喜乐宁颗粒治疗轻中度抑郁症肝郁脾虚证的研究
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摘要
[研究背景]
抑郁症是一种高患病率、高复发率、高自杀率的心理疾患。世界卫生组织(WHO)2001年发表的《世界卫生报告》中指出抑郁症已经成为世界第四大疾患,预计2020年将成为发展中国家最严重的疾病负担之一。抑郁症的治疗主要以药物和心理治疗为主,但仍有20%～30%的抑郁症患者使用药物治疗无效,50%的患者缺乏良好疗效,也有部分患者服用药物后不能耐受药物的副作用而不能坚持治疗。心理治疗因受到中国传统文化和国人就医意识形态、认知、文化层次的影响,在国内的应用情况并不乐观,不仅如此,心理治疗一般需要较长的疗程。与此同时更多的抑郁症患者倾向于寻求中医的帮助,中医中药因其临床疗效好、毒副作用少、基本无停药综合征等特点受到国内患者的肯定,寻求有效的、安全的天然抗抑郁药物和中药复方的研究成为了当下的发展趋势。中药复方喜乐宁颗粒是国医大师路志正教授根据脏腑辨证和抑郁症临床发病的主要证候特点以及临床经验所创的治疗抑郁症的验方,前期应用于抑郁症个案研究显示临床疗效较好。
[目的]
1.观察喜乐宁颗粒对轻中度抑郁症肝郁脾虚证的临床疗效及安全性,为抑郁症的临床治疗提供一种有效的治疗方法；
2.观察喜乐宁颗粒对抑郁症患者血浆单胺类神经递质5-HT、NE的影响,探讨喜乐宁颗粒治疗抑郁症的临床作用机制。
[方法]
第一部分：临床研究采用随机、双盲、双模拟、安慰剂对照的方法,以轻、中度抑郁症患者为研究对象,将120例患者随机分为中药组、西药组、对照组,每组各40例患者。疗程为8周,观察各组治疗前后汉密尔顿抑郁量表(HAMD)、蒙哥马利抑郁量表(MADRS)、五态人格量表、中医证候评分等指标的变化,观察中药复方喜乐宁颗粒治疗轻中度抑郁症肝郁脾虚证的有效性和安全性。
第二部分：临床基础研究采用前瞻、对照的研究方法,观察喜乐宁颗粒对轻中度抑郁症血浆5-HT、NE水平的影响,探讨喜乐宁颗粒抗抑郁作用的生理病理机制。
[结果]
第一部分：临床研究部分
1.中药组的疾病总有效率为79.49%,西药组的疾病总有效率为76.32%,对照组的疾病总有效率为25.71%,25.71%为安慰剂效应。疗后三组疾病有效率的比较差异有统计学意义(P<0.05),中药组和西药组的疾病有效率比较无显著性差异(P>0.05),中药组与对照组、西药组与对照组疾病有效率的比较差异有统计学意义(P<0.05)；
2.中药组的中医证候有效率为74.36%,西药组的中医证候有效率为63.16%,对照组的中医证候有效率为28.57%。三组中医证候有效率比较有显著性差异(P<0.05),中药组和西药组的中医证候有效率比较差异无统计学意义(P>0.05),中药组与对照组、西药组与对照组的中医证候有效率比较差异有统计学意义(P<0.05)；
3.三组各个观察时点的HAMD评分总分、MADRS评分总分比较都有统计学差异(P<0.05)。治疗2周、4周后,中药组与西药组HAMD评分总分、MADRS评分总分不同(P<0.05),治疗6周、8周后,两组HAMD评分总分、MADRS评分总分变化无明显差异(P>0.05)；中药组与对照组、西药组与对照组各个观察时点HAMD评分总分、MADRS评分总分比较差异有统计学意义(P<0.05)；中药组、西药组治疗后HAMD评分、MADRS评分总分都有显著的下降,对照组的下降趋势不明显,中药组较西药组在起效时间上更有优势；
4.三组各个观察时点中医证候评分比较差异有统计学意义(P<0.05),治疗2周、4周后,中药组、西药组中医证候评分减分变化不同(P<0.05),治疗6周、8周后,两组中医证候评分无显著差异(P>0.05)；中药组与对照组、西药组与对照组各观察时点中医证候评分比较不同(P<0.05)；中药组、西药组的中医证候评分都呈下降趋势,对照组减分倾向不显著,中药组起效更快；在改善精神抑郁、胸胁胀满、善太息主要症状方面,三组各个观察时点主症评分比较不同(P<0.05),中药组、西药组主症评分变化比较基本一致(P>0.05),中药组与对照组、西药组与对照组的主症评分比较差异有统计学意义(P<0.05),中药组、西药组较对照组在降低主症评分方面更为显著；在改善失眠、健忘、疲乏无力等次症方面,三组在治疗的前4周,次症评分比较基本一致(P>0.05),治疗6周、8周后次症评分变化不同(P<0.05)；中药组、西药组各观察时点次症减分情况基本一致(P>0.05)；中药组与对照组、西药组与对照组各观察时点次症评分比较有统计学差异(P<0.05)；
5.治疗前三组的少阳、太阴评分不同于中国常模(P<0.05),抑郁症患者的少阳评分低于中国常模,太阴评分高于中国常模。三组治疗8周中医五态人格量表评分太阳、阴阳和平、少阴比较基本一致(P>0.05),三组的少阳、太阴得分不同(P<0.05)；中药组与西药组之间中医五态人格量表各因子评分基本一致(P>0.05)；中药组与对照组、西药组与对照组各因子评分进行比较,太阳、阴阳和平、少阴得分无显著性差异(P>0.05),少阳、太阴得分不同(P<0.05)；治疗8周后,中药组、西药组各维度与中国常模比较基本一致(P>0.05),对照组少阳、太阴得分与常模不同(P<0.05),治疗后中药组、西药组少阳得分升高、太阴评分下降,与中国常模相当,对照组的少阳因子评分仍低于中国常模,太阴因子评分高于中国常模；
