唑吡坦对失眠症病人多导睡眠图的影响

目的:应用多导睡眠图(PSG)探讨唑吡坦对失眠症病人睡眠脑电活动的影响。方法:对26例失眠症病人连续进行3夜PSG描记,其中第3晚睡前予唑吡坦10 mg,观察用药后PSG的变化。正常对照组33名,作1夜适应和1夜基础PSG监测。结果:失眠症病人服用唑吡坦后夜间PSG显示睡眠效率提高(P<0.05),觉醒时间减少(P<0.01),S1百分比减少(P<0.01),S2百分比增加(P<0.01),睡眠潜伏期缩短(P<0.01)。结论:唑吡坦对失眠症病人夜间多导睡眠脑电参数有影响。     

Sublingual zolpidem tartrate lozenge for the treatment of insomnia

Sublingual zolpidem tartrate (SZT) is a sublingual lozenge containing a low dose of the nonbenzodiazepine hypnotic zolpidem tartrate. Pharmacokinetic evaluations suggest that this formulation produces higher drug plasma levels within the first 15–20 min after dosing than the standard oral tablet using only approximately 30% of the standard dose. Published data suggest that SZT is generally safe and effective at rapidly inducing sedation without residual next-day effects, as long as the patient has at least 4 h remaining in bed at the time of administration. SZT is currently being reviewed by the US FDA for potential approval for insomnia characterized by middle-of-the-night awakenings with difficulty returning to sleep.     

Comparative efficacy of zolpidem and temazepam in transient insomnia

This study compared hypnotic effects of zolpidem 10 mg, temazepam 15 mg and placebo in healthy adults. Two factors expected to promote insomnia, the 'first night effect' and a 2-hour phase advance, were combined in a single night laboratory-based double-blinded protocol. This was a multi-center study, with data collected in 13 sleep laboratories. Subjects with normal sleep histories and without prior sleep laboratory experience were randomly assigned to treatment groups. Medications were administered 15 min before lights out, with polysomnographic monitoring for 7.5 h. Subjective questionnaires and performance tests, digit symbol substitution test (DSST) and symbol copying test (SCT), were administered at study entry and after arising. 630 subjects completed the study and provided data analyzed using repeated measures ANOVAs. Neither agent significantly reduced objective sleep latency relative to placebo. Zolpidem reduced awakenings and wake after sleep onset (WASO); temazepam did not. Both agents improved sleep efficiency and most subjective sleep measures relative to placebo, with zolpidem superior for five of six subjective outcome measures compared to temazepam. SCT, morning sleepiness and morning concentration were not altered by any treatment. Zolpidem significantly reduced morning DSST performance; temazepam did not. Zolpidem 10 mg provided greater subjective hypnotic efficacy than temazepam 15 mg in this model of transient insomnia, with reduced polysomnographic awakenings and WASO. Impairment of DSST was seen with zolpidem but not temazepam. Copyright 2001 John Wiley & Sons, Ltd.     

舒眠片联合唑吡坦治疗失眠症的临床研究

目的 探讨舒眠片联合酒石酸唑吡坦片治疗失眠症的疗效。方法 选择2020年9月—2021年9月在天津市泰达医院就诊的60例失眠患者,随机分为对照组和治疗组,每组各30例。对照组口服酒石酸唑吡坦片,10 mg/次,1次/d。在对照组的基础上,治疗组睡前口服舒眠片,3片/次,2次/d。两组治疗14 d。观察两组患者临床疗效,比较治疗前后两组患者症状好转时间,匹兹堡睡眠质量调查表（PSQI）评分,血清因子白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）水平,及不良反应情况。结果 治疗后,治疗组临床有效率为96.67%,明显高于对照组的73.33%（P＜0.05）。治疗后,治疗组临床症状好转时间均早于对照组（P＜0.05）。治疗后,两组PSQI评分、IL-1β、TNF-α水平均明显降低（P＜0.05）,且治疗后治疗组PSQI评分、IL-1β、TNF-α水平均明显低于对照组（P＜0.05）。治疗期间,治疗组不良反应发生率（6.67%）明显低于对照组（16.67%,P＜0.05）。结论 舒眠片联合酒石酸唑吡坦片治疗失眠症疗效显著,可有效改善患者的睡眠质量,并能改善机体炎症反应,且安全有效。     

