小劑量米安色林治療慢性失眠的臨床療效觀察

滑宏巨　張華　雷冰冰　董彤珺　黃曉波

摘要 目的：觀察對(duì)比小劑量米安色林和艾司唑侖治療慢性失眠的臨床療效，驗(yàn)證藥物治療失眠的效果和不良反應(yīng)。方法：選擇寧夏中醫(yī)研究院睡眠醫(yī)學(xué)門診入睡困難為主的慢性失眠患者60例作為研究對(duì)象，隨機(jī)分為觀察組與對(duì)照組。觀察組：米安色林7.5 mg/d;對(duì)照組：艾司唑侖片1/d，夜間睡前空腹。治療初期每組每周1次睡眠衛(wèi)生教育和適當(dāng)?shù)拈T診心理疏導(dǎo)。每周用AIS觀察評(píng)估1次藥物療效記錄1次不良反應(yīng)。觀察組4周后檢查1次血常規(guī)，觀察白細(xì)胞變化。結(jié)果：1）2組睡眠因子評(píng)分在治療后均叫治療前減小，2組療效比較差異無統(tǒng)計(jì)學(xué)意義（P>0.05）。2）組間因子同期比較：入睡時(shí)間觀察組在第1周至4周評(píng)分與對(duì)照組比較（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），睡眠時(shí)間和睡眠質(zhì)量在第1周、第2周、第4周評(píng)分觀察組與對(duì)照組比較（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）差異有統(tǒng)計(jì)學(xué)意義（P<0.05），結(jié)果提示觀察組改善入睡時(shí)間及治療初期增加睡眠時(shí)間、改善睡眠質(zhì)量較對(duì)照組效果差，但后期效果較對(duì)照組好。3）觀察組初期有不良反應(yīng)，主要是頭暈思睡、不寧腿樣癥狀、體質(zhì)量增加。結(jié)論：SDM治療慢性失眠有效;與艾司唑侖比較，改善入睡時(shí)間較艾司唑侖差，最終增加睡眠時(shí)間改善睡眠質(zhì)量效果較艾司唑侖好。SDM臨床應(yīng)用存在一些不良反應(yīng)，但影響較小。

關(guān)鍵詞 米安色林;失眠;臨床療效

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 討論

國(guó)外研究小劑量多塞平治療慢性性失眠效果好[8]，近期受到良好評(píng)價(jià)[9]。而我們?cè)谘芯啃┝慷嗳街委熓邥r(shí)[10]，根據(jù)類似藥物作用相同的機(jī)制應(yīng)用了SDM治療慢性失眠，結(jié)果顯示SDM治療慢性失眠有效。米安色林是抗焦慮、抗抑郁藥物，長(zhǎng)期應(yīng)用有白細(xì)胞減少，肝功能損傷等不良反應(yīng)。SDM用于治療失眠目前沒有搜集到相關(guān)報(bào)道，其改善睡眠作用與其阻滯中樞性組胺受體H1作用有關(guān)。

綜上所述，研究顯示SDM治療慢性失眠有效，有改善入睡困難效用。但與艾司唑侖比較，SDM改善入睡時(shí)間效果較艾司唑侖效果差。治療初期增加睡眠時(shí)間、改善睡眠質(zhì)量、白天情緒不如艾司唑侖好，最終效果較艾司唑侖效果好，也是該藥的最主要優(yōu)點(diǎn)。改善白天功能初期效果不如艾司唑侖好。SDM治療初期有白天思睡現(xiàn)象，長(zhǎng)期治療沒有。

不良反應(yīng)：SDM不良反應(yīng)不嚴(yán)重，藥物毒性與藥物劑量相關(guān)[11]，劑量越小不良反應(yīng)越少，治療1個(gè)月無明顯白細(xì)胞減少。

結(jié)論：SDM治療慢性失眠有效，與艾司唑侖對(duì)比改善入睡時(shí)間效果不如艾司唑侖好。治療后期增加睡眠時(shí)間改善睡眠質(zhì)量，調(diào)節(jié)白天情緒效果均較艾司唑侖好。SDM有不良反應(yīng)，主要在治療初期，不嚴(yán)重。本研究?jī)H僅提示SDM治療慢性失眠有效，研究時(shí)間短，臨床需要繼續(xù)治療。研究揭示了藥物改善睡眠的特點(diǎn)，缺點(diǎn)是方法傳統(tǒng)不夠客觀，小劑量米安色林（<8 mg）目前沒有標(biāo)準(zhǔn)，作者提出治療失眠藥物劑量有利于藥物進(jìn)一步研究，開辟藥物治療失眠新路徑。

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基金項(xiàng)目：寧夏自治區(qū)重點(diǎn)研發(fā)計(jì)劃項(xiàng)目（2016KJHM97）

作者簡(jiǎn)介：滑宏巨（1962.08—），主任醫(yī)師，研究方向：睡眠醫(yī)學(xué)研究，E-mail：hhjhhj46@163.com