加味柴胡桂枝汤合并文拉法辛治疗中重度抑郁症的回顾性研究

  本文关键词：加味柴胡桂枝汤合并文拉法辛治疗中重度抑郁症的回顾性研究，由笔耕文化传播整理发布。

        课题背景：抑郁症通常指的是情感障碍,是一种常见的心境障碍,可由各种原因引起,以显著而持久的心境低落为主要临床特征,且心境低落与其处境不相称,临床表现可以从闷闷不乐到悲痛欲绝,甚至发生木僵；部分病例有明显的焦虑和运动性激越；严重者可出现幻觉、妄想等精神病性症状。多数病例有反复发作的倾向,每次发作大多数可以缓解,部分可有残留症状或转为慢性。世界卫生组织的一项以15个城市为中心的全球性合作研究,调查综合医院就诊者中的心理障碍,发现患抑郁症和恶劣心境者达12.5%。在10个国家和地区(包括美国、加拿大、黎巴嫩、韩国、中国台湾等)的对38000个体的社区调查,发现各国抑郁症的终生患病率相差悬殊,中国台湾仅为1.5%,而黎巴嫩高达19.0%；年发病率在中国台湾为0.8%,美国新泽西则为5.8%。WHO(1993)的多中心全球合作研究中,上海调查表明,在综合医院内科门诊的抑郁症患病率为4.0%,恶劣心境为0.6%。台湾、香港等地华人的抑郁症患病率也较低,台湾人群中抑郁症终生患病率为1.5%,远低于其他亚洲地区(韩国2倍于台湾地区)。在对中国台湾老年抑郁症患者的23项横断面的流行病学调查资料的综合分析显示,抑郁症的患病率为3.86%,农村的抑郁症发病危险率为5.07%,高于城市的2.61%,远低于西方国家的患病率。WHO(1993)的全球疾病负担(GBD)的合作研究表明,全球的神经精神疾病负担中抑郁症、自杀分别为17.3%、15.9%,高居榜首；抑郁症占伤残调整生命年(DALY)减少的4.2%；抑郁症和自杀占5.9%。提示抑郁症、自杀/自伤是精神障碍中导致疾病负担损失最大的问题,应予以重视。研究还预测,到2020年抑郁症将成为继冠心病后的第二大疾病负担源。预测从1990-2020年中国的神经精神疾病负担将从14.2%增至15.5%,加上自杀与自伤,将从18.1%升至20.2%,占全部疾病负担的1/5。精神障碍与自杀所占疾病负担将名列第1、2位(20.2%),抑郁症、自杀与自伤,以及老年痴呆的疾病负担明显增加,而抑郁症仍是精神疾病负担中的最主要问题(1990年为44%,预测2020年将为47%)。抑郁障碍具有高发病、高复发、高致残的特点,所带来的后果就是沉重的经济负担,给社会造成巨大的经济损失。美国(1994)总的健康费用中4%用于治疗抑郁障碍,高达430亿美元；其中仅90亿美元(28%)是直接医疗费用,其余340亿美元则是因患者致病或致残后所造成的各种损失。目前诊治的情况不容乐观,对抑郁障碍的总体识别率较低,尤其是在综合医院。WHO的多中心合作研究显示,15个不同国家或地区的内科医生对抑郁症的识别率平均为55.6%,中国上海的识别率为21%,远远低于国外水平。因此,加强抑郁症的防治,寻找积极有效的治疗方法,具有非常重要的社会和经济意义。抑郁症治疗目前主要有药物治疗、心理治疗及电惊厥治疗等多种方式,而当前最为普遍的治疗方法仍为抗抑郁药物治疗。相关资料表明,10%-30%的病人对于抗抑郁药的治疗反应差。除此之外,对于抗抑郁制剂疗法表现出很多负面作用,如性欲降低、恶心,呕吐,震颤,尿阻滞,生理失调,肥胖等。以SSRI类及SNRI类为代表的新型抗抑郁药较传统抗抑郁药毒副作用减弱,但作用机制和三环类药物本质上一致,只能针对单一发病机制,只能缓解部分症状,不足以兼顾多种致病因素,无法解决抑郁症多种发病病因及发病机制的问题。且其药效和应用范围并不优于传统药物,仅50%的患者可以完全解除症状。其药效起效延迟,药理作用在2-4周时开始发挥作用,无法迅速解决患者主诉症状。文拉法辛是一种5-羟色胺与去甲肾上腺素再摄取抑制剂,其双重活性的作用机制对抑郁症的治疗效果较选择性5-羟色胺再摄取抑制剂更有优势,在转换策略上较SSRI有潜在的优势。在安全性与耐受性方面,纳入的试验统计文拉法辛与SSRI的副反应主要是恶心、呕吐、口干等消化系统症状；头昏、头痛等神经系统症状,两者无明显差异。提示文拉法辛是一种具有良好安全性与耐受性的抗抑郁药。抑郁症属中医“郁病”范畴,由气机郁滞,脏腑功能失调而至心情抑郁,情绪不宁,胸部满闷,胁肋胀痛,或易怒欲哭,或咽中有异物感等症为主要临床特征。祖国医学对郁病的认识由来已久,传统中医认为抑郁症的病因有内外两个方面,其外因为情志所伤,其内因为脏气易郁。其病机主要为气机郁滞,脏腑功能失调。郁病初起病变以气滞为主,气郁日久,则可引起血瘀、化火、痰结、食滞、湿停等,多属实证,日久则易由实转虚,随其影响的脏腑及损耗气血阴阳的不同,而形成心、肝、脾、肾亏虚的不同病变。理气开郁、怡情易性是治疗的基本原则。加味柴胡桂枝汤是国家名老中医陈宝田教授在多年治疗抑郁症的临床经验的基础上,参阅古今文献,经过多年潜心研究,针对抑郁症肝郁伤神为重要病机,在经方柴胡桂枝汤的基础上拟定的以疏肝理气、解郁安神,兼以平阴阳、调五神、和营卫为特点的经验方。柴胡桂枝汤具有疏肝理气、化痰之功,生龙牡和灵磁石能镇肝、平肝,夜交藤、茯神解郁安神,诸药合用,达到疏肝理气、镇肝平肝、健脾养心、解郁安神之效。近年来,我们在临床上多采用加味柴胡桂枝汤合并文拉法辛的方式对抑郁症开展治疗,获得了一定的疗效。因此,结合我们对既往治疗的疗效观察,进行回顾性分析加味柴胡桂枝汤合并文拉法辛治疗中重度抑郁症的疗效。本课题将更多关注患者服药后副反应的缓解及改善情况,中药对降低抗抑郁剂的副作用,缓解抑郁症的核心症状及周边症状的有效性和安全性。目的：通过对105例抑郁症患者的回顾性分析,进一步评价中西医结合治疗抑郁症的有效性及安全性,尤其是中药在提高抗抑郁疗效及减轻西药副作用的影响。对象和方法：1.对象2010年1月～2011年12月在南方医科大学南方医院中医科门诊、病房及中西医结合医院脑病科门诊、病房诊断为抑郁症的患者105例。2.纳入及排除标准抑郁症的诊断标准：均符合中国精神疾病分类与诊断标准第3版(CCMD-3)抑郁症诊断标准。纳入标准：(1)符合CCMD-3抑郁症诊断标准的病例；(2)汉密尔顿抑郁量表(HAMD-17)评分≥17分；(3)性别与种族不限,住院与门诊病人不限；(4)年龄>18岁；(5)病程≥30天以上；(6)完善常规检查,未见明显严重器质性病变；(7)完成12周治疗的患者。排除标准：(1)排除不符合CCMD-3抑郁症诊断标准的其他精神疾病；(2)出现严重自杀倾向者；(3)年龄<18岁；(4)完善常规检查,伴有明显严重器质性病变；(5)孕妇、哺乳期妇女；(6)对本药物过敏者；(7)长期服用精神类药物且剂量不稳定、单胺氧化酶抑制剂、锂剂及丙戊酸、卡马西平等抗癫痫剂；(8)凡不符合纳入标准,未按规定服药,无法判定疗效或资料不全等影响疗效和安全性判断者。3.方法试验方法：回顾性研究。选择病例标准：包括诊断标准、纳入标准及排除标准。其中诊断标准参照中国精神疾病分类与诊断标准第3版(CCMD-3)抑郁症诊断标准,同时结合中医辩证标准。治疗药物：治疗组给予文拉法辛缓释片基础上联合加味柴胡桂枝汤(柴胡、半夏、党参、甘草、黄芩、桂枝、白芍、生姜、大枣、生龙骨、生牡蛎、灵磁石、夜交藤、茯神等)；对照组单用文拉法辛缓释片。用药方法：两组均给予文拉法辛缓释片,治疗组联合中药加味柴胡桂枝汤。治疗周期为12周。合并用药规定：用药期间不得合并使用任何抗精神病药,抗抑郁药,心境稳定剂等药物。用药期间若严重失眠者,可以适当合用唑吡坦或阿普唑仑,佐匹克隆和短效苯二氮卓镇静药,如舒乐安定等。观测指标：包括人口学资料、影响疗效因素、一般体格检查及实验室检查。疗效判定标准：包括抑郁症疗效判定标准,治疗前后相关量表分数的变化情况。不良事件的观察：不良事件的术语涵盖了在临床研究期间,受试者出现并会影响健康的任何临床证候、症状、综合征或某种疾病出现或恶化。不良事件可能是：新的疾病；治疗状态症状或体征的恶化,或伴随疾病的恶化；对照药物的作用；与参加该试验无关；一个或多个因素的组合。所以,“不良事件”这一术语并不意味着与试验药物的因果关系。4.统计学处理所有数据采用SPSS13.0统计软件包进行统计分析。计量资料作正态性检验,如样本符合正态分布以均数士标准差(x士SD)表示。服药前后各时间点的量表评分变化数据采用重复测量方差分析。治疗后两组HAMD减分疗效分析采用广义估计方程(generalized estimating equations, GEE)。计数资料用例数(%)表示,组间比较采用X2检验；如数据出现理论值<1,则用Fisher确切概率法。等级资料采用秩和检验。P<0.05为差异有统计学意义。结果：1HAMD量表评分变化：给药前后两组不同时间点之间差异均有统计学意义(F=1204.507,P=0.000),治疗组F=295.401、P=0.000,对照组F=167.256、P=0.000。两组之间HAMD量表评分差异有统计学意义(F=7.776,P=0.006),从各时间点看,除基线期HAMD量表评分差异无统计学意义(t=-0.6)8,P=0.538)外,服药1周、2周、4周、6周、8周及12周后两组HAMD量表评分差异均有统计学意义(t值分别为2.654、3.397、3.203、2.840、3.322、3.821,P值分别为0.009、0.001、0.002、0.005、0.001、0.000),表明自患者服药1周以后的各时间点,抑郁症患者HAMD量表评分的降低幅度治疗组均优于对照组。两组与服药时间之间存在交互效应(F=7.667,P=0.000),与前面不同时间点两组之间多重比较结果分析相吻合,表明两组抑郁症患者HAMD量表评分的变化随给药时间的延长呈下降趋势。