
==== Front
Medicine (Baltimore)
Medicine (Baltimore)
MD
Medicine
0025-7974
1536-5964
Lippincott Williams & Wilkins Hagerstown, MD

MD-D-23-10668
00060
10.1097/MD.0000000000039489
3
6500
Research Article
Systematic Review and Meta-Analysis
Efficacy and safety of a Chinese medicine formula Diankuang Mengxing Decoction combined with antipsychotics in the treatment of schizophrenia: A meta-analysis of randomized controlled trials
https://orcid.org/0000-0001-7963-4708
Lam Lai Kwan MD 1926786051@qq.com
a
Poon Lee Yam MD 378204181@qq.com
b
Xu Peng-Li MD 15638436961@163.com
a
Xie Peng-Cheng MM wzfs2017@126.com
a
Xie Ting MM wzfs2017@126.com
a
Xiao Ya MD xiaoya0527@126.com
a
Chen Li-Guo MD a*
a School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
b School of Medicine, Xiamen University, Xiamen, Fujian, China.
* Correspondence: Li-Guo Chen, School of Traditional Chinese Medicine, Jinan University, No.601 West Huangpu Avenue, Guangzhou, China (e-mail: tchenly@jnu.edu.cn).
06 9 2024
06 9 2024
103 36 e3948927 11 2023
06 8 2024
08 8 2024
Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

Background:

In patients with schizophrenia, Diankuang Mengxing Decoction with antipsychotics is one of the treatments for it. However, little information is available regarding the difference between the therapeutic effect of Diankuang Mengxing Decoction with antipsychotics and other treatments. Systematic evaluation is conducted to assess the efficacy and safety of Diankuang Mengxing Decoction and other antipsychotics, which are used to treat schizophrenia.

Methods:

We performed a systematic review (PROSPERO ID: CRD42023414603). This entailed a computerized search of several research databases from their respective dates of establishment until April 11, 2023, which collected clinical randomized controlled trials of Diankuang Mengxing Decoction combined with antipsychotics. The databases that contributed to this study were PubMed, Web of Science, Embase, EBSCOhost, Cochrane, Scopus, and Google Scholar. Each publication was screened according to defined inclusion and exclusion criteria, and appropriate literature was extracted and evaluated for quality, for which meta-analysis was performed using RevMan 5.4.

Results:

A literature review of 456 publications resulted in the inclusion of 18 randomized controlled trials with data collected from a total of 1636 patients. Meta-analytical results showed combination with risperidone, olanzapine, chlorpromazine, clozapine, ziprasidone, or aripiprazole increased the overall effectiveness of Diankuang Mengxing Decoction when treating schizophrenia (P < . 00001), among whom olanzapine demonstrated the greatest enhancement (Z = 3.65, odds ratio = 4.26, 95% CI: 1.96–9.28, P = .0003). The 4-week/30-day treatment (P = .0003) and a dosage of 400 mL/d of Diankuang Mengxing Decoction (P = .0004) were more effective. Also, there were widespread reductions to the Positive And Negative Syndrome Scale (PANSS) total scores, PANSS-positive symptom scores, PANSS-negative symptom scores, general psychopathology scores (P < .05 for all), as well as the incidence of adverse effects (Z = 2.79, odds ratio = 0.34, 95% CI: 0.16–0.73, P = .005) in patients with schizophrenia.

Conclusion:

The combination of Diankuang Mengxing Decoction with different antipsychotics can improve the overall prognosis of patients with schizophrenia; Diankuang Mengxing Decoction combined olanzapine, a dosage of 400 mL/d and a duration of 4 weeks/30 days being the best in this regard, by alleviating the symptoms and diminishing the disorder’s adverse effects. To build on this work, more large-sample, multi-center, and high-quality clinical studies in the future would help to further validate our findings.

antipsychotics
Diankuang Mengxing Decoction
meta-analysis
randomized controlled trial
schizophrenia
OPEN-ACCESSTRUE
==== Body
pmc1. Introduction

