Frequencies and prescription patterns of traditional Chinese medicine use among elderly patients in Taiwan: A population-based study

Journal of Ethnopharmacology 169 (2015) 328–334

Contents lists available at ScienceDirect

Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jep

Frequencies and prescription patterns of traditional Chinese medicine use among elderly patients in Taiwan: A population-based study Pei-Rung Yang a, Hwey-Fang Liang b, Yen-Hua Chu a, Pau-Chung Chen c,d,e, Yin-Yin Lin a,n a

Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chia-Yi 61363, Taiwan Department of Nursing, Chang Gung University of Science and Technology, Chia-Yi 61363, Taiwan c Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei 10055, Taiwan d Department of Public Health, National Taiwan University College of Public Health, Taipei 10055, Taiwan e Department of Environmental and Occupational Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10055, Taiwan b

art ic l e i nf o

a b s t r a c t

Article history: Received 24 January 2015 Received in revised form 13 April 2015 Accepted 25 April 2015 Available online 5 May 2015

Ethnopharmacological relevance: Traditional Chinese medicine (TCM), one of the most commonly used complementary and alternative medicines, has been receiving increasing attention among elderly patients. However, epidemiological reports and prescription patterns of geriatric TCM users are few. The aim of this study is to use data from a nationwide cohort database to analyze TCM use by the geriatric population in Taiwan from 2005 to 2009. Materials and methods: TCM outpatient claims data was obtained from the Taiwan National Health Insurance database. Data for elderly patients aged 65 years and older were included in the analysis during the study period. The demographic data, disease distributions, and frequencies and prescription patterns of TCM use by the geriatric population were analyzed. Results: The geriatric cohort included 97,210 patients, in which 46,883 patients (48%) had used TCM at least once, with a total of 723,478 TCM outpatient visits. Of these, 175,857 visits (24.3%) were prompted by “diseases of the musculoskeletal system and connective tissue”; more than half of patients with such diseases were treated using acupuncture and traumatology manipulative therapies. Overall, among the 552,835 visits during which Chinese herbal products (CHP) were prescribed, Shu-Jing-Huo-Xie-Tang and Dan Shen (Radix Salvia Miltiorrhizae) were the most frequently prescribed herbal formula and single herb, respectively, for elderly patients. In addition, Shu-Jing-Huo-Xie-Tang was also the most prescribed herbal formula for the most common disease categories of “diseases of the musculoskeletal system and connective tissue” among TCM elderly patients, followed by Du-Huo-Ji-Sheng-Tang, and Shao-Yao-GanCao-Tang. Conclusion: This study elucidated the TCM utilization patterns of the geriatric population. However, additional studies are warranted to determine the safety and efficacy of these CHPs for use by elderly patients in further clinical trials. & 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical compounds studied in this article: Jujuboside A (PubChem CID: 171446) Miltirone ( PubChem CID: 160142) Tanshinone IIA (PubChem CID: 164676) Salvianolic acid B (PubChem CID: 13991587) Tetrahydropalmatine (PubChem CID: 72301) Keywords: Traditional Chinese medicine elderly National Health Insurance Research Database

1. Introduction With the increasing aging population and life expectancy, improving the health of elderly people is crucial for reducing age-related morbidities and mortality and improving quality of life. In 1993, the proportion of the elderly population in Taiwan reached 7%, officially an “aging society”, and is expected to exceed 14% in 2018. Only 25 years are required to enter an “aged society” according to the World Health Organization (WHO) (National Development Council, 2014). n Correspondence to: Department of Traditional Chinese Medicine, Chia-Yi Chang Gung Memorial Hospital, No.6, W. Sec., Jiapu RD., Puzi City, Chia-Yi County 61363, Taiwan. Tel.: þ 886 5 3621000. E-mail address: [email protected] (Y.-Y. Lin).

http://dx.doi.org/10.1016/j.jep.2015.04.046 0378-8741/& 2015 Elsevier Ireland Ltd. All rights reserved.

The rates of chronic medical illnesses are high in the geriatric population. Chronic diseases, the leading causes of death among elderly people, cause disability and pain, reduce quality of life, and increase healthcare costs (Centers for Disease Control and Prevention and The Merck Company Foundation, 2007). There is a strong association between the activities of daily living dependence and the presence of geriatric syndromes or aging-related ailments such as frailty, dizziness, falls, incontinence, vision or hearing disorder, and cognitive impairment (Cigolle et al., 2007). However, reduced independence and daily function are not inevitable consequences of aging. Using complementary and alternative medicine (CAM) has become increasingly widespread over the past years (Kessler et al., 2001; Tindle et al., 2005). Several studies have reported that the main reasons for CAM use among people older than 65 years of age were to

P.-R. Yang et al. / Journal of Ethnopharmacology 169 (2015) 328–334

One million cohort random sample of NHIRD Exclusion of people with age < 65 years old All elderly people Exclusion of elderly people without out patient clinical records Study population N= 97,210

TCM non-users N= 50,327

TCM users N= 46,883

329

1995. Approximately 99% of the population in Taiwan was included in the scheme by the end of 2010 (Insurance BoNH, 2010). The NHIRD website offers electronic claims database, which includes patient medical records and information such as patient age, date of birth, sex, date of encounters, medical care facilities and specialties, management and treatment, prescribed drugs, transferred identification number, and three major diagnoses based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. To protect personal privacy, the data regarding patient identity and institutions visited are cryptographically scrambled. Thus, the NHIRD is an optimal platform for surveying the utilization patterns of TCM, prescribed by licensed TCM physicians, among the geriatric population in Taiwan. We analyzed a sample of one million randomly selected participants from the 22 million beneficiaries in the NHI program from 2005 to 2009. The sampled cohort in this study was representative of all beneficiaries, including people aged 65 years and older. 2.2. Study subjects

Fig. 1. Flow recruitment chart of subjects from the one million random samples obtained from the National Health Insurance Research Database (NHIRD), 2005 to 2009, in Taiwan.

