Abstract
Objective. To analyze and evaluate the effectiveness of traditional Chinese medicine decoction (TCMD) in the treatment of cardiac neurosis (CN) complicated with depression and anxiety. Methods. Relevant literature on TCMD in the treatment of CN complicated with depression and anxiety was retrieved from Chinese and English databases, and the retrieved literature was included and excluded. The quality of the retrieved literature was evaluated according to the Cochrane system, and the meta-analysis was undertaken with RevMan5.3 software. Results. A total of 10 papers were included, including 686 patients and 349 patients in the treatment group (131 males and 218 females), and there were 337 cases in the control group (131 males and 206 females). The results of the meta-analysis showed that compared with the control group, TCMD could significantly improve palpitation (MD = 0.78, 95% CI = 0.55–1.01, ), chest tightness/chest pain (MD = 0.53, 95% CI = 0.10–0.97, ), shortness of breath (MD = 0.60, 95% CI = 0.26–0.93, ), and TCM syndrome score (MD = 5.91, 95% CI = 4.32–7.49, ), reduce resting heart rate (MD = 13.21, 95% CI = 9.01–17.40, ), and could reduce psychological scale scores, such as Zung’s self-rating Depression Scale (MD = 7.90, 95% CI = 4.98–10.83, ), Zung’s self-rating Anxiety Scale (MD = 6.55, 95% CI = 4.25–8.86, ), Hamilton Depression Scale (MD = 4.46, 95% CI = 3.00–5.92, ), and Hamilton Anxiety Scale (MD = 3.35, 95% CI = 1.85–4.85, ). The differences were statistically significant. Tonic drugs were commonly used; Angelica sinensis, Poria cocos, Polygala tenuifolia, Wild jujube kernel, and Bupleurum were the most frequently used traditional Chinese medicines. Conclusion. TCMD mainly composed of tonic and tranquilizing herbs could significantly improve the clinical symptoms of patients with CN and reduce heart rate, anxiety, and depression scores. However, the evidence grade of the clinical research was limited by the quality of the included literature, and more high-quality clinical trials are still needed for further verification. This trial was registered with PROSPERO: CRD42022312164
1. Introduction
Cardiac neurosis, also known as cardiovascular neurosis, is a psychological and physiological syndrome characterized by circulatory symptoms in the absence of underlying organic disease. The syndrome is characterized by dyspnea, precordial pain, palpitations, and shortness of breath as common symptoms. In recent years, the prevalence of CN has increased significantly, accounting for more than 30% of the total number of patients in cardiology [1, 2]. The study found that most patients with CN are mainly mental workers, and CN is most common in young and middle-aged people and more often in females than males, especially in menopausal women. [1, 3, 4].
At present, the etiology and pathogenesis of CN are not fully understood, and mental state, physical state, nervous system, genetic factors, and external environmental stimuli may all be related to the disease. Clinically, Western medical treatment is mainly based on antidepressants, antianxiety, neuromodulators, and β-blocker drugs, which have moderate short-term effects but poor long-term efficacy.[5].
The treatment of CN in traditional Chinese medicine had formed its characteristics before modern medicine and has unique insights in clinical practice and rehabilitation methods, which have certain advantages in relieving clinical symptoms, improving quality of life, and improving function. The treatment of CN mainly focuses on clinical symptoms, such as “sleeplessness,” “heart palpitation,” and “depression,” and is aimed at regulating the deficiency of internal organs and the imbalance of Qi mechanisms [5–7]. In this study, we investigated the efficacy of TCMD in the treatment of CN and conducted a systematic Meta-analysis, aiming to provide an evidence-based basis for the treatment of CN.
2. Methods
Our meta-analysis was conducted based on preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Ethical approval was not required. The study protocol was registered in the PROSPERO international prospective register of systematic review (CRD42022312164).
2.1. Search Strategy
The English search terms “Chinese medicine decoction,” “Chinese herb medicine,” “medicinal broth,” “cardiovascular neurosis,” and “cardiac neurosis” were searched in Clinical Trials, MEDLINE, EMBASE, PubMed, and The Cochrane Library of Evidence-Based Medicine. And the Chinese search terms “traditional Chinese medicine decoction,” “decoction,” “Cardiac neurosis,” “Cardiovascular neurosis,” etc. were searched in China National Knowledge Internet (CNKI), China Clinical Trials Registry, Wanfang database, VIP database (VIP), and China Biomedical Literature Service. The search time range was from the earliest inclusion in the database to December 2021.