Schizophrenia is a complex syndrome, which most often develops during early adulthood, with a variety of symptoms. Typically, these symptoms can be divided into those that are positive, negative, or cognitive. Positive symptoms include hyper or abnormal mental functioning, such as hallucinations, hallucinations, delusions, unusual thinking, etc. Negative symptoms include lack of or reduced mental functioning, such as emotional retardation, social avoidance, emotional communication disorders, etc. Cognitive dysfunction relates to exhibiting difficulty with abstract thinking, attention deficit, and conceptual disturbance.[1] The causes of schizophrenia are similarly complex and can be derived from factors that are genetic, environmental, or a combination of both. In any event, they result in some degree of disruption to the brain’s development. Studies point to dysfunction in dopaminergic neurotransmission contributing to the onset of psychotic symptoms.[2] Currently, the main treatment methods include a combination of medication, psychotherapy, social support, and rehabilitation. For first-episode schizophrenia, antipsychotics are the mainstay for achieving relief of psychotic symptoms.[3] In China, available antipsychotic medications approved for schizophrenia include risperidone, clozapine, olanzapine, chlorpromazine, aripiprazole, and ziprasidone.[4]

Traditional Chinese medicine (TCM) does not have a term that corresponds directly to schizophrenia, though according to diagnoses provided by TCM, it is classified as epilepsy based on its symptoms.[5] As such, Chinese herbal medicine and acupuncture have been widely used in the treatment of patients with epilepsy and symptoms of schizophrenia for thousands of years, and studies have demonstrated the efficacy of combining Chinese herbal medicine with antipsychotics in the treatment of schizophrenia.[6] There is little evidence of adverse reactions even in TCM.[7] This combination can produce a superimposed effect,[8] which is capable of effectively diminishing clinical symptoms and enhancing patients’ quality of life.[9,10] Diankuang Mengxing Decoction was first prescribed by Wang Qingren, a famous doctor in the Qing dynasty, and it is composed of Radix paeoniae rubra, Semen persicae, Radix bupleuri, Pericarpium citri reticulatae viride, Cyperus rotundus, Citri reticulatae pericarpium, Pinellia ternata, Cortex mori radicis, Pericarpium arecae, Fructus perillae, Akebia quinata, and Glycyrrhiza uralensis. To further clarify Diankuang Mengxing Decoction’s potential, this study incorporated existing literature to conduct a meta-analysis that assessed its overall benefit when combined with antipsychotics in the treatment of patients with schizophrenia. Also, its effects on the functioning of different symptoms were generalized to obtain and provide medically valid evidence on the efficacy and safety of this formula as an adjunctive treatment for schizophrenia for clinical purposes.

2. Methods

The systematic review was conducted following the preferred reporting item (PRISMA) guidelines for systematic review and meta-analysis. This study protocol has been registered on the International Prospective Register of Systematic Reviews (PROSPERO); PROSPERO ID is CRD42021266760.

2.1. Search strategy

Computer searches were conducted with the abovementioned criteria on the following databases: PubMed, Web of Science, Embase, EBSCOhost, Cochrane, Scopus, and Google Scholar. The search period started at the date of the database’s establishment and ended on April 11, 2023. Search terms included “Diankuang Mengxing Decoction” AND “schizophrenia” AND “efficacy observation” OR “efficacy analysis” AND “randomized controlled trial,” and its all related medical subject headings, in both Chinese and English.

2.2. Inclusion and exclusion criteria

The screening process applied the following inclusion criteria: only original and randomized controlled clinical studies; subjects met the clinical diagnostic criteria of schizophrenia, with no serious organic lesions and no significant difference in general information between the control and subject groups; treatment regimens were such that both the subject and control groups were treated with the same antipsychotics, while the subject group was also treated with Diankuang Mengxing Decoction (number of doses and the length of treatment were not restricted); and the primary reported outcome was the overall effective rate, but other indicators should include the mean change in overall symptoms from baseline to endpoint as assessed by Positive And Negative Syndrome Scale (PANSS) total scores, PANSS-positive symptom scores, PANSS-negative symptom scores, and general psychopathology scores.

