【作者】 高延秋；

【导师】 刘坤申； 籍振国；

【作者基本信息】 河北医科大学 ， 内科学， 2007， 硕士

【摘要】 目的:心血管神经症是心内科门诊的常见病,该病无器质性心脏病的证据,与体质、行为、神经精神类型、外周环境、遗传等因素有关。现代医学对此症尚无满意疗法,并容易复发。中医中药采用疏肝理气、调和营卫、和胃降逆、镇静安神等,为本病的治疗提供了有效方法。本研究的目的是观察服用疏肝理气中药组方柴胡安心胶囊(院内制剂)对心血管神经症的疗效与安全性。方法:选择2006年1月-2006年10月我院门诊和住院的心血管神经症患者,有多种心血管系统的躯体症状,如胸痛、胸闷、心悸、头晕、失眠、多梦、气短、憋气、叹息等,但经客观检查无器质性心脏病证据,同时符合中医郁症诊断标准。中医辨证为肝郁气滞,营卫失调,心神不宁证,症状分级量化标准总积分为6分以上的患者,并经汉密尔顿(Hamilton)焦虑和抑郁量表等检查符合焦虑症和(或)抑郁症者。共入选102例,年龄18-65岁,其中男性32例,女性70例。除外冠心病心绞痛、高血压、椎-基底动脉或慢性脑供血不足、器质性上消化道疾病、器质性神经、精神疾病;并除外合并重度高血压,重度心肺功能不全,重度心律失常,肝、肾、造血系统等严重原发性疾病者;妊娠或哺乳期妇女;过敏体质或对多种药物过敏者。对所有入选患者随机分为柴胡安心胶囊治疗组和黛力新对照组,治疗组给予柴胡安心胶囊口服,2-4粒,日三次。对照组给予黛力新口服,一片,日二次(早、午服),心率偏快者可给予美托洛尔或普萘洛尔配合治疗,且服药期间不再服用其他任何药物。若服药期间出现严重不良反应,试验过程中出现严重并发症或症状恶化,必须采取紧急措施者应停药。对所有入选患者于试验开始前均测量血压、心率,做心电图,行血尿便常规、肝肾功能检查;并按中医症状分级量化标准和汉密尔顿(Hamilton)焦虑、抑郁量表进行评分。并分别于治疗后第一、二、三、四周观察所选病例的症状改善情况(采用等级评分),且于治疗后第四周进行上述安全性指标(血尿常规、肝肾功能)的监测,记录各项指标。所用数据输入SAS统计分析系统进行统计,计量资料用均数±标准差表示,组内治疗前后比较用配对t检验,组间比较采用t检验,计数资料采用X2检验。P<0.05为统计学有显著性差异。结果:1总样本数102例,无死亡和失访病例。其中男性32例,女性70例,性别比例(男:女)≈1:2。年龄:18~29组8例,30~39组14例,40~49组29例,50~59组36例,60~65组15例。其中主要表现为焦虑状态患者79例,占77.45%,主要表现抑郁状态患者9例,占8.82%,焦虑抑郁状态患者14例,占13.73%。2两组患者治疗前血压、心率、血尿便常规、肝肾功能等无统计学差异(P>0.05),资料均衡,具有可比性,治疗后与治疗前相比,上述指标无显著变化(P>0.05)。3采用中医症状评分判定,柴胡安心胶囊治疗28天后其总有效率为100%,黛力新治疗28天后其总有效率为92%,治疗均有效,但两组的总有效率无差别(X2=2.467 P=0.116>0.05)。(见附表1、附图1)4柴胡安心胶囊与黛力新均可明显改善心血管神经症患者的症状,治疗28天后与治疗前相比,中医症状分级量化评分和汉密尔顿(Hamilton)焦虑(HAMA)、抑郁量表(HAMD)评分比较均有显著改善(P<0.001),且柴胡安心胶囊疗效发挥更快,疗效更高。(见附表2、3、4、5、6、7及附图1、2、3)5两组中医症状分级量化评分与治疗前相比均有降低,但两组之间无统计学差异(t=0.61 P=0.54>0.05)(见附表2、附图1),但柴胡安心胶囊在治疗后第二周与第三周时比黛力新更有效(P<0.05),说明柴胡安心胶囊疗效发挥更快,疗效更高。(见附表7)6两组汉密尔顿(Hamilton)焦虑量表评分比较,柴胡安心胶囊组比黛力新组对于心血管神经症患者的疗效好,两组之间有显著性差异(4.75±1.64vs6.98±1.67;t=3.24 P=0.0016<0.01)(见附表3、附图2),且治疗开始后各阶段柴胡安心胶囊组均比黛力新组更有效,两组之间有显著性差异(P<0.001)。(见附表7)7两组汉密尔顿(Hamilton)抑郁量表评分与治疗前相比均有降低,但两组间无统计学差异(4.13±0.82vs4.70±1.57;t=0.57 P=0.5668>0.05)(见附表4、附图3),且治疗开始后的各阶段两组的有效率无差别(P>0.05)。(见附表7)8两组对肝肾功能均无影响:治疗28天后,ALT、AST、BUN、CRE各指标与治疗前比较无显著变化(P>0.05)。9安全性分析:全程观察治疗后的结果中102例均无不良反应,安全性属1级。结论:1柴胡安心胶囊治疗心血管神经症总有效率达100%,优于抗焦虑、抗抑郁有效药物黛力新,疗效确切,无不良反应。为安全有效的中药制剂。2柴胡安心胶囊治疗焦虑型神经症伴有躯体症状者疗效优于黛力新,而对抑郁型表现则无显著差异。3初步观察提示心血管神经症患者的神经精神类型以焦虑型的患者居多。更多还原

【Abstract】 Objective: Cardiac neurosis is a frequent disease in the cardiology clinic, which is associated with body constitution, nerves, behavior, environment, and heredity. However, there is no evidence organic heart disease. The symptoms of cardiac neurosis are highly variable and durable. During seeking the treatment for cardiac neurosis, most of the patients find it very difficult to cure after many attempts. Generally, modern western medicine is lacking efficacy in curing this disease, because of many drawbacks: severe side effects, poor patients’adherence, and high rate of recurrence. Conversely, Traditional Chinese Medicine has many advantages over Western Medicine due to its features of differentiation of symptoms and signs to treat. According to the theory of Traditional Chinese Medicine, unfolding liver and gloomy, calming the adverse-rising energy, making