Analysis of TCM Syndrome Types of Manic Disorder: Data from Clinical Therapy of TCM and Western Medicine

Objective: to analyze the distribution characteristics and composition ratio of Chinese medicine syndrome in manic disease from the published literature on the combined treatment of manic mania by Chinese and Western medicine. Methods: to collect literature from Chinese database, to analyze and classify the cases that meet the standard combined treatment of Chinese and Western medicine, analyze the distribution of different syndromes and composition ratio. Results: 1385 cases were studied. Among them, 48.95% were phlegm fire disturbance to the mind, 20.50% were stagnation of phlegm and heat, 12.37% were liver and gall depression heat, 10.76% were qi stagnation and blood stasis, and 7.51% were fire injury Yin. Conclusion: The first three syndrome can cover more than 80% of the proportion. The contribution degree of the first three is also higher.


Introduction
Bipolar disorder (BD) has a substantial lifetime prevalence in the population at 4%. Because the manic or depressive symptoms of BD tend to be severe and recurrent over a patient's lifetime, the condition is associated with significant burden to the individual, caregivers, and society. Clinician awareness that BD may be present increases the likelihood of successful recognition and appropriate treatment. A number of pharmacological and nonpharmacological treatments are available for acute and maintenance treatments, with the prospect of achieving reduced symptom burden and increased functioning for many patients [1]. In bipolar disorder, there are two states of depression and mania, and they alternate or change each other. Mania is characterized by excitement, talkative, restless, emotional upsurge, impulse, energy and so on. Those who are serious may have violent tendency or behavior [2], which are all typical mania in traditional Chinese medicine (TCM), and so called psychotic mania or "TCM crazy" (Chinese language: Kuangbing) [3]. In many current clinical models about the treatment of mania with the combination of Chinese and Western medicine, almost all of them are diagnosed by western medicine first and then treated by syndrome differentiation of traditional Chinese medicine [4][5][6]. Among them, the mania related to this mania should be divided into several types which are suitable for clinical use [7,8]. Although there is a saying that "all manias belong to fire", there are still some differences in the classification of mania syndrome types in TCM, no matter the number of syndrome types or the characteristics of syndrome types [9,10]. Therefore, we collected the literature of mania treated by combination of Chinese and Western medicine, analyzed and evaluated the TCM syndrome types of mania included in the literature, in order to evaluate the distribution characteristics and composition ratio of TCM syndrome types of mania.

Inclusion Criteria
(1) manic phase of bipolar disorder or manic phase diagnosed by the diagnostic criteria of manic or manic episode diagnosis in CCMD-3, ICD-10 or DSM-5; (2) The treatment mode is combination of TCM and Western medicine, (3) The combination of TCM and Western medicine must be study group and control group must be treated only by Western medicine; (4) The corresponding syndrome types of traditional Chinese medicine are only a TCM a syndrome type; (5) The formula is unified with the syndrome types, and there can be addition and subtraction; (6) The observation time is not less than 4 weeks; (7) There are specific methods to evaluate the efficacy or severity by manic scale; (8) Our study just is the study group that be given the combination of traditional Chinese and Western medicine. The literature is only limited to the Chinese literature published in China Contributions, excluding Hong Kong, Macao and Taiwan literature.

Literature Collection Method
Searches were applied to the following electronic databases, but only in china: Chinese Biomedical Database (CBM), China National Knowledge Infrastructure (CNKI), WANFANG and Chinese Social Sciences Citation Index (VIP) databases. The search strategy was based on combination treatment of TCM and western medicine for mania The Search terms of literature retrieval are combination of Chinese and Western medicine, mania (bipolar disorder or affective psychosis). Then artificial screening was carried out, and the key words were mania (disease), traditional Chinese medicine.

General Information
There are a total of 33 research papers. Among them, 27 were single syndrome type and 6 were multi syndrome type [11,12].

Statistical Methods
The number of cases and the proportion of each syndrome type in this study were calculated. Then we combine the similar syndrome types and count the average ratio of the same syndrome type and the overall composition ratio and contribution degree of each syndrome type.

The Similar Syndromes Were Merged
The phlegm fire disturbance to the heart, phlegm fire disturbance to internal, phlegm fire disturbance to the mind are called by a joint name as phlegm fire disturbance to the mind (Chinese language: Tanhuoraoshen). Phlegm fire Yongsheng, phlegm heat depression, phlegm qi depression are similar and called by a joint name as phlegm heat stagnation (Chinese language: tanreyujie). Qi and blood stagnation is similar to stagnation of Qi and blood stasis and be called name as stagnation of Qi and blood stasis (Chinese language: qizhixueyu). Yin deficiency and fire flourishing are similar to fire injury Yin and are called by a joint name as fire injury Yin (Chinese language: huoshengshangyin), which are collectively referred to as fire hyperactivity and Yin injury. Qi stagnation and fire melting, liver fire hyperactivity, and liver and gall depression heat are all related to liver, which are collectively called a name of liver and gall depression heat (Chinese language: gandanyure). So there were 284 cases (6) of phlegm heat depression, 149 cases (4) of qi stagnation and blood stasis, 678 cases (19) of phlegm fire disturbance to the mind, 170 cases (5) of liver and gall depression heat, and 104 cases (6) of fire injury Yin. There were 1385 cases in total. Among them, 48.95% were caused by phlegm fire disturbance to the mind, 20.50% by phlegm and heat stagnation, 12.37% were liver and gall depression heat, 10.76% were qi stagnation and blood stasis, and 7.51% were fire injury Yin. The first three syndrome accounted for 81.73% and the first four 92.49%.

