Prescription Patterns of Chinese Herbal Products in Patients with Sleep Disorder and Major Depressive Disorder in Taiwan: a Nationwide Population-based Study
Yi-Lin Chen,1 Chien-Ying Lee,2,3 Kuang-Hua Huang,4 Ming Chen,1* 1. Beijing University of Chinese Medicine, China
2. Department of Pharmacology, Chung Shan Medical University 3. Department of Pharmacy, Chung Shan Medical University Hospital
4. Department of Health Service Administration, College of Public Health, China Medical University
*Correspondence: Ming Chen
Address: Beijing University of Chinese Medicine, Chaoyang District, Beijing 100029, PChina.
Tel: +86-10-64287073, +86-139-10729606
E-mail: cmwg185@sina.com
Abstract： Background:
Sleep disorder and major depressive disorder (MDD) are common diseases. Chinese herbal products (CHP) are commonly used in sleep disorder and MDD patients to alleviate sleeping problems and and depressive symptoms.
Aim:
The aim of this study is to investigate the prescription patterns of Chinese herbal products or Western medicine in patients with sleep disorder and MDD patients in Taiwan and also analyze the frequency of use in single herbs and herbal formulas. Materials and methods:
This retrospective population-based study was based on secondary data analysis from Taiwan’s Longitudinal Health Insurance Database (LHID) between January 2007 and December 2011.In total, 1,000,000 participants from the LHID were randomly selected from the 2010 registry for beneficiaries of the national health insurance research database (NHIRD). The sleep disorder patients were identified based on ICD-9-CM CODE 307.40 and MDD based on ICD-9-CM CODE 311.
Result：
A total of 11,030 sleep disorder patients, among these patients, 9,619 used Western medicine, 1,334 used CHP, and 77 used Western medicine and CHP. A total of 11,571 MDD patients among these patients, 11,389 used Western medicine, 131 used
CHP, and 51 used Western medicine and CHP. No matter sleep disorder or MDD patients, female were more than male, the majority of these patients were aged 22-44 years old, NT 17,281-22,800 per monthly income, Level 1 urbanization. 1,411 sleep disorder patients ever used CHP and came to clinic 5,298 times. 182 MDD patients ever used CHP and came to clinic 755 times. The top three most commonly used, single herb (SH) is Polygoni Multiflori Caulis, Ziziphi Spinosae Semen and Polygalae Radix, herbal formula (HF) isJia-Wei-Xiao-Yao-San, Suan-Zao-Ren-Tang and Chai-Hu-Chia-Lung-Ku-Mu-LiI-Tang.
Conclusion:
CHP including SH and HF are widely used in patients with sleep disorder and MDD, still need to evaluate the efficacy of CHP for sleep disorder and MDD in the further.
1. Introduction:
Insomnia is the most common sleep complaint syndrome, with approximately 9-15% of the general population worldwide suffering from insomnia symptoms
accompanied by daytime consequences(1). The epidemiologic studies suggest that the
link between insomnia and depression is bidirectional. For instance, about 20% of patients with insomnia exhibit some depressive symptoms(2), whereas depression and
depressive symptoms have been shown to be the largest and most consistent risk factors for insomnia(3). During the last decade, several studies indicated that insomnia
could be more than a symptom of depression. These studies suggested that insomnia may indeed have a negative effect on depression in some cases. These findings are consistent with other study that insomnia is a risk factor for onset of MDD(4).
Western medicine for treatment of insomnia and depression may have some adverse drug effects, such benzodiazepines may increase the risk of falling in elderly persons (5). Zolpidem, a nonbenzodiazepine hypnotic, is widely prescribed in clinical
practice for the treatment of insomnia and reported that had few systemic descriptions of the adverse effects (especially for psychotic reactions)(6), sleepwalking(7).Tricyclic
antidepressants for the treatment of MDD was related with cardiac toxicity(8) and
eventually lose their response. Some patients are searching for complementary and alternative medicine (CAM), far fewer side effects and may provide an alternative treatment(10, 11).
One study indicated that a number of herbal medicines show promise in the management of mild-to-moderate depression(12). Use of CAM for treatment of
insomnia, either single herbal or herbal formula could be traced more than 2000 years ago in Chinese medical text book. Another study showed that more than 40% of individuals prescribed with antidepressant treatments for depression used TCM services. Younger age, female gender, the presence of certain comorbid mental/physical illnesses or
painful physical symptoms, as well as having fewer psychiatric service contacts were found to be associated with the use of TCM services(13). Up to date, there is no correlation study
to explore Chinese herbal products for patients with insomnia andMDD from NHI database in Taiwan. The aim of this study is to investigate the prescription patterns of Chinese herbal products or Western medicine in sleep disorder and MDD patients in Taiwan and also analyze the frequency of use in single herbs and herbal formulas.