唑吡坦联合帕罗西汀治疗抑郁失眠的临床研究

目的探讨酒石酸唑吡坦片联合盐酸帕罗西汀片治疗抑郁失眠的临床疗效和安全性。方法选取2012年12月—2014年12月上海中医药大学附属龙华医院就诊的抑郁症患者86例,随机分为对照组和治疗组,每组各43例。对照组患者饭后口服盐酸帕罗西汀片10 mg,1次/d。治疗组在对照组治疗的基础上睡前服用酒石酸唑吡坦片10 mg,1次/d。两组药物初始剂量均为10 mg,治疗1周后酌情增加至20 mg。两组均连续治疗4周。治疗后,评价两组的临床疗效,同时比较两组治疗前后PSQI、HAMD-17、HAMA评分,血生化指标水平以及不良反应发生情况。结果治疗后,对照组、治疗组的总有效率分别为76.74%、93.02%,两组总有效率比较差异具有统计学意义(P0.05)。治疗1周后,两组HAMA评分均显著降低,同组治疗前后差异有统计学意义(P0.05)。治疗2、4周后,两组PSQI、HAMD-17、HAMA评分均显著降低,同组治疗前后差异有统计学意义(P0.05);且治疗组这些观察指标同期的降低程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组γ-氨基丁酸(GABA)、5-羟色胺(5-HT)水平均显著升高,同组治疗前后差异具有统计学意义(P0.05);且治疗组这些观察指标的升高程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。出现的主要不良反应有头晕、恶心与食欲不振、口干、腹泻,两组不良反应发生率比较无统计学意义。结论酒石酸唑吡坦片联合盐酸帕罗西汀片治疗抑郁失眠具有良好的疗效,可以缓解失眠症状,增加GABA和5-HT水平,不增加不良反应,具有一定的临床推广应用价值。     

枣仁安神胶囊联合唑吡坦治疗失眠症的临床研究

目的探讨枣仁安神胶囊联合唑吡坦治疗失眠症的临床疗效。方法选取2017年6月—2018年6月在沈阳市安宁医院诊治的失眠症患者86例,根据用药差别分为对照组(43例)和治疗组(43例)。对照组患者睡前口服酒石酸唑吡坦片,10 mg/次,1次/d;治疗组在对照组基础上睡前口服枣仁安神胶囊,5粒/次,1次/d。两组患者均经4周治疗。观察两组患者临床疗效,同时比较治疗前后两组患者PSQI、HADS、PHQ-9、中医症状总积分、QLQ-C30和WEMWBS评分、睡眠质量和血清学指标。结果治疗后,对照组临床总有效率为81.40%,显著低于治疗组的95.35%,两组比较差异具有统计学意义(P0.05)。经治疗,两组PSQI、HADS、PHQ-9、中医症状总积分均显著降低(P0.05),QLQ-C30、WEMWBS评分显著升高(P0.05),且治疗组患者这些项目评分明显好于对照组(P0.05)。治疗后,两组患者总睡眠时间、REM睡眠时间及睡眠效率明显提高(P0.05),睡眠潜伏期和觉醒时间明显缩短(P0.05),且治疗组睡眠质量明显好于对照组(P0.05)。治疗后,两组患者血清5-羟色胺(5-HT)水平显著升高(P0.05),定皮质醇(COR)、白细胞介素-2(IL-2)、食欲素A(Orexin-A)、白细胞介素-6(IL-6)水平显著降低(P0.05),且治疗组患者血清5-HT、Orexin-A、COR、IL-2、IL-6水平明显好于对照组(P0.05)。结论枣仁安神胶囊联合唑吡坦治疗失眠症可有效改善患者相关症状,提高睡眠质量和生活质量,有利于患者焦虑抑郁状态和心理健康状态改善。     

