从肝脾相关治疗老年轻型抑郁的理论研究和探讨

【作者】 张皞珺；

【导师】 郭霞珍；

【作者基本信息】 北京中医药大学 ， 中医基础理论， 2010， 博士

【摘要】 抑郁是老年人中最常见的精神疾患,它严重危害着老年人的健康和生存质量。在社会日益老龄化的今天,有效防治老年抑郁,对提高老年人的生活质量有重要意义。本课题以逍遥散为研究对象,在文献研究的基础上,通过病证结合的方法,进行前瞻性实用性随机对照临床试验,初步规范了老年轻型抑郁逍遥散证的适应症,以期指导群众合理使用逍遥散成药防治抑郁,并为规范中成药适应症,推广中成药的合理使用探索方法。本论文主要分为两部分：理论研究和临床研究。1理论研究：理论研究部分通过古今文献的整理、归纳,从生理功能及五行关系上探讨了肝脾的相关性,指出抑郁与肝脾两脏关系密切,老年轻型抑郁的基本病机是肝气血不足,气机郁滞,逍遥散通过健脾养肝以补肝体而助肝用,药性中和,切中老年抑郁肝气血不足,气机郁滞的基本病机,是老年抑郁的对证之方2临床研究：临床研究采用实用性随机对照试验,以老年轻型抑郁为切入点,在文献研究的基础上,结合预调查的结果及专家意见,初步确定逍遥散老年轻型抑郁的适应症,以流调用抑郁量表结合初步确定的逍遥散适应症在社区筛查受试者。本次试验共收集十个社区126名受试者,采用整群随机分组,试验组71人,对照组55人,试验组口服逍遥丸,对照组给予中医情志养生健康教育讲座,每次50分钟左右,然后进行小组讨论,每次30分钟左右,观察6周。治疗前后以HAMD量表进行评分,治疗0、2、4、6周以中医证候的评分表进行评分,观察两种干预的疗效以及各种症状改善的差异。结果：1按HAMD减分率评估临床总疗效ITT分析显示,治疗后试验组的总有效率是77.46%,对照组是18.18%,经X2检验,两组间差异有显著统计学意义(P=0.000)。PP分析显示,试验组总有效率是83.33%,对照组是18.87%,经X2检验,两组间差异有显著统计学意义(P=0.000)。PP分析和ITT分析结果一致。说明试验组临床总疗效优于对照组。2按中医证候积分减分率评估中医证候疗效ITT分析显示,治疗后试验组的总有效率是87.32%,对照组是10.91%,经X2检验,两组间差异有显著统计学意义(P=0.000)。PP分析显示,试验组总有效率是92.42%,对照组是11.32%,经X2检验,两组间差异有显著统计学意义(P=0.000)。PP分析和ITT分析结果一致。说明在中医证候疗效方面,试验组优于对照组。3按HAMD减分率评估试验组不同性别患者的临床疗效ITT分析显示,试验组治疗后男性总有效率63.16%,女性总有效率82.69%,经X2检验,两组差异无统计学意义(P>0.05)；PP分析显示,试验组男性总有效率66.67%,女性总有效率87.5%,经X2检验,两组差异无统计学意义(P>0.05)。PP分析和ITT分析结果一致。说明逍遥丸治疗老年轻型抑郁的临床疗效无性别差异。4按中医证候积分减分率评估试验组不同性别患者的临床疗效ITT分析显示,治疗后试验组男性总有效率78.95%,女性总有效率88.46%,经X2检验,两组差异无统计学意义(P>0.05)；PP分析显示,试验组男性总有效率88.9%,女性总有效率91.8%,经X2检验,两组差异无统计学意义(P>0.05)。PP分析和ITT分析结果一致。说明逍遥丸治疗老年轻型抑郁的中医证候疗效无性别差异。5中医症状疗效在文献研究的基础上,结合预调查的结果及专家意见,初步确定逍遥散老年轻型抑郁的适应症是抑郁情绪、急躁易怒、悲伤易哭、神疲倦怠、食少、胸闷、咽喉异物感、失眠、头昏、口干、潮热汗出、寒热往来12个指标。本研究显示,老年轻型抑郁逍遥散证患者常见症状(以频率>80%为标准)是抑郁情绪,急躁易怒,悲伤情绪,失眠,神疲倦怠；症状较明显(以症状均值≥最高分值的70%为标准)的是咽喉异物感,口干,神疲倦怠,失眠,食少,寒热往来。失眠,神疲倦怠是老年轻型抑郁逍遥散证常见并表现明显的症状。对老年轻型抑郁逍遥散的适应症进行重复测量方差分析,结果表明,除口干外其他11个指标干预主效应均有统计学意义(p<0.05),即不考虑时间因素,干预不同,患者抑郁情绪、急躁易怒、悲伤易哭、神疲倦怠、食少、胸闷、咽喉异物感、失眠、头昏、潮热汗出、寒热往来的得分有差异；12个指标的时间主效应有统计学意义(p<0.01),即不考虑干预的因素,抑郁情绪、急躁易怒、悲伤易哭、神疲倦怠、食少、胸闷、咽喉异物感、失眠、头昏、口干、潮热汗出、寒热往来的得分随时间的变化而变化。交互图显示,干预后,随时间的变化,试验组抑郁情绪、急躁易怒、悲伤易哭、神疲倦怠、食少、胸闷、咽喉异物感、失眠、头昏、潮热汗出、寒热往来的得分明显低于对照组。PP分析和ITT分析结果一致。说明试验组的抑郁情绪、急躁易怒、悲伤易哭、神疲倦怠、食少、胸闷、咽喉异物感、失眠、头昏、潮热汗出、寒热往来11个症状改善优于对照组。本研究结束时,试验组症状改善较明显的是食少,神疲倦怠,头昏和咽喉异物感,症状改善程度较少的是失眠和寒热往来。6试验组不同性别患者中医症状的疗效分析本研究显示,老年女性轻型抑郁逍遥散证患者常见症状(以频率≥80%为标准)是抑郁情绪,急躁易怒,悲伤情绪,失眠,神疲倦怠；症状较明显(以症状均值≥最高分值的70%为标准)的是口干,咽喉异物感,神疲倦怠,失眠,头昏,寒热往来。失眠,神疲倦怠是老年女性轻型抑郁逍遥散证常见并表现明显的症状。老年男性轻型抑郁逍遥散证患者常见症状(以频率≥80%为标准)是抑郁情绪,急躁易怒,失眠,神疲倦怠；症状较明显(以症状均值≥最高分值的70%为标准)的是咽喉异物感,食少,口干,神疲倦怠,失眠,头昏。失眠,神疲倦怠是老年男性轻型抑郁逍遥散证常见并表现明显的症状。本研究结束时,试验组女性较男性改善明显的症状是头昏,神疲倦怠,急躁易怒,失眠,寒热往来。男性较女性改善明显的症状是胸闷,潮热汗出；男女患者在食少,咽喉异物感,抑郁情绪,悲伤情绪方面改善程度相当。结论：1以肝脾相关理论指导老年轻型抑郁的治疗具有临床意义。2肝郁血虚脾弱是逍遥散的主治证。老年轻型抑郁逍遥散证的临床表现是情绪抑郁,急躁易怒,悲伤情绪,神疲倦怠,食少,寒热往来,潮热汗出,头昏,失眠,胸闷,咽中异物感。其舌脉宜为舌质淡、舌苔白、脉弦。3老年轻型抑郁逍遥散证患者经逍遥丸干预后症状有一定程度的改善,症状改善较明显的是食少,神疲倦怠,头昏和咽喉异物感,症状改善程度较少的是失眠和寒热往来。性别不同,改善明显的症状不尽相同,女性较男性改善明显的症状是头昏,神疲倦怠,急躁易怒,失眠,寒热往来。男性较女性改善明显的症状是胸闷,潮热汗出。4与老年抑郁量表比较,中医症状与流调用抑郁自评量表相结合更适合作为在社区筛查老年抑郁的调查工具。更多还原

