Journal of Ethnopharmacology 171 (2015) 307–316

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Prescription patterns of Chinese herbal products for patients with sleep disorder and major depressive disorder in Taiwan Yi-Lin Chen a, Chien-Ying Lee b,c,1, Kuang-Hua Huang d, Yu-Hsiang Kuan b,c, Ming Chen a,n,1 a

Beijing University of Chinese Medicine, Chaoyang District, Beijing 100029, China Department of Pharmacology, Chung Shan Medical University, Taichung, Taiwan c Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan d Department of Health Service Administration, College of Public Health, China Medical University, Taichung, Taiwan b

art ic l e i nf o

a b s t r a c t

Article history: Received 17 February 2015 Received in revised form 27 May 2015 Accepted 29 May 2015 Available online 9 June 2015

Ethnopharmacological relevance: Chinese herbal products (CHPs) are commonly prescribed for sleep disorder and major depressive disorder (MDD). The aim of this study was to investigate the prescription patterns of CHPs and Western medicine for patients with these disorders in Taiwan, and analyze the frequency of using single herbs (SHs) and herbal formulas (HFs). Materials and methods: In this retrospective population-based study secondary data analysis was performed using data from Taiwan’s Longitudinal Health Insurance Database (LHID) between January 2007 and December 2011. In total, 1000,000 beneficiaries from the LHID were randomly selected from the 2010 registry for beneficiaries of the National Health Insurance Research Database. Patients with sleep disorder and MDD according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes 307.40 and 311, respectively. Results: Among a total of 11,030 patients with sleep disorder, 9619 used Western medicine, 1334 used CHPs, and 77 used both, Among a total of 11,571 patients with MDD, 11,389 used Western medicine, 131 used CHPs, and 51 used both. Regardless of disorder type, women were predominant The majority of the patients were aged 22–44 years, had a monthly income of NT$17,281–NT$22,800, and lived in an area with Level 1 and Level 2 urbanization. Of the patients with sleep disorder, 1411 had used CHPs and visited a clinic 5298 times on average. Of the patients with MDD, 182 had used CHPs and visited a clinic 755 times on average. The three most commonly used SHs and HFs were Ziziphi Spinosae Semen, Polygoni Multiflori Caulis, and Polygalae Radix, and Jia-Wei-Xiao-Yao-San, Suan-Zao-Ren-Tang, and Chai-Hu-ChiaLung-Ku-Mu-Li-Tang, respectively. Conclusion: Chinese herbal products including SHs and HFs are prescribed for patients with sleep disorder and MDD. However, the efficacy and safety of CHPs for sleep disorder and MDD need to be further evaluated. & 2015 Published by Elsevier Ireland Ltd.

Chemical compounds studied in this article: Benzodiazepine (PubChem CID: 134664) Zolpidem (PubChem CID: 5732) Imipramine (PubChem CID: 3696) Clomipramine (PubChem CID: 2801) Doxepin (PubChem CID: 667477) Maprotiline (PubChem CID: 4011) Escitalopram (PubChem CID: 146571) Fluoxetine (PubChem CID: 62857) Paroxetine (PubChem CID: 43815) Sertraline (PubChem CID: 68617) Keywords: Sleep disorder Major depressive disorder (MDD) Chinese herbal product (CHP) Ziziphi spinosae semen Jia-Wei-Xiao-Yao-San National Health Insurance Research Database (NHIRD)

1. Introduction Insomnia is the most common sleep complaint. Approximately 9–15% of the general population worldwide experience insomnia symptoms, which affect the body’s daytime physiological functioning (Ohayon, 2002). Epidemiologic studies have suggested that the link

Abbreviations list: CHP, Chinese herbal product; MDD, major depressive disorder; SHs, single herbs; HFs, herbal formulas; LHID, Longitudinal Health Insurance Database; CAMs, complementary and alternative medicines; TCM, traditional Chinese medicine; NHIRD, National Health Insurance Research Database; BFM, bupleurum falcatum; GMDZ-Tang, Gan-Mai-Da-Zao-Tang n Corresponding author. Tel.: þ 86 10 64287073; fax: þ86 139 10729606. E-mail address: [email protected] (M. Chen). 1 Ming Chen and Chien-Ying Lee contributed equally to this study. http://dx.doi.org/10.1016/j.jep.2015.05.045 0378-8741/& 2015 Published by Elsevier Ireland Ltd.