Use of zolpidem 10 mg as a benzodiazepine substitute in 84 patients with insomnia

The antagonistic effects of zolpidem 10 mg on withdrawal symptoms caused by abrupt or gradual discontinuation (half-dose over 4 nights) of triazolam 0·25 mg in patients with chronic insomnia, who had been receiving regular treatment for over one month, were assessed in a randomized, double-blind, placebo-controlled clinical trial in general practice. Eighty-four patients were enrolled, mostly women (67·9%), with a mean age of 54·3±11·0 years. Twenty-one different general practitioners were solicitated for the recruitment. The subjects were randomized into four groups, and all received triazolam 0·25 mg during the run-in phase from day 1 (D1) to day 3 (D3). The following treatments were given from D4 to D7: triazolam 0·125 mg+zolpidem 10 mg (Group 1); zolpidem 10 mg (Group 2); placebo (Group 3); or triazolam 0·125 mg+placebo (Group 4). Groups 1 and 2 received zolpidem 10 mg from D7 to D24, while Groups 3 and 4 received placebo. Finally, all four groups received placebo (blind withdrawal phase) from D25 to D28. The following assessment criteria were used: clinical global impression (CGI) scale completed by the practitioner; patient questionnaire based on routine sleep criteria, wakefulness and daytime alertness. Secondary criteria were sleep diaries and visual analogue scales. Study drop-outs were reported and explained. The effectiveness/tolerance ratio was found to be statistically significant using the CGI (p<0·007) in favour of zolpidem 10 mg. There was no significant difference in patients subjective assessment between the groups except for nightmares (p<0·04) less frequent in patients receiving zolpidem. Zolpidem was found to be more effective than placebo at D21 (CGI) according to sleep diaries; the zolpidem group showed a statistically significant difference as compared to the three other concerning four sleep parameters: number of awakenings, anxiety, sleep duration, energy. Drop-out rates were significantly lower in the zolpidem group than in other ones (p<0·01). Abrupt and gradual triazolam withdrawal over 4 nights induced withdrawal symptoms. Equally no specific phenomena were observed at the end of the trial during the blind withdrawal phase. This study shows that zolpidem 10 mg improves sleep quality and reduces withdrawal symptoms after abrupt or gradual discontinuation of triazolam 0·25 mg in chronic patients with chronic insomnia. Copyright © 1998 John Wiley & Sons, Ltd.     

唑吡坦对老年不稳定性心绞痛伴自述失眠患者的临床疗效评价

目的:观察唑吡坦对老年不稳定性心绞痛(UAP)伴自述失眠(SRI)患者治疗30 d临床疗效及预后的影响.方法:选取2016年6月至2019年6月收治的99例老年UAP伴SRI患者,随机分为对照组50例和治疗组49例,2组均给予常规冠心病二级预防用药.治疗组同时加用唑吡坦5 mg每晚睡前口服,对照组则给予安慰剂,2组疗程...     

Transient insomnia associated with a 3-hour phase advance of sleep time and treatment with zolpidem

A 3-hour phase advance of sleep time was employed to produce a model of transient insomnia. The degree to which this manipulation was effective varied substantially among young, healthy normal sleepers. Zolpidem, an imidazopyridine hypnotic compound, was effective in reversing the sleep disruption in those individuals displaying transient insomnia in this model.     