【Abstract】 Depression is the most common mental illness in the older people, which have seriously influenced on the older people’s health and quality of life. With the coming of the aging society, it is important and necessary to improve older persons’quality of life through effective prevention and treatment of minor depression in older adults.The research object is xiaoyao powder. Based on the research in the literature, a Practical randomized controlled trial was done to find symptoms improved by xiaoyao pill for minor depression in older adults. The research aimed to promote rational use of xiaoyao pill in community.The paper text is divided two parts:theoretical and clinical research.1 Theoretical research:We begin to work from the literature reorganization, study the relationship between liver and spleen from their different physiological and the five elements theory angle, think that there are close relationship between liver-spleen disorder and depression.Studies shown that the syndrome of stagnation of liver qi and it’s movement was the most commonly seen cases. The basic pathogenesis of elderly minor depression is deficiency of liver qi and blood, and then causes the stagnation of liver qi. To invigorate the spleen and nourish the liver, to soothe liver qi and alleviate mental depression are the actions of xiaoyao powder, so we selected xiaoyao powder for treating elderly minor depression.2 Practical randomized controlled trials:based on the research in the literature, combined with pre-survey results and expert opinion, a summery was made and a quantitative form was designed. A randomized controlled trial with practical was done. cases were collected with Center for Epidemiological Survey,Depression Scale (CES-D) and face to face interview.Observations made on of 126 cases in total,71 cases of the treatment group and 55 cases of the control group with treatment time for six weeks.The treatment group were given XiaoYao pill, control group were given psychological intervention.Before and afer trial, Patients were evaluated with Hamilton Depression Rating Scale (HAMD), and the syndrome of Chinese Medicine Evaluation Form were conducted after two weeks, four weeks and six weeks..Results:1 Clinical curative effect of xiaoyao pill on minor depression in older adultsClinical treatment effect outcomes were assessed using HAMD scale.ITT (intention to treat) analysis showed the total rate of effect in the treatment group was 77.46%, whereas it was 18.18% in the control group.PP (explanatory analysis) analysis showed that they were 83.33% and 11.32%, respectively.Significant difference between two groups was detected (p=0.000).Treatment group is better than control group in total effect rate. 2 Curative effects were assessed using Chinese medicine criteria ITT (intention to treat) analysis showed the total rate of effect in the treatment group was 87.32%,whereas it was 10.91% in the control group.PP (explanatory analysis) analysis showed that they were 92.42% and 11.32%,respectively.Significant difference between two groups was detected(p=0.000).Treatment group is better than control group in total effect rate. 3 Clinical effect of XiaoYao pill on different sex older adults with minor depressionITT (intention to treat) analysis showed the total rate of effect in the male treatment group was 63.16%,whereas it was 82.69% in the female treatment group.PP (explanatory analysis) analysis showed that they were 66.67% and 87.5%,respectively.No significant difference between two groups was detected(p>0.05).No adverse effect was found. 