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. 2023 Jun 16;14:1201240. doi: 10.3389/fphar.2023.1201240

Utilization patterns and prescription characteristics of traditional Chinese medicine among patients with irritable bowel syndrome in Taiwan

Ye Gu 1, Yu-Tung Lai 2, Fang-Rong Chang 1,3,4,*, Chung-Yu Chen 2,3,5,*
PMCID: PMC10311911  PMID: 37397480

Abstract

Background: Few studies have investigated traditional Chinese medicine (TCM) utilization patterns for irritable bowel syndrome (IBS), despite the potential benefits of exploring TCM utilization patterns in optimizing TCM management. This study aimed to evaluate TCM utilization patterns and clinical features for IBS patterns in Taiwan.

Methods: This was a population-based cross-sectional study using claim data from the National Health Insurance Research Database between 2012 and 2018. Patients newly diagnosed with IBS and aged over 20 years were included. The TCM utilization patterns and characteristics, including Chinese herbal medicine (CHM) treatment types and prescription patterns, were evaluated.

Results: A total of 73,306 patients newly diagnosed with IBS used TCM for IBS at least once. Females used TCM for IBS more than males (female-to-male ratio = 1.89: 1). The age distribution showed a peak at 30–39 years (27.29%), followed by 40–49 years (20.74%) and 20–29 years (20.71%). Patients who received Western medications for IBS had a lower tendency to seek TCM. CHM was the most commonly used TCM modality (98.22%), with Jia-wei-xiao-yao-san being the most commonly prescribed Chinese herbal formula and Bai-zhu being the most frequently prescribed single Chinese herb.

Conclusion: This study enhances our understanding of TCM usage patterns for IBS, particularly CHM prescriptions. Further research is needed to investigate commonly used TCM formulas and individual herbs.

Keywords: traditional Chinese medicine, irritable bowel syndrome (IBS), Chinese herbal medicine, utilization patterns, real-world data

Introduction

Irritable bowel syndrome (IBS) is a prevalent chronic gastrointestinal (GI) disorder affecting around 11.2% of the global population (Lovell and Ford, 2012). In Taiwan, the average annual incidence and prevalence showed a decreasing trend from 2012 to 2018, the use of International Classification of Diseases (ICD) codes rather than rigorous research criteria to identify IBS diagnoses may have led to upcoding or misdiagnosis, which could have affected the reported incidence and prevalence of IBS (Lai et al., 2021). Despite the high prevalence of IBS, its pathophysiology remains incompletely understood (Soares, 2014). The IBS symptoms include chronic or recurring abdominal pain and changes in bowel habits without any structural or biochemical abnormalities or the presence of any organic cause (Masuy et al., 2020). IBS management aims to alleviate symptoms and improve the quality of life, since the condition can negatively impact mental and physical wellbeing (Black and Ford, 2020). Treatment typically involves a combination of psychological support, lifestyle and dietary modifications, physical activity, and pharmaceutical interventions. Non-pharmaceutical treatments are recommended as the first-line approach and can be tailored to the individual’s predominant symptoms such as stress management and dietary modifications for bowel symptoms (Smith, 2006). Pharmaceutical treatment is considered for patients who do not respond to non-pharmaceutical therapies. Beneficial to non-GI symptoms and comorbidities, which can improve health-related quality of life and symptom severity (Gwee et al., 2019; Moayyedi et al., 2019; Masuy et al., 2020; Fukudo et al., 2021; Lacy et al., 2021). Many patients with IBS are unsatisfied with conventional treatment and seek complementary and alternative medicine (CAM) (Li and Li, 2015; Ford et al., 2017), such as traditional Chinese medicine (TCM), which is commonly used in East Asia for IBS treatment (Wu et al., 2021). High-quality studies suggest that TCM formulas, including Tong-xie-yao-fang granule and Shen-ling-bai-zhu-san, effectively manage IBS global symptoms (M Chen et al., 2018; M. Chen et al., 2018; Wang et al., 2020; Xiao et al., 2015), but their use lacks consensus and mainly depends on experiences of TCM practitioners. Thus, this cross-sectional study aimed to investigate TCM utilization patterns and clinical characteristics among patients newly diagnosed with IBS to address the knowledge gap regarding TCM use in IBS treatment in Taiwan.

Methods

Data sources

This was a population-based study using data from the National Health Insurance Research Database (NHIRD) in Taiwan from 2011 to 2018. The National Health Insurance (NHI) program offers universal health insurance to nearly all of the local population, and the NHIRD holds complete and excellent data on demographics, clinical visits, hospitalizations, and prescriptions. The diagnoses are based on the International Classification of Diseases, Ninth and 10th Editions and Clinical Modification (ICD-9-CM and ICD-10-CM) codes. The prescriptions, including Chinese herbal medicine (CHM), contain generic names, brand names, and dosages. This study was approved by the Institutional Review Board (IRB) of Kaohsiung Medical University Chung-Ho Memorial Hospital [KMUHIRB-E(II)-20190359]. Individual identification numbers were encrypted with unique and anonymous identifiers to protect privacy; thus, the requirement for consent was waived by the IRB.