The analogous exclusion criteria were as follows: nonrandomized controlled clinical trials; literature that reported the application of complementary treatments other than Diankuang Mengxing Decoction in the trial group; absence of results for the required outcome indicators; studies that featured other comorbidities; duplicate publications or retrieved literature; papers lacking their full text; and presence of incorrect or incomplete study data.

2.3. Evaluation of endpoint outcome

The PANSS total scores, PANSS-negative symptom scores, PANSS-positive symptom scores, general psychopathology scores, and total rate of effectiveness were selected for evaluation. Also, clinical cure, improvement, and efficacy were included when recording the range of effectiveness, from which the total effective rate was calculated and collated. In addition, adverse reactions were recorded for the safety evaluation.

2.4. Data extraction and quality assessment

All literature obtained from the search was extracted by 2 full-time members of the research team using Endnote and Excel software to produce a table with basic information about the paper in question. The information included (at an absolute minimum), but was not limited to: author; year of publication; subject gender; sample size; duration of disease; interventions carried out; duration of treatment; and outcome indicators. If disagreements arose during the process, a third member of the team was consulted, and discussions were held to find resolution. The Risk of Bias Assessment Tool provided in the Cochrane Handbook 6.2 was used by the team for independent quality assessment, with discussion similar to the abovementioned if any problems arose during the process. The evaluation included 7 aspects: whether there was random sequence generation; allocation concealment; subjects and trial participants took part blind to test conditions; outcome assessments were similarly blind; incomplete outcome data; selective reporting; and all other biases.

2.5. Statistical analysis

The Review Manager 5.4, as recommended by Cochrane, was used for the analysis of the extracted outcome indicator data. The magnitude of the combined effect was expressed as odds ratio (OR) for categorical variables and mean difference for continuous variables. The extent of effect upon efficacy for both groups was expressed at a 95% confidence interval (CI), with a statistically significant difference of P < .05. Heterogeneity was tested using Q test and I², and when P ≥ .10 and I² ≤ 50%, there was no heterogeneity, whereupon merging was performed with a fixed-effects model, but when P < .10 and I² > 50%, there was heterogeneity, and merging was performed with a random-effects model. Meta-analytical results are presented as forest plots, publication bias as funnel plots, and risk of bias as risk of bias plots.

3. Results

3.1. Search and screening results

The initial search yielded a total of 456 Chinese and 0 foreign language documents. Using EndNote to find duplicate papers (which eliminated 106 duplicates), 350 papers were thus obtained after preliminary screening. The titles and abstracts were checked, leading to the identification of a further 320 papers that did not fit the inclusion criteria. Finally, after reading the full text of the remainder, 12 papers without key indicators were discounted, leaving 18 publications, which were finally included for our study.[11–28] The literature screening process is shown in Figure 1.

Figure 1. Flow chart of literature search and screening results.

3.2. Characteristics of studies

Across 18 randomized controlled trials,[11–28] a total of 1636 patients with schizophrenia were included, of which the trial and control groups consisted of 831 and 805 patients, respectively. The antipsychotics used for treatment in both groups were risperidone, olanzapine, chlorpromazine, ziprasidone, clozapine, and aripiprazole. The characteristics of the featured studies are detailed in Table 1.

Table 1 Characteristics of included studies.