Double-blind,placebo-controlled comparison of zolpidem,triazolam, and temazepam in elderly patients with insomnia

Sleep disturbances and need for hypnotics are disproportionately greater in the elderly compared to younger adults. The present study provides a placebo-controlled subjective hypnotic efficacy of zolpidem, triazolam, and temazepam in elderly insomniacs. After a single-blind placebo screening week (DSM-III-R criteria), 335 elderly insomniacs (ages 60 to 85) were randomized to 28 days of double-blind treatment with zolpidem 5 mg, triazolam 0.125 mg, temazepam 15 mg, or placebo, followed by a 4-day single-blind, placebo withdrawal period. The primary efficacy parameters were self-reported sleep latency (SSL) and self-reported total sleep duration (SSD); they were measured by responses on daily Morning Questionnaires. SSL values were compared by Cox proportional hazards regression technique. SSD values were compared by ANOVA. Compared to placebo, zolpidem and temazepam produced significantly shorter SSL over the 4 treatment weeks, but triazolam did not. In the zolpidem group, SSL was significantly shorter than in the placebo group at all four treatment weeks; in the temazepam group, SSL was significantly shorter than in the placebo group at weeks 1, 3, and 4. SSD was increased above baseline levels in all groups. No tolerance to the subjective effects or rebound above baseline levels occurred in any of the treatment groups. Overall, the drugs were well tolerated. No difference was found among the placebo and treatment groups in overall adverse event incidence rates. However, compared with zolpidem and placebo, temazepam produced significantly higher incidences of drowsiness and fatigue, and triazolam produced a significantly higher incidence of nervousness than zolpidem. Drug Dev. Res. 40:230–238, 1997. © 1997 Wiley-Liss, Inc.     

Effects of zolpidem and flunitrazepam on nocturnal sleep of women subjectively complaining of insomnia

Eighteen non-pregnant woman complaining about insomnia were polysomnographically investigated for 3 nights with weekly intervals. They received placebo, 2 mg flunitrazepam or 10 mg zolpidem according to a cross-over double blind design. The patients were selected by general practitioners on the basis of subjective complaints. Zolpidem is a recently introduced short-acting imidazopyridine hypnotic, binding to a subunit of the benzodiazepine 1 receptor. Flunitrazepam is a well-known hypnotic, binding to both the benzodiazepine 1 and 2 receptor subtypes. Objective recording did not substantiate the subjective complaint of insomnia. Sleep patterns during placebo differed only little from that expected from age matched healthy persons. Both flunitrazepam and zolpidem significantly shortened sleep onset (5 min of continuous sleep beginning with NREM 1 sleep). The sleep composition following flunitrazepam was characterized by an increase in NREM 2, a prolongation of the time to REM sleep, a reduction of REM sleep and an increase in NREM 3–4 sleep during the first 2 h of sleep. The sleep composition following zolpidem resembled more that seen in persons without sleep complaints. However, as compared to placebo, there was a decrease of the time spent awake during sleep and an increase in NREM 3–4 during the first 2 of sleep.     

Advances in the management of insomnia

Insomnia is a prevalent disorder, altering night time sleep, daytime mood and performance. Current treatment strategies, used separately or in combination, include pharmacological, circadian, behavioural and cognitive therapy. An increased diversity of available hypnotics with different potency, pharmacodynamic and pharmacokinetic profiles and improved side effect profiles provides more flexibility in designing individual treatment strategies. Melatonin, a pineal hormone with acute sleep-promoting and chronobiotic properties, allows additional possibilities in treating insomnia and circadian sleep disorders. Current studies of processes involved in normal sleep regulation and pathophysiology of insomnia should result in the development of new medications based on physiological mechanisms of sleep.     

Advances in the management of insomnia

Insomnia is a prevalent disorder, altering night time sleep, daytime mood and performance. Current treatment strategies, used separately or in combination, include pharmacological, circadian, behavioural and cognitive therapy. An increased diversity of available hypnotics with different potency, pharmacodynamic and pharmacokinetic profiles and improved side effect profiles provides more flexibility in designing individual treatment strategies. Melatonin, a pineal hormone with acute sleep-promoting and chronobiotic properties, allows additional possibilities in treating insomnia and circadian sleep disorders. Current studies of processes involved in normal sleep regulation and pathophysiology of insomnia should result in the development of new medications based on physiological mechanisms of sleep.     