Study population

Patients aged 20 years or above with at least one outpatient visit or hospitalization for IBS (ICD-9-CM code: 564.1 and ICD-10-CM code: K58.0 and K58.9) from 2012 to 2017 were enrolled. Exclusion criteria included patients with missing age and gender information and those with a prior IBS diagnosis before 2012 to ensure that all patients were newly diagnosed with IBS. Patients were then categorized as either TCM or non-TCM users. TCM users were defined as those who received an IBS diagnosis after their initial diagnosis and sought for treatment at TCM clinics.

Study variables

Data, including demographics, comorbidities, and comedications, were collected to analyze the independent variables that influence the use of TCM for IBS. Patients were divided into six age groups for both genders (20–29, 30–39, 40–49, 50–59, 60–69, and ≥70). Urbanization levels in Taiwan were classified into seven tiers, with 1 being the most urbanized and 7 being the least. Residential areas were categorized as levels 1 and 2 (urban areas), levels 3 and 4 (suburban areas), and levels 5 and above (rural areas). Insurance premiums in New Taiwan Dollars (NT$) are determined based on the monthly income of the insured individual and can be used as an indicator of their economic status. The premiums are categorized into three groups: <NT$18,780, NT$18,780–NT$29,000, and >NT$29,000 in this study. This study investigated the comorbidities and prescribed comedication in IBS patients to better understand their disease status. Comorbidities were defined as having at least two ambulatory or outpatient diagnoses or one inpatient diagnosis before IBS diagnosis and identified using the ICD-9-CM and ICD-10-CM codes (Supplementary Table S1). Comedications were defined as the use of medications of interest for a minimum of 14 days before IBS diagnosis and identified using Anatomical Therapeutic Chemical codes, which included laxatives, antidiarrheals, antispasmodics, antidepressants, and probiotics (Supplementary Table S2). The NHIRD provides detailed information on TCM utilization, including TCM diagnoses, CHM prescription, and related claim data. A list of reimbursed CHM was obtained from the Taiwan National Health Insurance Administration website, including NHI codes and names of Chinese herbs and formulas, to identify CHM use in the NHIRD. Treatment codes were extracted from TCM clinical records of patients with IBS to assess the TCM treatment types used, including CHM and acupuncture. CHM prescription patterns were analyzed to identify the most frequently prescribed CHM for patients with IBS, the number of prescriptions, the average duration of prescriptions (in days), the average dose (in grams), and the average daily dose (in grams) was estimated. Average daily dose (g) = Average dose (g)/Average duration for prescriptions (days).

Statistical analysis

Continuous variables were presented as means ± standard deviation, and categorical variables were presented as numbers (percentages). A multivariate logistic regression analysis was performed to examine the clinical characteristics associated with the utilization of TCM. Case was defended as TCM group and control was non-TCM group. Odd ratio (OR) was over 1 means IBS patients prefer to TCM treatment. Statistical significance was defined as a two-sided p-value < 0.05. The statistical analysis was conducted by SAS version 9.4 software program (SAS Institute, Inc., Cary, North. Carolina).

Results

Out of the 1,193,490 patients newly diagnosed with IBS in NHIRD between 2012 and 2017, 73,306 patients (6.14%) used TCM with routine western-medicine care (TCM users) for IBS at least once during their follow-up year (Figure 1). 1,120,184 patients were non-TCM users. The female proportion was higher in both TCM and non-TCM users. Females had a significantly higher ratio of TCM use than males, with a female-to-male ratio of 1.89: 1. Additionally, the mean age of TCM users (42.94 years) was lower than that of non-TCM users (50.40 years). The age distribution of TCM users peaked in the 30–39 age group (27.29%), followed by the 40–49 (20.74%) and 20–29 age groups (20.71%), whereas the age distribution of non-TCM users peaked in the 50–59 age group (19.66%), followed by the 40–49 (17.90%) and 30–39 age groups (17.65%). Patients residing in urban areas or with an income >NT$29,000 were more likely to seek TCM consultation (Table 1).

FIGURE 1.

FIGURE 1

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Flowchart of study population. NHIRD, National Health Insurance Research Database; ICD code, The International Classification of Diseases, Version 9/10, Clinical Modification (ICD-9-CM code: 564.1 and ICD-10-CM code: K58.0 and K58.9); IBS, Irritable bowel syndrome.

TABLE 1.

Demographic characteristics of IBS population with TCM care in Taiwan.