2. Materials and methods Data sources and data extraction:
This study was a retrospective study to SAS 9.3 (SAS Institute, Cary, NC, USA) were secondary database analysis, Our data come from the National Health Insurance Research Database (NHIRD), which is a source based on the national health care system that is native to Taiwan. NHIRD contains detailed clinical records on every visit for each patient. The database also included primary and secondary diagnostic codes, prescription orders.
This retrospective population-based study was based on secondary data analysis from Taiwan’s Longitudinal Health Insurance Database (LHID) between January 2007 and December 2011. In total, 1,000,000 participants from the LHID were randomly selected from the 2010 registry for beneficiaries of the national health insurance research database (NHIRD).There are approximately 27.38 million individuals in this registry. There was no significant difference in the gender distribution (χ2=0.067, df=1, p-value=0.796) between the patients. The sleep disorder patients were identified based on ICD-9-CM CODE 307.40 and MDD based on ICD-9-CM CODE 311. Statistical analysis:
This study had visited patients between 2007-2011 because of sleep disorder or MDD for medical treatment, we divided into three groups," using only Western medicine ",
And analyze the three groups of patients of gender, age, salary insurance coverage and urbanized areas and other basic characteristics. the health insurance of salary grade group announcement by department of the ministry of health and welfare, the urbanization rate of insured zones as grading standards was studied by Liu et al. the first level to a higher degree of urbanized areas, seventh level to the more remote areas.This study analyzed sleep disorder and MDD, the use of Chinese herbal products therapy , the top ten single herbs and herbal formulas, as well as analyzed two types of the disease, the use of Chinese herbal products therapy the top six single herbs and herbal formulas.
3. Result
This retrospective population-based study retrieved data from the Longitudinal Health Insurance Database (LHID) in Taiwan. In total, 1,000,000 participants from the LHID were randomly selected from the 2010 registry for beneficiaries of the NHI Research Database (NHIRD). Total 21,442 patients of Sleep Disorder (ICD-9-CM CODE: 307.40) and MDD (ICD-9-CM CODE:311.XX ) for clinical visited: A total of 11,030 sleep disorder patients, among these patients, 9,619 used Western medicine, 1,334 used CHP, and 77 used Western medicine and CHP. A total of 11,571 MDD patients among these patients, 11,389 used Western medicine, 131 used CHP, and 51 used Western medicine and CHP.(Table 1)
Basic characteristics of usage of CHP and Western medicine in clinic patients with sleep disorder in Taiwan. (Table 2) Basic characteristics of usage of CHP and Western medicine in clinic patients with MDD in Taiwan. (Table 3) No matter sleep disorder or MDD patients, female were more than male, the majority of these patients were aged 25-44 years old, NT 17,281-22,800 per monthly income, Level 1
urbanization.
1,411 sleep disorder patients ever used CHP and came to clinic 5,298 times. 182 MDD patients ever used CHP and came to clinic 755 times.
Top 10 of single herbs and herbal formulas for patients with sleep Disorder in Taiwan during 2007-2011. (Table 4) The most commonly three prescribed single herbs for the treatment of sleep disorder in clinic are Ziziphi Spinosae Semen and Polygalae Radix, and Polygoni Multiflori Caulis. The most commonly three prescribed herbal formulas are Jia-wei-xiao-yao-san, Suan-zao-ren-tangand Chai-Hu-Chia-Lung-Ku-Mu-LiI-Tang. Top 10 of single herbs and herbal formulas for MDD in Taiwan during 2007-2011. (Table 5) The most commonly three prescribed single herbs for the treatment of MDD are Polygoni Multiflori Caulis, Cortex Albiziae, andZiziphi Spinosae Semen. The most commonly three prescribed herbal formulas are Gan-Mai-Da-Zao-Tang, Jia-Wei-Xiao-Yao-San, and Chai-Hu-Chia-Lung-Ku-Mu-LiI-Tang. Top 6 of single herb and herbal formulas for patients with sleep disorder and MDD in Taiwan during 2007-2011. (Table 6) The most commonly three prescribed single herbs for patients with sleep disorder and MDD are Ziziphi Spinosae Semen,
Polygoni Multiflori Caulis and Radix Polygalae. The most commonly three prescribed herbal formulas are Jia-Wei-Xiao-Yao-San, Suan-Zao-Ren-Tang and Chai-Hu-Chia-Lung-Ku-Mu-LiI-Tang.