relieve pain, resolve muscular and psychological problems, maintain physical and mental health, improve quality of life (Williamson et al., 2003), and even control chronic ailments (Eisenberg et al., 1998; Thomas and Coleman, 2004). Traditional Chinese medicine (TCM), which includes acupuncture, traumatology manipulative therapies, and decoctions, is one of the most commonly used CAMs that has played a crucial role in the health care of Chinese populations (Park et al., 2012). Some previous studies have reported that elderly people may use herbal medicine extensively, primarily because of their cultural backgrounds, in which herb use was common (Wong et al., 2010; Zhang et al., 2007). Other study reported the potential benefits of Chinese herbal medicine for elderly patients with chronic illness such as cardiovascular diseases (CVDs) (Luo et al., 2013). In Taiwan, TCM is frequently used (Chen et al., 2007). Depending on patient conditions, TCM physicians widely prescribe Chinese herbal products (CHP), a modern form of convenient and high-quality decoctions, according to TCM theory. Certain studies have documented the efficacy of TCM in a variety of populations and when treating numerous diseases (Efferth et al., 2007; Yuan and Lin, 2000). However, epidemiologic investigations about geriatric TCM users in large-scale population studies are few. The factors that influence TCM use among the geriatric population in Taiwan remain uncharacterized. Because healthcare providers offering CHPs, acupuncture, and traumatology manipulative therapies have been regularly reimbursed under the National Health Insurance (NHI) program since 1995 in Taiwan, the claims database is an optimal platform for understanding TCM utilization. We used data from the National Health Insurance Research Database (NHIRD) to investigate the medical conditions and demographic factors associated with TCM use and to analyze the frequencies and prescription patterns of TCM among the geriatric population in Taiwan from 2005 to 2009. By referencing this study, clinical practitioners can learn more about the demands and preferences of elderly TCM users and provide more reliable information about TCM use.

2. Materials and methods 2.1. Data source Expenditures associated with Western and Chinese medicines have been reimbursed under the NHI program, which was executed in

Most developed countries have accepted the chronological age of 65 years as the beginning of older age, according to a WHO statement. Therefore, people aged 65 years and older from the random sampling cohort were included as the study subjects. In the elderly population, patients who had at least one TCM outpatient clinical visit from 2005 to 2009 were defined as TCM users, whereas those with no TCM outpatient records were defined as non-TCM users (Fig. 1). All geriatric population-related medical records from during the study period were analyzed. We considered the first diagnosis coded according to the ICD-9-CM codes to be the major diagnosis, as described in the outpatient department visit records, and then grouped the diagnoses into a series of broader categories. In addition, we obtained the files containing the prescription records of CHPs related to patient outpatient visits to evaluate the frequencies and prescription patterns among this population. 2.3. Traditional Chinese medicine TCM, comprising CHPs, acupuncture, and traumatology manipulative therapies, has been most widely adopted by patients in Taiwan and has developed over the past millennia. Prescriptions prescribed by TCM physicians may comprise one or more herbs (formulae) depending on the various symptoms and signs of patients, evaluated on the basis of the TCM theory. Chinese herbal formulae or drugs are manufactured into fine granules or powders that can be mixed easily in a single prescription. The Department of Chinese Medicine and Pharmacy website provides information regarding reimbursed CHPs that includes the name of each CHP, the proportion of each component, the period and date of approval as a drug, and the manufacturer's name and code. 2.4. Statistical analysis Drug registration numbers from the Department of Chinese Medicine and Pharmacy website were linked to the outpatient visit records of the study cohort. The frequency, percentage, average daily dose (g), and average duration (days) of herbal formulae or single herbs use were analyzed and calculated. Data analysis was performed on descriptive statistics that included the prescription rates of TCM users stratified using patient demographic features and disease indications for the prescription of TCM. The main indications were categorized on the basis of the ICD-9-CM codes. The database software, SAS version 9.2

330

P.-R. Yang et al. / Journal of Ethnopharmacology 169 (2015) 328–334

Table 1 Demographic characteristics of TCM and Non-TCM users among elderly people in Taiwan during 2005–2009. Characteristics

Gender Female Male Insured salaries (NTD$/month)a 0þ 1–15840 15841–25000 425000 Urbanization levelb 1 (most) 2 3 4 (least) Comorbidities (ICD-9-CM) Hypertension(401-405) TypeII diabetes mellitus(250) Chronic obstructive pulmonary disease(490–496) Chronic kidney disease(585) Neoplasm(140–239) Hyperlipidemia(272) Insomnia(780.5) Total a b

Non-TCM users

TCM users

No.

%

No.

%

22838 27489

45.4 54.6

25745 21138

54.9 45.1

13729 9594 22789 4215

27.3 19.1 45.3 8.4

12126 7225 22514 5018

25.9 15.4 48.0 10.7

12705 20173 11001 6448

25.2 40.1 21.9 12.8

11932 19787 9438 5726

25.5 42.2 20.1 12.2

31146 16285 15302 4363 3757 14034 8689 50327

61.9 32.4 30.4 8.7 7.5 27.9 17.3 100

32787 16408 15292 3812 3351 19317 13241 46883

69.9 35.0 32.6 8.1 7.2 41.2 28.2 100

NTD, New Taiwan dollar. 1:most urbanization; 4:least urbanization.

(SAS Institute Inc., Cary, NC, USA), was used for data processing and analysis.