between insomnia and depression is bidirectional. For example, approximately 20% of patients with insomnia exhibit depressive symptoms (Soldatos, 1994), whereas depression and depressive symptoms have been shown to be the largest and most consistent risk factors for insomnia (Ohayon et al., 1998). During the last decade, several studies have indicated that insomnia could be more than a depressive symptom and negatively affects depression. These findings are consistent with those of another study, which determined that insomnia is a risk factor for major depressive disorder (MDD) onset (Manber et al., 2008). Western medicine used to treat insomnia and depression may have adverse drug effects; for example, benzodiazepines may increase the risk of falling in elderly people (McCurry et al., 2007). Zolpidem, a nonbenzodiazepine hypnotic, is widely prescribed in clinical practice to treat insomnia; however, studies have reported

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adverse effects such as psychotic reactions (Markowitz and Brewerton, 1996) and sleepwalking (Hoque and Chesson, 2009). Tricyclic antidepressants used to treat MDD can cause cardiac toxicity (Emamhadi et al., 2012) and selective serotonin reuptake inhibitors are associated with sexual dysfunction (Montejo et al., 2001). Because some patients have difficulty tolerating the side effects of Western medications, do not respond adequately, or eventually exhibit a reduced response, they search for complementary and alternative medicines (CAMs) that have fewer side effects (Knaudt et al., 1999; Brown and Gerbarg, 2001). Chinese herbal medicine is one of the most commonly used modalities of complementary and alternative medicine therapies, especially in Chinese culture (Hsu et al., 2008). Recent studies suggest that herbal medicines show promise in managing mild to moderate depression (Dwyer et al., 2011) and isolated plant constituents, such as jujuboside, may prove to be a valuable source of lead compounds for the development of novel hypnotics (Cao et al., 2010). The current study suggests that factors can influence the use and cost of traditional Chinese medicine (TCM) services for patients with depression. Utilizing TCM services could substantially affect the use of psychiatric services and the healthcare costs for patients with depression (Pan et al., 2013). Currently, no correlation studies have explored the Chinese herbal products (CHPs) prescribed for patients with insomnia and MDD in the Taiwan Health Insurance Research Database. Thus, the aim of this study was to investigate the prescription patterns of CHPs and Western medicine for patients with sleep disorder and MDD in Taiwan. In addition, the frequency of SH and HF use was analyzed.

In this retrospective population-based study, secondary data analysis was performed using data from the Longitudinal Health Insurance Database (LHID) between January 2007 and December 2011. In total, 1000,000 beneficiaries from the LHID were randomly selected from the approximately 27.38 million people recorded in the 2010 registry for beneficiaries of the NHIRD. There was no significant difference in the sex distribution (χ2 ¼0.067, df¼ 1, p¼0.796) among patients. Patients with sleep disorder and MDD were identified according to International Classification of Diseases, Ninth Revision, Clinical Modification codes 307.40 and 311, respectively.

2. Materials and methods

Table 1 Distribution of usage of Western medicine and CHP in patients with sleep disorder and MDD patients.

2.1. Data sources and extraction In this retrospective study, SAS software Version 9.3 (SAS Institute, Cary, NC, USA) was used for secondary database analysis. Data were obtained from the NHIRD, which includes data such as detailed clinical records from patient visits, primary and secondary diagnostic codes, and prescription orders, for all beneficiaries in the Taiwan Health Insurance program.

2.2. Statistical analysis The patients in this study had visited clinics between 2007 and 2011 to seek medical treatment for sleep disorder or MDD. We divided patients into three groups: those who used only Western medicine, those who used only CHP, and those who used both Western medicine and CHP. Data analysis was performed (Fig. 1) using data from the LHID between January 2007 and December 2011. The sex, age, salary, insurance coverage, urbanization level of area of residence and other basic characteristics of the patients in the three groups were analyzed. The health insurance of salary grade group was assessed according to an announcement by the Ministry of Health and Welfare. We adopted the urbanization rate of insured zone studied by Liu (Liu, 2006), and ranging from Level 1 (highly urban) to Level 7 (highly rural), as standards with which to assess urbanization. In this study, we analyzed the basic

Total clinic patients CHP Western medicine Western medicine and CHP

Sleep disorder

MDD

11,030 1,334 9,619 77

11,571 131 11,389 51

MDD: Major depressive disorder; CHP: Chinese herbal products.