2.SDS量表评分变化：给药前后两组不同时间点之间差异均有统计学意义(F=2012.564,P=0.000),治疗组F=610.854、P=0.000,对照组F=68.278、P=0.000。两组之间SDS量表评分差异有统计学意义(F=116.876,P=0.000),从各时间点看,除基线期SDS量表评分差异无统计学意义(t=-1.529,P=0.129)外,服药1周、2周、4周、6周、8周及12周后两组SDS量表评分差异均有统计学意义(t值分别为3.037、7.126、11.466、16.711、21.326、23.747,P值分别为0.003、0.000、0.000、0.000、0.000、0.000),表明自患者服药1周以后的各时间点,抑郁症患者SDS量表评分的降低幅度治疗组均优于对照组。两组与服药时间之间存在交互效应(F=258.781,P=0.000),与前面不同时间点两组之间多重比较结果分析相吻合,表明两组抑郁症患者SDS量表评分的变化随给药时间的延长呈下降趋势。3.SAS量表评分变化：给药前后两组不同时间点之间差异均有统计学意义(F=1123.184,P=0.000),治疗组F=402.742、P=0.000,对照组F=60.464、P=0.000。两组之间SAS量表评分差异有统计学意义(F=92.576,P=0.000),从各时间点看,除基线期SAS量表评分差异无统计学意义(t=-1.712,P=0.090)外,服药1周、2周、4周、6周、8周及12周后两组SAS量表评分差异均有统计学意义(t值分别为2.209、6.873、12.002、17.548、17.172、18.394,P值分别为0.029、0.000、0.000、0.000、0.000、0.000),表明自患者服药1周以后的各时间点,抑郁症患者SAS量表评分的降低幅度治疗组均优于对照组。两组与服药时间之间存在交互效应(F=150.707,P=0.000),与前面不同时间点两组之间多重比较结果分析相吻合,表明两组抑郁症患者SAS量表评分的变化随给药时间的延长呈下降趋势。4HAMD睡眠障碍分析比较：给药前后两组不同时间点之间差异均有统计学意义(F=531.498,P=0.000),两组与服药时间之间存在交互效应(F=7.657,P=0.000)。治疗组F=137.232、P=0.000,对照组F=72.397、P=0.000。两组之间睡眠障碍评分差异有统计学意义(F=27.041,P=0.000),从各时间点看,除基线期睡眠障碍因子评分差异无统计学意义(t=0.518,P=0.605)外,服药1周、2周、4周、6周、8周及12周后两组睡眠障碍评分差异均有统计学意义(t值分别为3.946、5.417、4.636、5.787、5.739、5.357,P值分别为0.000、0.000、0.000、0.000、0.000、0.000),表明治疗前两组患者睡眠障碍评分处于同一水平,具有可比性。自患者服药1周以后的各时间点,抑郁症患者HAMD‘睡眠障碍评分的降低幅度治疗组均优于对照组。5HAMD抑郁和焦虑反应分析比较：给药前后两组不同时间点之间差异均有统计学意义(F=546.509,P=0.000),两组与服药时间之间存在交互效应(F=2.911,P<0.008)。治疗组F=133.542、P=0.000,对照组F=79.791、P=0.000。两组之间抑郁和焦虑反应评分差异无统计学意义(F=2.032,P=0.157),从各时间点看,基线期及服药1周、2周、4周、6周抑郁和焦虑反应评分差异无统计学意义(t值分别为-0.658、1.368、1.904、1.573、1.444,P值分别为0.512、0.174、0.060、0.119、0.152),8周及12周后两组抑郁和焦虑反应评分差异有统计学意义(t值分别为2.578、2.125,P值分别为0.011、0.037),表明治疗前两组患者抑郁和焦虑反应因子处于同一水平,具有可比性,并且自患者服药1周、2周、4周、6周内,两组抑郁症患者HAMD抑郁和焦虑反应评分的降低幅度相当。但自患者服药8周及12周后,HAMD抑郁和焦虑反应评分的降低幅度开始出现治疗组优于对照组。6HAMD情感淡漠分析比较：给药前后两组不同时间点之间差异均有统计学意义(F=125.812,P=0.000),两组与服药时间之间不存在交互效应(F=0.660,P=0.682)。治疗组F=27.778、P=0.000,对照组F=19.172、P=0.000。两组之间情感淡漠评分差异无统计学意义(F=0.003,P=0.954),从各时间点看,基线期及服药1周、2周、4周、6周、8周、12周后两组情感淡漠评分差异均无统计学意义(t值分别为-0.801、0.036、0.343、0.521、-0.037、-0.174、-0.243,P值分别为0.425、0.971、0.732、0.604、0.970、0.862、0.808),表明治疗前两组患者情感淡漠评分处于同一水平,具有可比性,并且自患者服药1周以后的各时间点,两组抑郁症患者HAMD情感淡漠评分的降低幅度相当。7HAMD躯体症状分析比较：给药前后两组不同时间点之间差异均有统计学意义(F=421.576,P=0.000),两组与服药时间之间不存在交互效应(F=1.675,P=0.125)。治疗组F=114.595、P=0.000,对照组F=96.139、P=0.000。两组之间躯体症状评分差异无统计学意义(F=0.886,P=0.349),从各时间点看,基线期及服药1周、2周、4周、6周、8周、12周后两组躯体症状评分差异均无统计学意义(t值分别为-0.418、1.447、1.186、1.583、0.904、0.472、0.399,P值分别为0.677、0.151、0.238、0.116、0.368、0.638、0.691),表明治疗前两组患者躯体症状因子处于同一水平,具有可比性,并且自患者服药1周以后的各时间点,两组抑郁症患者HAMD躯体症状评分的降低幅度相当。8HAMD减分疗效分析：治疗组和对照组有显著差异(Z=3.82,P<0.001),治疗组疗效优于对照组；不同时间点间有显著差异(Z=13.64,P<0.001),随着时间的延长,疗效愈好；组别和时间点间没有交互效应(Z=-0.43,P=0.668)。用药后1周、2周、4周、6周、8周、12周的各时间点,治疗组与对照组疗效级别秩次分别为：55.63、49.50；61.85、41.20；60.50、43.00；63.21、39.39；58.83、45.22；60.43、43.09。两组在用药后的各时间点差异均有统计学意义(Z=-2.360,P=0.018；Z=-3.985,P<0.000；Z=-3.714,P<0.000；Z=-4.403,P<0.000：Z=-2.723,P=0.006；Z=-3.809,P<0.000)。9.起效时间分析：在治疗第1周时,治疗组和对照组在起效时间上差异有统计学意义(X2=16.293,P<0.000),治疗组30%患者获得起效,而对照组未见明显起效。而在治疗第2周时,治疗组和对照组在起效时间上差异更显著(X2=19.604,P<0.000),治疗组88.3%患者获得起效,而对照组仅48.9%患者获得起效。10.治疗12周末治愈率比较：治疗组和对照组在临床治愈率比较上差异有统计学意义(X2=14.463,P<0.000)。在治疗12周末,治疗组临床治愈率为88.3%,而对照组临床治愈率仅为55.6%。11.不良反应分析：治疗组各种不良反应发生率均低于对照组,两组在口干(X2=10.423,P<0.001)、便秘(X2=6.099,P=0.014<0.05)及性功能障碍(X2=4.257,P=0.039<0.05)等发生率上相比差异具有统计学意义,治疗组在口干、便秘及性功能障碍等发生率明显低于对照组。结论：1.加味柴胡桂枝汤合并文拉法辛对抑郁症及合并焦虑症的改善作用优于单用文拉法辛,而且随治疗时间的延长,对抑郁症及焦虑症的改善作用可能更稳定。2.加味柴胡桂枝汤合并文拉法辛对睡眠障碍的改善优于单用文拉法辛组。而对抑郁和焦虑反应的改善,一直到治疗8周后,才出现优于单用文拉法辛组,这可能提示随着治疗时间的延长,改善抑郁和焦虑反应的疗效会逐渐明显。而对情感淡漠及躯体症状的改善,疗效表现不明显。3.加味柴胡桂枝汤合并文拉法辛临床治愈率为88.3%,而单用文拉法辛组临床治愈率仅为55.6%。提示加味柴胡桂枝汤联合文拉法辛临床治愈率可能要高于单用文拉法辛。4.加味柴胡桂枝汤合并文拉法辛在第一周出现30%患者获得起效,治疗两周后,起效达到88.3%。同时,单用文拉法辛仅在第二周出现48.9%患者获得起效。提示在起效时间上要明显快于单用文拉法辛。5.加味柴胡桂枝汤合并文拉法辛可能在不同程度上减轻文拉法辛的副作用,尤其在减轻口干、便秘及性功能障碍等不良反应上表现可能更显著。

