摘要
研究背景
失眠是最常见的睡眠障碍,通常指患者对睡眠时间和(或)质量不满足,并影响白天社会功能的一种主观体验。全球约每10-12人中有1人患失眠,影响人们身心健康、生活质量和工作效率的第一问题是失眠。失眠是一种主观体验。患者的主观感受常常与客观的表现存在较大的差异。研究发现,失眠病人倾向于低估睡眠时间、高估睡眠潜伏期。目前,对失眠症的诊断,主要是通过患者主诉和医生问诊来诊断评估。
西医治疗失眠包括非药物性治疗和药物治疗两方面。认知行为疗法等非药物治疗避免了药物治疗的副作用,具有可靠的临床疗效,缺点是起效时间长,见效慢。西医药物治疗起效时间短,见效快,但长期服用安眠药物会出现多种副作用,形成对安眠药物的依赖,引起药源性疾病。突然停药还可引起戒断症状,患者往往存在恐惧心理,不愿意使用。
中医药治疗失眠强调天人合一,辨证论治,治病求本。采取的是个体化治疗,通过祛除影响睡眠的病邪,全面调理机体的阴阳气血,以恢复人体正常的睡眠。疗效相对稳定,且无西医镇静安眠药的副作用。周绍华教授天王补心丹加减方是周教授近些年从临床实践的治验和失败病例中摸索出来的。跟师学习期间临床见证了许多有效的验案,尤其以治疗心阴虚型失眠症者为多。
标准的RCT证据和复杂的临床实际难以吻合。西医的“病”和中医的“病—证”概念存在质性区别,方与“病—证”对应后用西医疾病的疗效标准判断不合中医医理。中医学和新兴的定性研究都遵从归纳分析的法则、自然的法则、开放的法则和整体观的法则。研究者希望在临床实际的现实条件下,运用定性研究和定量研究相结合的新思路探讨周绍华教授天王补心丹加减方治疗心阴虚型失眠症的临床疗效和治疗优势。
本研究分为两部分：文献综述和临床研究。1文献综述
从中西医对睡眠及失眠的认识及研究进展与研究中使用的有关定性研究和访谈法等方面分三部分进行综述。
2临床研究
目的：探索周绍华教授临床运用天王补心丹加减方治疗心阴虚型失眠症的思维模式和学术特点；明确周绍华教授天王补心丹加减方临床治疗心阴虚型失眠症的适应“病—证”和禁忌“病—证”要素；研究周绍华教授天王补心丹加减方治疗心阴虚型失眠症临床疗效；探讨影响天王补心丹加减方治疗心阴虚型失眠症临床疗效的因素及其与西药治疗比较的优势。
方法：
1应用半结构访谈法对应用天王补心丹加减方的周绍华教授及其3位徒弟医师以及16位接受天王补心丹加减方治疗的失眠症患者进行访谈,运用关联比较法,进行跨个案分析、归纳与总结。
2采用回顾性分析的方法,对门诊跟师诊治的心阴虚型失眠症病例进行“病—证”要素的分析。所有可能构成“病—证”要素的临床症状和舌象、脉象按频数统计,所有数据输入Excel表,频数为计数资料,采用频数、构成比等进行分析。根据著名数学家华罗庚教授推广的“优选法”中最著名的“黄金分割法”,以38.2%、61.8%为分割点,按“优选法”原则筛选周绍华教授天王补心丹加减方的主要“病—证”要素。
3采用前瞻性非随机对照临床试验。根据患者意愿,选择服用西药或中药,顺序纳入中药治疗组或西药治疗组。中药组予天王补心丹加减方,西药对照组予艾司唑仑。所有数据输入Epidata数据库,采用SPSS16.0软件分析。所有的统计检验均采用双侧检验,P值<0.05被认为差异有显著性意义。
4采用“三角互证法”对上述研究的结果进行三角互证。
结果：
1周绍华教授对失眠症病因病机的认识：周绍华教授通过对古方的改造,使之适应于现代人所患失眠症的病因病机。现在年轻人工作压力大,家庭生活压力大,用脑过度,伤心伤血,血不养心,出现失眠症。失眠症的关键病位在“心”,和肝、脾、肾有关系。心阴虚型失眠症的关键病机在阴虚。
2周绍华教授对失眠症辨病辨证的认识：(1)中医诊断失眠症,既要辨病,也要辨证,要以辩证为主。(2)心阴虚型失眠症患者除失眠症状外,还表现出焦虑情绪,也有抑郁。失眠后往往伴随出现抑郁焦虑的情绪,反之抑郁焦虑又影响睡眠,容易形成恶性循环。(3)辨证注重症状与舌象。
3周绍华教授应用天王补心丹治疗失眠加减的特色：周绍华教授认为,近些年临床表现以心阴虚型的失眠症患者增多,治疗心阴虚的首选方是天王补心丹。但要古为今用,要在古方基础上对天王补心丹进行改造：(1)阴虚主张用凉性药,如生地、玄参、麦冬、沙参等等。(2)增加清心除烦的抗焦虑药：莲子心、灯芯草、栀子清心除烦比较好。(3)增加解郁药：用花类、柴胡、香附等。认为花类让人心情舒畅,还入血分。(4)增加重镇安神药,如珍珠粉等。(5)焦虑属于有热,治疗要清热除烦。(6)药性太燥的药不宜用,如厚朴、木香之类。
4146例门诊病例回顾性分析发现,心阴虚型失眠症患者临床最多见的主病症状一睡眠障碍的症状是入睡困难,占82.19%；其次是眠浅易醒,占55.48%；而早醒为21.92%,多梦为25.34%。
反映心阴虚证主要证候的症状中,依次是心烦不安,占45.89%；多虑40.41%；疲倦乏力32.88%；心悸30.14%；口干少津28.77%；健忘25.34%；紧张23.97%；其他如头晕、手足心热、颧红潮热、自汗,盗汗、抑郁情绪等症状所占百分比均不足20%。
心阴虚型失眠症的舌象以舌红,苔薄黄者为最多,占45.21%；典型的舌红,苔少只占6.85%。脉象出现频率最高的是细脉,占58.22%,其次是沉脉,占37.67%,数脉占17.12%。