6.在临床应用安全性方面,中药组出现1例可能与治疗无关的轻度不良事件,西药组有6例出现可能与药物干预有关的轻度不良反应,对照组出现1例可能与干预无关的轻度不良事件,总体来看本研究显示喜乐宁颗粒的临床安全性优于盐酸文拉法辛片。第二部分：基础研究部分
1.治疗前抑郁症患者与正常健康者的血浆5-HT、NE水平不同(P<0.05),抑郁症患者血浆5-HT、NE水平低于健康对照者。治疗12周后抑郁症患者血浆5-HT、NE水平与正常健康者比较有统计学差异(P<0.05)。治疗后抑郁症患者的血浆5-HT、NE水平仍低于健康对照者；
2.喜乐宁颗粒治疗前后血浆5-HT水平、IAMD评分不同(P<0.05)。治疗前后的血浆NE水平基本无变化(P>0.05)。治疗12周后,血浆5-HT水平升高,而血浆NE水平变化不明显；
3.抑郁症患者血浆5-HT水平与HAMD积分的相关性分析发现,R=-0.134,P<0.05,血浆5-HT水平与HAMD积分呈负相关。
[结论]
1.喜乐宁颗粒能够降低抑郁症患者的HAMD、MADRS的评分,有效地改善抑郁症患者的临床症状,喜乐宁颗粒与盐酸文拉法辛治疗轻中度抑郁症的临床疾病疗效相当,在起效时间方面,喜乐宁颗粒比盐酸文拉法辛更有优势；
2.喜乐宁颗粒可能通过改善抑郁症患者的临床症状对中医五态人格量表量表少阳、太阴两个维度产生了一定的影响；
3.喜乐宁颗粒可能是通过提高抑郁症患者单胺类递质5-HT的水平从而发挥治疗作用；
4.喜乐宁颗粒临床应用安全性较好。
Depression is a mental disorder which has the character of high prevalence, high recurrence rate and high suicide rates.In2001,World Health Organization published "The World Health Report" that depression has already become the world's fourth largest disease. Beyond of this, depression is expected to be one of the most severe burden diseases in developing countries in2020.There are diverse therapies for depression which mainly focus on medication and psychological therapy. New antidepressant medicine constantly applied in clinical treatment, while there are still20%-30%of patients are ineffective in drugs.Also some patients cann't adhere to the treatment for not tolerating with the side effects of drug. Western psychotherapy applied not optimistically in the country for the reason of Chinese traditional culture, the ideology of treatment, cognitive, and cultural levels etc.Beyond of this, psychotherapy usually needs long therapy. At the same time, more Chinese depressive patients prefer to traditional Chinese medical therapy. Depressive patients believe that TCM has better clinical efficacy, fewer side effects, almost no withdrawal syndrome.So it becomes the trend that we search for more effective and safe non-artificial antidepressant and compound herbal at this moment. Xi Le Ning Granule is a traditional Chinese medicine which is created by professor Lu Zhizheng, one of State Medical Masters, according to Chinese medical syndrome differentiation, major clinical syndrome character and clinical experience. Case studies showed that it had a good clinical efficacy for depression.
