右旋与消旋佐匹克隆治疗睡眠障碍的随机双盲双模拟临床试验

目的以消旋佐匹克隆为阳性对照药评价右旋佐匹克隆治疗睡眠障碍的疗效及安全性。方法用双盲双模拟随机对照临床试验方法，每晚睡前，分别口服（试验与对照药）右旋和消旋佐匹克隆口服3，7．5mg，疗程为14天。结果右旋佐匹克隆（试验组）为68例，痊愈率为20．59％；消旋佐匹克隆（对照组）为57例，痊愈率为14．04％。药物不良反应发生率分别为36．76％，49．12％。2组临床疗效及药物不良反应发生率比较具有统计学差异。结论右旋佐匹克隆治疗睡眠障碍，安全、有效。     

右佐匹克隆治疗失眠症92例

目的 评价右佐匹克隆和佐匹克隆治疗失眠症的疗效和安全性.方法 将183例失眠症患者随机分成2组,治疗组92例,对照组91例.治疗组给予右佐匹克隆片3 mg·d-1,睡前服;对照组给予佐匹克隆胶囊7.5～15.0 mg·d-1,睡前服;两组疗程均为15 d,治疗前及治疗第8,15天后采用睡眠障碍量表(SDRS)、临床总体印象量表(CGI)和不良反应量表(TESS)评定临床疗效和不良反应.结果 两组治疗结束时SDRS评分较基线均有显著下降(P＜0.01),治疗组显效率83.7%,对照组显效率81.3%,两组疗效及不良反应比较差异无显著性(P＞0.05).结论 失眠症患者服用右佐匹克隆后睡眠状况明显改善,且不良反应少,患者易于接受.     

佐匹克隆与氯硝西冸治疗睡眠障碍的临床对照观察

目的:观察佐匹克隆治疗睡眠障碍的疗效。方法:将96例睡眠障碍患者随机分为2组,治疗组59例,对照组37例。治疗组患者每晚睡前口服国产佐匹克隆7.5mg,对照组每晚睡前口服氯硝西冸2mg,观察2周。对患者的睡眠状况(包括入睡时间、总睡眠时间、觉醒次数)和日间情况(包括头痛、乏力、思睡)进行评定。结果:佐匹克隆和氯硝西冸均能改善患者睡眠状况,但日间情况治疗组明显优于对照组。结论:睡眠障碍患者服用佐匹克隆后睡眠状况明显改善,且不良反应少,患者易接受。     

右佐匹克隆与佐匹克隆辅助治疗抑郁症睡眠障碍对照研究

目的探讨右佐匹克隆辅助治疗抑郁发作睡眠障碍的疗效及安全性。方法选取符合ICD-10抑郁发作诊断标准的门诊抑郁发作伴失眠患者，按随机分为右佐匹克隆组和佐匹克隆组，两组均观察两周。两组患者均在治疗前、治疗后第二周末采用PSQI、HAMD、TESS评定。以PSQI的减分率判定疗效。结果右佐匹克隆组和佐匹克隆组治疗后PSQI评分经I检验差异无统计学意义（P〉0．05）；但两组各因子分比较，治疗后日间功能障碍因子右佐匹克隆组显著低于佐匹克隆组（P〈O．05）；两组不良反应发生率差异无统计学意义（P〉0．05）。结‘论右佐匹克隆辅助治疗抑郁发作睡眠障碍疗效显著，对日间功能的影响显著低于佐匹克隆，安全性好，耐受性高。     

右佐匹克隆治疗失眠症的疗效

目的:观察右佐匹克隆治疗失眠症的临床疗效与不良反应。方法:140例失眠症患者随机分为治疗组(70)例和对照组(70)例。治疗组患者每晚睡前服用右佐匹克隆3~6 mg;对照组患者每晚睡前服用劳拉西泮1~2 mg。连续服用4周。在服药前、服药后1周末、第2周末、第4周末应用阿森斯失眠量表(ASDR)评定患者睡眠障碍的改善情况。应用副反应量表(TESS)评定药物的不良反应。结果:ASDR评分在治疗结束时,两组较基线均显著降低(P<0.01);研究组和对照组的有效率分别为81.4%和78.6%,两组比较无显著性差异(P>0.05)。但研究组患者的起效时间较对照组快,总的睡眠质量更好。研究组不良反应发生率低于对照组(P<0.01)。结论:右佐匹克隆治疗失眠症患者疗效好,且不良反应少,是一种治疗失眠症安全而有效的新药。     