Variables Total, n (%) Non-TCM users, n (%) TCM users, n (%)
Gender
Male 546615 (45.80) 521312 (46.54) 25303 (34.52)
Female 646875 (54.20) 598872 (53.46) 48003 (65.48)
Age, mean (SD) 49.94 (17.28) 50.4 (17.32) 42.94 (15.09)
20–29 163481 (13.70) 148302 (13.24) 15179 (20.71)
30–39 217746 (18.24) 197738 (17.65) 20008 (27.29)
40–49 215684 (18.07) 200483 (17.90) 15201 (20.74)
50–59 234667 (19.66) 223197 (19.93) 11470 (15.65)
60–69 184571 (15.46) 177493 (15.84) 7078 (9.66)
≥70 177341 (14.86) 172971 (15.44) 4370 (5.96)
Urbanization (missing = 39507)
Rural 171289 (14.35) 165149 (14.74) 6140 (8.38)
Suburban 328792 (27.55) 313346 (27.97) 15446 (21.07)
Urban 653902 (54.79) 605486 (54.05) 48416 (66.05)
Insurance premium (missing = 157734)
>18780 227196 (19.04) 215444 (19.23) 11752 (16.03)
18780–29000 430742 (36.09) 408985 (36.51) 21757 (29.68)
29000> 377818 (31.66) 349579 (31.21) 28239 (38.52)
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The comorbidities and comedication of patients with IBS receiving TCM care are shown in Table 2. The top three common GI comorbidities were gastritis and duodenitis (16.37%), peptic ulcer (15.05%), and abdominal pain (12.55%) in non-TCM users and constipation (12.17%), gastritis and duodenitis (11.68%), and peptic ulcer (10.53%) in TCM users. The three most common non-GI comorbidities were hypertension (24.84%), dyslipidemia (16.06%), and diabetes (11.8%) in non-TCM users and allergic rhinitis (12.41%), hypertension (11.74%), and dyslipidemia (9.46%) in TCM users. However, the top three psychiatric comorbidities were sleep disorder (13.68% versus 17.13%), anxiety (9.47% versus 8.17%), and depression (4.66% versus 3.41%) in both non-TCM and TCM users. Comedication patterns were similar between non-TCM and TCM users, with antacids (28.78% versus 15.29%), propulsives (24.78% versus 15%), and anxiolytics (21.19% versus 11.90%) being the top three medications.

TABLE 2.

Baseline comorbidities and comedication of IBS population with TCM care in Taiwan.

Comorbid condition Total, n Non-TCM users, n (%) TCM users, n (%)
Gastrointestinal comorbidity
Gastritis and duodenitis 191938 183373 (16.37) 8565 (11.68)
Peptic ulcer 176261 168545 (15.05) 7716 (10.53)
Abdominal pain 146880 140622 (12.55) 6258 (8.54)
Gastroenteritis and colitis 123108 117904 (10.53) 5204 (7.10)
Gastroesophageal reflux disease 118580 113039 (10.09) 5541 (7.56)
Constipation 105814 96892 (8.65) 8922 (12.17)
Gastric functional disease 87886 80595 (7.19) 7291 (9.95)
Bloating 62410 55934 (4.99) 6476 (8.83)
Intestinal functional disease 60234 56626 (5.06) 3608 (4.92)
Infectious enterocolitis 36955 35278 (3.15) 1677 (2.29)
Diarrhea 23053 21115 (1.88) 1938 (2.64)
Inflammatory bowel disease 7257 6793 (0.61) 464 (0.63)
Colon cancer 5992 5763 (0.51) 229 (0.31)
Non-gastrointestinal comorbidity
Hypertension 286886 278282 (24.84) 8604 (11.74)
Dyslipidemia 186833 179901 (16.06) 6932 (9.46)
Diabetes 135762 132159 (11.8) 3603 (4.92)
Allergic rhinitis 115174 106076 (9.47) 9098 (12.41)
Chronic lung disease 105731 101099 (9.03) 4632 (6.32)
Fibromyalgia 97871 92531 (8.26) 5340 (7.28)
Chronic obstructive pulmonary disease 42233 40612 (3.63) 1621 (2.21)
Asthma 38654 37008 (3.3) 1646 (2.25)
Chronic kidney disease 29829 29169 (2.60) 660 (0.90)
Chronic fatigue syndrome 20791 18741 (1.67) 2050 (2.8)
Migraine 17666 15886 (1.42) 1780 (2.43)
Atopic dermatitis 9926 9396 (0.84) 530 (0.72)
Obesity 3409 3163 (0.28) 246 (0.34)
Psychiatric comorbidity
Sleep disorder 165828 153274 (13.68) 12554 (17.13)
Anxiety 112052 106063 (9.47) 5989 (8.17)
Depression 54753 52256 (4.66) 2497 (3.41)
Somatoform Disorders 17597 16911 (1.51) 686 (0.94)
Dementia 17279 16879 (1.51) 400 (0.55)
Psychotic disorders 11094 10621 (0.95) 473 (0.65)
Parkinson’s disease 9820 9595 (0.86) 225 (0.31)
Bipolar 5980 5676 (0.51) 304 (0.41)
Stress related disorders 3023 2878 (0.26) 145 (0.20)
Alzheimer’s disease 1530 1494 (0.13) 36 (0.05)
Eating disorder 292 271 (0.02) 21 (0.03)
Co-Medication
Antacids 333592 322387 (28.78) 11205 (15.29)
Anxiolytics 289200 277593 (24.78) 11607 (15.83)
Propulsives 246045 237324 (21.19) 8721 (11.90)
Laxatives 202179 195396 (17.44) 6783 (9.25)
Simethicone 190354 183915 (16.42) 6439 (8.78)
Proton pump inhibitors 129533 124587 (11.12) 4946 (6.75)
Antispasmodic 129265 124926 (11.15) 4339 (5.92)
Antidepressants 75830 72538 (6.48) 3292 (4.49)
Antidiarrheal 49157 47492 (4.24) 1665 (2.27)
Probiotic 52780 50849 (4.54) 1931 (2.63)
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The multiple regression analysis in Table 3 demonstrated that female (OR = 1.66; 95% confidence interval (CI), 1.63–1.69, p < 0.001) have a higher likelihood of utilizing TCM for IBS treatment compared to males. Otherwise, there were significantly increasing trend for visiting TCM treatments, including urban residents (OR = 1.82), insurance premiums above NT$ 29000 (OR = 1.21), peptic ulcer (OR = 1.06), gastric functional disease (OR = 1.85), intestinal functional disease (OR = 1.37), fibromyalgia (OR = 1.06), chronic obstructive pulmonary disease (OR = 1.25), chronic fatigue syndrome (OR = 1.97), migraine (OR = 1.61), obesity (OR = 1.37), sleep disorder (OR = 1.66). However, there was some factors decreasing visiting TCM treatment, the probability of seeking TCM care for IBS treatment varies among different age groups compared to the reference group (20–29 years), patients in the 30–39 age range showed a non-significant association. However, as age increases exhibited significantly decreasing for visiting TCM treatments for their IBS treatment. Moreover, also a significantly decreasing for visiting TCM treatments, including insurance premiums NT$ 18780–29000 (OR = 0.87), gastritis and duodenitis (OR = 0.84), gastroenteritis and colitis (OR = 0.74), infectious enterocolitis (OR = 0.85), hypertension (OR = 0.76), dyslipidemia (OR = 0.96), diabetes (OR = 0.75), chronic lung disease (OR = 094.), asthma (OR = 0.89), chronic kidney disease (OR = 0.79), depression (OR = 0.84), stress related disorders (OR = 0.81), and all co-medications, except for antidiarrheal drugs.