4 Effect of xiaoyao pill were assessed using Chinese medicine criteria in different sex older adults with minor depression.ITT (intention to treat) analysis showed the total rate of effect in the male treatment group was 78.95%,whereas it was 88.46% in the female treatment group.PP (explanatory analysis) analysis showed that they were 88.9% and 91.8%,respectively.No significant difference between two groups was detected(p>0.05).No adverse effect was found. 5 Clinical effect of xiaoyao pill on the clinical symptomsOn the basis of published literature studying and the suggestion of the expert, symptoms that xiaoyao pill can cure were primarily establish, they were depression,irritability and susceptibility to rage,easy crying due to sadness, spiritual lassitude and fatigue, dry mouth and throat,poor appetite, chest oppression,sensation of foreign body in the throat,insomnia,dizziness,tidal fever, alternate cold and fever. The signs should be whitish tongue, thin and white tongue, taut pulse.This study shows that the most common symptoms of the syndromes treated by Xiaoyao pill for minor depression in older adults are depression,irritability and susceptibility to rage,easy crying due to sadness, insomnia, spiritual lassitude and fatigue;Obvious symptoms are sensation of foreign body in the throat, dry mouth and throat, spiritual lassitude and fatigue, insomnia, poor appetite, alternate cold and fever. Insomnia, spiritual lassitude and fatigue are common and obvious symptoms.Repeated measures analysis of variance showed that the main effects of intervention on 11 clinical symptoms (depression,irritability and susceptibility to rage,easy crying due to sadness, spiritual lassitude and fatigue, poor appetite, chest oppression,sensation of foreign body in the throat,insomnia,dizziness, tidal fever, alternate cold and fever) were significant(p<0.05),in other word,the 11 clinical symptoms (depression,irritability and susceptibility to rage,easy crying due to sadness, spiritual lassitude and fatigue, poor appetite, chest oppression,sensation of foreign body in the throat,insomnia,dizziness, tidal fever, alternate cold and fever) were significantly different with the chang of the intervention level without taking account the change of time.The main effects of time on 12 clinical symptoms (depression,irritability and susceptibility to rage,easy crying due to sadness, spiritual lassitude and fatigue, dry mouth and throat,poor appetite, chest oppression,sensation of foreign body in the throat,insomnia,dizziness,tidal fever, alternate cold and fever) were significant(p<0.01).There were significant interactions between time and intervention on 11 clinical symptoms expect for dry mouth and throat. Interaction diagram indicated that the improvement degree of Depression,irritability and susceptibility to rage,easy crying due to sadness, spiritual lassitude and fatigue, poor appetite, chest oppression,sensation of foreign body in the throat,insomnia,dizziness, tidal fever, alternate cold and fever were lower in treatment group than that of control group. PP analysis and ITT analysis results are consistent.After intervention,more significantly improving symptoms are poor appetite, spiritual lassitude and fatigue, dizziness, sensation of foreign body in the throat,less significantly improving symptoms are insomnia and alternate cold and fever in treatment group. 