3. Results Among the one million randomly sampled patients, 97,210 elderly patients were included in the analysis. Throughout 2005– 2009, we identified 46,883 (48%) patients who had used TCM at least once, with 723,478 TCM outpatient visits overall. Table 1 summarizes the characteristics of the study cohort. TCM use was higher in females than in males. And among 48,583 female patients of the study cohort, 25,745(53%) had used TCM, while, 43% in 48,627 male patients. Elderly patients with higher insured salaries and urbanization levels sought TCM therapy frequently. In addition, we observed that the proportion of elderly patients with comorbidities such as insomnia and chronic medical diseases, including hypertension, diabetes mellitus, and hyperlipidemia, was higher in TCM use than in non-TCM use. Of the elderly people visiting TCM doctors, 552,835 (76.4%) were prescribed CHPs, whereas the remaining were prescribed acupuncture and traumatology manipulative therapies. Table 2 summarizes the analysis of the major disease categories for all TCM visits; “diseases of the musculoskeletal system and connective tissue” was the most common reason for using TCM (24.3%). CHPs were used primarily for treating “symptoms, signs, and illdefined conditions” (28.4%), followed by “diseases of the musculoskeletal system and connective tissue” (16.3%), “diseases of the digestive system” (15.2%), and “diseases of the respiratory system” (14.9%). However, acupuncture or traumatology manipulative therapies were used for managing more than half of the “diseases of the musculoskeletal system and connective tissue” and most injuries. Table 3 shows the most frequently prescribed herbal formulae and single herbs during the outpatient visits, frequency of prescription, average daily dose, and average prescription duration. The most commonly prescribed herbal formula for elderly patients was Shu-Jing-Huo-Xie-Tang (7.5%), followed by Du-Huo-Ji-Sheng-

Tang (6.1%), Shao-Yao-Gan-Cao-Tang (5.1%), Ping-Wei-San (4.5%), and Ma-Zi-Ren-Wan (4.3%). Moreover, Dan Shen (R. Salvia Miltiorrhizae) (6.8%) was the most commonly prescribed single herb for elderly patients, followed by Yan Hu Suo (Rhizoma Corydalis) (5.6%), Bei Mu (Bulbus Fritillariae Thunbergii) (4.8%), Du Zhong (Cortex Eucommiae) (4.4%), and Da Huang (Radix et Rhizoma Rhei) (4.4%). Table 4 lists the frequencies of the most commonly prescribed herbal formulae and single herbs for the four most frequent disease categories. Suan-Zao-Ren-Tang (7.4%) and Dan Shen (7.5%) were the most prescribed herbal formula and single herb, respectively, for the most common disease categories of “symptoms, signs, and ill-defined conditions” among the elderly patients using CHPs.

4. Discussion This is the first study involving a random nationwide sample that investigated the characteristics of TCM use in a Chinese geriatric population. The outcome measures were analyzed using the computerized insurance reimbursement data in Taiwan. Factors influencing TCM use were studied in 97,210 elderly patients aged 65 years and older. Of these, 48.2% had used TCM at least once during the study period. TCM use was higher in female elderly patients than in male elderly patients. These findings were consistent with those of previous TCM usage-related epidemiological studies (Chen et al., 2007). A previous study reported that elderly TCM users more likely had greater social support (Slivinske and Fitch, 1992). Our study also showed that patients with higher insured salaries sought TCM treatment more frequently than did others. In addition, TCM resources can be easily acquired in areas with high urbanization levels, and therefore, TCM users were greater in such areas (Table 1). Moreover, because elderly patients exhibit a large number of comorbidities such as chronic medical diseases, including hypertension, diabetes mellitus, or hyperlipidemia, they are more likely to use TCM for health regulation. For chronic illnesses, patients in Chinese populations generally seek

P.-R. Yang et al. / Journal of Ethnopharmacology 169 (2015) 328–334

331

Table 2 Frequency distribution of TCM elderly users by major disease categories (according to ICD-9-CM codes ) during 2005–2009 in Taiwan. ICD-9-CM code range Number of visits (%)

Major disease category

Infectious and parasitic diseases Neoplasms Endocrine, nutritional and metabolic diseases, and immunity disorders Mental disorders Diseases of the nervous system and sense organs Diseases of the circulatory system Diseases of the respiratory system Diseases of the digestive system Diseases of the genitourinary system Diseases of the skin and subcutaneous tissue Diseases of the musculoskeletal system and connective tissue Symptoms, signs and ill-defined conditions Injury and poisoning Othersa

001–139 140–239 240–279 290–319 320–389 390–459 460–519 520–579 580–629 680–709 710–739 780–799 800–999

Total a

Chinese herbal products

Acupuncture and traumatology

Total of TCM

2182 6316 13761 4424 28555 32263 82391 83895 19352 11593 90127 156779 17589 3608

0.4% 1.1% 2.5% 0.8% 5.2% 5.8% 14.9% 15.2% 3.5% 2.1% 16.3% 28.4% 3.2% 0.7%

90 256 213 328 5004 11312 349 240 128 144 85730 1245 64939 665

0.1% 0.2% 0.1% 0.2% 2.9% 6.6% 0.2% 0.1% 0.1% 0.1% 50.2% 0.7% 38.1% 0.4%

2272 6572 13974 4752 33559 43575 82740 84135 19480 11737 175857 158024 82528 4273

552835

100%

170643

100%

723478 100%

0.3% 0.9% 1.9% 0.7% 4.6% 6.0% 11.4% 11.6% 2.7% 1.6% 24.3% 21.8% 11.4% 0.6%

others include ICD-9-CM code range 280–289, 630–679, 740–799.

Table 3 Top ten herbal formulae and single herbs prescribed by traditional Chinese medicine doctors for elderly people (n¼ 552,835). Frequency of Average daily Average duration for prescription (days) prescription dose (g) n (%) Herbal formulae Shu-Jing-Huo-XieTang Du-Huo-Ji-ShengTang Shao-Yao-Gan-CaoTang Ping-Wei-San Ma-Zi-Ren-Wan Zhi-Gan-Cao-Tang Liu-Wei-Di-HuangWan Ji-Sheng-Shen-QiWan Ban-Xia-Xie-Xin-Tang Chuan-Qiong-ChaDiao-San Herb name Dan Shen (Radix Salvia Miltiorrhizae) Yan Hu Suo (Rhizoma Corydalis) Bei Mu (Bulbus Fritillariae Thunbergii) Du Zhong (Cortex Eucommiae) Da Huang (Radix et Rhizoma Rhei) Jie Geng (Radix Platycodonis) Niu Xi(Radix Achyranthis Bidentatae) Ge Gen (Radix Puerariae) Chuan Qi (Radix Notoginseng) Huang Qin (Scutellaria Baicalensis)