Study	Number (n)	Male/female	Age (years old)	Course of disease	Interventions	Duration (d)	Outcome indicators	
T	C	T	C	T	C	T	C	T	C	
Chen 2015[11]	40	40	-	-	32 ± 9	33 ± 8	4 ± 1.3 yr	4.2 ± 1.0 yr	Diankuang Mengxing Decoction + Risperidone	Risperidone	56	①②③	
Ouyang 2016[12]	50	50	30/20	28/22	34.26 ± 8.7	35 ± 9	9.3 ± 3.1 mo	9.2 ± 2.3 mo	Diankuang Mengxing Decoction + Olanzapine	Olanzapine	42	①②	
Li 2016[13]	86	85	20/66	20/65	31.4 ± 9.7	32.5 ± 10.2	5.1 ± 4.8 yr	4.9 ± 4.6 yr	Diankuang Mengxing Decoction + Chlorpromazine	Chlorpromazine	60	①	
Miao 2017[14]	30	30	14/16	12/18	32.07 ± 3.27	31.37 ± 2.92	2.61 ± 1.08 mo	2.72 ± 1.15 mo	Diankuang Mengxing Decoction + Risperidone	Risperidone	60	①②	
Liu 2017[15]	48	48	22/26	23/25	41.63 ± 5.20	41.25 ± 5.12	15.34 ± 5.21 mo	15.21 ± 5.13 mo	Diankuang Mengxing Decoction + Risperidone	Risperidone	56	②④⑤⑥⑦	
Yi 2017[16]	36	36	15/21	19/17	42.4 ± 3.5	41.7 ± 2.9	4.8 ± 1.7 yr	4.5 ± 1.4 yr	Diankuang Mengxing Decoction + Chlorpromazine	Chlorpromazine	60	①⑧⑨⑩⑪	
Yue 2018[17]	38	38	15/23	17/21	38.23 ± 6.04	38.71 ± 5.95	2.37 ± 0.63 yr	2.51 ± 0.59 yr	Diankuang Mengxing Decoction + Ziprasidone	Ziprasidone	56	①⑫⑬	
Ke 2018[18]	41	41	21/20	21/20	39.7 ± 4.1	39.7 ± 4.1	7 ± 0.6 yr	7 ± 0.6 yr	Diankuang Mengxing Decoction + Clozapine	Clozapine	90	①③⑧⑨⑩	
Luo 2019[19]	33	33	29/37	45.81 ± 5.37	-	-	Diankuang Mengxing Decoction + Risperidone	Risperidone	60	②③⑨	
Lin 2020[20]	28	28	13/15	16/12	33.5 ± 5.7	35.5 ± 5.9	-	-	Diankuang Mengxing Decoction + Risperidone	Risperidone	56	①②	
Zhang 2020[21]	49	48	27/22	25/23	46.68 ± 4.72	46.32 ± 4.88	7.46 ± 2.21 yr	10.27 ± 2.85 yr	Diankuang Mengxing Decoction + Olanzapine	Olanzapine	90	③⑧⑨⑩⑭	
Wang 2020[22]	63	63	39/24	38/25	51.9 ± 4.3	51.3 ± 4.6	-	-	Diankuang Mengxing Decoction + Olanzapine	Olanzapine	28	①③	
Zhou 2020[23]	35	32	35/0	32/0	38.0 ± 12.8	37.7 ± 12.9	13.6 ± 8.6 yr	13.9 ± 9.9 yr	Diankuang Mengxing Decoction + Aripiprazole	Aripiprazole	56	①②③⑧⑨⑩	
Wang 2021[24]	38	38	21/17	23/15	39.45 ± 6.12	38.79 ± 5.48	-	-	Diankuang Mengxing Decoction + Olanzapine	Olanzapine	30	①②	
Men 2021[25]	40	40	22/18	23/17	48.53 ± 10.42	48.36 ± 10.23	8.34 ± 3.15 yr	8.33 ± 3.12 yr	Diankuang Mengxing Decoction + Clozapine	Clozapine	30	①②⑥⑦⑫⑮	
Li 2021[26]	115	94	60/55	49/45	40.4 ± 2.8	41.7 ± 2.2	-	-	Diankuang Mengxing Decoction + Risperidone	Risperidone	56	①②③⑯	
Pan 2021[27]	36	36	22/14	19/17	53.49 ± 9.90	54.01 ± 9.13	4.85 ± 0.77 yr	4.99 ± 0.83 yr	Diankuang Mengxing Decoction + Aripiprazole	Aripiprazole	56	①③⑧⑨⑩⑰⑱⑲⑳㉑㉒㉓	
Liu 2022[28]	25	25	18/7	16/9	40.07 ± 5.33	39.49 ± 5.03	11.82 ± 5.36 yr	11.05 ± 4.88 yr	Diankuang Mengxing Decoction + Clozapine	Clozapine	56	②③⑧⑨⑩㉔㉕	
C = Control group, mo = month, T = Test group, yr = year. Outcomes: ① Total effective rate; ② Adverse events; ③ Positive And Negative Syndrome Scale (PANSS) total score; ④ Tumor necrosis factor-α; ⑤ Interleukin-6; ⑥ Simplified Acute Physiology score; ⑦ Scale for assessment of negative symptoms score; ⑧ PANSS-negative symptom score; ⑨ PANSS-positive symptom score; ⑩ PANSS-general psychopathological score; ⑪ Overall impression score; ⑫ Brief Psychiatric Rating Scale; ⑬ Quality of life of SF-36; ⑭ Brain-derived neurotrophic factor; ⑮ Cognitive function; ⑯ Cholinesterase; ⑰ Scale of social function in psychosis inpatients; ⑱ Hyperlipidemia; ⑲ Total cholesterol; ⑳ High-density lipoprotein cholesterol; ㉑ Low-density lipoprotein cholesterin; ㉒ High-sensitivity C-reactive protein; ㉓ Clinical Global Impression of severity of illness; ㉔ Wechsler memory scale; ㉕ Montreal Cognitive Assessment.