[Objection]
1. To observe the clinical efficacy and safety of that Xi Le Ning Granule treats mild and moderate depression of syndrome of liver qi stagnation and spleen deficiency. We want to provide an effective treatment method for the clinical therapy of depression;
2. To observe the influence on which Xi Le Ning Granule has to5-HT and NE of the depressive patients'plasma. We expect to explore the mechanism of Xi Le Ning Granule treating depression.
[Method]
Part I:In clinical research we used a randomized, double-blind, double-dummy, placebo-controlled approach to study the mild and moderate depression patients.120patients were randomly divided into three groups which is Chinese medicine group, Western medicine group and control group. Each group had40patients. Every patient was treated for eight weeks.We observed the Hamilton Depression Rating Scale, Montgomery Depression Scale, Five states Personality Inventory, TCM syndrome score before and after treatment in each group to research the clinical efficacy and safety of that Xi Le Ning Granule treats mild and moderate depression of syndrome of liver qi stagnation and spleen deficiency.
Part II:We used a prospective, controlled method in clinical and basic research to observe the influence on which Xi Le Ning Granule has to5-HT and NE of the depressive patients' plasma and to explore the physiological and pathological mechanism of antidepressant effect of Xi Le Ning Granule.
[Results]
Part I:Clinical Research
1. The total disease effective rate of Chinese medicine group was79.49%. Western medicine group's total disease effective rate was76.32%. Control group's total disease effective rate was25.71%.25.71%devoted to the placebo effect. The comparison of disease efficiency among three groups after treatment was significant (P<0.05).There was not a significant difference in diseases efficiency between Chinese medicine group and western medicine group (P>0.05).Also the comparisons of disease efficiency between Chinese medicine group and control group, western medicine group and control group were significant (P<0.05);
2. The syndromes effective rate of Chinese medicine group was74.36%. Wester medicine group's syndromes effective rate was63.16%.The control group's was28.57%. There was a significant difference in TCM syndromes efficiency among three groups (P<0.05).The comparison of TCM syndromes efficiency between Chinese medicine group and western medicine group was not significant (P>0.05).The syndromes effective rates' comparison between Chinese medicine group and control group, western medicine group and control group were significant (P<0.05);
3. There was a significant difference of HAMD score and MADRS score (P<0.05) among2w,4w,6w,8w in three groups. The HAMD total score and MADRS total score of Chinese medicine group were different with western medicine group (P<0.05) in2w and4w. The change of HAMD total score and MADRS total score was no significantly different (P>0.05) between two groups in6w and8w. There were statistically significant difference(P <0.05) in HAMD total score and MADRS total score between Chinese medicine group and control group, western medicine group and control group.The HAMD score and MADRS total score has significantly decreased after treatment in Chinese medicine group and western medicine group. But the Chinese medicine group had an advantage on the onset time than western medicine group and control group.