七叶神安片联合佐匹克隆治疗老年失眠症的对照研究

目的观察七叶神安片联合佐匹克隆片治疗老年失眠症的临床疗效与不良反应。方法将82例老年失眠症患者随机分为治疗组和对照组,治疗组42例,口服七叶神安片150mg.d-1,联合佐匹克隆片3.75mg.d-1,对照组40例,单用佐匹克隆片7.5mg.d-1,2组疗程均为四周,治疗前和治疗后2、4周末采用匹兹堡睡眠质量指数量表（PSQI）评价疗效,治疗药物副反应量表（TESS）评定药物副反应。结果两组均有明显疗效。两组在缩短入睡时间、延长睡眠时间、改善睡眠障碍方面无显著差异;治疗组在改善日间功能方面优于对照组,在治疗2周末两组间比较有显著性差异（P〈0.05）,在治疗4周末两组间比较有非常显著性差（P〈0.01）。治疗中两组不良反应发生情况不同,有显著性差异（P〈0.01）。结论七叶神安片150mg.d-1联合佐匹克隆片3.75mg.d-1治疗老年失眠症临床疗效与单用佐匹克隆片7.5mg.d-1总体疗效相当,在改善日间功能方面优于单用佐匹克隆片,可减少佐匹克隆用量,减轻不良反应,患者依从性更高。     

右佐匹克隆与氯硝西泮辅助治疗精神分裂症睡眠障碍对照研究

目的探讨右佐匹克隆辅助治疗精神分裂症睡眠障碍的疗效及安全性。方法 91例伴睡眠障碍的精神分裂症患者(均统一服用阿立哌唑10～20mg·d~(-1))随机分成2组,分别口服右佐匹克隆3～6mg·d~(-1)(n=45)或氯硝西泮2～4mg·d~(-1)(n=46),采用匹兹堡睡眠质量指数(PSQI)、阳性和阴性症状量表(PANSS)、副反应量表(TESS)评定疗效和安全性;观察3wk。结果 2组各完成43例。治疗3wk后,2组睡眠时间均显著延长,PSQI评分和PANSS评分显著下降(均P<0.01),2组间疗效无显著差异(P>0.05);右佐匹克隆组日间功能障碍的改善显著优于氯硝西泮组[(1.2±0.9)分vs.(1.6±0.7)分,P<0.05];2组TESS评分无显著差异(P>0.05),右佐匹克隆组嗜睡、头昏的发生率显著少于氯硝西泮组(P<0.05)。结论右佐匹克隆辅助治疗精神分裂症睡眠障碍疗效显著,安全性优于氯硝西泮。     

用多导睡眠图研究佐匹克隆/右佐匹克隆治疗失眠症疗效

目的 研究失眠症患者连续服用佐匹克隆或右佐匹克隆(镇静催眠药)于治疗前后多导睡眠图(PSG)的变化.方法 27例失眠症患者随机入组后,给予佐匹克隆或右佐匹克隆治疗2周,分析组内、组间PSG和睡眠障碍量表(SDRS)于治疗前后的变化.结果 佐匹克隆组,PSG各指标治疗后均有改变,但变化不显著;右佐匹克隆组,治疗后PSG示,总睡眠时间延长、睡眠效率升高、入睡后觉醒时间减少;治疗前后PSG各指标差值,组间比较差异无统计学意义.治疗后2组SDRS评分均明显降低;但治疗前后差值,组间比较差异无统计学意义.2组药物不良反应发生率分别为55.6%和60.0%.结论 佐匹克隆和右佐匹克隆对失眠症患者PSG各指标有相似的影响.     