41,243

7.5%

4.7

7.1

33,776

6.1%

4.9

7.9

28,075 5.1%

3.6

6.7

25,137 23,932 22,919 22,889

4.5% 4.3% 4.1% 4.1%

3.7 3.3 4.4 4.7

6.7 8.0 7.6 7.6

22,590 4.1%

4.7

8.4

21,247 3.8% 4.2 20,646 3.7% 4.6

7.1 6.1

37,617

6.8% 1.5

8.5

30,863 5.6% 1.5

7.0

26,770 4.8% 1.5

6.9

24,109

4.4% 1.5

8.3

24,068 4.4% 1.1

7.6

23,320 4.2% 1.5

6.5

22,870 4.1%

1.4

7.8

21,485

3.9% 1.7

6.9

21,476

3.9% 1.7

7.4

20,064 3.6% 1.5

7.3

Western therapies initially, but subsequently complement or substitute modern prescription medicine with TCM because of the long-term treatment administration and the potential adverse effects of Western medicine (Wong et al., 1995, 1998). Furthermore, some studies have reported that certain Chinese medicines have potential benefits for treating chronic medical diseases such as hypertension (Xiong et al., 2013), diabetes mellitus (Zhang and Jiang, 2012), and hyperlipidemia (Xie et al., 2012). Because the population is aging, chronic medical illnesses, such as CVDs, that are the leading cause of death will have a higher prevalence (Go et al., 2014). The effects of TCM for CVD treatment (Chen et al., 2012), particularly in elderly patients, have received great attention, because more physicians have been using TCM in CVD treatment and prevention. (Ferreira and Lopes, 2011; Luo et al., 2013; Xu and Chen, 2011). We observed that elderly people used TCM to treat insomnia, as shown in our Table 1. Several studies have reported that treatment with CHPs effectively prolonged sleep duration, improved sleep quality, and involved fewer adverse effects compared with treatment with Western medicines, which resulted in adverse effects such as lethargy, dizziness, and dry mouth (Chen and Hsieh, 1985; Yang et al., 2005). Among the TCM visits by the entire population of Taiwan, 14.1% of the visits were for acupuncture and traumatology manipulative therapies (Chen et al., 2007); in our study, 23.6% of TCM visits by elderly people were related to such therapies. A nationwide survey indicated that the highest number of TCM visits in the general population in Taiwan were for “diseases of the respiratory system” (Chen et al., 2007). However, in the geriatric population examined in our study, “diseases of the musculoskeletal system and connective tissue” prompted the most TCM visits, during which acupuncture and traumatology manipulative therapies were used to treat more than half of the patients (Table 2). Elderly patients tend to use more non-pharmacological therapies, such as acupuncture and traumatology manipulative therapies, to relieve myalgia- and arthralgia-associated discomfort, which is a common complaint observed in geriatric patients (Centers for Disease Control and Prevention and The Merck Company Foundation, 2007; Cheung et al., 2007). According to a previous study, most people use CAM for relieving chronic pain resulting from musculoskeletal system disorders or chronic illnesses (Linde et al., 2001), and another study reported that more than 80% of acupuncture visits were for

332

P.-R. Yang et al. / Journal of Ethnopharmacology 169 (2015) 328–334

Table 4 The three most commonbal formulae and single herbs in the four most frequent disease categories for elderly people. Disease category

Herbal formulae

Frequency of prescription n (%)

Herb name

Frequency of prescription n (%)

Symptoms, signs and ill-defined conditions

Suan-Zao-Ren-Tang

11624 (7.4%)

11,773 (7.5%)

Tian-Wang-Bu-XinDan Zhi-Gan-Cao-Tang Shu-Jing-Huo-XieTang Du-Huo-Ji-ShengTang Shao-Yao-Gan-CaoTang Ban-Xia-Xie-XinTang Ma-Zi-Ren-Wan Ping-Wei-San

11101 (7.1%)

Dan Shen (Radix Salvia Miltiorrhizae) Bei Mu (Bulbus Fritillariae Thunbergii) Jie Geng (Radix Platycodonis) Du Zhong (Cortex Eucommiae) Niu Xi (Radix Achyranthis Bidentatae) Xu Duan (Radix Dipsaci)

10053 (11.2%)

Diseases of the musculoskeletal system and connective tissue

Diseases of the digestive system

Diseases of the respiratory system

Ma-Xing-Gan-ShiTang Xiao-Qing-LongTang Shin-Yi-Ching-FeyTang

10818 (6.9%) 25947 (28.8%) 22434 (24.9%) 12122 (13.4%) 11589 (13.8%) 11419 (13.6%) 10625 (12.7%) 8620 (10.5%) 8312 (10.1%) 7792 (9.5%)