TABLE 3.

A multiple regression analysis of factors associated with TCM care in IBS population in Taiwan.

Variables Odds ratio (OR) 95% confidence interval (CI) p-value
Gender
Male 1
Female 1.66 (1.63, 1.69) <.0001
Age
20–29 1
30–39 0.99 (0.99, 1.04) = 0.076
40–49 0.77 (0.96, 1.01) <.0001
50–59 0.545 (0.75, 0.79) <.0001
60–69 0.50 (0.53, 0.56) <.0001
≥70 0.39 (0.48, 0.52) <.0001
Urbanization
Rural 1
Suburban 1.26 (1.22, 1.30) <.0001
Urban 1.82 (1.77, 1.87) <.0001
Insurance Premium
>18780 1
18780–29000 0.87 (0.85, 0.89) <.0001
29000> 1.21 (1.18, 1.24) <.0001
Gastrointestinal comorbidity
Gastritis and duodenitis 0.84 (0.82, 0.87) <.0001
Peptic ulcer 1.06 (1.03, 1.10) <.0001
Gastroenteritis and colitis 0.74 (0.71, 0.76) <.0001
GERD 1.03 (1.00, 1.07) = 0.0592
Gastric functional disease 1.85 (1.80, 1.91) <.0001
Intestinal functional disease 1.37 (1.32, 1.43) <.0001
Infectious enterocolitis 0.85 (0.80, 0.90) <.0001
Non-gastrointestinal comorbidity
Hypertension 0.76 (0.74, 0.79) <.0001
Dyslipidemia 0.96 (0.93, 0.99) = 0.0078
Diabetes 0.75 (0.72, 0.79) <.0001
Chronic lung disease 0.94 (0.90, 0.97) = 0.0002
Fibromyalgia 1.06 (1.03, 1.10) = 0.0002
COPD 1.25 (1.18, 1.32) <.0001
Asthma 0.89 (0.84, 0.94) <.0001
Chronic kidney disease 0.79 (0.73, 0.87) <.0001
Chronic fatigue syndrome 1.97 (1.87, 2.08) <.0001
Migraine 1.61 (1.52, 1.71) <.0001
Obesity 1.37 (1.19, 1.58) <.0001
Psychiatric comorbidity
Sleep disorder 1.66 (1.62, 1.70) <.0001
Anxiety 1.02 (0.99, 1.06) = 0.2088
Depression 0.84 (0.80, 0.88) <.0001
Stress related disorders 0.81 (0.68, 0.98) = 0.0318
Co-Medication
Laxative 1.34 (0.72, 0.77) <.0001
Antidiarrheal drugs 0.99 (0.95, 1.07) = 0.708
Antispasmodic drugs 1.40 (0.69, 0.74) <.0001
Probiotic 1.33 (0.64, 0.88) = 0.0004
Antidepressant 1.18 (0.81, 0.89) <.0001
Propulsives 1.60 (0.61, 0.65) <.0001
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Abbreviation: COPD, chronic obstructive pulmonary disease; GERD, gastroesophageal reflux disease.