4. The comparison of three groups'Chinese syndromes scores among each observation point was statistically significant different (P<0.05).The Chinese syndrome scores minus were different between Chinese medicine group and western medicine group (P<0.05) in2w or4w. But the minus scores were no significant different in6w or8w (P>0.05).The Chinese syndrome scores'comparison had significant difference between Chinese medicine group and control group, western medicine group and control group in2w,4w,6w, or8w(P<0.05).The Chinese syndrome scores of Chinese medicine group and western medicine group had decreased in8weeks.But control group had not such an apparent tendency. The Chinese medicine group had a faster onset than western medicine group or control group.There was a difference in comparison of main symptoms score in each observation point of three groups (P<0.05).The main symptoms included depression, chest fullness, sighing. The Chinese medicine group and western medicine group had the same efficacy in improving main symptoms (P>0.05).The comparison was statistically significant (P<0.05) between Chinese medicine group and control group, western medicine group and control group in main symptoms score.The main symptoms scores of Chinese medicine group or western medicine group descended more than control group. The total score of secondary symptoms which included insomnia, forgetfulness, fatigue, weakness etc.of three groups was basically the same in4weeks (P>0.05). But they were different after6weeks or8weeks (P<0.05).The reduction of secondary symptoms score of Chinese medicine group and western medicine group were the same in each observation point (P>0.05).There was a difference in comparison of secondary symptoms score in each observation point of three groups (P<0.05).
5. Shaoyang and taiyin scores of three groups were different with normal Chinese before treatment (P<0.05).The Shaoyang score of patients with depression was lower than normal Chinese. But taiyin score was higher than normal Chinese. Shaoyang and taiyin scores were different (P<0.05) among three groups except for others (P>0.05) after8weeks therapy. Each factor score of Five State TCM Personality Scale was consistent between Chinese medicine group and western medicine group (P>0.05).Taiyang, yin and yang peace, shaoyin scores were no significant difference (P>0.05) between Chinese medicine group and control group, western medicine group and the control group. But shaoyang, taiyin scores were different (P<0.05). Chinese medicine group and western medicine group had the same score level with normal Chinese after treatment (P>0.05).Shaoyang and taiyin scores of control group were different with normal Chinese (P<0.05).Shaoyang score increased and taiyin score decreased of Chinese medicine group and western medicine group after treatment. While shaoyang score was still lower and taiyin score was higher than normal Chinese.
6. Xi Le Ning Granule had one case of mild adverse events which may be not related to the treatment in clinical application. There were6patients in venlafaxine group who had mild adverse reactions that may be caused by medicine.The control group had one case of light may not interfere with the treatment. This study shown that Xi Le Ning Granule was safer than venlafaxine.
Part II:Basic Research
1. The plasma5-HT and NE levels of depressive patients were different with normal healthy people (P<0.05) before treatment. The plasma5-HT, NE levels of depression were lower than healthy ones. Although the plasma5-HT and NE levels of depression were still lower than healthy control. The plasma5-HT and NE levels between depression and healthy controls were statistically significant difference (P<0.05) after12weeks' treatment.
2. The plasma5-HT levels and HAMD score were different before and after Xi Le Ning Granule treating (P<0.05). But NE levels of plasma basically unchanged before and after the treatment (P>0.05). The5-HT levels of plasma elevated and NE levels did not significantly change after12weeks of treatment.
3. The correlation analysis of plasma5-HT levels and HAMD of patients with depression found that R=-0.134, P<0.05. Plasma5-HT levels of depression were negatively correlated with HAMD scores.