The Proportion and Contribution of Common TCM Syndromes
There are 40 studies of all TCM syndromes in total. The proportion of the number of studies involved in the five syndromes was normalized Among them, 19 / 40 = 47.5% for phlegm fire disturbance to the mind, 6 / 40 = 15% for phlegm and heat stagnation, 6 / 40 = 15% for fire injury Yin, 5 / 40 = 12.5% for liver and gall depression heat, and 4 / 40 = 10% for qi stagnation and blood stasis. The number of studies indicates the contribution degree that refer to Multiplying the proportion of styuties by the proportion of syndrome types. The contribution degree of phlegm fire disturbance to the mind is 0.4895x0.475 = 0.233, the contribution of phlegm heat stagnation is 0.205x0.15 = 0.031, the contribution of liver and gall depression heat is 0.1237x0.125 = 0.015, the contribution of fire injury Yin is 0.0751x0.15 = 0.011, the contribution of qi stagnation and blood stasis is 0.1076x0.1 = 0.011. The order of contribution degree was phlegm fire disturbance to the mind, phlegm and heat stagnation, liver and gall depression heat, qi stagnation and blood stasis, fire injury Yin.

Discussion
Traditional Chinese medicine pays special attention to the disturbance of phlegm and fire to the spirit in the understanding of mania or manic episode. The manic manifestations of bipolar disorder, such as exaggeration, talkative, sleep need reduction, mental wandering, thought running, behavior rashness, psychomotor excitement, control power reduction, disordered consumption, sexual behavior rashness and so on [1,13], are very similar to those caused by phlegm fire disturbance to the mind in traditional Chinese medicine [14,15], indicating that phlegm fire disturbance to the mind in manic syndrome in TCM are common. The results of this literature analysis also have similar conclusions. It has the most number of research projects and the largest proportion of composition, and the highest contribution degree. Bipolar disorder is characterized by manic and depressive symptoms alternating at the same time or in different stages in the same patient. The excitement, impulse, agitation, aggression, irritability, racing thinks are common symptoms in manic stage and lower energy, less interest, slower thinks and suicide behavior is more in depressive stage [ 1,11,13]. There are some patients with mixed of depressive and manic symptoms [14,15] or rapid cycle of rapid alternation of depression and mania [16,17]. But there is no medical term of bipolar disorder or affective psychosis in traditional Chinese Medicine. Although there is no medical term of bipolar disorder or affective psychosis in traditional Chinese medicine, there are many detailed descriptions about the explanation or discussion of the disease, which are "TCM manic disease" and "TCM depressive disease". Among them, the "crazy disease" is referring to now mania or manic episode of bipolar disorder. The early descriptions of "starts from craziness, sleeps less but does not starve, has high moral integrity, distinguishes wisdom from itself, has high self-esteem, and endures day and night" is very similar to the emotional upsurge, irritability, exaggeration and little sleep of now mania. Therefore, it is considered that the disease is related to internal injury of seven emotions, irregular diet, and congenital heredity. The Seven emotions and six depression, damage to liver qi, induced stagnation of liver qi. The stagnation of Qi continue to transform fire, then following reversal of liver and gall Qi, and opposing of wood and fire, suffering of body fluid, producing phlegm and fire at last. The disturbance of phlegm and turbidity blind the brain orifices and become insanity and madness [18,19]. It can be seen that the role of phlegm and fire is very important (19). Previously, liver stagnation was involved. Our conclusion shows that, phlegm fire disturbance to the mind accounted for 48.95%, phlegm and heat stagnation accounted for 20.50%, liver and gall depression heat accounted for 12.37%, the first three accounted for 81.73%, which also showed the pathogenesis of crazy in mania. Not only sthenia syndrome, heat syndrome, but also phlegm fire and phlegm heat play an important role in further development.
Mania or crazy is closely related to fire. Among them, there is a saying that "the more manic all belong to fire" in <<Neijing zhizhenyaodalun>>. Therefore, mania belongs to Yang, and it turns to sthenia syndrome. However, if the mania lasts for a long time, it will lead to Qi and Yin injury and deficiency of fire, or qi stagnation and blood stasis. Since then, the two syndromes have also been seen in mania, mostly in the long-term mania. From this description, it can be found that the description of the development and outcome of mania in traditional Chinese medicine is dynamic, reflecting that mania, as an important part of bipolar disorder, can not only alternate or transform with depression, but also develop in other directions, so that the disease is more complex and can also develop into refractory cases [20].
The shortcomings of this study are as follows: (1) this study is a secondary literature study, with certain limitations. (2) The syndrome types in this study have been combined. In fact, although some of them are similar, there are still some differences, which may be subjective; (3) this study only included cases of integrated traditional Chinese and Western medicine, not included cases of non integrated traditional Chinese and Western medicine, inevitably lost some meaningful information.

Fund Projects
Zhejiang ptovince science and technology program of traditional Chinese medicine (2020ZB040).