2.2. Inclusion and Exclusion Criteria
2.2.1. Inclusion Criteria
1 Study type: randomized controlled studies, domestic and foreign studies involving “traditional Chinese medicine decoction (TCMD) for the treatment of cardiac neurosis,” and the language of the literature selected for inclusion was Chinese or English. ②The study subjects should be patients with cardiac neurosis, cardiovascular dysfunction, and neurological manifestations and without organic heart disease after the examination. ③ The study subjects should be aged 14–80 years old and the syndrome type in TCM includes Qi stagnation in the heart and chest, Qi depression transforming into the fire, deficiency in the heart and spleen, and Qi and Yin deficiency; the Western medicine diagnosis should refer to the diagnostic criteria of Practical Internal Medicine (15th edition). ④ The treatment group was given TCMD treatment, and various relevant parameters were compared with the control group. ⑤ The result indicators were the Chinese medicine evidence points, heart rate analysis, and psychological scale points analysis [Zung’s Depression Self-Rating Scale (SDS), Zung’s Anxiety Self-Rating Scale (SAS), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Somatization Self-Rating Scale (SSS), etc.].
2.2.2. Exclusion Criteria
Exclusion criteria were as follows: ① clinical trial studies with unclear diagnostic criteria, ② research subjects that do not meet the diagnostic criteria of TCM and Western medicine, and ③ repeatedly published papers with no need for clinical outcome indicators.
2.3. Quality Evaluation Criteria and Data Extraction
In this study, Cochrane systematic evaluation was used to evaluate the quality of the included literature, including eight sequential items such as random sequence generation, allocation concealment, whether to apply blinding, blinded evaluation, withdrawal/missed visit handling, outcome data integrity, selective reporting of study results and other sources of bias, and evaluation summary. Data screening extraction was done by two investigators individually and eventually combined for analysis, and any disagreement was resolved by discussion and negotiation. The main elements of the evaluation information included the following: ① whether the random assignment was used to the research group, ② whether blinded methods were utilized to evaluate treatment subjects and outcomes, ③ whether the study used allocation concealment, ④ whether complete data were reported in the included literature, and ⑤ whether there were other risks of bias.
2.4. Statistical Methods
Meta-Analysis was performed using RevMan5.3 software for the statistical analysis studied in this paper. This analysis was performed using a fixed-effects model if there was statistical homogeneity between studies (, I2 < 50%) and a random-effects model for data analysis when there was statistical heterogeneity between studies (, I2 > 50%).
2.5. Ethical Statement
All study results and data analysis in this study evaluation system were approved by the Medical Ethics Committee, so no further approval from the Medical Ethics Committee or patient consent was required.
3. Results
3.1. Search and Screening Results
In this study, a total of 31 relevant literature in English and Chinese were initially retrieved, and by excluding studies in which the diagnostic criteria did not match those of Chinese and Western medicine, a total of 10 papers with 686 patients were finally included, with 349 cases in the treatment group, including 131 male patients and 218 female patients, and 337 cases in the control group, including 131 male patients and 206 female patients. The literature screening inclusion process was shown in Figure 1, and the basic characteristics of the literature were shown in Table 1.
3.2. Methodological Quality
A total of 4 included papers [9, 10, 12, 16] used the random number table method, 5 papers [11, 13–15, 17] used the randomized control method, 1 paper [8] grouping method was not described, the results of the included literature were not affected by the blinded method, the results data were complete and free of bias, no allocation concealment and withdrawal from follow-up or missed visits, and 1 [8] paper had selective reporting of study results. The methodological quality of the species included literature was evaluated in Figure 2 and Table 2.
3.3. Meta-Analysis Results
3.3.1. Analysis of TCM Evidence Points
(1) Heart Palpitations. 3 papers were included in this analysis [8, 14, 17], and there was heterogeneity in the findings (I2 = 93%, ), so a random-effects model was used for the combined analysis. The results showed that the treatment group was significantly better than the control group in improving palpitation symptoms, with a statistically significant difference (MD = 0.78, 95% CI = 0.55–1.01, ), as shown in Figure 3.