The majority of TCM users (n = 71,999; 98.22%) received CHM, which includes both Chinese single herbs and herbal formulas (Table 4). A smaller proportion of patients (n = 1,082; 1.48%) received a combination of CHM and acupuncture, whereas only 92 (0.13%) patients received acupuncture alone. A total of 133 (0.18%) patients received other TCM treatments, such as moxibustion and traumatology.

TABLE 4.

Distribution of 73306 patients with IBS with TCM care in Taiwan.

Treatments Frequency of TCM visits n (%)
1–3, n (%) 4–6,n (%) ≥7, n (%) All, n (%)
CHM 46343 (63.22) 10970 (15.24) 14686 (20.40) 71999 (98.22)
Acupuncture 82 (0.11) 4 (0.01) 6 (0.11) 92 (0.13)
CHM + Acupuncture 526 (0.72) 173 (0.24) 383 (0.52) 1082 (1.48)
Other 124 (0.17) 6 (0.01) 3 (0.00) 133 (0.18)
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The top 10 Chinese single herbs were Bai-zhu (n = 9,123; 12.45%), Hou-pu (6,784; 9.25%), Chen-pi (6,391; 8.72%), Dan-shen (6,379; 8.7%), Yan-hu-suo (6,320; 8.62%), Fu-ling (6,098; 8.32%), Hai-piao-xiao (5,819; 7.94%), Bai-shao (5,468; 7.46%), Xiang-fu (5,280; 7.2%), and Fang-feng (5,267; 7.18%). Bai-zhu was the most frequently prescribed Chinese single herb, and Hai-piao-xiao had the longest average duration of use (90.59 days), highest average dose (114.77 g), and highest average daily dose (1.827 g) (Table 5). Jia-wei-xiao-yao-san (n = 16,755; 22.86%) was the most frequently prescribed Chinese herbal formula. Ban-xia-xie-xin-tang (n = 11,469; 14.1%) and Xiang-sha-liu-jun-zi-tang (n = 9,977; 12.6%) were the second and third most commonly used formulas, respectively (Table 6). Among complex formulas and sigle herbs, Jia-wei-xiao-yao-san (n = 16,755; 22.86%) was the most commonly used herbal medicine, and Ma-zi-ren-wan had the longest average duration of use (90.59 days) and the highest average dose (300.47 g). TCM prefers the uses of complex formuals. However, Shen-ling-bai-zhu-san had the highest average daily dose (4.817 g) (Table 6) in the treatments.

TABLE 5.

Top 10 Chinese single herbs prescribed per person within 1 year for IBS in Taiwan (N = 73306).

Herb Number of prescriptions, n (%) Average duration for prescriptions (days) Average dose (g) Average daily dose (g)
Bai-zhu (Atractylodes macrocephala Koidz.) 9123 (12.45) 43.61 61.98 1.421
Hou-pu (Magnolia officinalis Rehd. et Wils) 6784 (9.25) 42.19 47.66 1.130
Chen-pi (Citrus reticulata Blanco) 6391 (8.72) 38.01 39.12 1.029
Dan-shen (Salvia miltiorrhiza Bge.) 6379 (8.70) 49.01 56.52 1.153
Yan-hu-suo (Corydalis yanhusuo W. T.Wang) 6320 (8.62) 35.20 42.18 1.198
Fu-ling (Poria cocos (Schw.) Wolf) 6098 (8.32) 39.17 53.76 1.372
Hai-piao-xiao (Sepiella maindroni de Rochebrune) 5819 (7.94) 62.82 114.77 1.827
(Sepia esculenta Hoyle)
Bai-shao (Paeonia lactiflora Pall.) 5468 (7.46) 39.20 48.45 1.236
Xiang-fu (Cyperus rotundus L.) 5280 (7.20) 40.47 39.52 0.976
Fang-feng (Saposhnikovia divaricata (Turcz.) Schischk.) 5267 (7.18) 35.21 37.25 1.058
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Average daily dose (g) = Average dose (g)/ Average duration for prescriptions (days).

TABLE 6.

Top 10 Chinese herbal formulas prescribed per person within 1 year for IBS in Taiwan (N = 73306).