lucid yang rise and turbid yin descend is the key point of the treatment.We designed this study to determine the efficacy and safety of chaihu anxin capsule in cardiac neurosis.Methods: From July 2005 to December 2006, we enrolled sixty cardiac neurosis patients in our hospital. The including criteria were unspecific body and nerve symptoms, such as chest pain, chest distress, palmus, dizziness, insomnia, dream, short breath, suffering breathing obstruction, sigh. However, there was no evidence of organic heart disease. Or diagnosed with melancholia according to differentiation of symptoms and signs of traditional Chinese medicine is stagnation of QI due to depression of the liver, yingqi and weiqi out of tune and being unpeaceful in mind. The total score of symptom of grade quantization standard reached at least 6, and, at the same time, with anxiety or depression disorder diagnosed with Hamilton anxious and depression scale.Exclusion criteria were: coronary heart disease, angina pectoris, hypertension, arteria basilaris disease, ischemic brain disease, organic upper digestive tract disease, organic nerve disease and mental disorders, severe heart and lung functional defect, arrhythmia, severe primary liver disease, primary kidney disease, primary hematopoietic system disease, pregnancy or lactation femme, hypersensitiveness constitution or hypersensitive with sorts of drugs in the capsule. In total, 102 patients (32 male and 70 female) were enrolled in the study.They were randomized into chaihu anxin capsule group and Dailixin group. The patients in chaihu anxin capsule group were given chaihu anxin capsule orally (2-4 pills, ter in die), whereas the patients in dailixin group took dailixin orally (one pill in morning and another in the noon). For those with rapid heart rate, metoprolol or propanolol was given. If there were any severe side effects or complications, participants could discontinue the drugs they took.The data of blood pressure, heart rate, electrocardiogram and been tested blood, urine and suitable routine, liver and renal function, score based on Chinese medical science symptom grade quantization reference, Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) were collected at baseline. We assessed the symptoms, score based on Chinese medical science symptom grade quantization reference, Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) at week 1, 2, 3 and 4 respectively. All the safety data were also collected at week 4.All statistical analyses were performed with two-sided alternatives and a typeⅠerror of 0.05 and with SAS software (version 6.12). Initially the homogeneity of variance among all the groups was analyzed. All the data were expressed as mean±standard deviation (mean±SD) and students t test was used to explore statistical significance. Chi-square test was used for analysis of categorical data.Results: 1 We enrolled 102 patients (32 males and 70 females) in total. Eight patients’age ranged 18 to 29; fourteen patients aged between 