(2) Chest Tightness/Chest Pain. 3 papers were included in this analysis [8, 14, 17], and there was heterogeneity in the study results (I2 = 98%, ), so a random-effects model was used for the combined analysis. The results showed that the treatment group improved chest tightness/chest pain symptoms significantly better than the control group, with a statistically significant difference (MD = 0.53, 95% CI = 0.10–0.97, ), as shown in Figure 4.
(3) Shortness of Breath. 3 papers were included in this analysis [8, 14, 17] and there was heterogeneity in the study results (I2 = 98%, ), so a random-effects model was used for the combined analysis. The results showed that the treatment group improved shortness of breath symptoms significantly better than the control group, with a statistically significant difference (MD = 0.60, 95% CI = 0.26–0.93, ), as shown in Figure 5.
(4) Total TCM Evidence Score. 6 papers were included in this analysis [10–13, 15, 17] and there was heterogeneity in the study results (I2 = 96%, ), so a random-effects model was used for the combined analysis. The results showed that the treatment group outperformed the control group in terms of improvement of clinical symptoms, with a statistically significant difference (MD = 5.91, 95% CI = 4.32–7.49, ), as shown in Figure 6.
3.4. Heart Rate Analysis
2 papers were included in this analysis [13, 15], and there was heterogeneity in the study results (I2 = 98%, ), so a random-effects model was used for the combined analysis. The results showed that the treatment group was superior to the control group in reducing resting heart rate, with a statistically significant difference (MD = 13.21, 95% CI = 9.01–17.40, ), as shown in Figure 7.
3.5. Analysis of Psychological Scale Scores
3.5.1. Zung’s Self-Rating Scale for Depression (SDS)
4 papers were included in this analysis [9, 15–17], and there was heterogeneity in the findings (I2 = 97%, ), so a random-effects model was used for the combined analysis. The results showed that the treatment group outperformed the control group in terms of self-rated antidepressants, with a statistically significant difference (MD = 7.90, 95% CI = 4.98–10.83, ), as shown in Figure 8.
3.5.2. Zung’s Self-Assessment Scale for Anxiety (SAS)
3 papers were included in this analysis [9, 15, 16], and there was heterogeneity in the study results (I2 = 93%, ), so a random-effects model was used for the combined analysis. The results showed that the treatment group outperformed the control group in terms of self-rated anxiolysis, with a statistically significant difference (MD = 6.55, 95% CI = 4.25–8.86, ), as shown in Figure 9.
3.5.3. Hamilton Depression Scale (HAMD)
4 papers were included in this analysis [8, 10, 11, 13], and there was heterogeneity in the study results (I2 = 100%, ), so a random-effects model was used for the combined analysis. The results showed that the treatment group was superior to the control group in terms of antidepressants, with a statistically significant difference (MD = 4.46, 95% CI = 3.00–5.92, ), as shown in Figure 10.
3.5.4. Hamilton Anxiety Inventory (HAMA)
6 papers were included in this analysis [8, 10, 11, 13, 14, 17], and there was heterogeneity in the study results (I2 = 99%, ), so a random-effects model was used for the combined analysis. The results showed that the treatment group was superior to the control group in terms of anxiolysis, with a statistically significant difference (MD = 3.35, 95% CI = 1.85–4.85, ), as shown in Figure 11.
3.6. Analysis of Traditional Chinese Medicines Use
Among the 10 literature studies included in this study for the treatment of CN, 55 TCMs were used, with a total frequency of 125 times. Among them, 8 TCMs were used 4 times or more, which were Angelica sinensis (6, 4.8%), Poria cocos (6, 4.8%), Polygala tenuifolia (6, 4.8%), Wild jujube kernel (6, 4.8%), Bupleurum (6, 4.8%), White peony (5, 4.0%), Chuanxiong (4, 3.2%), Gan song (4, 3.2%), and 23 TCMs were used once, as shown in Table 3. Among them, the most frequently used drugs were tonic drugs, 29 times in total, accounting for 23.2% of the total frequency, followed by tranquilizing drugs (21, 16.8%), antipyretic drugs (14, 11.2%), and surface relieving drugs (12, 9.6%), as shown in Table 4.