Herbal formula Compositions Number of prescriptions, n (%) Average duration for prescriptions (days) Average dose (g) Average daily dose (g)
Jia-wei-xiao-yao-san Angelicae Sinensis (Oliv.) Diels, Atractylodes macrocephala Koidz., Paeonia lactiflora Pall., Bupleurum chinense DC., Poria cocos (Schw.) Wolf, Glycyrrhiza uralensis Fisch., Paeonia suffruticosa Andr., Gardenia jasminoides Ellis, Zingiber officinale (Willd.) Rosc., Mentha haplocalyx Briq. 16755 (22.86) 55.39 235.08 4.244
Ban-xia-xie-xin-tang Pinellia ternata (Thunb.) Breit., Scutellaria baicalensis Georgi, Zingiber officinale (Willd.) Rosc., Panax ginseng C. A. Mey., Coptis chinensis Franch., Ziziphus jujuba Mill., Glycyrrhiza uralensis Fisch. 11469 (15.65) 54.83 215.33 3.927
Xiang-sha-liu-jun-zi-tang Panax ginseng C. A. Mey., Atractylodes macrocephala Koidz., Poria cocos (Schw.) Wolf, Glycyrrhiza uralensis Fisch., Citrus reticulata Blanco, Pinellia ternata (Thunb.) Breit., Amomum villosum Lour., Aucklandia lappa Decne., Zingiber officinale (Willd.) Rosc. 9977 (13.61) 63.87 264.97 4.149
Ma-zi-ren-wan Cannabis sativa L., Paeonia lactiflora Pall., Citrus aurantium L., Rheum palmatum L., Magnolia officinalis Rehd. et Wils, Prunus armeniaca L. var. ansu Masim. 8985 (12.26) 90.59 300.47 3.317
Shen-ling-bai-zhu-san Dolichos lablab L., Panax ginseng C. A. Mey., Poria cocos (Schw.) Wolf, Atractylodes macrocephala Koidz., Glycyrrhiza uralensis Fisch., Dioscorea opposita Thunb., Nelumbo nucifera Gaertn., Platycodon grandiflorum (Jacq.) A. DC., Coix lacryma-jobi L. var. ma-yuen (Roman.) Stapf, Amomum villosum Lour., Ziziphus jujuba Mill. 8559 (11.68) 45.29 218.17 4.817
Ping-wei-san Citrus reticulata Blanco, Magnolia officinalis Rehd. et Wils, Glycyrrhiza uralensis Fisch., Atractylodes lancea (Thunb.) DC., Zingiber officinale (Willd.) Rosc., Ziziphus jujuba Mill. 7222 (9.85) 41.09 163.46 3.978
Chai-hu-shu-gan-tang Citrus reticulata Blanco, Bupleurum chinense DC., Paeonia lactiflora Pall., Citrus aurantium L., Glycyrrhiza uralensis Fisch., Ligusticum chuanxiong Hort., Cyperus rotundus L. 7191 (9.81) 45.26 176.33 3.896
Qing-wei-san Angelica sinensis (Oliv.) Diels, Coptis chinensis Franch., Rehmannia glutinosa Libosch., Paeonia suffruticosa Andr., Cimicifuga heracleifolia Kom. 6176 (8.42) 31.57 133.80 4.238
Wen-dan-tang Pinellia ternata (Thunb.) Breit., Bambusa tuldoides Munro, Citrus aurantium L., Citrus reticulata Blanco, Zingiber officinale (Willd.) Rosc., Glycyrrhiza uralensis Fisch., Poria cocos (Schw.) Wolf, Ziziphus jujuba Mill. 5720 (7.80) 48.36 196.70 4.067
Li-zhong-tang Panax ginseng C. A. Mey., Glycyrrhiza uralensis Fisch.,Atractylodes macrocephala Koidz., Zingiber officinale (Willd.) Rosc. 5323 (7.26) 41.87 199.55 4.766
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Average daily dose (g) = Average dose (g)/Average duration for prescriptions (days).

Discussion

This study conducted the first population-based research demonstrated the TCM prescription patterns and clinical characteristics among patients with IBS in Taiwan. 73,306 patients (6.14%) of TCM treatment with routine western-medicine care (TCM users) and 1,120,184 patients with routine western-medicine (non-TCM users) for IBS were involved. This finding is similar to that reported by Fan et al., who reported that 6.8% of patients used TCM for IBS in China (Fan et al., 2017). In Taiwan, western medicine continues to be the predominant treatment for IBS. However, TCM plays an important role in additional to western medicine, and is covered by national health insurance in Taiwan.

As a previous study in Taiwan, Chinese herbal remedies were found to be the primary choice of TCM with a utilization rate of 85.9% (Chen et al., 2007a). Similarly, CHM was the preferred treatment option for 98.22% of IBS patients. Females with IBS syndromes were more likely to seek for TCM treatment than males. This finding is consistent with previous studies (Chang & Lu, 2009; Chen et al., 2007b; C. C; Shih et al., 2012). However, the reasons behind this phenomenon were not fully explained in the earlier reports. Nevertheless, the results of previous studies proposed that independent or affluent females may have a strong belief in TCM for gynecologic problems and chronic diseases (C.-C. Shih et al., 2012). Age distribution of TCM users peaked in the 30 s. Young age has also been found to be representative of a positive attitude toward CAM in a survey of German hospitals (Huber et al., 2004). This might be because age 30 s people are mainly the breadwinners in their families, and they have more stress and possible disposable money to care for IBS since the NHI does not cover Chinese herbal pieces. Additionally, living in urbanized areas with abundant public facilities, such as easy access to public transportation, and a high density of TCM practitioners was associated with the likelihood of TCM uses (Shih et al., 2010; Yeh et al., 2016). Furthermore, choosing TCM might also be attributed to the higher expectations of patients and the fact that it allows better long-term clinical outcomes and might improve their quality of life (Figueira et al., 2010). TCM was more likely to be chosen by elderly patients for improving health conditions (Pun, 2022). For IBS patients, the morbidity for age 30–60 s are a higher plateau (>200000 patients). However, IBS patients in their 30 s had the highest visit rate to TCM clinics, and visit rates to TCM clinics for patients over 40 years old decreased obviously with age (Table 1). In sleep disorder was found to be the most prevalent, followed by anxiety and depression. Moreover, TCM can be an alternative therapy for improving sleep quality and emotional wellbeing (Aung et al., 2013). TCM practitioners typically evaluate patients’ sleep and emotions during treatment, so patients with mental health conditions are more likely to seek TCM as a healthcare option (Gureje et al., 2015).