3.3. Literature quality assessment

The risk of bias was assessed for random sequence generation, allocation concealment, blinding, outcome data integrity, selective reporting, and other biases in the literature, with specific details noted subsequently. Random sequence generation: 4 papers[11,26–28] used the random number table method, 1[15] used computerized random grouping, and 1[23] used the drawing method, thus all 4 were rated as having a low risk of bias; 3 investigations[14,24,25] used treatment modality grouping and merited a high risk rating; and lastly, 9 studies[12,13,16–22] mentioned randomness only, thereby bearing an uncertain risk of bias. Allocation concealment: none of the assessed publications mentioned allocation concealment, meaning an uncertain risk of bias. Blind testing: none of the included studies mentioned subjects and trial participants as being blind to test conditions, so they rated the risk as uncertain. Outcome assessment blindness: again, this aspect was not referred to in any of the included literature, thus an uncertain risk. Incomplete outcome data: since none of the studies had incomplete outcome data, this was deemed a low risk. Selective reporting: again, this was not observed in any of the featured literature, leading to a low risk rating. Other biases: no other biases were identified, thus all were rated as uncertain risks of bias. The results of the risk of bias were shown in Figure 2 and Figure 3.

Figure 2. Risk of bias graph.

Figure 3. Risk of bias summary. Red (-)=high risk of bias; green (+)=low risk of bias; yellow (?)=unclear risk of bias.

3.4. Meta-analytical results

3.4.1. Total effective rate

Fourteen studies[11–14,16–27] reported the total effective rate of Diankuang Mengxing Decoction combined with antipsychotics for treating schizophrenia across a total of 1327 cases. Analysis of the collated outcomes showed good homogeneity between the groups (I2 = 0%, P = .96), leading to the selection of a fixed-effects model. The results demonstrated a statistically significant difference between the total effective rates in patients with schizophrenia before and after treatment with the combined Diankuang Mengxing Decoction and various antipsychotics, among which, the efficacy of the Diankuang Mengxing Decoction-olanzapine combination was the most significant (Z = 7.83, OR = 3.06, 95% CI: 2.31–4.06, P < .00001; risperidone: Z = 4.39, OR = 3.20, 95% CI: 1.90–5.93, P < .0001; olanzapine: Z = 3.65, OR = 4.26, 95% CI: 1.96–9.28, P = .0003; chlorpromazine: Z = 3.04, OR = 2.26, 95% CI: 1.34–3.82, P = .002; clozapine: Z = 2.67, OR = 2.79, 95% CI: 1.31–5.93, P = .008; aripiprazole: Z = 3.02, OR = 3.79, 95% CI: 1.60–9.03, P = .003; ziprasidone: Z = 2.02, OR = 4.17, 95% CI: 1.05–16.61, P = .04) (Fig. 4). The efficacy of the 4-week/30-day treatment (Z = 3.59, OR = 3.82, 95% CI: 1.84–7.97, P = .0003) (Fig. 5A) and the dosage of 400 mL/d of Diankuang Mengxing Decoction (Z = 3.54, OR = 4.97, 95% CI: 2.04–12.08, P = .0004) were the most significant (Fig. 5B).