4. Discussion
Cardiac neurosis is a typical psychosomatic disease of the circulatory system [18]. With the change in the modern lifestyle and the increase of social and environmental pressure, the transformation of the “Biological-Psychological-Social” medical model and various psychological factors such as anxiety and depression have been gradually emphasized in the development and regression of circulatory system diseases. CN is mainly manifested in heart palpitation, accelerated resting heart rate, chest tightness, chest pain, etc., but there are no signs of organic heart disease [2, 3]. CN mostly occurs in young and middle-aged people, more females than males, especially menopausal women, and mental workers outnumber manual workers [19]. The above somatic symptoms are related to emotion and brain function. Psychological factors are one of the key reasons, patients are usually accompanied by obvious psychological disorders such as anxiety, depression, or neurasthenia. Friedman [20] believes that the hypothalamus may be the site of CN, and the lesions in this area can cause anxiety and affect the functional regulation of many other systems.
Due to the lack of laboratory evidence, CN is generally diagnosed in patients with symptoms, few signs, and no organic heart disease [21]. In recent years, the incidence rate of CN has been increasing. When the psychological burden and mental pain borne by patients due to the disease are serious, it can affect their normal life and work, and the long-term development will further lead to or aggravate organic diseases [22]. At present, there is no effective drug treatment for CN in modern medicine, which mainly depends on psychotherapy combined with corresponding symptomatic treatment, such as oryzanol β-Receptor blockers, etc.; however, the problems such as large side effects, poor patient compliance, and severe relapse are more prominent.
CN mostly belongs to the category of “palpitation,” “depression syndrome,” and other diseases in TCM. The occurrence of CN is mostly caused by adverse changes such as constitution, diet, and emotion, resulting in the imbalance of Qi, blood, Yin, and Yang in the body, loss of support for the heart, loss of possession of the mind, or tangible solid evil blocking the heart pulse and loss of support for the mind. The occurrence of CN is closely related to the five organs. Tietao Deng [23], a master of TCM, believes that CN is most closely related to the spleen. The methods of regulating the spleen, protecting the heart, tonifying Qi, and removing phlegm are often used to treat the disease. Professor Shi [24] believes that middle-aged women are prone to this disease, which is related to the theory that women are blood-based and that women are born with depression. He believes that the pathogenesis of CN is usually blood deficiency and liver depression. Professor Xian [25] believes that the occurrence of CN is also related to the brain and connected with the heart and brain and advocates the treatment of “simultaneous treatment of heart and brain.” Professor Meng [26] believes that the disease is closely related to “Qi depression” and “blood stasis,” and Xuefu Zhuyu decoction is often used for treatment.
A number of clinical trials have shown that TCMD, as a traditional Chinese medicine dosage form, can significantly improve the clinical symptoms of patients with CN and has certain advantages in the treatment of CN. Therefore, it is of practical significance to explore the systematic evaluation of TCMD on the curative effect of CN. TCMD represented by Bupleurum and longbone oyster decoction, Bupleurum Shugan powder, Xiaoyao Powder, Ganmai Dazhao Decoction, and Guipi Decoction are mostly used in the treatment of CN with remarkable curative effect. Moreover, pharmacological studies on TCMD (e.g., Shugan Ningxin Decoction, Chaihu Guizhi Longgu oyster decoction, Jieyu Decoction, etc.) have shown that they have tranquilizing, anticonvulsant, and reducing skeletal muscle excitability effects, which is closely related to the effective treatment of CN [27].