musculoskeletal and neurological problems (Chen et al., 2006). Acupuncture has the advantage of directly stimulating the neurologic distribution of local soft tissue, and thus, is the most sought after option for treating musculoskeletal system disorders. In addition, because painkillers do not exert substantial effects and involve potential adverse effects after long-term administration (Tramer et al., 2000), the increased demand for TCM, particularly acupuncture and traumatology manipulative therapies, is not unexpected. As shown in Table 3, Shu-Jing-Huo-Xie-Tang was the most commonly prescribed herbal formula for elderly patients. Moreover, this formula was the most frequently used herbal formula for treating “diseases of the musculoskeletal system and connective tissue”. Shu-Jing-Huo-Xie-Tang is a combination of 17 single Chinese herbs, including Dang Gui (Radix Angelica Sinensis), Bai Shao (Radix Paeoniae Alba), Sheng Di Huang (Radix Rehmanniae), Cang Zhu (Rhizoma Atractylodis), Niu Xi (Radix Achyranthis Bidentatae), Chen Pi (Citrus Reticulata Blanco), Tao Ren (Semen Persicae), Wei Ling Xian (Radix clematidis Osbeck), Chuan Xiong (Rhizoma Ligustici Chuanxiong), Fang Ji (Radix Stephaniae Tetrandrae), Qiang Huo (Rhizoma Et Radix Notopterygii), Fang Feng (Radix Saposhinkoviae), Bai Zhi (Radix Angelicae Dahuricae), Long Dan Cao (Radix Gentianae Longdancao), Fu Ling(Sclerotium Poriae Cocos), Sheng Jiang (Rhizoma Zingiberis Officinalis), and Gan Cao (Radix Glycyrrhizae). TCM physicians often prescribe this formula to relieve muscle pain and arthralgia. In previous studies, Shu-Jing-Huo-XieTang has been frequently investigated in Taiwan (Hsieh et al., 2008) and was determined to be most commonly used herbal formula for treating “diseases of the musculoskeletal system and connective tissue” in climacteric women (Yang et al., 2009). One study reported that this formula exerted pain relieving effects by increasing blood circulation in the adjuvant arthritis rat models (Kanai et al., 2003). Although TCM physicians frequently prescribe this formula in clinical practice in Taiwan, a previous study has revealed that a combination of Shu-Jing-Huo-Xie-Tang and warfarin will enhance bleeding effects in animal models (Yang et al., 2013). Therefore, future clinical trials are warranted to confirm the safety and effectiveness of this formula. TCM physicians frequently prescribe Du-Huo-Ji-Sheng-Tang, the second most commonly used herbal formula for elderly patients, to treat “diseases of the musculoskeletal system and

Da Huang (Radix et Rhizoma Rhei) Mu Xiang (Radix Aucklandiae) Hou Po (Cortex Magnoliae Officinalis) Jie Geng (Radix Platycodonis)

9474 (6.0%) 9130 (5.8%) 11294 (12.5%)

9869 (11.0%) 7240 (8.6%) 5353 (6.4%) 5334 (6.4%) 9446 (11.5%)

Bei Mu (Bulbus Fritillariae 8943 (10.9%) Thunbergii) Xing Ren (Amygdalus Communis 7557 (9.2%) Vas)

connective tissue”. In previous studies, Du-Huo-Ji-Sheng-Tang was determined to be the most commonly used herbal formula for treating osteoarthritis (Chen et al., 2014) and osteoporosis in Taiwan (Shih et al., 2012). This formula was used to treat a combination of symptoms, such as stiffness, flaccidity, pain, and aversion to cold of the knee. The outcome of a 4-week prospective clinical research study has demonstrated the effectiveness of this formula in relieving stiffness and pain in the knee joint and improving physical function in osteoarthritis patients (Lai et al., 2007). An experimental study showed that Du-Huo-Ji-Sheng-Tang could regulate the expression of the vascular endothelial growth factor mRNA and hypoxia-inducible factor -1α mRNA and inhibit chondrocyte apoptosis in an animal model (Chen et al., 2011a). Although no drug reactions or adverse events were observed during the study period (Hsieh et al., 2010), further research is required to provide more evidence for establishing its efficacy and safety. “Symptoms, signs, and ill-defined conditions” was the most frequent disease category prompting TCM visits that involved CHP prescription. In general, TCM physicians prescribe various Chinese herbal formulae or single herbs to treat patients by differentiating the syndromes on the basis of the signs and symptoms of multiple diseases or various psychosomatic symptoms according to TCM principles, particularly for elderly people, rather than diagnosing according to specific diagnostic codes. We observed that SuanZao-Ren-Tang was the most commonly prescribed herbal formula for “symptoms, signs, and ill-defined conditions” (Table 4). In clinical practice, TCM physicians often use this formula to treat sleep disturbance, anxiety, and palpitations. Suan-Zao-Ren-Tang is frequently used for treating insomnia (Chen et al., 2011b) and was believed to act by stimulating the activity of gamma-aminobutyric acid A and serotonin receptors to regulate sleep in an experimental animal model (Yi et al., 2007a; Yi et al., 2007b). In particular, Suan-Zao-Ren (Semen Ziziphi Spinosae), the main ingredient of Suan-Zao-Ren-Tang, its extracted compound such as jujuboside A, one kind of triterpene saponins, exerts sedative and hypnotic effects (Jiang et al., 2007). The prevalence of insomnia increases with age, and a previous survey showed that 57% of elderly people have experienced this condition (Foley et al., 1995). Thus, we concluded that insomnia was the primary cause for the most frequently diagnosed category of “symptoms, signs, and