    Research background:Depression usually refers to affective disorder is a common mood disorder can be caused by a variety of reasons, significantly low long-lasting state of mind as the main clinical features, and the depressed state of mind and its not commensurate with the situation, clinical manifestations can be depressed to griefstricken, and even stupor; in some cases there is significant anxiety and agitation; severe cases, hallucinations, delusions and other psychotic symptoms. Most cases have a tendency to recurrent episodes of most of each attack can be alleviated, some may have residual symptoms or become chronic.World Health Organization of one to15cities as the center of global collaborative research to investigate the psychological barrier in the hospital who found suffering from depression and dysthymia of12.5%. Community survey of38,000individuals in10countries and regions (including the United States, Canada, Lebanon, Korea, China Taiwan) and found that the lifetime prevalence rate of the national depression disparities, China Taiwan only.5%up to19.0%in Lebanon; annual incidence in China Taiwan is0.8%, New Jersey, compared with5.8percent. WHO (1993), multi-center study of global cooperation, the Shanghai survey showed that the prevalence rate of4.0%in the general hospital medical outpatient depression, dysthymia0.6%. Chinese in Taiwan, Hong Kong, the prevalence of depression is low, the population of Taiwan depression lifetime prevalence rate of1.5%, much lower than other regions in Asia (South Korea2times in Taiwan). Shown in the comprehensive analysis of epidemiological data on the23cross-section of the Chinese elderly patients with depression in Taiwan, the prevalence of depression was3.86%incidence of depression in rural areas dangerous rate of5.07%, higher than the city’s2.61%, much lower than the prevalence of Western countries.WHO(1993)Global Burden of Disease (GBD) studies have shown that the global burden of neuropsychiatric disease, depression, suicide, respectively,17.3%,15.9%, topped the list; depression accounted for disability-adjusted life years(DALY)4.2%; reduce depression and suicide accounted for5.9%. Prompt depression, suicide/self-injury in mental disorders lead to the loss of the burden of disease the biggest problem, attention should be paid. The study also predicted that by2020depression will become the following coronary heart disease after the second largest disease burden of the source. Forecast from1990to2020, China’s burden of neuropsychiatric disease increased from14.2%to15.5%, coupled with suicide and self-injury, and from18.1%to20.2%, accounting for1/5of the total burden of disease. Mental disorders and suicide share of the burden of disease will be ranked1,2(20.2%), depression, suicide and self-injury, and Alzheimer’s disease burden increased significantly, while depression is the main burden of mental illness problems (44%in1990to predict2020will be47%).Depressive disorder with high incidence, high recurrence, high disability characteristics, the consequences of a heavy economic burden, causing huge economic losses to society. United States (1994) in total health costs4%for the treatment of major depressive disorder, up to$43billion; of which only$9,000,000,000(28%) is the direct medical costs, and the remaining$34billion of patients with disease or disability caused by the loss. Diagnosis and treatment of the situation is not optimistic, lower overall recognition rate of depressive disorder, especially in the General Hospital. WHO multi-center collaborative research shows that15different countries or regions physician average recognition rate of depression was55.6%, Shanghai, China, the identification rate of21percent, far below the level of foreign Therefore, to enhance the prevention and treatment of depression, to find a positive and effective treatment, has a very important social and economic significance.The treatment of depression medication, psychotherapy, and ECT treatment of a variety of ways, the most common treatment remain antidepressant drug treatment. The relevant data show that10%-30%of patients for poor treatment response to antidepressants. In addition, for the therapy of antidepressant agents showed a lot of negative effects, such as decreased libido, nausea, vomiting, tremor, urinary block, physiological disorders, obesity, etc. Of SSRI and SNRI antidepressants