Figure 4. Effect of Diankuang Mengxing Decoction combined with different antipsychotics on the total effective rate in patients with schizophrenia. CI = confidence interval.

Figure 5. Effect of Diankuang Mengxing Decoction combined with different antipsychotics on the total effective rate in patients with schizophrenia. (A) Duration of treatment and (B) dosage of treatment. CI = confidence interval.

3.4.2. PANSS total score

Of the evaluated studies, 9[11,18,19,21–23,26–28] reported PANSS total scores while also comparing them between Diankuang Mengxing Decoction combination and antipsychotic-only groups, across which there was an aggregate of 849 cases. For this aspect, there was heterogeneity between the groups (I2 = 96%, P < .0001), justifying the choice of a random-effects model. PANSS total scores were shown to be lower in the trial group than in the control group after intervention, with a difference which was statistically significant (Z = 7.98, weighted mean difference [WMD] = −12.48, 95% CI: −15.55 to −9.42, P < .00001) (Fig. 6A). The efficacy of 4-week/30-day, 8-week/60-day, and 90-day treatments all were significant, with the most significant effect observed in the 4-week/30-day treatment (Z = 45.96, WMD = −14.95, 95% CI: −15.59 to −14.31, P < .00001) (Fig. 6B).

Figure 6. Effect of Diankuang Mengxing Decoction combined with antipsychotics on PANSS total scores, PANSS-positive symptom scores, PANSS-negative symptom scores, and general psychopathology scores in patients with schizophrenia. (A) PANSS total scores; (B) effect of different durations of treatment on PANSS total scores; (C) PANSS-positive symptom scores; (D) PANSS-negative symptom scores; and (E) general psychopathology scores. CI = confidence interval.

3.4.3. PANSS-positive symptom scores

Seven of the 22 studies[16,18,19,21,23,27,28] reported and contrasted PANSS-positive symptom scores for a total of 506 cases. Similar to the PANSS total score, a random-effects model was used due to heterogeneity between the groups (I2 = 95%, P < .00001). Analysis revealed PANSS-positive symptom scores were lower in the test group than in the control group after the intervention, and the difference was statistically significant (Z = 2.76, WMD = −4.53, 95% CI: −7.75 to −1.31, P = .006) (Fig. 6C).

3.4.4. PANSS-negative symptom scores

Six studies[16,18,19,23,27,28] addressed PANSS-negative symptom scores, providing comparisons of this characteristic after treatment in 440 cases across groups who received treatment via antipsychotics with and without Diankuang Mengxing Decoction. Again, there was heterogeneity between the groups (I2 = 75%, P = .001), thus a random-effects model was used. Results, as given in Figure 6D, showed the diamond in the forest plot was crossed with a straight line, and the difference between the 2 groups was not statistically significant (Z = 3.08, WMD = −2.22, 95% CI: −3.63 to −0.81, P = .002) (Fig. 6D).

3.4.5. General psychopathology scores

The same 6 papers[16,18,19,23,27,28] that reported PANSS-negative scores also analyzed general psychopathology scores for a total of 440 cases. Once more, a random-effects model was chosen because of the heterogeneity between the groups (I2 = 78%, P = .0004). There were also statistically significant differences, with lower scores in the test group compared to the control (Z = 4.03, WMD = −4.30, 95% CI: −6.39 to −2.21, P < .0001) (Fig. 6E).

3.4.6. Adverse reactions

Adverse reactions were reported and analyzed in 10 publications,[12,14,15,19,20,24–26,28] which studied 860 cases in all. Heterogeneity between the test groups (I2 = 74%, P < .0001) meant use of a random-effects model. There were statistically significant differences, with the incidence of adverse reactions after treatment in the trial group being lower (Z = 2.79, OR = 0.34, 95% CI: 0.16–0.73, P = .005) (Fig. 7).

Figure 7. Incidence of Diankuang Mengxing Decoction combined with antipsychotics on adverse reactions in patients with schizophrenia. CI = confidence interval.