艾司佐匹克隆治疗失眠症的疗效比较研究

目的观察艾司佐匹克隆治疗失眠症的临床疗效与不良反应。方法 150例失眠症患者随机分为治疗组（75）例和对照组（75）例。治疗组患者每晚睡前服用艾司佐匹克隆3～6mg;对照组患者每晚睡前服用劳拉西泮1～2mg。连续服用4周。在服药前、服药后一周末、第二周末、第四周末应用＂阿森斯失眠量表（ASDR）＂评定患者睡眠障碍的改善情况。应用＂副反应量表（TESS）＂评定药物的不良反应。结果 ASDR评分在治疗结束时,两组较基线均显著降低（P〈0.01）;研究组和对照组的有效率分别为80%和76%,两组比较无显著性差异（P〉0.05）。但研究组患者的起效时间较对照组快,总的睡眠质量更好。研究组不良反应发生率低于对照组（P〈0.01）。结论艾司佐匹克隆治疗失眠症患者疗效好,且不良反应少,是一种治疗失眠症安全而有效的新药。     

艾司佐匹克隆的临床研究进展及应用

艾司佐匹克隆（eszopiclone）是佐匹克隆的立体异构体（S）-zopiclone，是最近被美国FDA批准上市的新型镇静催眠药，适应证为慢性失眠证。该药通过作用于苯二氮[艹卓]类（Ω-1型受体）-GABAA受体复合物特异的结合位点，使GABAA受体发生特异性构型改变，作为GABAA受体复合物的超效激动剂发挥镇静摧眠效果。艾司佐匹克隆对中枢苯二氮[艹卓]受体的亲和力比佐匹克隆强50倍。该药吸收快速完全，药动学特征与佐匹克隆相似。临床研究显示该药能有效地缩短睡眠潜伏期、改善睡眠维持和提高睡眠质量、延长总睡眠时间，无白天的后遗效应和精神运动性损害。现对其临床研究进展及临床应用进行综述。     

Eszopiclone.

PURPOSE: The pharmacology, pharmacokinetics, indications, clinical efficacy, adverse effects, drug interactions, dosing, and administration of eszopiclone are discussed. SUMMARY: The pharmacology of eszopiclone is not well understood. Eszopiclone is the S-isomer of racemic zopiclone. The relative bioavailability of oral racemic zopiclone is about 80%. Eszopiclone is rapidly absorbed after oral administration, with peak serum concentrations ranging from 1 to 1.3 hours. The efficacy of eszopiclone has been evaluated in healthy adults, including elderly patients, for the treatment of transient and chronic insomnia. Compared with placebo, eszopiclone has been shown to considerably reduce sleep induction and improve sleep maintenance, duration, quality, and depth, as well as next-day functioning. The most common adverse effects reported are unpleasant taste, headache, and dry mouth. Dosing should be individualized, and the lowest effective dose should be used to minimize the risk of adverse events. The recommended starting dosage for nonelderly patients is 2 mg immediately before bedtime, with adjustment to 3 mg if clinically indicated. Dosage adjustment is necessary in patients with severe hepatic disease and in those receiving concomitant potent cytochrome P-450 isoenzyme 3A4 inhibitors. No dosage adjustment is required for patients with renal dysfunction. The cost of eszopiclone is 3.70 dollars per tablet for all dosage strengths (1-, 2-, and 3-mg tablets). CONCLUSION: Its favorable adverse-effect profile and approved labeling for the treatment of chronic insomnia makes eszopiclone a viable alternative for insomnia treatment. Published data are limited, however, and more clinical trials, including comparator studies, are needed to further evaluate the use of this drug.     

A polysomnography study of eszopiclone in elderly patients with insomnia

OBJECTIVE: To evaluate the safety and efficacy of eszopiclone 2 mg in elderly patients (aged 64-86 years) with chronic insomnia. METHODS: This was a randomized, double-blind, placebo-controlled 2-week study. Patients meeting DSM-IV criteria for primary insomnia and screening polysomnography criteria (wakefulness after sleep onset [WASO] >or= 20 min and latency to persistent sleep >or= 20 min) were randomized to 2 weeks of nightly treatment with eszopiclone 2 mg (n = 136) or placebo (n = 128). Efficacy was assessed using polysomnography (Nights 1, 2, 13, and 14) and patient reports (Nights 1-14); safety was assessed using adverse events, clinical labs, physical examination, and vital signs. The mean of all efficacy results during the double-blind period was used for the efficacy analysis. RESULTS: Results indicated that eszopiclone was associated with significantly shorter sleep onset, less WASO, higher sleep efficiency, more total sleep time, and greater patient-reported quality and depth of sleep scores than placebo (p < 0.05 for all) with a trend in patient-reported morning sleepiness (p = 0.07). Other measures of daytime functioning (ability to function, daytime alertness, and sense of well-being) were not significantly different between the two treatment groups. Among patients who napped, eszopiclone patients reported fewer naps (p = 0.03) and less cumulative naptime (median: 98 min placebo, 70 min eszopiclone, p = 0.07). Unpleasant taste, dry mouth, somnolence, and dizziness were higher in the eszopiclone group (12.5%, 8.8%, 6.6%, and 6.6%, respectively) than in the placebo group (0%, 1.6%, 5.5%, and 1.6%, respectively). CONCLUSION: In this study, eszopiclone was well tolerated and produced significant improvements in both polysomnographic and patient-reported measures of sleep maintenance, sleep induction, and sleep duration in elderly patients with chronic primary insomnia.     

