; 95% CI 0.03 to 1.17; 2 RCTs, 139 women; I² = 61%). AUTHORS' CONCLUSIONS: We found insufficient evidence that Chinese herbal medicines were any more or less effective than placebo or HT for the relief of vasomotor symptoms. Effects on safety were inconclusive. The quality of the evidence ranged from very low to moderate; there is a need for well-designed randomised controlled studies.

Dependence, misuse, and beliefs regarding use of hypnotics by elderly psychiatric patients taking zolpidem, estazolam, or flunitrazepam.

INTRODUCTION: To examine the prevalence rates and correlates of dependence on, misuse of, and beliefs regarding use of hypnotics in elderly psychiatric patients with long-term use of zolpidem, estazolam, or flunitrazepam. METHODS: A total of 139 psychiatric outpatients 65 or more years of age who used zolpidem, estazolam, or flunitrazepam for at least 3 months were studied. The levels of hypnotic dependence and beliefs regarding hypnotic use (necessity and concern) were assessed. Three patterns of hypnotic misuse in the past 1 month were also explored. The correlates of high dependence, misuse, and unfavorable attitude and high concern toward hypnotic use were examined using logistic regression analyses. RESULTS: A total of 28.8%, 7.9%, 12.2%, and 22.3% of participants reported high dependence on, misuse of, unfavorable attitude toward, and high concern toward hypnotic use, respectively. Males were more likely to report unfavorable attitude toward hypnotic use than females. Elders with significant depression were more likely to report high concern toward hypnotic use than those without significant depression. Elders with high concern toward hypnotic use were more likely to report high dependence on hypnotics than those with low concern. Elders with significant depression and taking zolpidem were more likely to misuse hypnotics than those without significant depression and taking estazolam or flunitrazepam, respectively. DISCUSSION: Clinicians should monitor the possibility of dependence on and misuse of hypnotics among elderly psychiatric patients who had the correlates identified in this study.

Low Resistance Thought Induction Sleep-regulating Technique (TIP3-2) combined with medication for primary insomnia: a randomized controlled trial.

BACKGROUND: Cognitive behavioral therapy for insomnia (CBT-I) is well-validated in the western countries. However, it has not been widely adopted or disseminated in China. One possibility is that therapeutic approaches drawn from traditional Chinese medicine (TCM) will be more widely accepted. PURPOSE: This study aimed to evaluate the efficacy of medication in combination with a therapeutic approach drawn from TCM, Low Resistance Thought Induction Sleep-regulating Technique (TIP3-2), for acute treatment of insomnia. METHOD: A randomized controlled trial was conducted. Ninety primary insomnia patients were randomly assigned to receive TIP3-2 combined with medication (n = 45) or medication only (n = 45) for 4 weeks. Medication consisted of 1-2 mg Estazolam nightly. On the basis of taking Estazolam, TIP3-2 combined with medication group was given Low Resistance Thought Induction Sleep-regulating Technique (TIP3-2) treatment twice a week. Outcomes were assessed with the Pittsburgh sleep quality index (PSQI) and polysomnography (PSG) before and after treatment. RESULTS: Both groups demonstrated significant improvements in the PSQI and polysomnography indices. The TIP3-2+ medication group demonstrated a significant difference between the two groups in PSQI total score, sleep medication use, daytime dysfunction, subjective sleep quality, as well as polysomnography indices of sleep efficiency and awakening times (P < 0.05). CONCLUSION: Among patients with primary insomnia, the addition of TIP3-2 provided benefits above and beyond the role of medication alone.

Trends in anxiolytic-hypnotic use and polypharmacy in Taiwan, 2002-2009: a nationwide, population-based survey.

