咪达唑仑和艾司唑仑治疗高血压患者长期失眠的临床疗效

目的 比较咪达唑仑（midazolam）和艾司唑仑（estazolam）治疗高血压患者长期失眠的疗效和安全性.方法 采用多中心、开放、随机对照临床试验,高血压140 mm Hg（ 1 mm Hg=0.133 kPa）≤收缩压＜180 mm Hg,舒张压＜110 mm Hg或在治疗中的高血压患者伴有长期失眠,入选217例患者随机分成2组,咪达唑仑组（113例）睡前口服咪达唑仑片7.5～15 mg.艾司唑仑组（104例）睡前口服艾司唑仑片1～2 mg.均按需服用,第2天起床后15 min内完成睡眠日记的记录.完成8次睡眠日记（在1个月内）的记录或1个月后结束随访.研究者收集患者的病史日记,并对患者再次进行疗效评估,测量血压和心率,记录不良事件.疗程为期4周.结果 （1）两组治疗后血压均较治疗前下降,咪达唑仑组血压下降11.8/7.3 mm Hg,艾司唑仑组血压下降9.1/5.6 mm Hg, 两组治疗前后比较差异有统计学意义（P＜0.05）,而组间比较差异无统计学意义（P＞0.05）.（2）两组治疗后睡眠评估总得分均较治疗前减小,各组内与治疗前比较差异有统计学意义（P＜0.01）,咪达唑仑组治疗后在入睡时间、觉醒次数、睡眠评价、日间困倦方面均优于艾司唑仑组, 总得分前者小于后者, 两组间相比差异有统计学意义.但在睡眠时间和做梦程度组间比较差异无统计学意义.（3）主要不良反应：头晕、头痛和恶心, 咪达唑仑组发生率小于艾司唑仑组,分别为3%和7%,但组间比较差异无统计学意义（P＞0.05）.结论 按需服用咪达唑仑和艾司唑仑治疗高血压长期失眠安全,且可能有辅助降压疗效;但咪达唑仑在入睡时间,觉醒次数,睡眠评价,日间困倦等改善优于艾司唑仑.

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 sleepness, 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.