以“黄金分割法”38.2%为分割点,按“优选法”原则筛选周绍华教授天王补心丹加减方的主要“病一证”要素包括：入睡困难、眠浅易醒,心烦不安、多虑,舌红、苔薄黄,脉细。
5临床非随机对照研究的结果发现：中药组治疗前后改良的匹兹堡睡眠指数量表(PSQI)评分平均减分值为8.97。对照组治疗前后减分值为6.50。中药组治疗前后失眠严重指数量表(ISI)评分平均减分值为4.86,对照组治疗前后减分值为5.26。说明天王补心丹按照西医临床疗效的判断标准,和对照组使用艾司唑仑治疗比较,并无疗效优势。
虽然治疗前两组之间PSQI评分、ISI评分以及SAS、SDS评分都均衡可比,两组患者辨证都属于心阴虚型,但选择中药治疗患者的中医症状评分明显高于对照组。中药组治疗前中医症状评分量表为47.33±11.37,天工补心丹加减方治疗2周后为20.77±9.64。对照组治疗前为39.67±12.44,艾司唑仑治疗2周后为30.40±10.03。中药组和西药对照组治疗前后中医症状评分量表平均减分值比较,可见天王补心丹治疗组中医症状的改善最为显著。天王补心丹加减方的疗效体现在“心阴虚证”较西药有优势。
6失眠症是一种比较复杂的神经精神疾病,临床除辨证用药准确精当是影响疗效的主要因素外,还要注意患者是否合并躯体疾病,是否使用过西药,药物的煎服方法,医生临诊的言语举止都会一定程度上影响临床疗效。
7中医治疗失眠症与西医比较的优势：(1)中医治病是整体观思想指导下的治疗,不仅治病,还要针对有病的人进行干预。(2)中医辨病辨证相结合治疗疾病,灵活变通。(3)中医是全方位、多靶点治疗,在“症”的治疗方面效果好。
结论：
1周绍华教授天王补心丹加减方治疗心阴虚型失眠症临床疗效确切。和西药艾司唑仑的非随机对照临床研究也初步证实了该方治疗失眠症的临床疗效。
2周绍华教授天王补心丹加减方治疗失眠症的疗效来源于对失眠症病因病机的正确把握。辨证用药精准是临床疗效的关键,是影响临床疗效的主要因素。
3周绍华教授天王补心丹加减方的主要“病—证”要素包括：入睡困难、眠浅易醒,心烦不安、多虑,舌红、苔薄黄,脉细。
4中医对疗效的判断既是对“病”的疗效判断,更是对“病之证”的疗效判断。使用现行的西医失眠症临床疗效标准判断一种相对固定的中药方剂治疗失眠症的临床疗效不适用。天王补心丹加减方的疗效体现在“心阴虚证”较西药有优势,而体现在“失眠症”较西药没有优势。
5到中医院就诊并选择中药治疗的失眠症患者病情往往更为复杂。中医治疗伴躯体疾病的失眠症、失眠症伴多系统慢性疾病可能存在优势。
Introduction
Insomnia is one of the most common sleeping disorders. It refers to a kind of subjective dissatisfied experience of patients to their sleeping time or sleeping quality, which even affects their daily social function. One of every10-12people around the world suffers from insomnia, it has became the first problem that hurt our health, lower our quality of life and reduce our efficiency of work. Currently, insomnia is assessed mainly according to the complaint of a patient and the inquiry of a doctor.
In western medicine (WM), the management of insomnia includes non-drug therapy and drug therapy. Non-drug therapy like cognitive behavior therapy has shown reliable effect, it avoids the side effects of sleeping pills, but needs time to see the desired result. Drug therapy has short onset time, but causes dependence and a variety of side effects under long-term medication.
Traditional Chinese medicine (TCM) has its advantage of stable clinical effect to regain normal sleep without adverse reaction in the treatment of insomnia. TCM performs individual therapy, emphasizes that man is an integral part of nature, searches for the primary cause of insomnia. TCM doctors treat insomnia through syndrome differentiation to dispel pathogenic factors that influence sleep, and recover the balance between yin and yang, qi and blood.