6 Clinical effect of XiaoYao pill on the clinical symptoms in different sexThis study shows that the most common symptoms of the syndromes treated by Xiaoyao pill for minor depression in female older adults are depression,irritability and susceptibility to rage,easy crying due to sadness, insomnia, spiritual lassitude and fatigue;Obvious symptoms are dry mouth and throat,sensation of foreign body in the throat, spiritual lassitude and fatigue, insomnia, dizziness, alternate cold and fever. Insomnia, spiritual lassitude and fatigue are common and obvious symptoms.The most frequently symptoms of the syndromes treated by Xiaoyao pill for minor depression in male older adults are depression,irritability and susceptibility to rage, insomnia, spiritual lassitude and fatigue;Obvious symptoms are sensation of foreign body in the throat, poor appetite,dry mouth and throat, spiritual lassitude and fatigue, insomnia, dizziness. Insomnia, spiritual lassitude and fatigue are common and obvious symptoms.After intervention, the symptoms which were improved more significantly among the female than male in treatment group are dizziness, spiritual lassitude and fatigue, irritability and susceptibility to rage, insomnia, alternate cold and fever.The symptoms which were improved more significantly among the male than femmale in treatment group are chest oppression, tidal fever. The Male and female patients had similar effection on poor appetite, sensation of foreign body in the throat, depression, easy crying due to sadness. Conclusio:1 To rely the theory of liver-spleen correlation in treating elderly minor depression got satisfaction curative effects2 symptoms of the syndromes treated by Xiaoyao pill for minor depression in older adults are depression,irritability and susceptibility to rage,easy crying due to sadness, spiritual lassitude and fatigue, poor appetite, chest oppression,sensation of foreign body in the throat,insomnia,dizziness,tidal fever, alternate cold and fever. The signs should be whitish tongue, thin and white tongue, and taut pulse. 3 symptoms of minor depression in older adults belong to syndrome treated by xiaoyao pill were improved after intervention by xiaoyao pill.More significantly improving symptoms are poor appetite, spiritual lassitude and fatigue, dizziness, sensation of foreign body in the throat,less significantly improving symptoms are insomnia and alternate cold and fever. The significantly improving symptoms are different in different sex patient. the symptoms which were improved more significantly among the female than male in treatment group are dizziness, spiritual lassitude and fatigue, irritability and susceptibility to rage, insomnia, alternate cold and fever.The symptoms which were improved more significantly among the male than femmale in treatment group are chest oppression, tidal fever.4 Compared with the geriatric depression scale, center for epidemiological survey depression scale with clinical symptoms is more suitable as screening survey tool for elderly depression in the community.更多还原