Over 10% of IBS patients will have allergy related syndromes, such as allergic rhinitis, asthma, atopic dermatitis, etc. In diagnostic theories of TCM, the “Fei” (lungs) are believed to govern the body’s “Qi” and aid in bowel movement by regulating metabolism and waterways, Additionally, the “Fei” are closely associated with the skin. The “Da-chang” (large intestine) smoothly transport and lower waste. The “Fei” and the “Da-chang” are believed to have a close relationship in terms of their functions and interactions within the body. This connection allows for the exchange of “Qi” and other substances between the two organs, and helps to maintain balance and harmony within the body. When there is an imbalance or dysfunction in either the “Fei” or “Da-chang”, it can affect the function of the other organ as well (Wang and Zhu, 2011). While “Da-chang” is not functioning properly, such as IBS, a higher incidences of allergy related syndromes will also company (Table 2). The core patterns of these allergic syndromes can be characterized by “Fei” and “Qi” deficiencies (Tai et al., 2007; Yang et al., 2012).

Most frequently prescribed single herb for patients with IBS in Taiwan was “Bai-zhu” (Table 5), which has similar results reported as an effective agent for diarrhea-predominant IBS (IBS-D) (Park et al., 2015). Most top 10 single herbs were selected because of “Qi” circulation and reduce bloating and relieve pain caused by abdominal or muscle spasms. Research has verified the effectiveness of Tong-Xie-Yao-Fang in reducing IBS-D symptoms (M Chen et al., 2018). This formula comprises four herbals, Bai-zhu, Chen-pi, Bai-shao, and Fang-feng, which are among the top 10 Chinese single herbs prescribed for patients with IBS in Taiwan. In a previous study, it showed that Hai-piao-xiao was the most commonly prescribed single herb for patients with peptic ulcers in Taiwan (C.-Y. Huang et al., 2015). Its main component is calcium carbonate (Li et al., 2010), which may act as an antacid, helping to relieve discomfort caused by excess gastric acid. It has a significant antacid effect and is most likely to have a gratifying outcome.

The most commonly prescribed herbal formula For IBS was “Jia-wei-xiao-yao-san.” It is also commonly used to treat psychological disorders, including depression and insomnia (F. P. Chen et al., 2011; Chen et al., 2015; Park et al., 2014; Su et al., 2019). Additionally, it has been reported to be effective in regulating abnormal gastric motility and myoelectrical activity in IBS patients with functional dyspepsia (FD) (Qu et al., 2010) and ameliorating depression-like behaviors induced by chronic stress in mice by regulating the gut microbiome and brain metabolome in relation to purine metabolism (Ji et al., 2022). Brain-gut interaction is definitely affected by IBS, and numerous studies that firmly established the existence of microbiota and brain-gut interaction (Lydiard, 2001; Coss-Adame and Rao, 2014; Serafini et al., 2022). Furthermore, several studies showed a correlation among IBS with anxiety, depression, and antidepressant use (Wessely et al., 1999; Posserud et al., 2004; Lee et al., 2015). Furthermore, it may soothe the “Gan” (liver) and regulates “Qi” in TCM theories, which is beneficial for individuals aged 30–39, who are mostly working under high levels of stress. In this study, these comorbidities were common for TCM consultation, which may lead to the higher prescription rate of Jia-wei-xiao-yao-san in patients with IBS.