From 2007 to 2011, diagnoses of sleep disorder or depression numbered 946,538

From 2007 to 2011, 21,442 patients were diagnosed with sleep disorder or depression

Among 11,030 patients with sleep disorder, I. 9,619 used Western medicine II. 1,334 used CHPs III. 77 used both

Among 11,571 patients with MDD, I.

11,389 used Western medicine

II. 131 used CHPs III. 51 used both

Fig. 1. Flowchart showing the recruitment of patients from the 1 million people randomly sampled from the National Health Insurance Research Database (NHIRD) from 2007 to 2010 in Taiwan.

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309

3. Results

characteristics of clinic patients with sleep disorders and MDD, as well as the top 10 most commonly prescribed single herbs (SHs) and herbal formulas (HFs). In addition, also analyzed clinic patients with sleep disorder combined with MDD and top 3 commonly prescribed SHs and HFs.

In this study, among the 1000,000 beneficiaries from the LHID, A total of 11,030 patients had sleep disorder, of whom 9619 used Western medicine, 1334 used CHP, and 77 used both. A total of

Table 2 Basic characteristics of usage of CHP and Western medicine in clinic patients with sleep disorder in Taiwan. CHP

Total Gender

Age (year)

Female Male Missing 0–18 19–24 25–44 45–64 65þ Missing Average age (MEAN, SD)

Monthly income (NTD)

Urbanization

0–17280 17,281–22,800 22,801–28,800 28,801–36,300 36,301þ Missing Level 1 Level 2 Level 3 Level 4 Level 5 Level 6 Level 7 Missing

Western medicine and CHP

Western medicine

Total

N

%

N

%

N

%

N

%

1334 969 364 1 43 87 563 516 125 1 43.80 300 221 322 104 107 280 1 487 450 175 163 9 27 23 1

12.09 72.9 27.31 – 3.22 6.52 42.20 38.68 9.37 – 15.44 22.49 16.57 24.14 7.80 8.02 20.99 – 36.51 33.73 13.12 12.22 0.67 2.02 1.72 –

77 51 25 1 0 2 26 30 19 1 50.60 16 15 24 4 3 15 1 21 30 8 13 0 3 1 1

0.70 67.11 32.89 – 0.00 2.60 33.77 38.96 24.68 – 15.99 20.78 19.48 31.17 5.19 3.90 19.48 – 27.63 39.47 10.53 17.11 0.00 3.95 1.32 –

9619 5923 3673 23 165 281 2865 3948 2360 23 51.83 2524 2127 2529 627 572 1240 23 3354 2969 1358 1198 177 266 288 23

87.21 61.72 38.28 – 1.72 2.92 29.78 41.04 24.53 – 17.13 26.24 22.11 26.29 6.52 5.95 12.89 – 34.90 30.89 14.13 12.47 1.84 2.77 3.00 –

11030 6943 4062 25 208 370 3454 4494 2504 25 50.85 2840 2363 2875 735 682 1535 25 3862 3449 1541 1374 186 296 312 25

100.00 63.09 36.91 – 1.89 3.35 31.31 40.74 22.70 – 17.13 25.75 21.42 26.07 6.66 6.18 13.92 – 35.05 31.30 13.98 12.47 1.69 2.69 2.83 –

CHP: Chinese herbal products. Table 3 Basic characteristics of usage of CHP and Western medicine in clinic patients with MDD in Taiwan. CHP

Total Gender

Age (year)

Female Male Missing 0–18 19–24 25–44 45–64 65 þ Missing Average age (MEAN, SD)

Monthly income (NTD)

Urbanization

0–17,280 17281–22800 22,801–28,800 28,801–36,300 36,301þ Missing Level 1 Level 2 Level 3 Level 4 Level 5 Level 6 Level 7 Missing

Western medicine and CHP

Western medicine

Total

N

%

N

%

N

%

N

%

131 97 34 0 2 7 63 43 16 0 45.35 24 35 38 4 9 21 0 39 45 15 23 1 7 1 0

1.13 74.05 25.95 – 1.53 5.34 48.09 32.82 12.21 – 13.97 18.32 26.72 29.01 3.05 6.87 16.03 – 29.77 34.35 11.45 17.56 0.76 5.34 0.76 –