右佐匹克隆治疗老年期失眠症的对照研究

目的评估右佐匹克隆治疗老年期失眠症的疗效和安全性。方法符合失眠症诊断标准,年龄≥65岁患者,共入组80例,研究组40例,对照组40例,分别服右佐匹克隆（3～6 mg）或阿普唑仑（0.4～0.8 mg）,共2周。用匹兹堡睡眠质量指数（PSQI）、汉密顿抑郁量表（HAMD）、汉密顿焦虑量表（HAMA）评估失眠严重程度和疗效,不良事件报告评价安全性。结果研究组有效率75.0%,对照组67.5%,两组无统计学意义（P〉0.05）。1周和2周末,两组PSQI因子分及总分、HAMD、HAMA、CGI-SI分较治疗前均显著降低（P〈0.01）,研究组睡眠潜伏期、睡眠效率、白天功能紊乱因子分及PSQI总分显著低于对照组（P〈0.05或P〈0.01）,PSQI平均减分率较对照组高（P〈0.05）。对照组不良反应高于研究组（P〈0.05）。结论右佐匹克隆治疗老年期失眠症安全、有效,改善主观睡眠质量优于阿普唑仑,不良反应少。     

A polysomnography study of eszopiclone in elderly patients with insomnia

ABSTRACT

Objective: To evaluate the safety and efficacy of eszopiclone 2?mg in elderly patients (aged 64-86 years) with chronic insomnia.

Methods: This was a randomized, double-blind, placebo-controlled 2‐week study. Patients meeting DSM-IV criteria for primary insomnia and screening polysomnography criteria (wakefulness after sleep onset [WASO] ≥ 20?min and latency to persistent sleep ≥ 20?min) were randomized to 2 weeks of nightly treatment with eszopiclone 2?mg (n = 136) or placebo (n = 128). Efficacy was assessed using polysomnography (Nights 1, 2, 13, and 14) and patient reports (Nights 1–14); safety was assessed using adverse events, clinical labs, physical examination, and vital signs. The mean of all efficacy results during the double-blind period was used for the efficacy analysis.

Results: Results indicated that eszopiclone was associated with significantly shorter sleep onset, less WASO, higher sleep efficiency, more total sleep time, and greater patient-reported quality and depth of sleep scores than placebo (?p < 0.05 for all) with a trend in patient-reported morning sleepiness (?p = 0.07). Other measures of daytime functioning (ability to function, daytime alertness, and sense of well-being) were not significantly different between the two treatment groups. Among patients who napped, eszopiclone patients reported fewer naps (?p = 0.03) and less cumulative naptime (median: 98?min placebo, 70?min eszopiclone, p = 0.07). Unpleasant taste, dry mouth, somnolence, and dizziness were higher in the eszopiclone group (12.5%, 8.8%, 6.6%, and 6.6%, respectively) than in the placebo group (0%, 1.6%, 5.5%, and 1.6%, respectively).

Conclusion: In this study, eszopiclone was well tolerated and produced significant improvements in both polysomnographic and patient-reported measures of sleep maintenance, sleep induction, and sleep duration in elderly patients with chronic primary insomnia.     

