Scharf M B, Roth T, Vogel G W, Walsh J K
Center for Research in Sleep Disorders, Mercy Hospital of Hamilton, Fairfield, Cincinnati, Ohio 45246.
J Clin Psychiatry. 1994 May;55(5):192-9.
Zolpidem is a short-acting, nonbenzodiazepine hypnotic with rapid onset of action. Even though it is not a benzodiazepine, it binds to one of three types of central benzodiazepine receptors, showing selective binding to the type 1 benzodiazepine receptor subtype. Therapeutic hypnotic dosages do not disturb normal sleep patterns (sleep architecture).
A randomized, double-blind, placebo-controlled, parallel group multicenter trial was conducted to determine the effectiveness of 10 mg and 15 mg of zolpidem in the long-term (35 nights) treatment of chronic insomnia in 75 patients. Sleep stage effects and motor and cognitive effects during the 35-night treatment period and the 3-night posttreatment period were also investigated.
Within the first week of treatment, 10 mg of zolpidem had a significant effect on latency to persistent sleep and sleep efficiency. Efficacy was maintained throughout the 35 nights of drug administration. There was no evidence of residual effect with 10 mg of zolpidem. Stage 3-4 sleep was preserved at both the 10-mg and 15-mg zolpidem dosages. There was no evidence of tolerance at either dose and no significant treatment differences between the 10-mg zolpidem group and placebo in latency to persistent sleep or sleep efficiency during the posttreatment period. Also, the 10-mg zolpidem dosage was judged by the patients to have helped them fall asleep. Similar results were observed with the 15-mg zolpidem dosage. However, there were significant decreases in REM sleep at Weeks 3 and 4 with 15 mg of zolpidem compared with placebo. Overall, incidence rates of treatment-emergent adverse events in the zolpidem groups were similar to those in the placebo group.
This is the first sleep laboratory study using a parallel placebo group to demonstrate efficacy for longer than 4 weeks with a hypnotic agent. In this study 10 mg of zolpidem was found to be safe and effective for the long-term treatment of chronic insomnia, demonstrating hypnotic efficacy without affecting sleep stages or producing tolerance effects, rebound effects, or detrimental effects on psychomotor performance. The 15-mg zolpidem dosage provided no clinical advantage over the 10-mg zolpidem dosage.
唑吡坦是一种短效非苯二氮䓬类催眠药，起效迅速。尽管它不是苯二氮䓬类药物，但它能与三种中枢苯二氮䓬受体之一结合，对1型苯二氮䓬受体亚型表现出选择性结合。治疗性催眠剂量不会干扰正常睡眠模式（睡眠结构）。
进行了一项随机、双盲、安慰剂对照、平行组多中心试验，以确定10毫克和15毫克唑吡坦对75例慢性失眠患者进行长期（35晚）治疗的有效性。还研究了35晚治疗期和3晚治疗后期的睡眠阶段效应以及运动和认知效应。
在治疗的第一周内，10毫克唑吡坦对持续睡眠潜伏期和睡眠效率有显著影响。在整个35晚的给药过程中疗效得以维持。没有证据表明10毫克唑吡坦有残留效应。10毫克和15毫克唑吡坦剂量下3-4期睡眠均得以保留。两种剂量均未出现耐受性证据，在治疗后期，10毫克唑吡坦组和安慰剂组在持续睡眠潜伏期或睡眠效率方面没有显著治疗差异。此外，患者认为10毫克唑吡坦剂量有助于他们入睡。15毫克唑吡坦剂量也观察到类似结果。然而，与安慰剂相比，15毫克唑吡坦在第3周和第4周时快速眼动睡眠显著减少。总体而言，唑吡坦组治疗中出现的不良事件发生率与安慰剂组相似。
这是第一项使用平行安慰剂组的睡眠实验室研究，证明一种催眠药的疗效超过4周。在本研究中，发现10毫克唑吡坦对慢性失眠的长期治疗安全有效，显示出催眠疗效，且不影响睡眠阶段，也不产生耐受性效应、反跳效应或对精神运动表现的有害影响。15毫克唑吡坦剂量与10毫克唑吡坦剂量相比没有临床优势。