51 41 10 0 0 2 21 23 5 0 46.55 13 12 10 3 5 8 0 18 15 11 6 1 0 0 0

0.44 80.39 19.61 – 0.00 3.92 41.18 45.10 9.80 – 14.94 25.49 23.53 19.61 5.88 9.80 15.69 – 35.29 29.41 21.57 11.76 1.96 0.00 0.00 –

11389 7122 4201 66 398 670 3927 3906 2488 66 48.69 3051 2961 2929 636 630 1182 66 3523 3744 1741 1366 195 405 395 66

98.43 62.90 37.10 – 3.49 5.88 34.48 34.30 21.85 – 18.34 26.79 26.00 25.72 5.58 5.53 10.38 – 30.99 32.93 15.31 12.02 1.72 3.56 3.47 –

11571 7260 4245 66 400 679 4011 3972 2509 66 48.65 3088 3008 2977 643 644 1211 66 3580 3804 1767 1395 197 412 396 66

100.00 63.10 36.90 – 3.46 5.87 34.66 34.33 21.68 – 18.29 26.69 26.00 25.73 5.56 5.57 10.47 – 30.99 32.93 15.30 12.08 1.71 3.57 3.43 –

CHP: Chinese herbal products; MDD: Major depressive disorder.

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Table 4 Top 10 of single herbs and herbal formulas for patients with sleep disorder in Taiwan during 2007–2011. No. SHs

%

HFs

Number of herbs

Contain drug

%

10

AngelicaeSinensisRadix (Dang-Gui), Angelica sinensis (Oliv.) Diels PaeoniaeRadixAlba (Bai-Shao), Paeonia lactiflora Pall. BupleuriRadix (Chai-Hu), Bupleurum abchasicum Manden. SclerotiumPoriaeCocos (Fu-Ling), Poria cocos (Schw.) Wolf. AtractylodisMacrocephalaeRhizoma (Bai-Zhu), Atractylodes macrocephala Koidz. GlycyrrhizaeRadix (Gan-Cao), Glycyrrhiza uralensis Fisch. MoutanCortex (Mu-Dan-Pi), Moutan officinalis (L.) Lindl. & Paxton. ZingiberisRhizomaTostum (Wei-Jiang), Zingiber officinale Roscoe. MenthaeHerba (Bo-He), Mentha haplocalyx Briq. GardeniaeFructus (Zhi-Zi), Gardenia jasminoides J.Ellis ZizyphiSpinosae Semen (Suan-Zao-Ren), Ziziphus jujuba Mill. SclerotiumPoriaeCocos (Fu-Ling), Poria cocos (Schw.) Wolf. RhizomaAnemarrhenae (Zhi-Mu), Anemarrhena asphodeloides Bge. Radix LigusticiWallichii (Chuan-Xiong), Laserpitium striatum Wall. Glycyrrhizae Radix (Gan- Cao), Glycyrrhiza uralensis Fisch. BupleuriRadix (Chai-Hu), Bupleurum abchasicum Manden. ZingiberisRhizomaRecens (Sheng-Jiang), Zingiber officinale Roscoe Scutellariae Radix (Huang-Qin), Scutellaria baicalensis Georgi. JujubaeFructus (Da-Zao), Ziziphus jujuba Mill. SclerotiumPoriaeCocos (Fu-Ling), Poria cocos (Schw.) Wolf. GinsengRadix (Ren-Shen), Talinum paniculatum (Jacq.) Gaertn. RheiRadixetRhizoma (Da-Huang) Rheum palmatum L. RhizomaPinelliaePreparata (Zhi-Ban-Xia), Pinellia ternata (Thunb.) Makino. OstreaeTesta (Mu-Li (Duan)), Ostrea gigas Thunb. RamulusCinnamomi (Gui-Zhi), Cinnamomum cassia Presl. OsDraconis (FossiliaOssiaMastodi) (long gu) Fossilia Ossia Mastodi RhizomaPinelliaePreparata (Zhi-Ban-Xia), Pinellia ternata (Thunb.) Makino. Caulis Bambusae In Taeniis (Zhu-Ru), Bambusa tuldoides Munro. FructusAurantiiImmaturus (Zhi Shi), Citrus aurantium L. PericarpiumCitriReticulatae (Chen-Pi), Citrus reticulata Blanco. SclerotiumPoriaeCocos (Fu-Ling), Poria cocos (Schw.) Wolf. Glycyrrhizae Radix (Gan-Cao), Glycyrrhiza uralensis Fisch. ZingiberisRhizomaRecens (Sheng-Jiang), Zingiber officinale Roscoe. JujubaeFructus (Da-Zao) Ziziphus jujuba Mill. RehmanniaeRadix (Sheng-Di-Huang), Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & C.A. Mey. AngelicaeSinensisRadix (Dang-Gui), Angelica sinensis (Oliv.) Diels ZiziphiSpinosiSemen (Suan-Zao-Ren), Ziziphus jujuba Mill.