3.4.7. Publication bias

A comparative-corrected funnel plot of the overall effectiveness of the combination treatment exhibited a fair symmetry with respect to left-right distribution, as per Figure 7, suggesting a possible publication bias. As the volume of literature for subgroup analyses of other outcome indicators was <10, such a bias could not be assessed using funnel plots or Egger linear regression. Therefore, this study may also have had potential publication bias (Fig. 8).

Figure 8. Publication bias of the comparison of total treatment effectiveness. OR = odds ratio.

4. Discussion and Conclusion

Schizophrenia, a common psychiatric disorder categorized as a form of “epilepsy” in TCM, affects patients’ emotions, way of thinking, and behavior. It is a diverse condition, and a better treatment needs to be found. Wang Qingren, a famous Qing dynasty physician, created the classic remedy, Diankuang Mengxing Decoction, to treat epileptic symptoms. He believed these symptoms were due to stagnation of the Qi and blood and a lack of connection between the Qi of the brain and that of the internal organs.[29] In Wang’s formulation: Radix paeoniae rubra and Semen persicae invigorate blood stasis; Radix bupleuri, Pericarpium citri reticulatae viride, and Cyperus rotundus dredge the liver and regulate the qi; Citri reticulatae pericarpium and Pinellia ternata dry “dampness” and resolve phlegm; Cortex mori radicis, Pericarpium arecae, and Fructus perillae resolve phlegm and promote qi circulation to alleviate middle energizer; while Akebia quinata subdues “heart fire” and clears the blood vessels. Glycyrrhiza uralensis harmonizes the herbs.[30] This formula has the effect of invigorating blood circulation, resolving blood stasis, and resolving phlegm. Qi stagnation and blood stasis are the 2 main symptoms for one of the common types of schizophrenia.[31] In addition to these symptoms, this type of schizophrenia is characterized by dullness of the face, skin pigmentation or purple spots, purple coloration to the lips or tongue (whether with stasis or to veins at the base of the tongue), and thin and astringent veins. Studies have shown that treating affected patients by activating blood circulation and resolving blood stasis can improve their condition and blood rheological indices.[32] The effects of this treatment also serve as an objective basis for evidence of qi stagnation and blood stasis in schizophrenia. The effective mechanism of action is related to the upregulation of brain-derived neurotrophic factor levels,[33] and it can be used to treat schizophrenia by regulating the type 1 T helper/type 2 T helper balance, which may be related to the condition’s development, and reversing type 1 T helper/type 2 T helper drift.[34]

4.1. Meta-analysis of clinical effect

The clinical efficacy of treating schizophrenia was significantly improved with the addition of Diankuang Mengxing Decoction to antipsychotics over application of the antipsychotics alone (P < .00001). The greatest improvement came from the combined treatment alongside olanzapine (P = .0003). It was found that the 4-week/30-day treatment regimen (P = .0003, P < .00001) and the dosage of 400 mL/d of Diankuang Mengxing Decoction (P = .0004) were most significantly effective; it is suggested that the treatment regimen be continued for a minimum of 4 weeks/30 days and with a dosage of 400 mL/d to achieve better therapeutic effects. The synergistic, toxicity-reducing interactions between Chinese and Western medicines are the topic of extensive research. The investigations have been conducted on the mechanism of action for different types of anti-infective drugs when combined with Chinese medicines in terms of synergistic or inhibitory effects and how the efficacy of anti-infective drugs can be increased and their side effects reduced.[35,36] More positive interactions may exist, but no pharmacokinetic and pharmacodynamic studies are available and, therefore, need to be considered with caution and further confirmation.