P.-R. Yang et al. / Journal of Ethnopharmacology 169 (2015) 328–334

ill-defined conditions” with CHP usage among the geriatric population. Dan Shen, the dried root and the rhizome of Salvia miltiorrhiza Bge (Labiatae), is the most frequently prescribed single herb for elderly people and is commonly used for treating “symptoms, signs, and ill-defined conditions” among elderly patients. In Taiwan, Dan Shen was a commonly prescribed Chinese single herb by TCM physicians (Hsieh et al., 2008). A previous study reported the sedative effects of miltirone, extracted compound of the herb, for treating sleep disorders (Imanshahidi and Hosseinzadeh, 2006). Other studies have reported numerous major ingredients of Dan Shen such as Tanshinone IIA, and Salvianolic acid B, with multiple pharmacological activities in the cardiovascular system, including anti-thrombosis (Shen and Li, 1997), anti-atherosclerosis (Wu et al., 1998), anti-hypertension (Kang et al., 2002), antioxidative (Ling et al., 2005), and cardioprotection (Cao et al., 2003); in addition, it improves the microcirculation in the brain and heart (Yu, 1988). Dan Shen products are safe for use, with no reports of any major adverse effect for over five decades (Cheng, 2007). However, some studies have reported side effects of its interactions with warfarin, salicylate, diazepam, and ginseng (Chan, 2001; Gupta et al., 2002; Jinping et al., 2003); therefore, clinical physicians should exercise caution when prescribing a combination of Western medicines and Dan Shen. Yan Hu Suo, the second most commonly used Chinese single herb for treating elderly people, is a widely used CHP (Hsieh et al., 2008). It has been used by TCM physicians for treating spastic pain, abdominal pain, and pain caused by injury and for promoting blood circulation. The main chemical constituents of Yan Hu Suo are alkaloids; among them, some alkaloids such as tetrahydropalmatine, exhibited remarkable effects on the dopaminergic system in the central nervous system, which play a crucial role in regulating nociception to alleviate pain (Yang et al., 2014). Other commonly prescribed formulae and single herbs continue to be used for relieving spasmodic pain in the musculoskeletal system, including the joints, back, and soft tissues (Shao-YaoGan-Cao-Tang); relieving chronic pain in the lower back and knees and strengthening the muscles and bones (Du Zhong); relieving gastrointestinal discomfort (Ping-Wei-San) and constipation (Ma-Zi-Ren-Wan, Da Huang); and treating ailments of the chest and the respiratory system (Bei Mu) according to the ancient TCM literature. These findings are identical with those of other studies: TCM is valued among elderly people for its effectiveness in improving physiological and musculoskeletal problems, particularly in reducing pain and promoting mobility, and can be used to manage multiple chronic diseases and treat psychological disorders to improve health and well-being (Cartwright, 2007; Cheung et al., 2007; Gozum and Unsal, 2004; Najm et al., 2003; Wong et al., 2010). The NHI in Taiwan only reimburses CHP and not decoction. The proportions of CHPs formulated into finished herbal products remain unaltered.Therefore, TCM physicians combine various formulae or herbs for each prescription to treat patients based on syndrome differentiation theory. Besides, the prescription patterns were different among TCM physicians because of their individual experience. That is the reason why there were many kinds of prescription patterns for the same disease. Thus, the frequency of prescriptions for herbal formulae and single herbs for each condition is not very high, observed in the present study. The present study had two limitations. First, the therapeutic methods and principles of TCM are based on the results of “syndrome differentiation” according to TCM theory. However, this technique is not applicable for ICD-9-CM diagnoses, the current disease coding system that is used by TCM physicians for diagnosis in clinical practice in Taiwan. The development of a coding system for TCM diagnostic classifications is important to

333

assist TCM research greatly in the future. Second, the costs of decoctions and CHPs provided by pharmacies were not reimbursed by the NHI, thus, this may have caused underestimating the frequency of TCM utilization.

5. Conclusion We analyzed a sample cohort of one million randomly selected elderly patients from the NHIRD from 2005 to 2009. The data provided information regarding the frequencies and prescription patterns of TCM use by the geriatric population in outpatient clinical visits in Taiwan. Shu-Jing-Huo-Xie-Tang and Dan Shen were the most frequently prescribed herbal formula and single herb, respectively. Future research must be conducted to strengthen the available clinical evidence regarding the safety and efficacy of these frequently used CHPs in elderly people.

Conflict of Interests The authors have no conflicts of interests to declare.

Acknowledgments The authors would like to thank the Center of Excellence for Chang Gung Research Datalink (Grant No. CORPG6D0161) for the comments and assistance with the data analysis. This study was supported by a grant from Chang Gung Memorial Hospital, Chia-yi Branch, and was based on data in the NHIRD provided by the Central Bureau of NHI and the Department of Health and managed by the National Health Research Institutes (NHRI). The interpretation and conclusions contained herein do not represent those of the Bureau of NHI, the Department of Health, or the NHRI. References Cao, C.M., Xia, Q., Zhang, X., Xu, W.H., Jiang, H.D., Chen, J.Z., 2003. Salvia miltiorrhiza attenuates the changes in contraction and intracellular calcium induced by anoxia and reoxygenation in rat cardiomyocytes. Life Sci. 72, 2451–2463. Cartwright, T., 2007. ‘Getting on with life’: the experiences of older people using complementary health care. Soc. Sci. Med. 64, 1692–1703. Centers for Disease Control and Prevention and The Merck Company Foundation, 2007. The State of Aging and Health in America. The Merck Company Foundation, Whitehouse Station, NJ 2007. Available at: 〈http://www.cdc.gov/ aging/pdf/saha_2007.pdf〉 (accessed 12.04.12). Chan, T.Y., 2001. Interaction between warfarin and danshen (Salvia miltiorrhiza). Ann. Pharmacother. 35, 501–504. Chen, C.W., Sun, J., Li, Y.M., Shen, P.A., Chen, Y.Q., 2011a. Action mechanisms of duhuo-ji-sheng-tang on cartilage degradation in a rabbit model of osteoarthritis. Evid.-Based Complement. Altern. Med. 2011, 571479. Chen, F.P., Chang, C.M., Hwang, S.J., Chen, Y.C., Chen, F.J., 2014. Chinese herbal prescriptions for osteoarthritis in Taiwan: analysis of National Health Insurance dataset. BMC Complement. Altern. Med. 14, 91. Chen, F.P., Chen, T.J., Kung, Y.Y., Chen, Y.C., Chou, L.F., Chen, F.J., Hwang, S.J., 2007. Use frequency of traditional Chinese medicine in Taiwan. BMC Health Serv. Res. 7, 26. Chen, F.P., Jong, M.S., Chen, Y.C., Kung, Y.Y., Chen, T.J., Chen, F.J., Hwang, S.J., 2011b. Prescriptions of Chinese herbal medicines for insomnia in Taiwan during 2002. Evid.-Based Complement. Altern. Med. 2011, 236341. Chen, F.P., Kung, Y.Y., Chen, T.J., Hwang, S.J., 2006. Demographics and patterns of acupuncture use in the Chinese population: the Taiwan experience. J. Altern. Complement. Med. 12, 379–387. Chen, H.C., Hsieh, M.T., 1985. Clinical trial of suanzaorentang in the treatment of insomnia. Clin. Ther. 7, 334–337. Chen, K.J., Hui, K.K., Lee, M.S., Xu, H., 2012. The potential benefit of complementary/ alternative medicine in cardiovascular diseases. Evid.-Based Complement. Altern. Med. 2012, 125029. Cheng, T.O., 2007. Cardiovascular effects of Danshen. Int. J. Cardiol. 121, 9–22. Cheung, C.K., Wyman, J.F., Halcon, L.L., 2007. Use of complementary and alternative therapies in community-dwelling older adults. J. Altern. Complement. Med. 13, 997–1006.