OBJECTIVES: Use of anxiolytics-hypnotics, including benzodiazepines and "z" hypnotics, is a public health concern. This study aimed to investigate the trends in prevalence of anxiolytic-hypnotic drug use and polypharmacy (simultaneous use of two or more anxiolytics-hypnotics) in Taiwan. METHODS: A dynamic sample of one million individuals who were randomly selected from the National Health Insurance database was used to detect populationwide trends in the use of anxiolytics-hypnotics in Taiwan between 2002 and 2009. The analyses included drugs that are administered orally, intravenously, or intramuscularly as well as single or compound drugs. The authors identified the number of individuals who used the drugs, the sum of days of reported drug use for all individuals (person-days), and the distribution of anxiolytic-hypnotic polypharmacy for all claims for ambulatory, pharmacy, and hospital care. RESULTS: Annual prevalence of any anxiolytic-hypnotic use in Taiwan was higher than 20%. The number of person-days greatly increased from 2002 (4.0%) to 2009 (6.6%). The increases in use between 2002 and 2009 were greatest for clonazepam (prevalence, 7% versus 1.8%; person-days, .2% versus .6%) and zolpidem (prevalence, 2.4% versus 4.2%; person-days, .5% versus 1.5%). Polypharmacy accounted for almost 70% of all person-days of anxiolytic-hypnotic use. CONCLUSIONS: This nationwide, population-based survey presents real-world epidemiological evidence about anxiolytic-hypnotic use. The adverse effects of the long-term use of anxiolytics-hypnotics have been established, and unnecessary use of these drugs, particularly in polypharmacy regimens, should be avoided.

Efficacy of repetitive transcranial magnetic stimulation in the treatment of patients with chronic primary insomnia.

This study assessed the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of patients with chronic primary insomnia. Hundred and twenty patients with chronic primary insomnia were randomly assigned to three study groups (n = 40 per group): rTMS, medication, or psychotherapy treatment (both latter as controls). The treatments proceeded for 2 weeks, after which treatment efficacies were assessed in each study group based on changes in polysomnography parameters, Pittsburgh sleep quality index, and indices of HPA and HPT axes (serum cortisol, adrenocorticotropic hormone, highly sensitive thyrotropin, free T3, and free T4). Further, the relapse and recurrence rates within 3 months after respective treatments were also measured. rTMS treatment significantly better (p < 0.05) improved stage III sleep and REM sleep cycle compared with both control groups. Further, rTMS treatment group was more advantageous in improving the indices of HPA and HPT axes (p < 0.05 vs. both control groups). In addition, the relapse and recurrence rates were also the lowest in rTMS treatment group. In conclusion, rTMS treatment is more advantageous than both medication and psychotherapy treatments in improving the sleep architecture. Further, rTMS significantly decreases the body awakening level and provides a better long-term treatment effect.

A randomized, double-blind, double-dummy, multicenter, controlled trial on brotizolam intervention in outpatients with insomnia.

AIM: To investigate the efficacy and safety of brotizolam in outpatients with insomnia. METHODS: This randomized, double-blind, double-dummy, multicenter, controlled trial recruited 253 outpatients randomized to receive either brotizolam (n = 126) or estazolam (n = 127) for 14 days followed by 1 week of follow-up for rebound detection. Sleep Dysfunction Rating Scale (SDRS) and Clinical General Impression Scale were applied for efficacy evaluation. Safety evaluation was based on data regarding vital signs, physical examination, lab tests, ECG and collection of adverse events. RESULTS: Full Analyses Set (FAS) and Safety Set (SS) included data of 251 subjects, with 126 from brotizolam group and 125 from estazolam group. Per Protocol Set (PPS) analysis included data of 235 subjects, with 121 and 114 from each group. After 14 days of treatment, there was no difference with statistical significance between the two groups regarding SDRS total score change from baseline. FAS and PPS analysis showed that the brotizolam is non-inferior to estazolam in efficacy evaluation. There was also no difference with statistical significance regarding rebound rate between brotizolam and estazolam group in FAS. The rate of adverse event in two groups was with no statistically significant difference in SS. CONCLUSION: Brotizolam is effective and safe in relieving the symptoms of insomnia.

The XIA's No. 1 sleeping Prescription for the treatment of insomnia of the deficiency type: a clinical observation of 60 cases.