side effects than traditional antidepressants weaken, but the mechanism of action and tricyclic drug is essentially the same, only for a single pathogenesis, only relieve some symptoms, not enough to take into account a variety of risk factors, depression can not solve a variety of problem incidence etiology and pathogenesis. And the efficacy and scope of application is not superior to conventional drugs, only50%of patients are completely relieved of symptoms. Its efficacy, onset latency, the pharmacological effects play a role can not be quickly resolved the patient complained of symptoms in2-4weeks.Venlafaxine is a5-serotonin and norepinephrine reuptake inhibitors, the mechanism of action of its dual activity in the treatment of depression than selective5 -HT reuptake inhibitors have an advantage, in the conversion strategycompared with SSRI has potential advantages. Safety and tolerability of the test statistics into the venlafaxine and SSRI side effects are nausea, vomiting, dry mouth and other digestive symptoms; dizziness, headaches and other neurological symptoms, no significant difference between the two. Prompt venlafaxine is a good safety and tolerability of antidepressants.Depression is a traditional Chinese medicine "depressive" category by qi stagnation, dysfunctional organs to the depressed, restless mood, chest stuffiness, flank pain, or irritability Yuku, or foreign body sensation in the pharynxdisease as the main clinical features. Understanding of the motherland medicine depressive for a long time, traditional Chinese medicine practitioners believe that the cause of depression has both internal and external, external because the emotional hurt, because dirty air, Yi Yu. Its pathogenesis is for qi stagnation, dysfunctional organs. The beginning of the depressive disease mainly to stagnation of qi, qi long time can cause blood stasis of the fire, phlegm knot, food stagnation, wet stop, and more true the card falling is easy to turn by the real imaginary, with its affect the organs and loss of blood, yin and yang are different, while the formation of a virtual lesion of heart, liver, spleen, kidney malfunction. The qi Gloomy builds easy is the basic principle of the treatment.The Modified Chaihuguizhi the soup national old TCM Professor Chen Baotian refer to the ancient and modern literature, on the basis of many years of clinical experience treating depression, after years of painstaking research, the important pathogenesis of depression, liver depression and exhausting, the by side Chaihuguizhi soupprepared on the basis of the Liver qi, stagnation and soothe the nerves of the level of yin and yang, five gods of the tune, and business health is characterized by the experience side. Chaihuguizhi soup Shugan Qi, phlegm achievements, raw Longmu and spiritual magnet town liver, Liver and Caulis, Fu Shen stagnation and soothe the nerves of various drugs to reach the liver and gas town liver Pinggan spleen and nourishing the heart, stagnation and sedative effect.In recent years, we have in clinical practice, using the Modified Chaihuguizhi soup merger venlafaxine treatment of depression carried out to obtain a certain effect. Clinical observation, combined with our previous treatment of moderate to severe depression in a retrospective analysis of flavored Chaihuguizhi soup combined with venlafaxine in the treatment efficacy. This topic will be more concerned about the mitigation of adverse reactions in patients with medication and to improve the situation, the efficacy and safety of traditional Chinese medicine to reduce the side effects of antidepressants to alleviate the core symptoms of depression and peripheral symptoms.Objective:Integrative efficacy and safety of the treatment of depression through a retrospective analysis of105patients with depression, further evaluation, especially of Chinese medicine in the antidepressant efficacy and alleviate Western medicine side effects. Objects and methods:1.ObjectsNanfang Hospital of Traditional Chinese Medicine clinic, ward and Chinese and Western