Standard randomized controlled trial (RCT) evidences are not identical in mazy actual clinical practice. And the target of a special treatment in western medicine is a disease, but in TCM is a syndrome of a disease. To judge the effect of a TCM formula with western medicine criterion of therapeutic effect does not conform the theory of TCM, in which correspondence of a formula with its syndrome of a disease is advocated.
TCM follows the same principle with qualitative research of natural property, inductive method, open character and holism concept. The author tried to combine both qualitative and quantitative methods in the investigation of clinical effect and superiority of modified Tianwang Buxindan for insomnia of heart-yin deficiency.
Object
1To explore the thinking model and academic properties of Professor Zhou Shaohua in his clinical application of modified Tianwang Buxindan.
2To clarify the TCM "disease-syndrome" indications and contraindications of modified Tianwang Buxindan for insomnia of heart-yin deficiency.
3To study the clinical effect of modified Tianwang Buxindan for insomnia of heart-yin deficiency.
4To probe factors influence the clinical result of modified Tianwang Buxindan for insomnia of heart-yin deficiency.
5To investigate the advantage of modified Tianwang Buxindan for insomnia of heart-yin deficiency, compared with western medicine.
Method
1Semi-structured interview was applied to Professor Zhou Shaohua, his3apprentice doctors and16insomnia patients treated with modified Tianwang Buxindan in the study. Cross case analysis and induction was proceeded with association comparison.
2A prospective non-randomized controlled clinical trial of60cases was carried out among out-patients of insomnia of heart-yin deficiency. All subjects were orderly enrolled to herbal medicine group or western medicine group according to their personal intention. Patients to the TCM group were prescribed with modified Tianwang Buxindan, and patients to the WM group were prescribed with1-2mg of Estazolam.