12.63

1

ZiziphiSpinosae Semen (Suan-Zao-Ren) Ziziphus jujuba Mill.

4.69 Jia-Wei-Xiao-YaoSan

2

Polygalae Radix (Yuan-Zhi) Polygala tenuifolia Willd.

3.44 Suan-Zao-Ren-Tang

5

3

PolygoniMultiflori Caulis (Ye-Jiao-Teng) Polygonum multiflorum Thunb.

3.21 Chai-Hu-Chia-LungKu-Mu-LiI-Tang

11

4

Scutellariae Radix (Huang-Qin) Scutellaria baicalensis Georgi.

3.09 Wen-Dan-Tang

5

SalviaeMiltiorrhizae Radix (Dan-Shen) Salvia miltiorrhiza 2.28 Tian-Wang-Bu-Shin- 13 Bunge. Dan

8

9.21

5.42

4.91

4.81

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311

Table 4 (continued ) No. SHs

%

HFs

Number of herbs

6

Rehmanniae Radix (Sheng-Di-Huang) Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & C.A. Mey.

2.14 Gan-Mai-Da-ZaoTang

7

CoptidisRhizoma (Huang-Lian) Pistacia chinensis Bunge.

1.99 Gui-Pi-Tang

10

8

Platycladi Semen (Bai-Zi-Ren) Platycladus orientalis (L.) Franco.

1.71 Gan-Lu-Yin

10

9

Corydalis Rhizoma

1.65 Zhi-Gan-Cao-Tang

(Yan-Hu-Suo) Corydalis gyrophylla Lidén.

3

9

Contain drug

Ophiopogonis Radix (Mai-Men-Dong), Ophiopogon japonicus (Thunb.) Ker Gawl. PolygalaeRadix (Yuan-Zhi), Polygala tenuifolia Willd. AsparagiRadix (Tian-Men-Dong), Asparagus cochinchinensis (Lour.) Merr. PlatycladiSemen (Bai-Zi-Ren), Platycladus orientalis (L.) Franco. SchisandraeFructus (Wu-Wei-Zi), Schisandra chinensis (Turcz.) Baill. SclerotiumPoriaeCocos (Fu-Ling), Poria cocos (Schw.) Wolf. PlatycodonisRadix (Jie-Geng), Platycodon grandiflorus (Jacq.) A. DC. GinsengRadix (Ren-Shen), Talinum paniculatum (Jacq.) Gaertn. SalviaeMiltiorrhizaeRadix (Dan-Shen), Salvia miltiorrhiza Bunge. ScrophulariaeRadix (Xuan-Shen), Scrophularia ningpoensis Hemsl. Glycyrrhizae Radix (Gan-Cao), Glycyrrhiza uralensis Fisch. Semen Tritici Levis (Xiao-Mai), Triticum aestivum L. FructusJujubae (Da Zao), Ziziphus jujuba Mill. Panax ginseng (Ren-Shen), Talinum paniculatum (Jacq.) Gaertn. Astragalusmembranaceous (Huang-Qi), Astragalus stalinskyi Sirj. Atractylodesmacrocephala (Bai-Zhu), Atractylodes macrocephala Koidz. SclerotiumPoriaeCocos (Fu-Ling), Poria cocos (Schw.) Wolf. Ziziphusspinosa (Suan Zao Ren), Ziziphus jujuba Mill. Longan (Long-Yan-Rou), Dimocarpus longan Lour. Auklandia (Mu-Xiang), Dolomiaea berardioidea (Franch.) C.Shih. Glycyrrhizauralensis (Zhi-Gan-Cao), Glycyrrhiza uralensis Fisch. Angelica sinensis (Dang -Gui), Angelica sinensis (Oliv.) Diels Polygala (Yuan-Zhi), Polygala tenuifolia Willd. RehmanniaeRadixPraeparata (Shu-Di-Huang), Rehmannia glutinosa Libosch. RehmanniaeRadix (Sheng-Di-Huang), Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & C.A. Mey. ArtemisiaeScopariaeHerba (Yin-Chen), Artemisia scoparia Waldst. & Kitam. Scutellariae Radix (Huang-Qin), Scutellaria baicalensis Georgi. AurantiiFructus (Zhi-Ke), Citrus  aurantium L. EriobotryaeFolium (Pi-Pa-Ye), Eriobotrya japonica (Thunb.) Lindl. DendrobiiHerba (Shi-Hu), Dendrobium officinale Kimura & Migo. GlycyrrhizaeRadixC (Gan-Cao), Glycyrrhiza uralensis Fisch. AsparagiRadix (Tian-Men-Dong), Asparagus cochinchinensis (Lour.) Merr. OphiopogonisRadixD (Mai-Men-Dong) Ophiopogon japonicus (Thunb.) Ker Gawl. RehmanniaeRadix (Sheng-Di-Huang), Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & C.A. Mey. OphiopogonisRadixD (Mai-Men-Dong), Ophiopogon japonicus (Thunb.) Ker Gawl. GinsengRadix (Ren-Shen), Talinum paniculatum (Jacq.) Gaertn. GlycyrrhizaeRadixcumLiquidoFricta (Zhi-Gan-Cao), Glycyrrhiza uralensis Fisch. CinnamomiRamulus (Gui-Zhi),