4. Discussion
In Taiwan, the total direct medical costs of adult depression increased continuously over the period from 2000 to2002(14). The prevalence of use of three
kinds of psychotropic drugs (antidepressants, mood stabilizers, and anxiolytic-hypnotic drugs) increased greatly from 1997 to 2004(15). In general, the prevalence
study found that about 30-40% of adults in the year there had been reported by short-term insomnia, and up to 10-15% suffered from chronic insomnia(16). Insomnia is a
risk factor for the onset of severe depression, some study have demonstrated that MDD at baseline was the strongest predictor of developing insomnia(17). Therefore, in
order to prevent insomnia and depression is an important public issue.
In our study indicated that for some patients with sleep disorder and MDD may prefer combination therapy of CHP and Western medicine. This result is similar to one study indicated that integrated traditional and Western medicine based therapies for the syndrome differentiation of depression significantly improved the Hamilton depression scale (HAMD), illustrating that combining therapies from integrated traditional and Western medicine for treatment of depression is better than Western medicine alone(18). We found that some patients no matter sleep disorder or MDD
patients, female were more than male is similar to one study expressed that for adults, prevalence of insomnia was estimated of 17.3 to 22.3% for men and 20.5 to 21.5% for
women(19). We also foud that prevalence was higher among patients 25 to 44 years
old. This may be related with more psychosocial stress and work overload in these patients. In the current economic environment, stress is a constant companion for many people. Our results demonstrated that these patients lived in the city of level 1 urbanization may be associated with high stress and high prevalence in insomnia
Our study showed that top 2 of single herbsfor sleep disorder during 2007-2011 was Ziziphi Spinosae Semen and Polygalae Radix. Ziziphi Spinosae Semen
has been used widely in clinic for the treatment of insomnia, anxiety, dreaminess, and night sweats. Modern pharmacological studies show that possesses multiple activities, antihyperlipidemia, immuno- potentiation and anxiolytic effects. Fufang Suanzaoren decoction, a famous TCM preparation, has been used widely for the treatment of insomnia in clinical practice(20). One study suggested that the hypnotic
effect of jujuboside from Semen Ziziphi Spinosae in normal rats may be influenced by circadian rhythm and the serotonergic system may involve in the hypnotic effect of jujuboside. Jujuboside may be good source of lead compounds for novel hypnotics(21).
Polygalae Radix is mainly used for the treatment of insomnia, depression, palpitations with anxiety, restlessness and disorientation, and to prevent dementia and memory failure. Modern pharmacological studies have demonstrated that there components
shared many beneficial activities, such as cognitive improving, potential antipsychotic efficacy, antioxidant activity and anti-inflammatory effects(22).
Our study also showed that top 3 of s herbal formulas for sleep disorder during 2007-2011 wasJia-wei-xiao-yao-san,Suan-zao-ren-tang and Chai-Hu-Chia-Lung-Ku-Mu-LiI-Tang. This result is similar to one study indicated that Suan-zao-ren-tang was the most commonly prescribed Chinese herbal formula for subjects with insomnia, followed by Jia-wei-xiao-yao-san, other frequently prescribed formulas was Tian-Wang-Bu-Xin-Dan, Gan-Mai-Da-Zao-Tang, and Chai-Hu-Jia-Long-Gu-Mu-Li-Tang. These formulas had been used for a long history in Taiwan. They are frequently prescribed by TCM practitioners to alleviate sleep disturbances(23).
Another clinical trials demonstrated that the most commonly two prescribed CHP for patients with insomia was Jia-Wei-Xiao-Yao-San and Suan-Zao-Ren-Tang may be an efficacious therapy for improving sleep quality(24, 25). A systematic review on the efficacy, safety and types of Chinese herbal medicine (CHM) for depression, including Chai-Hu-Jia-Long-Gu-Mu-Li-Tang, Jia-Wei-Xiao-Yao-San. This study showed that CHM was more effective than placebo and as effective as
Our study showed that top 2 of single herbs for MDD in Taiwan during 2007-2011 was Polygoni Multiflori Caulis and Polygala Tenuifolia. The sedative-hypnotic effect of Polygoni multiflori caulis decoction was found in animal model(27). Polygala
Tenuifolia was used to tranquilize the mind and disperse the depressed vital energy and for emotional upset, depression, insomnia(28). One study showed that as preclinical
evidence Radix Polygalae extract exerts rapid-onset antidepressant effects by
modulating glutamatergic synapses in critical brain circuits of depression and may be worthy of further evaluation as a safe substitute(29).