334

P.-R. Yang et al. / Journal of Ethnopharmacology 169 (2015) 328–334

Cigolle, C.T., Langa, K.M., Kabeto, M.U., Tian, Z., Blaum, C.S., 2007. Geriatric conditions and disability: the health and retirement study. Ann. Intern. Med. 147, 156–164. Efferth, T., Li, P.C., Konkimalla, V.S., Kaina, B., 2007. From traditional Chinese medicine to rational cancer therapy. Trends Mol. Med. 13, 353–361. Eisenberg, D.M., Davis, R.B., Ettner, S.L., Appel, S., Wilkey, S., Van Rompay, M., Kessler, R.C., 1998. Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey. Jama 280, 1569–1575. Ferreira, A.S., Lopes, A.J., 2011. Chinese medicine pattern differentiation and its implications for clinical practice. Chin. J. Integr. Med. 17, 818–823. Foley, D.J., Monjan, A.A., Brown, S.L., Simonsick, E.M., Wallace, R.B., Blazer, D.G., 1995. Sleep complaints among elderly persons: an epidemiologic study of three communities. Sleep 18, 425–432. Go, A.S., Mozaffarian, D., Roger, V.L., Benjamin, E.J., Berry, J.D., Blaha, M.J., Dai, S., Ford, E.S., Fox, C.S., Franco, S., Fullerton, H.J., Gillespie, C., Hailpern, S.M., Heit, J.A., Howard, V.J., Huffman, M.D., Judd, S.E., Kissela, B.M., Kittner, S.J., Lackland, D.T., Lichtman, J.H., Lisabeth, L.D., Mackey, R.H., Magid, D.J., Marcus, G.M., Marelli, A., Matchar, D.B., McGuire, D.K., Mohler 3rd, E.R., Moy, C.S., Mussolino, M.E., Neumar, R.W., Nichol, G., Pandey, D.K., Paynter, N.P., Reeves, M.J., Sorlie, P. D., Stein, J., Towfighi, A., Turan, T.N., Virani, S.S., Wong, N.D., Woo, D., Turner, M. B., 2014. Heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation 129, e28–e292. Gozum, S., Unsal, A., 2004. Use of herbal therapies by older, community-dwelling women. J. Adv. Nurs. 46, 171–178. Gupta, D., Jalali, M., Wells, A., Dasgupta, A., 2002. Drug-herb interactions: unexpected suppression of free Danshen concentrations by salicylate. J.Clin. Lab. Anal. 16, 290–294. Hsieh, S.C., Lai, J.N., Chen, P.C., Chen, C.C., Chen, H.J., Wang, J.D., 2010. Is Duhuo Jisheng Tang containing Xixin safe? A four-week safety study. Chin. Med. 5, 6. Hsieh, S.C., Lai, J.N., Lee, C.F., Hu, F.C., Tseng, W.L., Wang, J.D., 2008. The prescribing of Chinese herbal products in Taiwan: a cross-sectional analysis of the national health insurance reimbursement database. Pharmacoepidemiol. Drug Saf. 17, 609–619. Imanshahidi, M., Hosseinzadeh, H., 2006. The pharmacological effects of Salvia species on the central nervous system. Phytother. Res. 20, 427–437. Insurance BoNH, 2010. The National Health Insurance Annual Statistical Report. Bureau of National Health Insurance, Taipei,Taiwan. Jiang, J.G., Huang, X.J., Chen, J., 2007. Separation and purification of saponins from Semen Ziziphus jujuba and their sedative and hypnotic effects. J. Pharm. Pharmacol. 59, 1175–1180. Jinping, Q., Peiling, H., Yawei, L., Abliz, Z., 2003. Effects of the aqueous extract from Salvia miltiorrhiza Bge on the pharmacokinetics of diazepam and on liver microsomal cytochrome P450 enzyme activity in rats. J. Pharm. pharmacol. 55, 1163–1167. Kanai, S., Taniguchi, N., Higashino, H., 2003. Study of sokei-kakketu-to (shu-jinghuo-xue-tang) in adjuvant arthritis rats. Am. J. Chin. Med. 31, 879–884. Kang, D.G., Yun, Y.G., Ryoo, J.H., Lee, H.S., 2002. Anti-hypertensive effect of water extract of danshen on renovascular hypertension through inhibition of the renin angiotensin system. Am. J. Chin. Med. 30, 87–93. Kessler, R.C., Davis, R.B., Foster, D.F., Van Rompay, M.I., Walters, E.E., Wilkey, S.A., Kaptchuk, T.J., Eisenberg, D.M., 2001. Long-term trends in the use of complementary and alternative medical therapies in the United States. Ann. Intern. Med. 135, 262–268. Lai, J.N., Chen, H.J., Chen, C.C., Lin, J.H., Hwang, J.S., Wang, J.D., 2007. Duhuo jisheng tang for treating osteoarthritis of the knee: a prospective clinical observation. Chin. Med. 2, 4. Linde, K., Vickers, A., Hondras, M., Riet, G. ter, Thormahlen, J., Berman, B., Melchart, D., 2001. Systematic reviews of complementary therapies—an annotated bibliography Part 1: acupuncture. BMC Complement. Alternat. Med. 1, 3. Ling, S., Dai, A., Guo, Z., Yan, X., Komesaroff, P.A., 2005. Effects of a Chinese herbal preparation on vascular cells in culture: mechanisms of cardiovascular protection. Clin. Exp. Pharmacol. Physiol. 32, 571–578. Luo, J., Xu, H., Chen, K.J., 2013. Potential benefits of Chinese Herbal Medicine for elderly patients with cardiovascular diseases. J. Geriatr. Cardiology 10, 305–309. Najm, W., Reinsch, S., Hoehler, F., Tobis, J., 2003. Use of complementary and alternative medicine among the ethnic elderly. Alternat. Ther. Health Med. 9, 50–57. National Development Council, 2014. Aging changes in the speed by Selected Countries (in Chinese). Available at: 〈http://www.ndc.gov.tw/m1.aspx? sNo=0061529#.VIsJ7j9O6zw〉 (accessed 29.09.14).

