小剂量米安色林治疗慢性失眠的临床疗效观察

滑宏巨　张华　雷冰冰　董彤珺　黄晓波

摘要 目的：觀察对比小剂量米安色林和艾司唑仑治疗慢性失眠的临床疗效，验证药物治疗失眠的效果和不良反应。方法：选择宁夏中医研究院睡眠医学门诊入睡困难为主的慢性失眠患者60例作为研究对象，随机分为观察组与对照组。观察组：米安色林7.5 mg/d;对照组：艾司唑仑片1/d，夜间睡前空腹。治疗初期每组每周1次睡眠卫生教育和适当的门诊心理疏导。每周用AIS观察评估1次药物疗效记录1次不良反应。观察组4周后检查1次血常规，观察白细胞变化。结果：1）2组睡眠因子评分在治疗后均叫治疗前减小，2组疗效比较差异无统计学意义（P>0.05）。2）组间因子同期比较：入睡时间观察组在第1周至4周评分与对照组比较（1.70±0.70/0.10±0.31，1.03±1.10/0.13±0.35，1.03±1.10/0.17±0.38，1.00±1.08/0.57±1.01），睡眠时间和睡眠质量在第1周、第2周、第4周评分观察组与对照组比较（0.73±0.91/0.23±0.43，0.50±0.63/0.23±0.43），（0.37±0.61/0.66±0.80，0.47±0.77/0.67±0.80）差异有统计学意义（P<0.05），结果提示观察组改善入睡时间及治疗初期增加睡眠时间、改善睡眠质量较对照组效果差，但后期效果较对照组好。3）观察组初期有不良反应，主要是头晕思睡、不宁腿样症状、体质量增加。结论：SDM治疗慢性失眠有效;与艾司唑仑比较，改善入睡时间较艾司唑仑差，最终增加睡眠时间改善睡眠质量效果较艾司唑仑好。SDM临床应用存在一些不良反应，但影响较小。

关键词 米安色林;失眠;临床疗效

Clinical Observation on the Treatment of Chronic Insomnia with Small Dose of Mianserin

HUA Hongju1，ZHANG Hua2，LEI Bingbing3，DONG Tongjun1，HUANG Xiaobo4

（1 Ningxia Academy of Traditional Chinese Medicine，Yinchuan 750021，China; 2 Ningxia Kangya Pharmaceutical Co Ltd，Yinchuan 750001，China; 3 North Minzu University，Yinchuan 7500021，China; 4 The First People′s Hospital of Yinchuan，Yinchuan 750001，China）

Abstract Objective：To observe and compare with clinical efficacy of Small dose mianserin and Estazolam in the treatment of chronic insomnia，and to verify the efficacy and adverse reactions of SDM in the treatment of chronic insomnia.Methods：A total of 60 patients with chronic insomnia of sleep initiation were randomly divided into two groups.Treatment group：mianserin 7.5 mg/d，control group：Estazolam tablets 1 mg/d.Have an empty stomach before going to bed at night.At the beginning of treatment，sleep health education and appropriate psychological counseling were given once a week.AIS once a week，and adverse drug reactions were observed by TESS.In the treatment group，blood routine tests were performed once a month.Results：1）The sleep factor scores of the two groups decreased after treatment，There was no significant difference in efficacy.2）Comparison of the same period between groups of treatment and control：the scores of sleep latency from the first week to the fourth week（1.70±0.70/0.10±0.31，1.03±1.10 /0.13±0.35，1.03±1.10/0.17±0.38，1.00±1.08/0.57±1.01），the scores of sleep time and sleep quality in the first week，the second week and the fourth week（0.73±0.91/0.23±0.43，0.50±0.63/0.23±0.43.0.37±0.61/0.66±0.80，0.47±0.77/0.67±0.80）were statistically significant（P<0.05）.The effect of improving sleep latency in the treatment group was worse than that in the control group.The effect of improving total sleep duration and sleep quality in the early stage of the treatment group was worse than that in the control group，but the later effect was better than that in the control group.3）The treatment group had adverse reactions at the beginning，mainly dizziness and sleepiness，restless legs like symptoms，weight gain.Conclusion：SDM is effective in the treatment of chronic insomnia disorder.The effect of initial treatment is worse than that of estazolam，especially the effect of improving sleep latency is worse than that of estazolam.The overall effect of improving total sleep duration and overall quality was better than that of estazolamin finally.There are some adverse reactions in the clinical application of SDM，but the influence is small.

3 讨论

国外研究小剂量多塞平治疗慢性性失眠效果好[8]，近期受到良好评价[9]。而我们在研究小剂量多塞平治疗失眠时[10]，根据类似药物作用相同的机制应用了SDM治疗慢性失眠，结果显示SDM治疗慢性失眠有效。米安色林是抗焦虑、抗抑郁药物，长期应用有白细胞减少，肝功能损伤等不良反应。SDM用于治疗失眠目前没有搜集到相关报道，其改善睡眠作用与其阻滞中枢性组胺受体H1作用有关。

综上所述，研究显示SDM治疗慢性失眠有效，有改善入睡困难效用。但与艾司唑仑比较，SDM改善入睡时间效果较艾司唑仑效果差。治疗初期增加睡眠时间、改善睡眠质量、白天情绪不如艾司唑仑好，最终效果较艾司唑仑效果好，也是该药的最主要优点。改善白天功能初期效果不如艾司唑仑好。SDM治疗初期有白天思睡现象，长期治疗没有。

不良反应：SDM不良反应不严重，药物毒性与药物剂量相关[11]，剂量越小不良反应越少，治疗1个月无明显白细胞减少。

结论：SDM治疗慢性失眠有效，与艾司唑仑对比改善入睡时间效果不如艾司唑仑好。治疗后期增加睡眠时间改善睡眠质量，调节白天情绪效果均较艾司唑仑好。SDM有不良反应，主要在治疗初期，不严重。本研究仅仅提示SDM治疗慢性失眠有效，研究时间短，临床需要继续治疗。研究揭示了药物改善睡眠的特点，缺点是方法传统不够客观，小剂量米安色林（<8 mg）目前没有标准，作者提出治疗失眠药物剂量有利于药物进一步研究，开辟药物治疗失眠新路径。

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基金项目：宁夏自治区重点研发计划项目（2016KJHM97）

作者简介：滑宏巨（1962.08—），主任医师，研究方向：睡眠医学研究，E-mail：hhjhhj46@163.com