Our study showed that top 10 of herbal formulas for MDD in Taiwan during 2007-2011 was Gan-mai-da-zao-tang, Jia-wei-xiao-yao-san and Chai-Hu-Chia-Lung-Ku-Mu-LiI-Tang. Gan-mai-da-zao-tang has been shown to inhibit the
hyperexcitability of neuronal membranes and may have sedative effects(23). Gan Mai
Da Zao (GMDZ) decoction is one of the most well-known herbal prescriptions for depression, and the systematic review will provide a detailed summary of the current state of evidence on the effectiveness of the herbal medicine GMDZ decoction in treating the symptoms of patients with depression. The composition of GMDZ decoction includes the three herbs Glycyrrhiza, Triticum and Zizyphi Fructus. Many pharmaceutical companies around the world manufacture GMDZ to manage
ability of anti-stress by affecting the different taches of the hypothalamus-pituitary-adrenal gland axle and change the stress behaviors(31).
The most commonly prescribed herbal formulas for patients with sleep disorder and MDD is Jia-Wei-Xia-Yao-San and Chai-Hu-Chia-Lung-Ku-Mu-Li-Tang.
These two herbal formulas have the same ingredient is Bupleurum falcatum (BFM), Bupleurum falcatum (BFM), widely used in oriental medicine. BFM as the treatment for depression, some researchers reported that a few decoctions that included BFM as a major ingredient ameliorated the chronic stress-induced depressive state(32, 33).
BFM was also used as one of the major ingredients to treat psychosomatic disorders in oriental traditional medicine(34).
In our study, depressive insomnia could be divided into 6 syndromes, including the syndrome of stagnation of liver Qi, and spleen deficiency, transforming into fire, the syndrome of spleen and stomach qi deficiency, resulting from deficiency of blood to nourish the heart spirit, the syndrome of including outer and inner part of the body ,heat as a pathogenic factor that causes heat syndrome, heat syndrome disturb the mental activities, the syndrome of kidney and heart deficiency and deficiency of yin and blood, transforming into fire, the syndrome of deficiency of liver blood and transforming into fire and disturb mental spirit unable to sleep, the syndrome of deficiency of stomach Qi and gallbladder Qi and disturbing phlegm.
Ingredients and indication of Chinese herbal formulas was summarized as the following table 7.
5. Conclusion
CHP including SH and HF are widely used in patients with sleep disorder and MDD, still need to evaluate the efficacy of CHP for sleep disorder and MDD in the further.
Study limitation
There are some limitations in our study. First, the estimated top 10 single herbs and herbal formulas were searched from the National Health Insurance database records according to the patient's main symptoms and secondary symptoms, may be ruled out form the secondary symptoms rather than the main symptoms. Secondly, the use of these drugs for treatment of sleep disorder and MDD, the dose-response relationship and efficacy was unknown.
Acknowledgement
The authors express our sincere thanks to Chung Shan Medical University professor Lee and China Medical University professor Huang and the whole team members who assisted this work.
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Table 1 Distribution of usage of Western medicine and CHP in patients with sleep disorder and MDD patients
sleep disorder MDD
total clinic patients 11,030 11,571
CHP 1,334 131
Western medicine 9,619 11,389
Western medicine and CHP
77 51
Table 2 Basic characteristics of usage of CHP and Western medicine in clinic patients with sleep disorder in Taiwan.