[Conclusion]
1. Xi Le Ning Granule could reduce the HAMD, MADRS scores and effectively improve the clinical symptoms of depression patients. Xi Le Ning Granule and Venlafaxine had the same efficacy of treating mild and moderate depression. But Xi Le Ning Granule had advantage on onset time. It had shorter onset time than venlafaxine;
2. Xi Le Ning Granule maybe impact on Shaoyang,and Taiyin score by improving clinical symptomsof depression;
3. Xi Le Ning Granule maybe play a therapeutic role through the mechanism of increasing5-HT of depressive patients;
4. Xi Le Ning Granule had better security in clinical application.
抑郁症是一种高患病率、高复发率、高自杀率的心理疾患。世界卫生组织(WHO)2001年发表的《世界卫生报告》中指出抑郁症已经成为世界第四大疾患,预计2020年将成为发展中国家最严重的疾病负担之一。抑郁症的治疗主要以药物和心理治疗为主,但仍有20%～30%的抑郁症患者使用药物治疗无效,50%的患者缺乏良好疗效,也有部分患者服用药物后不能耐受药物的副作用而不能坚持治疗。心理治疗因受到中国传统文化和国人就医意识形态、认知、文化层次的影响,在国内的应用情况并不乐观,不仅如此,心理治疗一般需要较长的疗程。与此同时更多的抑郁症患者倾向于寻求中医的帮助,中医中药因其临床疗效好、毒副作用少、基本无停药综合征等特点受到国内患者的肯定,寻求有效的、安全的天然抗抑郁药物和中药复方的研究成为了当下的发展趋势。中药复方喜乐宁颗粒是国医大师路志正教授根据脏腑辨证和抑郁症临床发病的主要证候特点以及临床经验所创的治疗抑郁症的验方,前期应用于抑郁症个案研究显示临床疗效较好。
[目的]
1.观察喜乐宁颗粒对轻中度抑郁症肝郁脾虚证的临床疗效及安全性,为抑郁症的临床治疗提供一种有效的治疗方法；
2.观察喜乐宁颗粒对抑郁症患者血浆单胺类神经递质5-HT、NE的影响,探讨喜乐宁颗粒治疗抑郁症的临床作用机制。
[方法]
第一部分：临床研究采用随机、双盲、双模拟、安慰剂对照的方法,以轻、中度抑郁症患者为研究对象,将120例患者随机分为中药组、西药组、对照组,每组各40例患者。疗程为8周,观察各组治疗前后汉密尔顿抑郁量表(HAMD)、蒙哥马利抑郁量表(MADRS)、五态人格量表、中医证候评分等指标的变化,观察中药复方喜乐宁颗粒治疗轻中度抑郁症肝郁脾虚证的有效性和安全性。
第二部分：临床基础研究采用前瞻、对照的研究方法,观察喜乐宁颗粒对轻中度抑郁症血浆5-HT、NE水平的影响,探讨喜乐宁颗粒抗抑郁作用的生理病理机制。
[结果]
第一部分：临床研究部分
1.中药组的疾病总有效率为79.49%,西药组的疾病总有效率为76.32%,对照组的疾病总有效率为25.71%,25.71%为安慰剂效应。疗后三组疾病有效率的比较差异有统计学意义(P<0.05),中药组和西药组的疾病有效率比较无显著性差异(P>0.05),中药组与对照组、西药组与对照组疾病有效率的比较差异有统计学意义(P<0.05)；
2.中药组的中医证候有效率为74.36%,西药组的中医证候有效率为63.16%,对照组的中医证候有效率为28.57%。三组中医证候有效率比较有显著性差异(P<0.05),中药组和西药组的中医证候有效率比较差异无统计学意义(P>0.05),中药组与对照组、西药组与对照组的中医证候有效率比较差异有统计学意义(P<0.05)；
3.三组各个观察时点的HAMD评分总分、MADRS评分总分比较都有统计学差异(P<0.05)。治疗2周、4周后,中药组与西药组HAMD评分总分、MADRS评分总分不同(P<0.05),治疗6周、8周后,两组HAMD评分总分、MADRS评分总分变化无明显差异(P>0.05)；中药组与对照组、西药组与对照组各个观察时点HAMD评分总分、MADRS评分总分比较差异有统计学意义(P<0.05)；中药组、西药组治疗后HAMD评分、MADRS评分总分都有显著的下降,对照组的下降趋势不明显,中药组较西药组在起效时间上更有优势；
4.三组各个观察时点中医证候评分比较差异有统计学意义(P<0.05),治疗2周、4周后,中药组、西药组中医证候评分减分变化不同(P<0.05),治疗6周、8周后,两组中医证候评分无显著差异(P>0.05)；中药组与对照组、西药组与对照组各观察时点中医证候评分比较不同(P<0.05)；中药组、西药组的中医证候评分都呈下降趋势,对照组减分倾向不显著,中药组起效更快；在改善精神抑郁、胸胁胀满、善太息主要症状方面,三组各个观察时点主症评分比较不同(P<0.05),中药组、西药组主症评分变化比较基本一致(P>0.05),中药组与对照组、西药组与对照组的主症评分比较差异有统计学意义(P<0.05),中药组、西药组较对照组在降低主症评分方面更为显著；在改善失眠、健忘、疲乏无力等次症方面,三组在治疗的前4周,次症评分比较基本一致(P>0.05),治疗6周、8周后次症评分变化不同(P<0.05)；中药组、西药组各观察时点次症减分情况基本一致(P>0.05)；中药组与对照组、西药组与对照组各观察时点次症评分比较有统计学差异(P<0.05)；
