Allen R P, Mendels J, Nevins D B, Chernik D A, Hoddes E
Johns Hopkins Sleep Disorder Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224.
J Clin Pharmacol. 1987 Oct;27(10):768-75. doi: 10.1002/j.1552-4604.1987.tb02994.x.
Midazolam (15 mg) was compared with temazepam (30 mg) in a randomized, double-blind, parallel group study. An initial screening period was followed by 3 days of placebo baseline, 4 to 12 weeks of nightly oral use of the medication and a 4-day placebo withdrawal period. One hundred seventy-five patients with chronic insomnia participated in this multicenter outpatient study. Because the elimination half-life of midazolam, a new trizolobenzodiazepine hypnotic, is short (1.3-2.2 hr) compared to temazepam's (12-16 hr), more problems with tolerance and rebound insomnia were expected to occur. Hypnotic efficacy (increased total sleep time, decreased wake time, and decreased sleep latency) was demonstrated for both medications over the entire 3-month period without the development of tolerance. In fact, if anything, efficacy increased with time on medication, suggesting possible facilitation or "inverse tolerance" effect. On withdrawal, sleep was improved compared with baseline, suggesting partial resolution of the insomniac condition rather than rebound insomnia. These effects were both statistically and clinically significant for midazolam, with 16% to 50% improvement in sleep measures. The results of this study suggest that patients with chronic insomnia may benefit from 30 to 90 days of treatment. A three-factor model that separates pharmacologic from behavioral and psychologic effects of hypnotics was proposed to explain these results in part.
在一项随机、双盲、平行组研究中，对咪达唑仑（15毫克）和替马西泮（30毫克）进行了比较。初始筛查期之后是3天的安慰剂基线期、4至12周每晚口服药物期以及4天的安慰剂撤药期。175名慢性失眠患者参与了这项多中心门诊研究。由于新型三唑并苯二氮䓬类催眠药咪达唑仑的消除半衰期（1.3 - 2.2小时）比替马西泮的（12 - 16小时）短，预计会出现更多耐受性和反弹性失眠问题。在整个3个月期间，两种药物均显示出催眠效果（总睡眠时间增加、觉醒时间减少和睡眠潜伏期缩短），且未产生耐受性。事实上，用药期间疗效随时间增加，提示可能存在促进作用或“反向耐受”效应。撤药时，睡眠与基线相比有所改善，表明失眠状况得到部分缓解而非反弹性失眠。这些效应在统计学和临床上对咪达唑仑均具有显著意义，睡眠指标改善了16%至50%。这项研究结果表明，慢性失眠患者可能从30至90天的治疗中获益。提出了一个三因素模型，将催眠药的药理作用与行为和心理作用区分开来，以部分解释这些结果。