OBJECTIVE: To evaluate the therapeutic effects and safety of the XIA's No.1 Sleeping Prescription for the treatment of insomnia of the deficiency type. METHODS: 120 cases conformed to the diagnostic criteria of the Chinese Classification of Mental Disorders-Version 3 (CCMD-3) and were diagnosed as having insomnia of the deficiency type were divided randomly into a treatment group and a control group, 60 cases in each group. The treatment group was treated with the XIA's No. 1 Sleeping Prescription, while the control group was given estazolam (1 mg) for 6 weeks. The Athens Insomnia Scale (AIS) was used to evaluate the clinical therapeutic effects, while the treatment emergent symptom scale (TESS) was used to evaluate adverse reactions. RESULTS: The total effective rate of the treatment group (80%) was higher than that of the control group (70%), but with no significant difference (P > 0.05). The effective rate for long-term insomnia was 77.8% in the treatment group and 52.4% in the control group, with a significant difference between the two groups (P < 0.05). The adverse reactions shown in the treatment group were obviously fewer and milder than those in the control group. CONCLUSION: The XIA's No. 1 Sleeping Prescription is effective for insomnia of the deficiency type and with no obvious toxic side effects.

[Analysis on somnipathy related factors in elderly patients with stroke and comparative study on the efficacy of treatment by traditional Chinese medicine and by estazolam].

OBJECTIVE: To analyze the somnipathy related factors in elderly patients with stroke and to compare effects of traditional Chinese medicine and estazolam on sleep and the followed nervous function. METHODS: The somnipathy related factors in 336 elderly patients with stroke, 221 accompanied with somnipathy and 115 with normal sleep, were studied and analyzed. Moreover, the 221 patients with somnipathy were assigned to two groups, 112 in the treated group treated with TCM according to syndrome differentiation, and 109 in the control group treated with estazolam. Changes of scores rated by neurological deficit scale (NDS), sleep dysfunction rating scale (SDRS), Hamilton anxiety rating scale (HAMA), Hamilton depression scale (HAMD), and treatment emergent symptom scale (TESS) were observed before and after treatment. RESULTS: The occurrence of somnipathy in patients with cerebral hemorrhage was significantly higher than in those with cerebral infarction; it was higher in patients with lesion in brain stem, cerebral hemisphere (frontal lobe), or basal ganglion than in those with lesion in other sites; and patients with severe neurological deficit were more liable to having somnipathy. TCM showed a significant effect in improving the insomnia symptoms in patients, with the total effective rate reaching 81.25% (91/112), which was higher than that in the control group, 65.14% (71/109, P < 0.01). Along with the improving of sleep, marked recovery of the nervous function was shown in both groups, with NDS score reduced significantly (P < 0.05). CONCLUSION: The occurrence of somnipathy in stroke patients was closely related with the property and site of lesion, and the neurological deficit degree of patients. Better sleep is surely favorable for recovery of the nervous function, and TCM shows a favorable efficacy on somnipathy.

[Effect of modified xiaoyao powder for improving sleep in patients with psychological stress insomnia].

OBJECTIVE: To subjectively and objectively assess the effect of Jiawei Xiaoyao Powder (JXYP) on sleep in patients with psychological stress insomnia. METHHODS: A randomized controlled study was conducted in 33 patients with psychological stress insomnia. They were assigned to 4 groups, 4 in the TCM group treated with JXYP, 5 in the Western medicine (WM) group treated with Estazolam, 9 in the integrated medicine (IM) group treated with JXYP plus Estazolam, and 10 in the control group treated with placebo. Quality of sleep in patients was assessed subjectively and objectively before treatment and 6 weeks after treatment by Pittsburgh sleep quality index (PSQI), self-rating scale of sleep (SRSS) and polysomnography (PSG), respectively. RESULTS: Subjective assessment on sleep showed that after 6-week treatment, the scores of PSQI and SRSS remarkably reduced in the TCM, IM and control groups (P < 0.05), while the decrease was insignificant in the WM group (P > 0.05), but no significant difference between groups was shown. The objective assessment by PSG showed that no significant change was found after treatment in parameters of total sleep time (TST), sleep time of phase 1 and 2, slow wave phase, rapid-eye-movement (REM) phase, sleep latency, REM sleep latency, also in long waking and short waking times in all group (P > 0.05), but a significant increase of sleep efficacy (P < 0.05) and an increasing trend of TST (P > 0.05) were shown in the IM group, and an increasing trend of both in the TCM group (P > 0.05). CONCLUSION: JXYP, combined with or without Estazolam, can improve the quality of sleep subjectively, and the combination of the two could enhance the efficacy of sleep in patients with psychological stress insomnia.