Park, H.L., Lee, H.S., Shin, B.C., Liu, J.P., Shang, Q., Yamashita, H., Lim, B., 2012. Traditional medicine in china, Korea, and Japan: a brief introduction and comparison. Evid.-Based Complement. Altern. Med., 429103. Shen, Y., Li, Y., 1997. Zhong yao yao li xue. Shanghai ke xue ji shu chu ban she, Shanghai. Shih, W.T., Yang, Y.H., Chen, P.C., 2012. Prescription patterns of chinese herbal products for osteoporosis in taiwan: a population-based study. Evid.-Based Complement. Altern. Med. 2012, 752837. Slivinske, L.R., Fitch, V.L., 1992. The effect of health care coverage on medical cost, utilization, and well-being of the aged. J. Health Soc. Policy 4, 1–11. Thomas, K., Coleman, P., 2004. Use of complementary or alternative medicine in a general population in Great Britain. Results from the National Omnibus survey. J Public Health 26, 152–157. Tindle, H.A., Davis, R.B., Phillips, R.S., Eisenberg, D.M., 2005. Trends in use of complementary and alternative medicine by US adults: 1997-2002. Alternat. Ther. Health Med. 11, 42–49. Tramer, M.R., Moore, R.A., Reynolds, D.J., McQuay, H.J., 2000. Quantitative estimation of rare adverse events which follow a biological progression: a new model applied to chronic NSAID use. Pain 85, 169–182. Williamson, A.T., Fletcher, P.C., Dawson, K.A., 2003. Complementary and alternative medicine. Use in an older population. J. Gerontolo. Nurs. 29, 20–28. Wong, E.L., Lam, J.K., Griffiths, S., Chung, V., Yeoh, E.K., 2010. Chinese medicine: its role and application in the institutionalised older people. J. Clini. Nurs. 19, 1084–1093. Wong, L.K., Jue, P., Lam, A., Yeung, W., Cham-Wah, Y., Birtwhistle, R., 1998. Chinese herbal medicine and acupuncture. How do patients who consult family physicians use these therapies? Can. family 44, 1009–1015. Wong, T.W., Wong, S.L., Donnan, S.P., 1995. Prevalence and determinants of the use of traditional Chinese medicine in Hong Kong. Asia-Paci. J. Public Health 8, 167–170. Wu, Y.J., Hong, C.Y., Lin, S.J., Wu, P., Shiao, M.S., 1998. Increase of vitamin E content in LDL and reduction of atherosclerosis in cholesterol-fed rabbits by a watersoluble antioxidant-rich fraction of Salvia miltiorrhiza. Arterioscler. Jhrombosis Vas. Biol. 18, 481–486. Xie, W., Zhao, Y., Du, L., 2012. Emerging approaches of traditional Chinese medicine formulas for the treatment of hyperlipidemia. J. Ethnopharmacolo 140, 345–367. Xiong, X., Yang, X., Liu, Y., Zhang, Y., Wang, P., Wang, J., 2013. Chinese herbal formulas for treating hypertension in traditional Chinese medicine: perspective of modern science. Hypertens. Res.: off. J. Jap.Soc. Hypertens 36, 570–579. Xu, H., Chen, K.J., 2011. Integrating traditional medicine with biomedicine towards a patient-centered healthcare system. Chin. J. integr. Med. 17, 83–84. Yang, S.H., Yu, C.L., Chen, H.Y., Lin, Y.H., 2013. A commonly used Chinese herbal formula, Shu-Jing-Hwo-Shiee-Tang, potentiates anticoagulant activity of warfarin in a rabbit model. Molecules 18, 11712–11723. Yang, X.B., Yang, X.W., Liu, J.X., 2014. Study on material base of corydalis rhizoma. Zhongguo Zhong yao za zhi 39, 20–27. Yang, Y., Li, H., Zhang, S., Li, Q., Yang, X., Chen, X., Zhao, D., Wang, Y., 2005. TCM treatment for 63 cases of senile dyssomnia. J. Tradit. Chin. Med. 25, 45–49. Yang, Y.H., Chen, P.C., Wang, J.D., Lee, C.H., Lai, J.N., 2009. Prescription pattern of traditional Chinese medicine for climacteric women in Taiwan. Climacteric 12, 541–547. Yi, P.L., Lin, C.P., Tsai, C.H., Lin, J.G., Chang, F.C., 2007a. The involvement of serotonin receptors in suanzaorentang-induced sleep alteration. J. Biomed. Sci. 14, 829–840. Yi, P.L., Tsai, C.H., Chen, Y.C., Chang, F.C., 2007b. Gamma-aminobutyric acid (GABA) receptor mediates suanzaorentang, a traditional Chinese herb remedy, -induced sleep alteration. J. Biomed. Sci. 14, 285–297. Yu, G.R., 1988. [Clinical and experimental study on the effect of Salvia miltiorrhiza on microcirculation and 2,3 diphosphoglyceric acid in patients with coronary heart disease]. Zhong Xi Yi Jie He Za Zhi 8 (596–598), 581. Yuan, R., Lin, Y., 2000. Traditional Chinese medicine: an approach to scientific proof and clinical validation. Pharmacol. Ther. 86, 191–198. Zhang, A.L., Xue, C.C., Lin, V., Story, D.F., 2007. Complementary and alternative medicine use by older Australians. Ann. N. Y. Acad. Sci. 1114, 204–215. Zhang, T.T., Jiang, J.G., 2012. Active ingredients of traditional Chinese medicine in the treatment of diabetes and diabetic complications. Expert Opin. Investigational drugs 21, 1625–1642.