5.治疗前三组的少阳、太阴评分不同于中国常模(P<0.05),抑郁症患者的少阳评分低于中国常模,太阴评分高于中国常模。三组治疗8周中医五态人格量表评分太阳、阴阳和平、少阴比较基本一致(P>0.05),三组的少阳、太阴得分不同(P<0.05)；中药组与西药组之间中医五态人格量表各因子评分基本一致(P>0.05)；中药组与对照组、西药组与对照组各因子评分进行比较,太阳、阴阳和平、少阴得分无显著性差异(P>0.05),少阳、太阴得分不同(P<0.05)；治疗8周后,中药组、西药组各维度与中国常模比较基本一致(P>0.05),对照组少阳、太阴得分与常模不同(P<0.05),治疗后中药组、西药组少阳得分升高、太阴评分下降,与中国常模相当,对照组的少阳因子评分仍低于中国常模,太阴因子评分高于中国常模；
6.在临床应用安全性方面,中药组出现1例可能与治疗无关的轻度不良事件,西药组有6例出现可能与药物干预有关的轻度不良反应,对照组出现1例可能与干预无关的轻度不良事件,总体来看本研究显示喜乐宁颗粒的临床安全性优于盐酸文拉法辛片。第二部分：基础研究部分
1.治疗前抑郁症患者与正常健康者的血浆5-HT、NE水平不同(P<0.05),抑郁症患者血浆5-HT、NE水平低于健康对照者。治疗12周后抑郁症患者血浆5-HT、NE水平与正常健康者比较有统计学差异(P<0.05)。治疗后抑郁症患者的血浆5-HT、NE水平仍低于健康对照者；
2.喜乐宁颗粒治疗前后血浆5-HT水平、IAMD评分不同(P<0.05)。治疗前后的血浆NE水平基本无变化(P>0.05)。治疗12周后,血浆5-HT水平升高,而血浆NE水平变化不明显；
3.抑郁症患者血浆5-HT水平与HAMD积分的相关性分析发现,R=-0.134,P<0.05,血浆5-HT水平与HAMD积分呈负相关。
[结论]
1.喜乐宁颗粒能够降低抑郁症患者的HAMD、MADRS的评分,有效地改善抑郁症患者的临床症状,喜乐宁颗粒与盐酸文拉法辛治疗轻中度抑郁症的临床疾病疗效相当,在起效时间方面,喜乐宁颗粒比盐酸文拉法辛更有优势；
2.喜乐宁颗粒可能通过改善抑郁症患者的临床症状对中医五态人格量表量表少阳、太阴两个维度产生了一定的影响；
3.喜乐宁颗粒可能是通过提高抑郁症患者单胺类递质5-HT的水平从而发挥治疗作用；
4.喜乐宁颗粒临床应用安全性较好。
Depression is a mental disorder which has the character of high prevalence, high recurrence rate and high suicide rates.In2001,World Health Organization published "The World Health Report" that depression has already become the world's fourth largest disease. Beyond of this, depression is expected to be one of the most severe burden diseases in developing countries in2020.There are diverse therapies for depression which mainly focus on medication and psychological therapy. New antidepressant medicine constantly applied in clinical treatment, while there are still20%-30%of patients are ineffective in drugs.Also some patients cann't adhere to the treatment for not tolerating with the side effects of drug. Western psychotherapy applied not optimistically in the country for the reason of Chinese traditional culture, the ideology of treatment, cognitive, and cultural levels etc.Beyond of this, psychotherapy usually needs long therapy. At the same time, more Chinese depressive patients prefer to traditional Chinese medical therapy. Depressive patients believe that TCM has better clinical efficacy, fewer side effects, almost no withdrawal syndrome.So it becomes the trend that we search for more effective and safe non-artificial antidepressant and compound herbal at this moment. Xi Le Ning Granule is a traditional Chinese medicine which is created by professor Lu Zhizheng, one of State Medical Masters, according to Chinese medical syndrome differentiation, major clinical syndrome character and clinical experience. Case studies showed that it had a good clinical efficacy for depression.