medicine combined with the out-patient clinic of the Hospital encephalopathy in January2010to December2011, the ward diagnosis of depression in105patients.2.Inclusion and exclusion criteriaDiagnostic criteria of depression:are in line with the Chinese mental illness classification and diagnostic criteria3(CCMD-3) diagnostic criteria of depression. Inclusion criteria:(1) meet the diagnostic criteria of the CCMD-3depression cases;(2) Hamilton Depression Rating Scale (of HAMD-17) score≥17points;(3) gender and race is not restricted, inpatient and outpatient is not restricted;(4) age>18years;(5) Duration of≥30days or more;(6) Improve the routine examination, no significant serious organic disease;(7) the patients with completed12weeks of treatment.Exclusion criteria:(1) rule out other mental illnesses that do not meet the diagnostic criteria of the CCMD-3depression;(2) patients with the serious risk of suicide;(3) age<18years of age;(4) Improve the routine examination, associated with significant serious organic disease;(5) Pregnant women, lactating women;(6) The drug allergy;(7) Long-term use of psychotropic drugs and the dose of instability, monoamine oxidase inhibitors, lithium agents and valproic acid, carbamazepine and other antiepileptic agents;(8) Who do not meet the criteria for inclusion, not to take medication as prescribed, to determine the efficacy or infonnation is not congruent effects on efficacy and safety of judge.3.MethodsTest Method:A retrospective study.Patient selection criteria:diagnostic criteria, inclusion criteria and exclusion criteria. Diagnostic criteria with reference to the Chinese mental illness classification and diagnostic criteria3(CCMD-3) diagnostic criteria of depression, combined with traditional Chinese medicine dialectical standards.Therapy:the treatment group received venlafaxine sustained release tablets based on the joint the Modified Chaihuguizhi Tang (Bupleurum, Pinellia, Codonopsis, Licorice, Scutellaria, Cinnamon Twig, white peony root, ginger, jujube, Health keel, raw oystersspiritual magnet Caulis, Fu Shen, etc.); the control group was treated with venlafaxine sustained release tablets. Medication methods:two groups were treated with venlafaxine tablets, the treatment group combined with traditional Chinese flavored Chaihuguizhi soup. The treatment period of12weeks.Combination therapy provides that:during the treatment may not be combined for the use of any antipsychotic, antidepressant, mood stabilizer drugs. During the treatment of severe insomnia, can be an appropriate combination of zolpidem or alprazolam, zopiclone and short-acting benzodiazepines Zhuozhen Jing drugs, such as estazolam.Outcome measures:including demographic data, the impact of therapeutic factors, general physical examination and laboratory tests.Clinical criteria:Clinical criteria including depression, changes in scale scores before and after treatment.Observation of adverse events:the term covers of adverse events during clinical studies, the subjects and will affect the health of any clinical symptoms, the emergence or worsening of symptoms, syndrome, or certain diseases. Adverse events: new disease; treatment status of symptoms or signs of deterioration, or accompanied by the deterioration of the disease; the role of drug control; to participate in the trial; combination of one or more factors. Therefore, the term "adverse events" does not mean that a causal relationship to study drug.4.Statistical analysisAll data SPSS13.0statistical package for statistical analysis. The measurement data for the normality tests, such as the samples comply with the normal distribution with mean±standard deviation (±SD) said. Medication before and after each time point scale score change data using a repeated measures analysis of variance. After treatment, the HAMD reduction the sub efficacy analysis using generalized estimating equations (generalized estimating equations, GEE).Count data with the number of cases (%) said that the groups were analyzed using the X2test; such as data the theoretical value