3Triangulation was used to prove mutually the above results
Results
1Understanding of Professor Zhou Shaohua to the etiology and pathology of insomnia in TCM:In modern society, young generations suffer more stress from their work and life. They overstrain their nerves, which injure the heart and consume blood, lead to insomnia. The key pathogenic location of insomnia is "heart". Liver, spleen and kidney are also affected. The critical pathogenic mechanism of heart-yin deficiency insomnia is "yin-deficiency". Professor Zhou Shaohua modified the ancient formula-Tianwang Buxindan to make it matched to the changed etiology and pathology of insomnia presently.
2Understanding of Professor Zhou to the diagnosis and syndrome differentiation: Syndrome differentiation is more important than disease diagnosis for insomnia. Anxious emotion is more common than depressive emotion in heart-yin deficiency insomnia, and both impact sleep into a vicious circle. So it manifested in clinic with a syndrome of heart-yin deficiency. Professor emphasizes more of differentiation of symptoms and tongue picture for the recognition of heart-yin deficiency insomnia.
3Characteristics of modified Tianwang Buxindan:(1) Herbs of cool property are selected to nourish yin.(2) Herbs with function to clear heart fire and relieve restlessness are added to the formula, which has action of anti-anxiety.(3) flowers to alleviate depression are added.(4) Sedative mineral medicine are needed to fortify action of tranquilization.
4A retrospective survey of146cases shown the most common symptom of insomnia of heart-yin deficiency was difficulty to fall asleep, take up82.19%; then was shallow sleep,55.48%; early awakening and dreaminess were not so common among heart-yin deficiency insomnia patients.
Difficulty to fall asleep, shallow sleep, fussiness and restlessness, anxiety, red tongue with thin yellow coating and thready pulse were found to be the key manifestations of the insomnia "disease-syndrome" for modified Tianwang Buxindan according to the analysis with optimization method, if the percentage of38.2%was taken as a cut point.
5The result of prospective non-randomized controlled clinical trial shown the average subtraction score of PSQI in TCM group was8.97, and in WM group6.50; the average subtraction score of ISI in TCM group was4.86, and in WM group5.26.
Although the values of PSQI, ISI, SAS and SDS in both groups before treatment were well balanced and comparable, the average TCM symptom scale score in TCM group was47.33±11.37, which was much higher than that in the control group, which was39.67±12.44. After treatment, the average TCM symptom scale score in TCM group went down to20.77±9.64, while in the control group to30.40±10.03.
6Insomnia is a complicate neuropsychiatric disorder. Besides of the critical factor of appropriate differentiation and medication, there were some important factors also influence the clinical effect, such as the complication of somatic problems, past experience of western medicine, preparation and administration of herbal medicine, even the language, behavior could weigh in some degree.
Conclusion
1Modified Tianwang Buxindan was effective for insomnia, with superiority to western medicine Estazolam especially for heart-yin deficiency insomnia.
2The effect of modified Tianwang Buxindan for insomnia was based on the right understanding of the etiology and pathology of insomnia of heart-yin deficiency. It is essential for better clinical result to make a correct syndrome differentiation and a proper modification of the formula.
3The key manifestations of insomnia "disease-syndrome" for modified Tianwang Buxindan were as follows:Difficulty to fall asleep, shallow sleep, fussiness and restlessness, anxiety, red tongue with thin yellow coating and thready pulse.
4From the view of TCM, a TCM doctor need not only to judge the effect of a formula for a special disease in WM, but also for a special TCM "syndrome". To value the effect of a TCM formula for a WM disease according to the WM criteria is not complete, nor proper. Modified Tianwang Buxindan has shown its superiority only for heart-yin deficiency insomnia, but not for insomnia generally, compared with western medicine.
5Those insomnia patients would choose TCM decoction treatment in a TCM hospital might have more complicate situation. Modified Tianwang Buxindan might have an advantage for insomnia cases accompanied with somatic disorders or chronic multi-systematic illnesses.
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