30~39; twenty nine patients was between 40 to 49 years old; thirty six patients were aged between 50 to 59; fifteen patients’age were between 60 to 65. Seventy nine patients presented with anxiety, making up 77.45 % in the population. Nine patients’major presentation was depression, making up 8.82% of the population. Fourteen patients presented with anxiety-depression, making up 13.73% of the population. All patients accomplished the follow up. There were no death and drop out during the study period.2 The clinical characteristics of the two groups matched well. Compared with baseline, there was no significant changes in the blood pressure, heart rate, blood, urine and suitable routine, liver and renal function after treatment (p>0.05).3 After 28-days treatment, the total effective rate was 100% in chaihu anxin capsule group and 92% in dailixin group. There was no significant difference between two groups (X2=2.467 P=0.116>0.05, Fig 1, table 1).4 Both chaihu anxin capsule and dailixin could significantly improved the symptoms of the Chinese medical science symptom score in patients with cardiac neurosis(P<0.001).Similar therapeutic effects occurred in HAMA and HAMD score (P<0.001,table 2,3,4,5,6,7 fig1,2,3).5 There was a trend that both both chaihu anxin capsule and dailixin could lower the score in Chinese medical science symptom grade quantization reference, however, there was no significant statistical difference (table 2, fig 1). But, the data showed chaihu anxin capsule had more effects at week 2 and week 3, compared with dailixin group, suggestive of chaihu anxin had more rapid therapeutic effects (table 7).6 Compared with dailixin, chaihu anxin capsule significantly improved the symptoms in patients with cardiac neurosis according to Hamilton anxiety scale in whole study period (4.75±1.64vs6.98±1.67;t=3.24 P=0.0016, fig 2, fig 3).7 As compared with baseline, both chaihu anxin capsule and dailixin had a trend to lower the score in Hamilton depression scale, however, there was no significant difference (P >0.05, fig 4, fig 5). This trend persisted the whole study period (fig 7).8 Both chaihu anxin capsule and dailixin had no impact on liver and renal function. After 28-day treatment, there were no significant changes in ALT, AST, BUN, CRE.9 Safety profile: There were no side effects reported during the study period.Conclusions: 1 The efficacy rate of chaihu anxin capsule in treatment of Cardiac neurosis was 100%, which was superior over anti-depression and anti-anxiety drug dailixin. There were no side effects documented in the study period. Thus, it maybe a promising drug with good safty profile.2 As compared with dailixin, chaihu anxin capsule could significant improve the symptoms of patients who presented with anxiety, unspecific body and nerve symptoms. However there was no significant difference between two drugs in cardiac neurosis prestented with depression.3 Our data also showed that most of patient with cardiac neurosis presented in the clinic with anxiety.更多还原