of<1, using Fisher’s exact test. Grade information Wilcoxon test was used. p<0.05was considered statistically significant.Results:1.HAMD scale score change:the difference between the two groups at different time points before and after administration were statistically significant (F=1204.507, P=0.000), treatment group, F=295.401, P=0.000, control group, F=167.256, P=0.000. HAMD scale score difference between the two groups was statistically significant (F=7.776, P=0.006) from each time point, with the exception of baseline HAMD scale score was no significant difference (t=-0.618, P=0.538), the medication for one week, two groups HAMD scale score differences were statistically significant (t=2weeks,4weeks,6weeks,8weeks-and12weeks-after-for2.654,3.397,3.203,2.840,3.322,3.821respectively, P=0.009,0.001,0.002,0.005,0.001,0.000), indicating that the medication from the patients at each time point, patients with depression HAMD scale scores decreased treatment group than the control group after one week. Between the two groups and taking time interaction effect (F=7.667, P=0.000), with the front at different time points between the two groups, multiple comparisons analysis coincide, indicating that changes in the two groups of patients with depression HAMD scale scores with to the medicine time to extend a downward trend.2.SDS scale score change:the difference between the two groups at different time points before and after administration were statistically significant (F=2012.564, P=0.000), treatment group, F=610.854, P=0.000, control group, F=68.278, P=0.000. SDS scale score differences between the two groups was statistically significant (F=116.876, P=0.000) from each time point of view, in addition to the baseline of SDS scale score difference was not statistically significant (t=-1.529, P=0.129), the medication for1week,2weeks,4weeks,6weeks,8weeks and12weeks after the two groups of SDS scale score differences were statistically significant (t=for3.037,7.126,11.466,16.711,21.326,23.747P value for0.003,0.000,0.000,0.000,0.000,0.000), show that the medication from patients at each time point, patients with depression SDS scale scores decreased treatment group than the control group after one week. Between the two groups and taking time interaction effect (F=258.781, P=0.000), with the front at different time points between the two groups, multiple comparisons analysis consistent, indicating that the two groups of patients with depression SDS scale score changes with to the medicine time to extend a downward trend.3.SAS scale score change:the difference between the two groups at different time points before and after administration were statistically significant (F=1123.184, P=0.000), treatment group, F=402.742, P=0.000, control group, F=60.464, P=0.000. SAS scale score difference between the two groups was statistically significant (F=92.576, P=0.000) from each time point of view, in addition to the baseline of SAS scale score difference was not statistically significant (t=-1.712, P=0.090), the medication for1week,2weeks,4weeks,6weeks,8weeks and12weeks after the two groups of SAS scale score differences were statistically significant (t=respectively2.209,6.873,12.002,17.548,17.172,18.394respectively,P=0.029,0.000,0.000,0.000,0.000,0.000), indicating that the medication from the patients at each time point, the depression scale scores of patients with SAS to reduce the magnitude of the treatment group than the control group after one week. Between the two groups and taking time interaction effect (F=150.707, P=0.000), with the front at different time points between the two groups, multiple comparisons analysis results coincide, indicating that changes in the two groups of depression scale scores of patients with SAS with to the medicine time to extend a downward trend. 