| Depression with anxiety has characteristics of high incidence, severe illness status, complex clinical symptoms, poor response to treatment, bad social function damage, high morbidity, high risk of suicide, easy relapse and chronicity, and normally costs more medical resources. Currently, even as the first-line treatment drugs of the disease, selective serotonin reuptake inhibitors still have disadvantages like side effects, withdrawn symptoms, drug combination risks, expensive, etc. Famous Chinese medicine doctors over the ages accumulated lots of precious experience on depression and anxiety, and established many effective prescriptions. So the purpose of the paper is to bring the simple, convenience, cheap and effective characteristics of traditional Chinese medicine into play. Basing on depression with anxiety, composing principles of ancient prescriptions are digged out, and under the guidance of which effective prescription is selected and tested by rigorous clinical trial.Objectives:1To dig the composing principles of ancient prescriptions which have dual treatment effect of the core symptoms of depression and anxiety.2To investigate the common syndrome distribution of depression with anxiety for the purpose of providing a basis for the clinical positioning of Chinese herbal medicine.3Specific to one of the common syndrome type of depression with anxiety, the treatment prescription is selected and of which the efficacy and safety of the prescription are tested.4Specific to the objective syndrome type of depression with anxiety, main syndrome indicators are selected which guide to disease and syndrome diagnosis and drug efficacy changes in order to help physicians and patients to prescribe or use the treatment prescription rationally.Methods: 1Using R-type clustering analysis to dig the composing principles of ancient prescriptions which have dual treatment effects of the core symptoms of depression and anxiety.2Using Delphi method to investigate the common syndrome distribution of depression with anxiety.3Specific to syndrome of qi depression transforming into fire of depression and anxiety and based on the composing principles of ancient prescriptions which have dual treatment effects of the core symptoms of depression and anxiety and literature to select treatment prescription. Using randomized double-blind, double simulation parallel controlled trial design to test the efficacy and safety of Jia-Wei-Xiao-Yao-San compared to sertraline on syndrome of qi depression transforming into fire of depression with lighter anxiety symptom and depression with heavier anxiety symptom subgroup.4Specific to syndrome of qi depression transforming into fire of depression with anxiety, using Delphi method to select main syndrome indicators which can guide to disease and syndrome diagnosis and drug efficacy changes.Results:1After data cleaning,151prescriptions and270Chinese herbal drugs are enrolled in the study and the whole database has41374data. By R-type clustering analysis,7clustering prescriptions and14moderate-related clustering matched pairs of herb (the clustering coefficient of correlation>0.4). The clustering prescriptions are atractylodes, rhizoma cyperi, jasmine, ligusticum wallichii, medicated leaven and scutellaria baicalensis, radix bupleuri, angelica sinensis, white paeony root, moutan bark and semen arecae, costusroot, mangnolia officinalis, purple perilla, caulis akebiae, pericarpium citri reticulatae viride, fructus aurantii, pinellia ternate, ginger and semen platycladi, semen ziziphi spinosae, astragalus, ginseng, dwarf lilyturf root and monkshood, as arum, dried ginger, cinnamon; borneol, musk, bezoar, donkey-hide gelatin, calamendiol, cinnabar, dens draconis and cistanche salsa, pilous antler, achyranthes bidentata, fructus schizandrae, rehmannia glutinosa, rhizoma dioscoreae. Clustering matched pair of herb are cistanche salsa and pilous antler, cistanche salsa and achyranthus bidentata blume, borneol and musk, concha ostreae and fossil fragments, borneol and calculus bovis, semen arecae and costusroot, perilla frutescens and caulis akebiae, angelica sinensis and white paeony root, perilla frutescens and pericarpium citri reticulatae viride, fructus schizandrae and radix rehmanniae preparata, atractylodes and rhizoma cyperi, perilla frutescens and fructus aurantii, atractylodes and gardenia, borneol and donkey-hide glue.2In the first round of survey,25specialists are selected, and the response rate is96%. The degree of familiarity on syndrome and quantization research and academic standards weights and professional degree of specialist are0.85,0.767,0.808respectively. And the weight coefficients of ten syndromes are larger than average weight coefficient. But the coordination degrees of specialists on the frequence extent of each syndrome type are fairly low (CV>0.25), and consistency among specialists over the survey is very low also (the Kendall’s coefficients.202, P<0.05). In the second round of survey,24specialists are selected, and the response rate is87.5%. The the degree of familiarity on syndrome and quantization research and academic standards weights and professional degree of specialist are0.86,0.79,0.82respectively. And the weight coefficients of nine syndromes are larger than average weight coefficient. And what is more, coordination degrees of specialists on the frequence extent of each syndrome type are fairly well (CV<0.25), and consistency among specialists over the survey is very high as well (the Kendall’s coefficient=0.610, P<0.05).3In the study mild-to-moderate depression with anxiety (syndrome of qi depression transforming into fire) treated by Jia-Wei-Xiao-Yao-San, total210patients were enrolled and among whom191patients finished the whole study. In main group and subgroup, Chinese drug group and western drug group has95VS96and62VS69subjects respectively. The baseline in the two groups has no statistical differences (P >0.05). At the end of treatment phase, the depression efficacy, anxiety efficacy, Chinese medicine symptom and CGI-EI in Chinese drug group are a little better than western drug group in both main group and subgroup, however, there are no statistically significant difference (P>0.05); but CGI-SI in Chinese group is dramatically relieved than western group(P<0.05); factors analysis show that the HAMD-sleep disturbance factors efficacies of Chinese drug group are better than western drug group in both main group and subgroup (P<0.05), and Chinese drug group can significantly decrease HAMD-anxiety/somatization symptoms factor score in subgroup also (P<0.05). During follow up phase, the efficacy of CGI-EI, decrease of HAMA score, HAMA-somatic anxiety factors and HAMA-psychic anxiety factors in Chinese drug group are significantly better than western drug group in both main group and subgroup (P<0.05). On safety comparison between the two groups, the side effects in Chinese drug group are slighter, and except in the first visit that western drug group has more side effects than Chinese drug group in subgroup(P<0.05), side effects in the latter group are a little more the former group but with no statistical differences in the rest visits and follow up regardless of in main group or subgroup(P>0.05). Chinese drug costs a patient Y4.73/day, while western drug costs Y7.14/day.4In the first round of survey,34specialists are selected, and the response rate is100%. The degree of familiarity on syndrome and quantization research and academic standards weights and professional degree of specialist are0.835,0.724,0.780respectively. And in the survey of important disease classification syndrome indicators, important syndrome classification syndrome indicators and important efficacy identification syndrome indicators, there are5,7,17syndrome indicators respectively of which the weight coefficients are larger than average weight coefficient. Although the coordination degrees of specialists on the importancies of each syndrome indicator in the three surveys are pretty high (CV=0.12-0.30), the consistencies among specialists over the three surveys are very low (the Kendall’s coefficient=0.202,0.355,0.230respectively, P<0.05). In the second round of survey,34specialists are selected, and the response rate is85.3%. The degree of familiarity on syndrome and quantization research and academic standards weights and professional degree of specialist are0.834,0.721,0.778respectively. And in the survey of important disease classification syndrome indicators, important syndrome classification syndrome indicators and important efficacy identification syndrome indicators, there are5,7,16syndrome indicators respectively of which the weight coefficients are larger man average weight coefficient. And what is more, in the three surveys, the coordination degrees of specialists on the importancies of each syndrome indicator are pretty high (CV of most indicators are lower than0.25), and the consistencies among specialists over the surveys are fairly high as well (the Kendall’s coefficient=0.527,0.420,0.504respectively, P<0.05).Conclusions:1Data mining shows that, in ancient prescriptions which have dual treatment effect of the core symptoms of depression and anxiety, warm property is the main herbal property, and cold and cool property take second place, and heat property comes to the last; and herbs mainly attribute to five zang and stomach meridian, among which spleen meridian herbs is a little more than others; and herbs are mainly classify to tonic herbs, and qi-regulating herbs, sedatives and tranquilizers herbs take the second place, awaking herbs, interior-warming herbs, blood-quickening stasis-transforming herbs, eliminate phlegm herbs, eliminate wet herbs, damp-clearing herbs, liver wind calmed herbs and astringent herbs come to the last. The composing principles of ancient prescriptions which have dual treatment effects of the core symptoms of depression and anxiety are adjusting motion of qi first, and mainly regulating liver and spleen later on, and herbs used in prescription should be bitter, pungent in nature and cool, moistening in taste; giving consideration to pathogenesis, such as removing phlegm and convulsion and tranquilizing by nourishing the heart; giving consideration to disease tendency and paying enough attention to tune up kidney yin and yang. 2The common syndrome of depression with anxiety are syndrome of liver-qi stagnation and syndrome of qi depression transforming into fire and syndrome of stagnation of liver qi and spleen deficiency and syndrome of deficiency of both heart and spleen and syndrome of liver-qi stagnation lead to hung up and syndrome of depression injuring spirit and syndrome of disharmony between heart and kidney and syndrome of lack of spirit preservation and syndrome of hyperactivity of fire due to yin deficiency.3Jia-Wei-Xiao-Yao-San has shown efficacy on mild-to-moderate depression with anxiety (syndrome of qi depression transforming into fire) and the therapeutic effect last a long time, and the drug has a quick and prominent effect and those characters are more suitable to patients with heavier anxiety symptoms, and the drug has advantages of high safety and inexpensive.4On depression with anxiety, melancholy, insomnia, irritable, abnormal sigh, languid are the main syndrome indicators for disease diagnosis; and on syndrome of qi depression transforming into fire of the disease, dysphoria, irascible, irritable, red tongue, stringy pulse, bitter taste in mouth and flanks pain are the main syndrome indicators for syndrome diagnosis; and irritable, melancholy, insomnia, languid, irascible, dysphoria, dreaminess, abnormal sigh, yellow fur, bitter taste, red tongue, cry, flanks pain, misgivings, sensation of lump in the throat headache, stringy pulse are the main syndrome indicator for efficacy changes. |
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