CHP Western medicine
and CHP Western medicine Total
N % N % N % N % Total 1334 12.09 77 0.70 9619 87.21 11030 100.00 gender female 969 72.9 51 67.11 5923 61.72 6943 63.09 male 364 27.31 25 32.89 3673 38.28 4062 36.91 missing 1 - 1 - 23 - 25 -Age(year) 0-18 43 3.22 0 0.00 165 1.72 208 1.89 19-24 87 6.52 2 2.60 281 2.92 370 3.35 25-44 563 42.20 26 33.77 2865 29.78 3454 31.31 45-64 516 38.68 30 38.96 3948 41.04 4494 40.74 65+ 125 9.37 19 24.68 2360 24.53 2504 22.70 missing 1 - 1 - 23 - 25 -Average age (MEAN, SD) 43.80 15.44 50.60 15.99 51.83 17.13 50.85 17.13 Monthly income (NTD) 300 22.49 16 20.78 2524 26.24 2840 25.75 0-17280 221 16.57 15 19.48 2127 22.11 2363 21.42 17281-22800 322 24.14 24 31.17 2529 26.29 2875 26.07 22801-28800 104 7.80 4 5.19 627 6.52 735 6.66 28801-36300 107 8.02 3 3.90 572 5.95 682 6.18 36301+ 280 20.99 15 19.48 1240 12.89 1535 13.92 missing 1 - 1 - 23 - 25 -Urbanizatio n Level 1 487 36.51 21 27.63 3354 34.90 3862 35.05 Level 2 450 33.73 30 39.47 2969 30.89 3449 31.30 Level 3 175 13.12 8 10.53 1358 14.13 1541 13.98 Level 4 163 12.22 13 17.11 1198 12.47 1374 12.47 Level 5 9 0.67 0 0.00 177 1.84 186 1.69
Level 6 27 2.02 3 3.95 266 2.77 296 2.69
Level 7 23 1.72 1 1.32 288 3.00 312 2.83
missing 1 - 1 - 23 - 25
Table 3 Basic characteristics of usage of CHP and Western medicine in clinic patients with MDD in Taiwan.
CHP Western medicine
and CHP Western medicine Total
N % N % N % N % Total 131 1.13 51 0.44 11389 98.43 11571 100.00 gender female 97 74.05 41 80.39 7122 62.90 7260 63.10 male 34 25.95 10 19.61 4201 37.10 4245 36.90 missing 0 - 0 - 66 - 66 -Age(year) 0-18 2 1.53 0 0.00 398 3.49 400 3.46 19-24 7 5.34 2 3.92 670 5.88 679 5.87 25-44 63 48.09 21 41.18 3927 34.48 4011 34.66 45-64 43 32.82 23 45.10 3906 34.30 3972 34.33 65+ 16 12.21 5 9.80 2488 21.85 2509 21.68 missing 0 - 0 - 66 - 66 -Average age (MEAN, SD) 45.35 13.97 46.55 14.94 48.69 18.34 48.65 18.29 Monthly income (NTD) 24 18.32 13 25.49 3051 26.79 3088 26.69 0-17280 35 26.72 12 23.53 2961 26.00 3008 26.00 17281-22800 38 29.01 10 19.61 2929 25.72 2977 25.73 22801-28800 4 3.05 3 5.88 636 5.58 643 5.56 28801-36300 9 6.87 5 9.80 630 5.53 644 5.57 36301+ 21 16.03 8 15.69 1182 10.38 1211 10.47 missing 0 - 0 - 66 - 66 -Urbanizatio n Level 1 39 29.77 18 35.29 3523 30.99 3580 30.99 Level 2 45 34.35 15 29.41 3744 32.93 3804 32.93 Level 3 15 11.45 11 21.57 1741 15.31 1767 15.30 Level 4 23 17.56 6 11.76 1366 12.02 1395 12.08 Level 5 1 0.76 1 1.96 195 1.72 197 1.71
Level 6 7 5.34 0 0.00 405 3.56 412 3.57
Level 7 1 0.76 0 0.00 395 3.47 396 3.43
missing 0 - 0 - 66 - 66
Table 4 top 10 of single herbs and herbal formulas for patients with sleep disorder in Taiwan during 2007-2011
no single herbs % herbal formulas %
1 Ziziphi Spinosae Semen
4.69
Jia Wei Xiao Yao San 12.63
2 Polygalae Radix 3.44 Suan Zao Ren Tang 9.21
3 Polygoni Multiflori Caulis
3.21
Chai-Hu-Chia-Lung-Ku-Mu-LiI-Tang 5.42
4 Scutellariae Radix 3.09 Wen Dan Tang 4.91
5 Salviae Miltiorrhizae Radix et Rhizoma
2.28
Tian Wang Bu Shin Dan 4.81
6 Rehmanniae Radix 2.14 Gan Mai Da Zao Tang 3.81
7 Coptidis Rhizoma 1.99 Gui Pi Tang 2.70