4.HAMD sleep disturbance analysis:before and after administration there were significant differences between the two different time points (F=531.498, P=0.000) between the two groups and taking time interaction effect (F=7.657, P=0.000). Treatment group, F=137.232, P=0.000, control group, F=72.397, p=.000. Sleep disturbance score difference between the two groups was statistically significant (F=27.041, P=0.000) from each time point, with the exception of baseline sleep disturbance score was no significant difference (t=0.518, P=0.605). In addition, medication1week,2weeks,4weeks,6weeks,8weeks and12weeks after the two sets of sleep disturbance score differences were statistically significant (t=3.946,5.417,4.636,5.787,5.739,5.3575,Pvalueswere0.000,0.000,0.000,0.000,0.000,0.000), indicating that the two groups before treatment in patients with sleep disturbance score at the same level are comparable. At each time point from one week after the patients with medication, depression in patients with HAMD sleep disturbance score decreased treatment group than the control group.5.HAMD depressive and anxiety reaction analysis:before and after administration there were significant differences between the two different time points (F=546.509, P=0.000) between the two groups and taking time interaction effect (F=2.911,P<0.008). Treatment group, F=133.542, P=0.000, control group, F=79.791, p=.000. Depressive and anxiety reaction differences in scores between the two groups was statistically significant (F=2.032, P=0.157) from each time point, the baseline period and medication for one week, two weeks, four weeks, six weeks of depressive and anxiety reaction score was no significant difference(t=-0.658,1.368,1.904,1.573,1.444,Pvalueswere0.512,0.174,0.060,0.119,0.152), the two groups after8weeks and12weeks of depressive and anxiety reaction score difference was statistically significant (t=2.578,2.125,P values were0.011,0.037), indicating that the two groups of patients with depressive and anxiety reaction score at the same level before treatment, comparable, and since the patients taking a week,2weeks,4weeks,6weeks, two groups of depression in patients with HAMD depressive and anxiety reaction score lower of considerable magnitude. However, since patients with medication for eight weeks and12weeks of HAMD response of depressive and anxiety reaction decreased after the treatment group than the control group.6.HAMD apathy analysis:There were significant differences between the two groups at different time points before and after administration (F=125.812, P=0.000) between the two groups and taking the time does not exist an interaction effect (F=0.660, P=0.682). Treatment group, F=27.778, P=0.000, control group, F=19.172, p=.000. Between the two groups apathy score was no significant difference (F=0.003. P=0.954) from each time point, the baseline period and medication for1week,2weeks,4weeks,6weeks,8weeks,12weeks after two sets of apathy score differences were not statistically significant (t values were-0.801,0.036,0.343,0.521,-0.037,-0.174,-0.243, P value for0.425,0.971,0.732,0.604,0.9700.862,0.808), indicating that the two groups of patients with emotional indifference in the pre-treatment score at the same level are comparable, and medication from patients at different time points after one week, two groups of patients with depression HAMD apathy reduction of the score of considerable magnitude.7.HAMD somatic symptoms analysis:before and after administration there were significant differences between the two different time points (F=421.576, P=0.000) between the two groups and taking the time does not exist an interaction effect (F=1.675, P=0.125). Treatment group, F=114.595, P=0.000, control group, F=96.139, p=0.000. Somatic symptoms score differences between the two groups was statistically significant (F=0.886, P=.349) from each time point, the baseline period and medication for1week,2weeks,4weeks,6weeks,8weeks,12weeks the two groups after the somatic symptoms score differences were not statistically significant (t value were-0.418,1.447,1.186,1.583.0.904,0.472,0.399, P values were0.677,0.151,0.238,0.116,0.368,0.638,0.691) that before treatment in patients with somatic symptoms score at the same level are comparable, and medication from patients at different time