[Objection]
1. To observe the clinical efficacy and safety of that Xi Le Ning Granule treats mild and moderate depression of syndrome of liver qi stagnation and spleen deficiency. We want to provide an effective treatment method for the clinical therapy of depression;
2. To observe the influence on which Xi Le Ning Granule has to5-HT and NE of the depressive patients'plasma. We expect to explore the mechanism of Xi Le Ning Granule treating depression.
[Method]
Part I:In clinical research we used a randomized, double-blind, double-dummy, placebo-controlled approach to study the mild and moderate depression patients.120patients were randomly divided into three groups which is Chinese medicine group, Western medicine group and control group. Each group had40patients. Every patient was treated for eight weeks.We observed the Hamilton Depression Rating Scale, Montgomery Depression Scale, Five states Personality Inventory, TCM syndrome score before and after treatment in each group to research the clinical efficacy and safety of that Xi Le Ning Granule treats mild and moderate depression of syndrome of liver qi stagnation and spleen deficiency.
Part II:We used a prospective, controlled method in clinical and basic research to observe the influence on which Xi Le Ning Granule has to5-HT and NE of the depressive patients' plasma and to explore the physiological and pathological mechanism of antidepressant effect of Xi Le Ning Granule.
[Results]
Part I:Clinical Research
1. The total disease effective rate of Chinese medicine group was79.49%. Western medicine group's total disease effective rate was76.32%. Control group's total disease effective rate was25.71%.25.71%devoted to the placebo effect. The comparison of disease efficiency among three groups after treatment was significant (P<0.05).There was not a significant difference in diseases efficiency between Chinese medicine group and western medicine group (P>0.05).Also the comparisons of disease efficiency between Chinese medicine group and control group, western medicine group and control group were significant (P<0.05);
2. The syndromes effective rate of Chinese medicine group was74.36%. Wester medicine group's syndromes effective rate was63.16%.The control group's was28.57%. There was a significant difference in TCM syndromes efficiency among three groups (P<0.05).The comparison of TCM syndromes efficiency between Chinese medicine group and western medicine group was not significant (P>0.05).The syndromes effective rates' comparison between Chinese medicine group and control group, western medicine group and control group were significant (P<0.05);
3. There was a significant difference of HAMD score and MADRS score (P<0.05) among2w,4w,6w,8w in three groups. The HAMD total score and MADRS total score of Chinese medicine group were different with western medicine group (P<0.05) in2w and4w. The change of HAMD total score and MADRS total score was no significantly different (P>0.05) between two groups in6w and8w. There were statistically significant difference(P <0.05) in HAMD total score and MADRS total score between Chinese medicine group and control group, western medicine group and control group.The HAMD score and MADRS total score has significantly decreased after treatment in Chinese medicine group and western medicine group. But the Chinese medicine group had an advantage on the onset time than western medicine group and control group.
