Clinical Study On Treatment From The Heart For Generalized Anxiety Disorder

Part Ⅰ:Literature ResearchGeneralized anxiety disorder (GAD) is a kind of anxiety as the main manifestations of neurosis, usually for no apparent reason and fixed content concerns, accompanied by autonomic nervous dysfunction.Patients with sleep disorders were frequently or continuously, no definite object or fixed content of the tension, excessive worry about things and trouble, often accompanied by depression and mental decline and other neurotic symptoms.Literature study of GAD shows research direction changes from neuroendocrine to genetic and neural structure in the last decade. Common western medicine includes traditional anti-anxiety drugs and antidepressants. Western medicine is effective, but also has withdraws, including adverse reactions, drug dependence and symptoms of recurrence, slow onset, tolerability of patients and the high price of new anti-anxiety drug. Therefore, patients of GAD are difficult to adhere to western medicine treatment. It is called the attention of Chinese medicine clinicians. With a history of2000years, Traditional Chinese Medicine ((hereinafter referred to as TCM) features of treatment based on syndrome differentiation of individual treatment. Although there is no name of GAD and no systematic method for GAD treatment in TCM, but Chinese medicine clinicians have accumulated rich experience in the treatment of GAD.Dr. Zhou Shaohua, a country-famous Chinese medicine clinician with extensive clinical experience with GAD treatment, has a profound understanding of the etiology and pathogenesis of GAD. Dr. Zhou found that in last ten years the number of GAD patients increased year by year in his more than50years experience of being doctor. The causes of GAD gradually changes from stagnation of liver Qi to mental stress and excessive anxiety. Excessive anxiety, loss of heart Yin, deficiency of heart blood, mind dystrophy, can cause heart arrhythmia, anxiety and tension, restless mood, palpitation, insomnia, forgetfulness and other symptoms, heart Yin deficiency, firelight hyperactivity, and appear upset irritability, hectic fever night sweat, five upset hot, dizziness and tinnitus, thready and other symptoms. Based on the above pathogenesis, Dr. Zhou selects Add and subtract Tianwangbuxin Dan to treat heart Yin deficiency type of GAD, which reflects "the Heart Governing Mind" theory. After years of clinical practice, Dr. Zhou extracts the "Treatment of generalized anxiety disorder from the heart" academic thought and put it in to practice.Part Ⅱ:Clinical Study on Add and Substract Tianwangbuxin Dan in the Treatment of Heart Yin deficiency GAD1The purpose of the study:In this study, Clinical research of methods is used to verify Tianwangbuxin Dan for the treatment of heart Yin deficiency type of GAD, to explore the neural endocrine laboratory indexes. With the advantages of TCM, It would provide new method to adapt to the growing needs for GAD treatment.2Research method:The study was a exploratory study, a randomized, positive-controlled trial. All cases, with a number of88patients, were selected from May2013to March2014in the first encephalopathy department of China Xiyuan Hospital.The selection criteria:(1) with "China classification and diagnostic criteria of mental disorders third edition"(CCMD-Ⅲ) diagnostic criteria for GAD;(2) the Hamilton Anxiety Scale (HAMA)>14points, and the anxiety and mood (item1) score>2points, depressed mood (item6) score<2points;(3) the age of18-65years;(4) heart yin deficiency type;(5) Hamilton Depression Scale (HAMD)<17points. TCM Group:They were orally taken Tianwangbuxin Danga daily, twice a day with200ml each time. Prescription of TCM:Suanzaoren30g, Bai Ziren10g, Ophiopogon japonicus12g, born15,12g of angelica, Radix Scrophulariae10g, Salvia30g, dangshen15g, Schisandra6g, Polygala6g, Poria30g, tuber fleeceflower stem30g, bupleurum10g, Cyperus10g, Albizia Flower12g, Rose lOg, Flower lOg, dragon’s teeth30g, Pearl powder3g。The western medicine group:they were given Paroxetine (production of GlaxoSmithKline Co, brand name Seroxat, specifications20mg*10) every morning with20mg orally; course of treatment:The treatment lasted4weeks. Patients were not allowed to take other sedative, anxiolytic and antidepressant medicine in the trial.Observation Index:two groups of patients were recorded with gender, age, comorbidity, HAMA scale score, TCM syndrome score before treatment. They were required to record the symptoms, HAMA score, TCM syndrome integral, the adverse reactions in second weeks and fourth weeks after the beginning of treatment. The records reflected the effectiveness of the treatment with horizon and vertical comparison. We conducted analysis of the changes of plasma levels of cortisol, epinephrine, norepinephrine,5hydroxytryptamine, corticotropin releasing hormone levels of two groups before and after treatment.Evaluation Criteria of Curative Effects:1, Hamilton Anxiety Scale (HAMA): clinical cure:most of the clinical symptoms disappeared, HMAM score<7or score decreased≥75%; effect:most of the clinical symptoms disappeared, a decline in HMAM score≥50%and <75%; effective:most of the clinical symptoms disappeared, HMAM score decreased≥25%and <50%invalid;:no significant changes of clinical symptoms, HMAM score decreased<25%.2, TCM Syndrome Scale:Cure:before and after the treatment of integral reduction rate≥95%; effect:before and after the treatment of integral reduction rate of<95%and≥70%; effective:before and after the treatment of