Eszopiclone: esopiclone, estorra, S-zopiclone, zopiclone--Sepracor

Eszopiclone [Lunesta, Estorra] is a short-acting hypnotic agent that is a stereoselective isomer of the agent zopiclone, which has been available in Europe since 1992. Eszopiclone is structurally unrelated to the benzodiazepines, and Sepracor (the originator of eszopiclone) has stated that the drug acts rapidly, with the duration of effect lasting up to 6 hours. This may result in improved sleep maintenance, with less nocturnal awakening.Originally, racemic zopiclone was developed and marketed by Rhone-Poulenc Rorer, which merged with Hoechst Marion Roussel to form Aventis. Sepracor anticipates that eszopiclone will have equivalent efficacy to the racemic version with potential for an improved side effect profile. In October 1999, Sepracor exclusively licensed Aventis Pharma's preclinical, clinical and postmarketing surveillance data package for zopiclone, its isomers and metabolites. The company intends to use this information in addition to data from Sepracor's own studies as part of the regulatory package to gain approval of eszopiclone in the US. In July 2004, Sepracor announced terms of an additional agreement with Aventis under which it would have the right to read and reference Aventis' regulatory filings related to zopiclone outside the US for the purpose of development and regulatory registration of eszopiclone outside the US. Additionally, Aventis would assign Sepracor the foreign counterparts to the US patent covering eszopiclone and its therapeutic use. In August 2004, Paul Royalty Fund II, an affiliate of Paul Capital Partners, purchased from Sanofi-Aventis the royalty rights on US sales of eszopiclone. In exchange for the rights, Sanofi-Aventis will receive fixed and milestone payments totalling up to US$115 million. In December 2004 the US FDA approved eszopiclone (Lunesta) for the treatment of insomnia. It is indicated for patients who experience difficulty falling asleep as well as for patients who have sleep maintenance difficulty, and is approved for long-term treatment. The recommended dosing to improve sleep onset and/or maintenance is 2mg or 3mg for adult patients (aged 18-64 years) and 2mg for older adult patients (aged > or =65 years). The 1mg dose is for sleep onset in older adult patients whose primary complaint is difficulty falling asleep. The launch of eszopiclone in the US is expected to take place in the first quarter of 2005. The approval follows an NDA submission in January 2003, an approvable letter in February 2004, and a resubmission of the NDA in June 2004. The NDA contained data from 24 clinical trials that included >2700 adult and elderly subjects, as well as data from >60 preclinical studies. Six phase III trials in adult and elderly patients with chronic or transient insomnias were also included in the data submission. Preliminary results from a completed phase IIIB/IV trial report that eszopiclone in combination with fluoxetine significantly improved sleep parameters among patients with insomnia and co-existing major depressive disorder. Furthermore the combination of eszopiclone and fluoxetine resulted in greater improvement in HAM-D17 scores in patients than the fluoxetine-placebo group. This trial and three other phase IIIB/IV were initiated in late 2003 to evaluate the efficacy of eszopiclone in the treatment of insomnia in patients with depression, rheumatoid arthritis, chronic insomnia, and in women who experience symptoms of perimenopause. Sepracor has been granted a US patent for eszopiclone [S-zopiclone, (+)-zopiclone, Lunesta, Estorra], a single isomer of zopiclone.US patents (Nos. 6,319,926 and 6,444,673) have been issued covering the use of eszopiclone for the treatment of insomnia, eszopiclone and pharmaceutical compositions comprising eszopiclone.     

Efficacy and safety of eszopiclone across 6-weeks of treatment for primary insomnia

OBJECTIVE: Eszopiclone is a new, single-isomer, non-benzodiazepine, cyclopyrrolone agent under investigation for the treatment of insomnia. The present study was a randomized, double-blind, multicenter, placebo-controlled trial conducted to assess the efficacy and safety of eszopiclone in adults with chronic primary insomnia. RESEARCH DESIGN AND METHODS: Patients (n = 308) were randomized to receive placebo or eszopiclone (2 mg or 3 mg) for 44 consecutive nights, followed by 2 nights of single-blind placebo. Efficacy was evaluated with polysomnography (Nights 1, 15 and 29) and patient-reports (Nights 1, 15, 29 and 43/44). Next-day residual effects were evaluated using the Digit-Symbol Substitution Test (DSST). RESULTS: Eszopiclone 3 mg had significantly less time to sleep onset (p < or = 0.0001), more total sleep time and sleep efficiency (p < or = 0.0001), better sleep maintenance (p < or = 0.01), and enhanced quality and depth of sleep (p < 0.05) across the double-blind period compared with placebo. Eszopiclone 2 mg had significantly less time to sleep onset (p < or = 0.001), more total sleep time (p < or = 0.01) and sleep efficiency (p < or = 0.001), and enhanced quality and depth of sleep (p < 0.05) compared with placebo, but did not significantly improve sleep maintenance. There was no evidence of tolerance or rebound insomnia after therapy discontinuation. Median DSST scores showed no decrement in psychomotor performance relative to baseline and did not differ from placebo in either eszopiclone group. Treatment was well tolerated; the most common adverse event related to eszopiclone was unpleasant taste. CONCLUSIONS: Patients treated with nightly eszopiclone 3 mg had better polysomnographic (through Night 29) and patient-reported measures (through Night 44) of sleep over the 6-week trial. There was no evidence of tolerance or rebound insomnia and no detrimental effects on next-day psychomotor performance using the DSST.     