And through the analysis of the 10 literature studies on the treatment of CN included in this study, it was found that 55 kinds of traditional Chinese medicines were used, with a total frequency of 125 times. Among them, Angelica sinensis, Poria cocos, Polygala tenuifolia, Wild jujube kernel, and Bupleurum were the most frequently used TCMs. CN is located in the heart and is closely related to the liver, spleen, and kidney. The pathogenesis is the loss of the heart and liver, the depression of the liver and the deficiency of the spleen, or the deficiency of the heart and liver yin, and the deficiency of the liver and kidney yin. The treatment should be based on soothing the liver and strengthening the spleen, nourishing the heart, and calming the mind. If the blood of the heart is blocked, it will lead to chest tightness, chest pain, and palpitation. If the heart is in charge of the spirit, it will lead to worry and anxiety. The liver is in charge of catharsis and regulating emotions. The heart and liver are closely related to mental and emotional diseases while Angelica sinensis belongs to the liver, heart, and spleen meridians and has the effect of supplementing blood and activating blood circulation. Modern pharmacological studies have proved that Angelica sinensis has the effects of regulating immunity [28], anti-inflammation [29], and promoting blood circulation [30] and has good therapeutic effects on the symptoms of CN such as chest tightness, chest pain, palpitation, and anxiety. Bupleurum can soothe the liver and relieve depression, directly reach Shaoyang, help the operation of the cardinal machine, and make the Fu Qi smooth and the spirit tranquil. It has a significant effect in the clinical treatment of sleep disorders and depression. Experimental pharmacological studies have found that Poria cocos and Wild jujube kernel play an antianxiety role by making the neuroendocrine-immune regulatory network reach a steady state, while Poria cocos, Polygala tenuifolia, and Wild jujube kernel nourish the blood, regulate the liver, nourish the heart, and calm mind. In modern clinical applications, they can significantly improve symptoms such as palpitation, insomnia, and anxiety caused by the deficiency of the heart and liver blood in CN.
This study finally included 10 papers with 686 patients, 349 in the treatment group, of which 131 were males and 218 were females, and 337 in the control group, of which 131 were males and 206 were females. 9 of the papers [9–17] mentioned the specific randomization method, 1 paper [8] did not describe it, and all of them did not mention the blinding method used, allocation concealment, lost visits, and withdrawal; 1 paper [8] selectively reported the study results; and 3 papers [8, 11, 13] reported adverse effects. Meta-analysis showed that CN, treated with herbal tonics, significantly improved palpitations compared with the control group (MD = 0.78, 95% CI = 0.55–1.01, ), chest tightness/chest pain (MD = 0.53, 95% CI = 0.10–0.97, ), shortness of breath symptoms (MD = 0.60, 95% CI = 0.26–0.93, ), and the TCM symptom score (MD = 5.91, 95% CI = 4.32–7.49, ), reduced resting heart rate (MD = 13.21, 95% CI = 9.01–17.40, ), and reduced depression and anxiety symptoms. [SDS (MD = 7.90, 95% CI = 4.98–10.83, ), SAS (MD = 6.55, 95% CI = 4.25–8.86, ), HAMD (MD = 4.46, 95% CI = 3.00–5.92, ), HAMA (MD = 3.35, 95% CI = 1.85–4.85, )], all with statistically significant differences. According to the analysis of this study, TCMD has a significant effect on improving the common clinical symptoms, depression, and anxiety of CN.
4.1. Limitations
There are some limitations that should be noted. To begin with, due to the high risk of performance bias and detection bias, unclear risk of selection bias, and reporting bias, we only got relatively low-grade evidence for TCMD in the treatment of CN complicated with depression and anxiety, which means further research is very likely to have an important impact on our confidence in the estimate of effects and is likely to change the estimate. What is more, the sample size of the papers was small, and there was a lack of evaluation indicators such as safety analysis and quality of life analysis. Finally, because CN is mainly manifested in physical symptoms and lacks clear laboratory index evidence, we had to evaluate the effectiveness of TCMD in the treatment of CN from the results of TCM syndrome scores and psychological scale scores. Accordingly, further validation of the effectiveness of TCMD in the treatment of CN through large sample, multicenter, scientifically designed, and rigorously implemented clinical trials are still needed in the future.
5. Conclusion
In conclusion, TCMD mainly composed of tonic and tranquilizing drugs could significantly improve the clinical symptoms of cases with CN and reduce heart rate, anxiety, and depression scores. However, the evidence strength of the research results was limited by the quality of the included literature, and more high-quality clinical trials are still needed for further verification.
Data Availability
The data used to support the findings of the study are available at https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=312164.
Conflicts of Interest
The authors declared that they have no conflicts of interest in this work.
Acknowledgments
The authors would like to acknowledge the Special Fund for Basic Scientific Research Business Expenses of Central Public Welfare Scientific Research Institutes (no. ZZ13-YQ-008) and Major Research Project of Scientific and Technological Innovation Project of Chinese Academy of Traditional Chinese Medicine (no. CI2021A03115).