integral reduction rate of<70%and≥30%; invalid:before and after the treatment of integral reduction rate of<30%.3Results:With88patients enrolled,80patients completed, while8patients dropped. There were60women,20men, which women accounted for75%, and male patients accounted for25%. The proportion of men to women was about1:3; age at onset of GAD, the average age of patients was47.825±10.032years. The male patients were mainly distributed between ages of35-55. The female patients have increased morbidity increased with age, which50%of female patients were over50-year-old. Two groups of patients had no difference in age, gender.Hamilton Anxiety Scale Analysis:There was a statistically significant different HAMA PTS before and after treatment, indicating that both were effective for GAD treatment. The comparison showed no significant difference in the total effective and HAMA points, suggesting that the total efficiency considerably. At the point after two weeks treatment, HAMA total score level, HAMA psychic anxiety points, there were significant differences between two groups, suggesting that the TCM group has obvious effect in first2weeks, faster onset than western medicine. Both were effective for somatic anxiety. As for HAMA somatic anxiety points, there were no significant changes after four weeks of treatment or during the treatment course. And therefore the TCM and Western medicine were similar in lowering somatic anxiety points.Analysis of TCM syndrome score:Vertical comparison, P<0.01, suggested that both treatments had significant effects on the heart Yin deficiency type of GAD. For2weeks,4weeks, differences between TCM syndromes were statistically between the two groups, suggesting that both have obvious effect on reducing the TCM Syndromes, but TCM worked faster than western medicine did. TCM have already succeeded in symptom scores fall below20points within first two weeks. After2weeks of treatment, two groups of TCM syndrome integral comparison of P<0.01core, prompted the TCM for the treatment of the core symptoms of TCM onset faster than western medicine. After4weeks, two groups of TCM syndrome integral and core reduction rate of P>0.05, suggested that at week4, TCM and Western medicine had same effect for TCM core symptoms. In two weeks of treatment, there are two relatively minor symptom score TCM significant difference, P<0.01, significantly lower than the integration of traditional Chinese medicine group medicine group. There were significant differences between the two groups minus scores, P<0.01,4weeks of treatment, TCM times to compare statistically significant difference in symptom score, P<0.01; Comparing with two point of time, the Medicines medicine secondary symptom scores were significantly lower than western medicine, TCM eased the symptoms of generalized anxiety, dry mouth, five upset hot,sweating, dizziness, constipation, suggesting TCM was more effective than western medicine.Sleep scores:After treatment, insomnia symptoms scores were significantly lower, which was a magnificent difference compared with scores of before treatment, suggesting that their sleep condition was improved by both medicine. Horizon comparison between the two groups, the sleeping points after two weeks treatment was P<0.01, which showed TCM group significantly lower than western medicine group. At the point of two weeks treatment, the sleep condition of TCM group improved dramatically more than sleep medicine group did. Sleep score was P>0.05after4weeks of treatment, suggested that TCM and western medicine was same effective for sleep improvement after four weeks.Laboratory data analysis:Chinese medicine group before and after treatment were examined fasting bloodserum cortisol, ACTH,5-serotonin, norepinephrine, epinephrine. Comparison of serum COR, NE,5-HT levels of P<0.05in Chinese medicine group before and after treatment, there were significant differences; traditional Chinese medicine group before treatment, serum ACTH, AD levels of P>0.05, no significant difference.Adverse Reactions:we took the possible comparison group intolerance into consideration when designing the research program. The original design was calculated with10%of88patients, of which80patients completed the study,4patients droped,4patients exempted. Four cases of drop were from TCM group, because patients lived far away and could not come for follow-up visits; while the other four cases of patients were from the western group of patients, because they failed to follow the instruction. They took other TCM and sleeping pills in addition to paroxetine, because they studies the medication instructions by themselves and thought its "side effects" was severe.Among those40patients who completed the western medicine course, nine patients had adverse reactions;4patients had nausea and vomiting;2patients occurred constipation;3patients had diarrhea; there were2patients with dizziness,2patients with irritability,2patients with palpitations,1patient with anorexia,1patient with drowsiness and1patient with dry mouth. The adverse reaction rate was22.5%, suggesting that the chance of adverse reactions in western medicine was bigger than that in TCM. The discomfort eased after taking medication for2weeks to3weeks, and its therapeutic effect became obvious. In this study, there were no adverse reactions on patient of TCM.40patients in TCM group were followed the instruction with a higher compliance and rapid onset. After two weeks treatment, their anxiety mood, sleep, physical discomfort aspects had a significant