As detailed above, the combination of Diankuang Mengxing Decoction with antipsychotic medication demonstrably improved the PANSS total score, positive symptom scores and negative symptom scores, as well as the general psychopathology score, suggesting it has an effect on schizophrenia. In 1 study,[16] there was no statistically significant difference between the pretreatment and posttreatment results of either type of symptom for the Diankuang Mengxing Decoction-thorazine combination. This was caused by the greater age range of the subjects when compared to another study,[13] which also studied the same combined treatment, with the mean age of the latter’s test and control groups being 41.63 ± 5.20 and 41.25 ± 5.12 years, while it was 31.4 ± 9.7 and 32.5 ± 10.2 years, respectively, in the former. In a potentially similar way, treatment via the Diankuang Mengxing Decoction-chlorpromazine combination may have different efficacy in patients of different age groups, but due to the small size of the available sample for evaluation, more data are needed to confirm this. Additionally, the combinations were, in general, effective for reducing the incidence of adverse reactions (P < .01), suggesting it is a safe complementary treatment and may have a discrete alleviating impact upon antipsychotics’ side effects. Some studies have shown that the combination of different Chinese herbal medicines can prevent hyperglycemia, hyperlipidemia, and other side effects caused by antipsychotics,[37] as well as cause extrapyramidal reactions with therapeutic effects.[38] Further studies related to Diankuang Mengxing Decoction focusing on this area can explore and determine the mechanisms of these effects.

The 18 clinical studies included as part of this paper were not conducted in the manner of blind testing or concealed protocols, while 3 studies were grouped by treatment modality. There is a risk of bias in all included studies, and even if positive results are achieved across included studies, more rigorous experimental design and data analysis should be undertaken to obtain high-quality results.

4.2. Limitations

This study was limited by a number of factors, including a lack of multicentered, large-sample randomized controlled clinical reports, all of which did not classify patients according to TCM theory. Also, only 6 studies classified patients as having phlegm-qi stagnation,[19,20] qi-stagnation-phlegm-clotting-blood,[13,20] qi-stagnation-blood stasis,[18] or phlegm-heat stagnation.[16] Notably, the antipsychotics used in the evaluated literature varied in type, dose, and duration of treatment, and follow-ups were not conducted at all. Despite the promising results, the limitations above may have affected the results; more rigorous experimental design and data arrangement should be considered in future studies.

4.3. Perspectives

In the future, large-sample, high-quality, rigorous double-blind randomized controlled clinical studies would be appropriate for further validation of the findings.

4.4. Conclusion

Diankuang Mengxing Decoction with antipsychotics demonstrated efficacy in the treatment for schizophrenia in improving the state of all symptoms with a high safety profile; its curative effect is more prominent than the application of the antipsychotics alone. These effects of Diankuang Mengxing Decoction with antipsychotics should be considered in the treatment for further verification.

Author contributions

Conceptualization: Lai Kwan Lam, Lee Yam Poon.

Data curation: Lai Kwan Lam, Lee Yam Poon, Peng-Li Xu.

Formal analysis: Lai Kwan Lam, Lee Yam Poon, Peng-Li Xu.

Investigation: Lai Kwan Lam, Lee Yam Poon.

Methodology: Lai Kwan Lam, Lee Yam Poon.

Project administration: Ya Xiao, Li-Guo Chen.

Resources: Lai Kwan Lam, Lee Yam Poon, Peng-Li Xu.

Software: Lai Kwan Lam, Lee Yam Poon

Supervision: Ya Xiao, Li-Guo Chen.

Validation: Lai Kwan Lam, Lee Yam Poon.

Visualization: Lai Kwan Lam, Lee Yam Poon.

Writing – original draft: Lai Kwan Lam, Lee Yam Poon, Peng-Cheng Xie, Ting Xie.

Writing – review & editing: Lai Kwan Lam, Lee Yam Poon, Ya Xiao, Li-Guo Chen.

Abbreviations:

CI confidence interval

OR odds ratio

PANSS Positive And Negative Syndrome Scale

TCM Traditional Chinese medicine

WMD weighted mean difference

The authors have no conflicts of interest to disclose.

All data generated or analyzed during this study are included in this published article [and its supplementary information files].

How to cite this article: Lam LK, Poon LY, Xu P-L, Xie P-C, Xie T, Xiao Y, Chen L-G. Efficacy and safety of a Chinese medicine formula Diankuang Mengxing Decoction combined with antipsychotics in the treatment of schizophrenia: A meta-analysis of randomized controlled trials. Medicine 2024;103:36(e39489).

LKL and LYP contributed to this article equally.
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