4. The comparison of three groups'Chinese syndromes scores among each observation point was statistically significant different (P<0.05).The Chinese syndrome scores minus were different between Chinese medicine group and western medicine group (P<0.05) in2w or4w. But the minus scores were no significant different in6w or8w (P>0.05).The Chinese syndrome scores'comparison had significant difference between Chinese medicine group and control group, western medicine group and control group in2w,4w,6w, or8w(P<0.05).The Chinese syndrome scores of Chinese medicine group and western medicine group had decreased in8weeks.But control group had not such an apparent tendency. The Chinese medicine group had a faster onset than western medicine group or control group.There was a difference in comparison of main symptoms score in each observation point of three groups (P<0.05).The main symptoms included depression, chest fullness, sighing. The Chinese medicine group and western medicine group had the same efficacy in improving main symptoms (P>0.05).The comparison was statistically significant (P<0.05) between Chinese medicine group and control group, western medicine group and control group in main symptoms score.The main symptoms scores of Chinese medicine group or western medicine group descended more than control group. The total score of secondary symptoms which included insomnia, forgetfulness, fatigue, weakness etc.of three groups was basically the same in4weeks (P>0.05). But they were different after6weeks or8weeks (P<0.05).The reduction of secondary symptoms score of Chinese medicine group and western medicine group were the same in each observation point (P>0.05).There was a difference in comparison of secondary symptoms score in each observation point of three groups (P<0.05).
5. Shaoyang and taiyin scores of three groups were different with normal Chinese before treatment (P<0.05).The Shaoyang score of patients with depression was lower than normal Chinese. But taiyin score was higher than normal Chinese. Shaoyang and taiyin scores were different (P<0.05) among three groups except for others (P>0.05) after8weeks therapy. Each factor score of Five State TCM Personality Scale was consistent between Chinese medicine group and western medicine group (P>0.05).Taiyang, yin and yang peace, shaoyin scores were no significant difference (P>0.05) between Chinese medicine group and control group, western medicine group and the control group. But shaoyang, taiyin scores were different (P<0.05). Chinese medicine group and western medicine group had the same score level with normal Chinese after treatment (P>0.05).Shaoyang and taiyin scores of control group were different with normal Chinese (P<0.05).Shaoyang score increased and taiyin score decreased of Chinese medicine group and western medicine group after treatment. While shaoyang score was still lower and taiyin score was higher than normal Chinese.
6. Xi Le Ning Granule had one case of mild adverse events which may be not related to the treatment in clinical application. There were6patients in venlafaxine group who had mild adverse reactions that may be caused by medicine.The control group had one case of light may not interfere with the treatment. This study shown that Xi Le Ning Granule was safer than venlafaxine.
Part II:Basic Research
1. The plasma5-HT and NE levels of depressive patients were different with normal healthy people (P<0.05) before treatment. The plasma5-HT, NE levels of depression were lower than healthy ones. Although the plasma5-HT and NE levels of depression were still lower than healthy control. The plasma5-HT and NE levels between depression and healthy controls were statistically significant difference (P<0.05) after12weeks' treatment.
2. The plasma5-HT levels and HAMD score were different before and after Xi Le Ning Granule treating (P<0.05). But NE levels of plasma basically unchanged before and after the treatment (P>0.05). The5-HT levels of plasma elevated and NE levels did not significantly change after12weeks of treatment.
3. The correlation analysis of plasma5-HT levels and HAMD of patients with depression found that R=-0.134, P<0.05. Plasma5-HT levels of depression were negatively correlated with HAMD scores.
[Conclusion]
1. Xi Le Ning Granule could reduce the HAMD, MADRS scores and effectively improve the clinical symptoms of depression patients. Xi Le Ning Granule and Venlafaxine had the same efficacy of treating mild and moderate depression. But Xi Le Ning Granule had advantage on onset time. It had shorter onset time than venlafaxine;
2. Xi Le Ning Granule maybe impact on Shaoyang,and Taiyin score by improving clinical symptomsof depression;
3. Xi Le Ning Granule maybe play a therapeutic role through the mechanism of increasing5-HT of depressive patients;
4. Xi Le Ning Granule had better security in clinical application.
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