8 Platycladi Semen 1.71 Gan Lu Yin 2.38
9 Corydalis Rhizoma 1.65 Zhi Gan Cao Tang 1.49
10 Rhei Radix et Rhizoma
1.60
Table 5 top 10 of single herbs and herbal formulas for patients with MDD in Taiwan during 2007-2011
no single herbs % herbal formulas %
1 Polygoni Multiflori
Caulis 7.42 Gan Mai Da Zao Tang
11.7 1 2
Cortex Albiziae 5.01 Jia Wei Xiao Yao San 11.1
2 3 Ziziphi Spinosae Semen 4.68 Chai-Hu-Chia-Lung-Ku-Mu-LiI-Tang 7.68
4 Curcumae Radix 4.60 Tian Wang Bu Shin Dan 6.93
5 Acori Graminei
Rhizoma 4.06 Wen Dan Tang
3.55
6 Polygalae Radix 3.94 Suan Zao Ren Tang 3.17
7 Cyperi Rhizoma 2.49 Ban Xia Hou Po Tang 2.15
8 Ostreae Testa 2.07 Xin Yi Qing Fei Tang 1.93
9 Salviae Miltiorrhizae
Radix et Rhizoma 1.95 Zhu Ru Wen Dan Tang
1.61 10 Platycladi Semen 1.78 Qing Zao Jiao Fei Tang 1.61 MDD: major depressive disorder
Table 6 top 6 of single herbs and herbal formulas for patients with sleep disorder and MDD in Taiwan during 2007-2011
no single herbs % ferbal formulas %
1 Ziziphi Spinosae Semen 4.69 Jia Wei Xiao Yao San 12.41
2 Polygoni Multiflori Caulis 3.69 Suan Zao Ren Tang 8.36
3 Polygalae Radix 3.49 Chai-Hu-Chia-Lung-Ku-Mu-LiI-Tang 5.74
4 Scutellariae Radix 2.82 Tian Wang Bu Shin Dan 5.11
5
Salviae Miltiorrhizae Radix et Rhizoma
2.24 Gan Mai Da Zao Tang 4.93
6 Rehmanniae Radix 1.97 Wen Dan Tang 4.72
Table 7 Ingredients and indication of Chinese herbal formulas Chinese herbal formulas
(Chinese name)
ingredients indication
Jia-wei-xiao-yao-san (Dan-zhi-xiao-yao-san)
Angelica sinensis (Asi), Atractylodes
macrocephala (Ama), Bupleurum chinense (Bch), Gardenia jasminoides (Gja), Gur, Mentha haplocalyx, Paeonia lactflora, Paeonia su ff rutcosa (Psu), Pco, Zingiber cinale (Zof)
Decoction of Jia-wei-xiao-yao-san for syndrome of stagnation of liver Qi, and spleen deficiency, transforming into fire
Gan-mai-da-zao-tang Gur, Triticum aestivum, Zju Decoction of
Gan-mai-da-zao-tangfor
syndrome of spleen and stomach qi deficiency ，resulting from deficiency of blood to nourish the heart spirit
Chai-hu-jia-long-gu-mu-li-tang
Bupleurum chinense, Cinnamomum cassia, Cpi, Os Draconis, O. gigas, Pinellia ternate (Pter), Pco, Rheum palmatum, Scutellaria baicalensis (Sba), Zof, Z. jujube (Zju),
Decoction of
Chai-hu-jia-long-gu-mu-li-tang for syndrome of including outer and inner part of the body ,heat as a pathogenic factor that causes heat syndrome,
heat syndrome disturb the mental activities
Tian-wang-bu-xin-dan Asi, Asparagus cochinchinensis,
Codonopsis pilosula (Cpi), Ophiopogon japonicus
(Oja), Platycladus orientalis, Platycodon grandiflorum, Polygala tenuifolia (Pte), Pco, Rehmannia glutinosa (Rgl), S. miltiorrhiza, Schisandra chinensis, Scrophularia ningpoensis, Zsp
Decoction of Tian-wang-bu-xin-dan for syndrome of kidney and heart deficiency and deficiency of yin and blood ， transforming into fire
Suan-zao-ren-tang A. asphodeloides, G. uralensis (Gur), Ligusticum chuanxiong, P. cocos (Pco), Z. spinosa (Zsp)
Decoction of Suan-zao-ren-tang for syndrome of
deficiency of liver blood and
transforming into fire and disturb mental spirit unable to sleep