improvement, increasing their confidence of overcoming the GAD.4Analysis and Discussion4.1The Basis for GAD Treatment with the Academic Thoughts of "the Heart Governing Mind"The idea of "the Heart Governing Mind" is the theoretical basis for the academic thoughts of GAD treatment from the heart. TCM believes the idea of "the Heart Governing Mind", and the emotions disease are closely connected with heart. In Dr. Zhou’s opinion, adverse external stimuli, such as overwhelming stress and excessive thinking, are acting on heart firstly, which raise mind damage, the heart-yin and the heart blood consumption, and other series of symptoms. TCM theory holds that the function of the heart depends on sufficient the heart-yin and the heart blood. The material basis for "the Heart Governing Mind" is the heart blood. Excessive stress and thinking consume the heart-yin and the heart blood, resulting in mind dystrophy, which is the key to resolve the GAD. As disorder of child-organ affacting the mother-organ, Heart yin deficiency cause stagnation of QI due to depression of the liver.Almost every GAD syndromes exist the pathogenesis of liver qi stagnation Stagnation of QI due to depression of the liver. But the treatment of qi stagnation takes temporary solution, while the treatment of Yin of the deficiency effects a permanent cure. Therefore when curing GAD, nourishing the heart yin should be treated as the starting point, and if with sparse Liver stagnation method the treatment could be more effective. GAD symptoms can be divided into two categories, including mental anxiety and somatic anxiety. Patients with the manifestations of mental anxiety are anxiety restlessness, irritability, anxiety and insomnia, while the somatic anxiety is accompanied by significant autonomic dysfunction symptoms and often appears with palpitations, hot flashes, sweating, constipation, fatigue, forgetfulness. These clinical symptoms are consistent with heart yin deficiency.4.2The Basis of Add and subtract Tianwangbuxin Dan as the representative prescription of academic thinkingThe material basis of "the Heart Governing Mind" is the heart-yin and the heart blood, which is the key to GAD treatment. Nourishing the heart yin as the starting point is the evidence-based treatment of GAD, which becomes Dr. Zhou’s the basic treatment of GAD. Dr. Zhou created nourishing yin as the core treatment of GAD, combined with Add and subtract Tianwangbuxin Dan as a supplementary to cure GAD. Therefore, Add and subtract Tianwangbuxin treatment represents Dr. Zhou’s treatment of GAD in theory of "the Heart Governing Mind" and he conducted clinical research as the representative.The characteristics of Add and subtract Tianwangbuxin Dan:(1) Heart Yin is the material basis of "the Heart Governing Mind", and the key to GAD treatment is nourishing yin with uneasiness of mind;(2) All prescriptions were played nourishing yin and clearing heat, tonifying qi and calming heart, dispersing stagnated liver qi for relieving qi stagnation, tranquilization with heavy material;(3) Floral drugs are chosen in the liver qi drugs to avoid damaging to Yin qi potency temperature and dry;(4) The drugs include raw dragon’s teeth, pearl powder which both are efficient to clear heat and calm the nerves.4.3Add and subtract Tianwangbuxin Dan shows advantage on the treatment from the heart for GAD.Based on the research results, Add and subtract Tianwangbuxin Dan shows advantage on the treatment from the heart for GAD:(1) The onset of the western medicine usually takes2-4weeks, and it needs4weeks to achieve the best therapeutic effect. During this period, patients are suffering lots of adverse reactions, which is the blind spot of western medicine treatment. Compared with the western medicine, application of Add and subtract Tianwangbuxin Dan in GAD treatment has obvious advantages. It takes obvious effect at2weeks of therapy, and patients have no adverse reaction, which is high safe and high patient compliance and tolerability.(2) The research mainly aims at the heart Yin deficiency type of GAD patients. The onset of Add and subtract Tianwangbuxin Dan is early, improving sleep quality, which enhances patients’ confidence, and is good for continuous treatment. It has significant effect on patients of the heart Yin deficiency syndrome diagnosis. In TCM Syndrome Scale, TCM treatment of GAD with somatic symptoms reflects the superiority, which embodies TCM treatment according to syndrome differentiation.(3)5-HT, NE, COR of TCM group have obvious changes before and after treatment, suggesting that the TCM improves anxiety status and plays an important role in the neuroendocrine and neurotransmitters. Thus it also proves that Tianwangbuxin Dan is an effective treatment of the GAD from the neuroendocrine and neurotransmitter aspect.Add and subtract Tianwangbuxin Dan can improve the clinical symptoms of heart Yin deficiency type of GAD, which is an effective prescription in treating heart Yin deficiency type of GAD. The results confirm the correctness of Dr. Zhou’s academic thinking. Add and subtract Tianwangbuxin Dan group has a rapid onset, and advantages of improving sleep quality, which fills in the blind spot of western anti-anxiety treatment. There are no adverse reactions of Add and subtract Tianwangbuxin Dan in treating yin deficiency and internal disturbance of GAD. Prescription of Add and subtract Tianwangbuxin Dan has influence on endocrine and neurotransmitters, which provides laboratory data for further study of the mechanism of TCM anti-anxiety treatment.