[Comparative study on treatment of somnipathy in patients with hypertension by traditional Chinese medicine and by estazolam].

OBJECTIVE: To study the efficacy of traditional Chinese medicine (TCM) in treating somnipathy in patients with hypertension, and to observe the change of blood pressure after sleep being improved. METHODS: Two hundred and thirty-nine patients with hypertension accompanied somnipathy were randomly assigned to two groups, 123 patients in the treated group were treated with TCM according to syndrome differentiation, and 116 in the control group treated with Estazolam. Changes of blood pressure, scores of sleep dysfunction rating scale (SDRS), Hamilton anxiety rating scale (HAMA) and treatment emergent symptom scale (TESS) before and after treatment were observed. RESULTS: TCM showed a significant effect on hypnagogic disturbance, and significantly reduced the scores of insomnia syndromes in early sleep stage, improve the quality of sleep, prolong the sleeping time to fulfill the physiological requirement, the total effective rate being 80.5% (99/123 cases), with the overall effect higher than that (66.4%, 77/116 cases) in the control group (P < 0.05). Along with the improving of sleep, blood pressure, both systolic and diastolic, reduced in both groups, but with the reduction in the treated group superior to that in the control group (P < 0.01), and the rate of reaching target BP (< 140/90 mmHg) in the former was also significantly higher than that in the latter (39.7%, 46/116 cases, P < 0.05). As compared with those in the control group, the occurence of adverse reaction, were less in the treated group (P < 0.05). CONCLUSION: TCM has better efficacy in treating somnipathy of hypertension patients than Estazolam. And the improvement of somnipathy is favorable for improving the hypertensive condition of patient.

[Effects of midazolam and estazolam as hypnotics in hypertensive patients with chronic insomnia: a multicentre, open labeled, randomized clinical trial].

OBJECTIVE: To compare the safety and efficacy of midazolam and estazolam in hypertensive patients with chronic insomnia. METHODS: In this multicentre, open labeled, randomized clinical trial, 217 adult (18 - 75 years) hypertensive patients (BP range 140 mm Hg or= 3 times/week for more than 1 month) were randomly divided into midazolam (7.5 - 15 mg before sleep, n = 113) or estazolam group (1 - 2 mg before sleep, n = 104). Patients took medication according to own need. Sleep diary should be completed within 15 minutes after getting up next morning. Follow-up analysis was performed in patients completed 8 sleep diaries or received midazolam or estazolam for 1 month. Patients' sleep diaries were evaluated, blood pressure and heart rate before and after therapy were measured and adverse events were recorded. RESULTS: (1) Blood pressure was equipotent reduced after both treatments (-11.8/7.3 mm Hg for midazolam group, and -9.1/5.6 mm Hg for estazolam group, all P < 0.05 vs. before treatment). (2) The total sleep score was also significantly decreased in both groups after medication (P < 0.01) and midazolam was significantly superior to estazolam in shortening sleep latency, reducing awakening frequency, improving objective sleep evaluation and decreasing daytime sleepiness, but there were no differences in dream frequency and total sleep time. (3) The adverse reactions such as dizziness, headache and nausea was similar in midazolam (3%) and estazolam group (7%, P > 0.05). CONCLUSIONS: It is safe to take midazolam or estazolam for hypertensive patients with chronic insomnia and both drugs reduced blood pressure. Midazolam is superior to estazolam in shortening sleep latency, reducing awakening frequency, improving objective sleep evaluation and decreasing daytime sleepiness.