艾司唑仑治疗失眠症临床疗效及安全性的网状Meta分析

目的 运用网状meta分析探究艾司唑仑、右佐匹克隆、佐匹克隆、米氮平、米氮平联合艾司唑仑在调节失眠症患者匹兹堡睡眠质量指数（PSQI）、睡眠障碍评定量表（SDRS）、睡眠自评量表（SRSS）、阿森斯失眠量表（AIS）、药物不良反应（TESS）的差异。方法 收集截止至2016年11月CNKI、维普、万方、Pubmed数据库中上述药物在治疗失眠症患者的临床试验资料,文章质量评估用Jadad评分,研究结果的分析用Gemtc 14.3、Stata 13、RevMan 5.3软件。结果 纳入13篇研究,Meta分析发现：与艾司唑仑相比,米氮平联合艾司唑仑的PSQI较低[WMD=-6.67,95% CI （-8.38,-4.96）,P<0.000 01];米氮平联合艾司唑仑的AIS较低[WMD=-3.73,95% CI （-4.51,-2.95）,P<0.000 01];佐匹克隆的SDRS较低[WMD=-2.50,95% CI （-3.71,-1.28）,P<0.000 1]。间接网状meta分析显示：SDRS依次为艾司唑仑>右佐匹克隆>佐匹克隆;AIS依次为艾司唑仑>佐匹克隆>米氮平联合艾司唑仑;TESS依次为艾司唑仑>佐匹克隆>右佐匹克隆。结论 艾司唑仑降低失眠患者SDRS、AIS、TESS均不具备明显优势,网状meta分析方法发掘药物疗效与安全性具有一定的参考价值。     

扎来普隆治疗失眠症的疗效及安全性

目的:评价扎来普隆治疗失眠症的有效性和安全性。方法:采用随机、双盲、对照、剂量可调整性研究。受试者分别口服扎来普隆胶囊5～10mg/d或佐匹克隆片7.5～15mg/d治疗14d。结果:在治疗结束时2组睡眠障碍量表评分较基线均显著性降低(P<0.01),有效率均为79.31%;扎来普隆组最常见的不良反应为口苦、头昏,未发现严重的不良反应。结论:扎来普隆胶囊具有与佐匹克隆片类似的疗效,不良反应相似,是治疗失眠症的安全、有效的药物。     

A method to assess the dissipation of residual hypnotics: eszopiclone versus zopiclone

ABSTRACT: Next-day residual effects of single evening doses of 3 mg of eszopiclone, 7.5 mg of zopiclone, and placebo were assessed in a randomized, double-blind, placebo-controlled, 3-way crossover study that used a mild sleep restriction protocol (sleep duration, 7 hours). During each period, 91 healthy volunteers spent 2 consecutive nights in the laboratory with time in bed restricted to 7 hours. Volunteers completed the Continuous Tracking Test, Critical Flicker Fusion task, Digit Symbol Substitution Test, N-back tasks, and Linear Analogue Rating Scales every half-hour from 7.5 to 11.5 hours after dose, commencing 15 minutes after awakening. Nighttime dosing of both eszopiclone (3 mg) and racemic zopiclone (7.5 mg) was associated with next-day performance impairment, and these residual effects dissipated over time. Eszopiclone did not differ from zopiclone on the primary end point, mean Continuous Tracking Test tracking error averaged from 7.5 to 9.5 hours after dose; however, a prespecified post hoc parametric analysis of reciprocal-transformed data favored eszopiclone over racemic zopiclone (P = 0.026).