points after one week, a considerable decrease of somatic symptoms in patients with HAMD scores of two groups of depression.8.HAMD points reduction efficacy analysis:Treatment group and control group (Z=3.82, P<0.001), treatment group than the control group; significant difference (Z=13.64, P<0.001) between the different time points, with time, the efficacy ofthe better; no interaction effect between group and time point (Z=-0.43, P=0.668).one week, two weeks after treatment,4weeks,6weeks,8weeks,12weeks each time point, treatment group and the level of efficacy in the control group Rank:55.63,49.50;61.85,41.20;60.50,43.00;63.21,39.39;58.83,45.22;60.43,43.09. The two groups after treatment at each time point differences were statistically significant (Z=-2.360, P=0.018; Z=-3.985, P<0.000; Z=-3.714, P<0.000; Z=-4.403, P <0.000; Z=-2.723, P=0.006; Z=-3.809, P<0.000).9.The onset time of analysis:one week of treatment, the treatment group and control group differences in the onset time was statistically significant (X2=16.293, P <0.000), treatment group,30%of patients the onset, while the control group did notapparent onset. In the first two weeks of treatment, treatment and control groups, more significant difference (X2=19.604, P<0.000), treatment group88.3%of patients on the onset time of onset, and control group, only48.9%in patients with onset.10.Treatment of the12th week cure rate:the treatment and control groups in clinical cure rates on the difference was statistically significant (X2=14.463, P0.000).12th week of treatment, the treatment group clinical cure rate was88.3%, while the control group, the clinical cure rate was only55.6%. 11.Analysis of adverse reactions:a variety of adverse effects of the treatment group were lower than the control group (X2=10.423, P<0.001), constipation (X2=6.099, P=0.014<0.05) and sexual dysfunction in both groups in the dry mouth (X2=4.257, P=0.039<0.05) differences compared to the incidence of statistically significant treatment group were significantly lower incidence of dry mouth, constipation and sexual dysfunction.Conclusions:1.Venlafaxine the Modified Chaihuguizhi soup merge text on the improvement of depression and with anxiety disorders is superior to single venlafaxine, but with the extension of the duration of treatment, the improvement of depression and anxiety disorders may be more stable.2.Modified Chaihuguizhi soup combined venlafaxine on sleep disorders to improve better than the venlafaxine group. Improvement in response to depression and anxiety, until after8weeks of treatment, venlafaxine group is superior to single, may be prompted with the treatment time, improve the efficacy of depression and anxiety reaction became clear. Of apathy and the improvement of physical symptoms, the efficacy of performance is not obvious.3.Modified Chaihuguizhi soup with venlafaxine clinical cure rate was88.3%, while only55.6%clinical cure rate in the venlafaxine group alone. Prompted the Modified Chaihuguizhi soup joint venlafaxine clinical cure rates may be higher than venlafaxine alone.4.Modified Chaihuguizhi soup combined venlafaxine30%in patients with onset during the first week, after two weeks of treatment, the onset of88.3percent. At the same time, a single venlafaxine only in the second week,48.9%in patients with onset. Tip the time of onset was significantly faster than venlafaxine alone.5.Modified Chaihuguizhi soup with venlafaxine may alleviate the side effects of venlafaxine in varying degrees, especially in reducing performance on adverse reactions such as dry mouth, constipation and sexual dysfunction may be more significant.

        加味柴胡桂枝汤合并文拉法辛治疗中重度抑郁症的回顾性研究

摘要3-12ABSTRACT12-25第一章 前言28-37    参考文献34-37第二章 临床研究37-66    第一节 研究对象37-39    第二节 研究方法39-43    第三节 研究结果43-66第三章 分析与讨论66-83    一、抑郁症的发病机制66-69    二、祖国医学对抑郁症的认识69-72    三、肝郁伤神是本病的重要病机72    四、柴胡桂枝汤抗抑郁作用研究72    五、组方配伍及方义72-75    六、临床疗效分析75-79    参考文献79-83第四章 全文总结83-85    一、主要研究结论83    二、展望与不足83-85综述85-97    参考文献93-97附录97-104在读期间发表论文情况104-105致谢105-107附件107

  本文关键词：加味柴胡桂枝汤合并文拉法辛治疗中重度抑郁症的回顾性研究，由笔耕文化传播整理发布。