失眠的药物治疗

本文总结了目前治疗失眠药物的种类、作用机制、适应证的批准及药物的应用现状,指出目前的药物治疗并不能治愈慢性失眠。提出要通过纠正失眠的病理生理机制失调来治愈慢性失眠的观点,合理使用抗抑郁药物可能是治疗慢性失眠的关键。     

Subjective hypnotic efficacy of trazodone and zolpidem in DSMIII–R primary insomnia

Trazodone is an antidepressant which is used at low doses as a hypnotic. The hypnotic efficacy of trazodone in non-depressed insomniacs is unknown, especially in comparison to hypnotic medications such as zolpidem. Following a placebo screening week, DSM-IIIR defined primary insomniacs were randomized into a parallel-group, double-blind, 14-day comparison of trazodone 50 mg, zolpidem 10 mg and placebo. Patients completed daily morning questionnaires and weekly office visits. Self-reported sleep latencies were compared by the Cox proportional hazards regression technique; self-reported sleep duration by ANOVA. During treatment Week 1, both drugs produced significantly shorter self-reported sleep latencies and longer self-reported sleep durations than placebo. Self-reported sleep latency was significantly shorter with zolpidem than with trazodone. During Week 2, only the zolpidem group maintained a significantly shorter sleep latency than the placebo group, and self-reported sleep duration did not vary significantly among groups. The incidence of adverse events was low in all groups. Both trazodone and zolpidem improved self-reported sleep latency and duration of non-depressed, primary insomniacs; zolpidem was somewhat more efficacious at the doses studied. © 1998 John Wiley & Sons, Ltd.     

New drugs for insomnia: comparative tolerability of zopiclone, zolpidem and zaleplon.

Insomnia affects 30-35% of people living in developed countries. The impact of insomnia on daytime functioning and its relationship with medical and psychiatric illnesses necessitate early treatment to prevent insomnia becoming persistent and to avoid the development of complications. However, pharmacological strategies must achieve a balance between sedative and adverse effects. In the last 30 years, benzodiazepines have been the preferred drugs for the treatment of insomnia. Benzodiazepines act nonselectively at two central receptor sites, named omega(1) and omega(2), which are located in different areas of the CNS. The sedative action of benzodiazepines is related to omega(1) receptors, whereas omega(2) receptors are responsible for their effects on memory and cognitive functioning. According to their pharmacokinetic profile, benzodiazepines can be classified into three groups: short half-life (<3 hours), medium half-life (8-24 hours) and long half-life (>24 hours). The newer non-benzodiazepine agents zopiclone, zolpidem and zaleplon have a hypnosedative action comparable with that of benzodiazepines, but they display specific pharmacokinetic and pharmacodynamic properties. These three 'Z' agents all share a short plasma half-life and limited duration of action. In addition, these agents are selective compounds that interact preferentially with omega(1) receptors (sedative effect), whereas benzodiazepines also interact with omega(2) receptors (adverse effects on cognitive performance and memory). Zaleplon is characterised by an ultrashort half-life (approximately 1 hour). Zolpidem and zopiclone have longer half-lives (approximately 2.4 and 5 hours, respectively). These properties, together with the low risk of residual effect, may explain the limited negative influences of these agents on daytime performance. Psychomotor tasks and memory capacities appear to be better preserved by non-benzodiazepine agents than by benzodiazepines. When present, cognitive deficits almost exclusively coincide with the peak plasma concentration. In particular, impairment can emerge in the first hours after drug administration, whereas psychomotor and memory tests carried out 7-8 hours later (i.e. in the morning) generally show no relevant alterations. As with benzodiazepines, the three 'Z' non-benzodiazepine agents should be used for a limited period, even in chronic relapsing conditions. Further evaluation is needed of the safety of hypnosedative medications in the long-term management of insomnia.