Ma-zi-ren-wan was reported to be effective in treating constipation and is the most commonly prescribed Chinese herbal formula for patients with this syndrome in Taiwan (Jong et al., 2010; Yang et al., 2021). The average duration of Ma-zi-ren-wan was used for the longest time and the highest dosage in average. Additionally, Ban-xia-xie-xin-tang was the second most commonly prescribed (Zeng et al., 2019). It not only relieves IBS symptoms but also provides greater benefits to FD and peptic ulcer symptoms. Consequently, it has become widely used in Taiwan for treating peptic ulcers (C. Y. Huang et al., 2015). Furthermore, Xiang-sha-liu-jun-zi-tang is frequently used for allergic related syndromes, functional abdominal pain syndrome and yields significant improvements in FD symptoms compared with prokinetic agents (Xiao et al., 2012; Liu et al., 2016). In an animal model, it promoted the expression of anti-inflammatory factors, enhanced immune response, and regulated intestinal flora, and modulated the ERK/p38 MAPK signaling pathway (Ma et al., 2019). Treatments using Shen-ling-bai-zhu-san and Chai-hu-shu-gan-tang showed significantly higher total effective rates than those of western medicine in IBS (Li et al., 2013). Moreover, an antacid effect had been reported for Shen-ling-bai-zhu-san (Wu et al., 2010). However, Ping-wei-san showed beneficial effects in reducing colonic damage in patients with colorectal cancer (Yeh et al., 2020), inhibiting inflammatory cytokine production and pathway activation of the NF-κB pathway and the NLRP3 inflammasome in mice (Zhang et al., 2019). Magnolia officinalis in Ping-wei-san can impede neuroinflammation and oxidative stress in the prefrontal cortex. Additionally, in a rodent model of depression, it could boost brain-derived neurotrophic factor protein levels in the hippocampus (Cheng et al., 2018; Zhang et al., 2020).

Qing-wei-san was used to treat various conditions related to heat in the stomach and blood, such as oral ulcers, periodontitis, and upper GI bleeding. It exerted anti-inflammatory effects by improving the pathological morphologies of gastric and oral mucosa in mice, reducing the levels of proinflammatory cytokines, and inhibiting the TLR4/MyD88/NF-κB signaling pathway (Shi et al., 2022). Wen-dan-tang had the potential to treat neurological and psychiatric disorders and digestive disorders (Pradhan et al., 2022). Most studies focused on insomnia and psychotic symptoms (Wu et al., 1999; Che et al., 2016; Deng and Xu, 2017; Yan et al., 2017). In Taiwan, Wen-dan-tang is commonly used for insomnia (F.-P. Chen et al., 2011). An animal study decrease insomnia-related anxiety (Wang et al., 2014). Furthermore, the inhibitory modulation of NF-κB and NLRP3 inflammasome activation by Wen-dan-tang may mediate its antidepressant effect (Jia et al., 2018). Overall, gastroesophageal reflux disease was reported to be associated with IBS (Ruigómez et al., 2009; Yarandi et al., 2010; de Bortoli et al., 2018). Wen-dan-tang consistently demonstrated significant improvement in symptom relief, and this efficacy was sustained over time in gastroesophageal reflux disease (Ling et al., 2015).

Li-zhong-tang enhanced antioxidative defense and improved mucosal immunity through the TLR-2/MyD88 signaling pathway (Song et al., 2020), it significantly restored intestinal microflora in Spleen-“Qi” deficient rats (Peng et al., 2008).

In this real-world survey, Chinese single herbs and complex formulas were suggested and may improve IBS. They are commonly prescribed to patients because they effectively alleviate comorbidities associated with IBS related disorders in physical and psychological aspects.

Limitations

This study has some limitations. First, NHI covers Chinese herbal remedies that come in scientific granular or powder forms (extraction and preparation forms with drug certificates). Thus, the traditional form of Chinese herbal remedies (crude drugs and their complex formulas) is not covered by reimbursement and hence was excluded from this study. Second, self-pay patients were excluded from this study. Thus, the uses of TCM may be underestimated in this study. Third, as the NHIRD did not include data on the severity of IBS and specific subtypes, TCM utilization might reflect IBS clinical symptoms to a certain extent.

Conclusion

This ethnopharmacological study reveals the prescription patterns of TCM for treating patients with IBS. The study benefits from the involvement of licensed physicians responsible for diagnosis and TCM prescriptions, increasing its credibility. Further research is needed to explore commonly used TCM formulas and single herbs. TCM can be considered for treating patients with IBS or GI disorders, as well as addressing their psychological conditions. However, clinical trials are required to support these findings.

Acknowledgments

This study was based in part on data from the NHIRD provided by the Bureau of National Health Insurance (BNHI) of the Ministry of Health and Welfare. The conclusion presented in this study are those of the authors and do not necessarily reflect the views of the BNHI, the Ministry of Health and Welfare. We thank the Center for Medical Informatics and Statistics of Kaohsiung Medical University for providing administrative and funding support. We would specially thank the Center for Research Resources and Development in Kaohsiung Medical University for the assistance.

Funding Statement

The research was also supported by grants from the National Science and Technology Council of Taiwan (NSTC 111-2320-B-037-022) awarded to C-YC. The research was also supported by grants from the National Science and Technology Council of Taiwan (NSTC 111-2321-B-037-004, and 111-2320-B-037-020-MY3) awarded to F-RC. In addition, this research was partially supported by the Drug Development and Value Creation Research Center, Kaohsiung Medical University and Department of Medical Research, Kaohsiung Medical University Hospital.

Data availability statement

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.

Ethics statement

The studies involving human participants were reviewed and approved by Institutional Review Board of Kaohsiung Medical University Chung-Ho Memorial Hospital [KMUHIRB-E(II)-20190359]. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

Author contributions

All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2023.1201240/full#supplementary-material

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Data Availability Statement

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