%

3.81

2.70

2.38

1.49

312

Y.-L. Chen et al. / Journal of Ethnopharmacology 171 (2015) 307–316

Table 4 (continued ) No. SHs

10

Rhei Radix et Rhizoma (Da-Huang) Rheum palmatum L.

%

HFs

Number of herbs

1.60 Ma-Tzu-Ren-Wan

11,571 patients had MDD, of whom 11,389 used Western medicine, 131 used CHP, and 51 used both (Table 1). Tables 2 and 3 show the basic characteristics of CHP and Western medicine use in patients with sleep disorder and MDD in Taiwan, respectively. Regardless of disorder type, women were predominant. The majority of the patients were aged 22–44 years, had a monthly income of NT$17,281–NT$22,800, and lived in an area with Level 1 and Level 2 urbanization. Of the patients with sleep disorder, 1411 had used CHPs and visited a clinic 5298 times on average. Of the patients with MDD, 182 had used CHPs and visited a clinic 755 times on average. Table 4 shows the top 10 SHs and HFs prescribed for patients with sleep disorder in Taiwan from 2007 to 2011. The three most commonly prescribed SHs were Ziziphi Spinosae Semen, Polygalae Radix, and Polygoni Multiflori Caulis. The three most commonly prescribed HFs were Jia-Wei-Xiao-Yao-San, Suan-Zao-Ren-Tang, and Chai-Hu-Chia-Lung-Ku-Mu-Li-Tang. Table 5 shows the top 10 SHs and HFs prescribed for patients with MDD in Taiwan during 2007 to 2011. The three most commonly prescribed SHs were Polygoni Multiflori Caulis, Cortex Albiziae, and Ziziphi Spinosae Semen. The three most commonly prescribed HFs were Gan-Mai-Da-Zao (GMDZ)-Tang, Jia-Wei-XiaoYao-San, and Chai-Hu-Chia-Lung-Ku-Mu-Li-Tang. Table 6 shows for clinic patients with sleep disorder combined with MDD, The top 3 commonly prescribed SHs were Ziziphi Spinosae Semen, Polygoni Multiflori Caulis, and Polygalae Radix. The top 3 commonly prescribed HFs were Jia-Wei-Xiao-Yao-San, Suan-Zao-Ren-Tang, and Chai-Hu-Chia-Lung-Ku-Mu-Li-Tang.

4. Discussion In Taiwan, the total direct medical costs for adult depression increased continually from 2000 to 2002 (Chan et al., 2006). The use prevalence of three types of psychotropic drugs (antidepressants, mood stabilizers, and anxiolytic–hypnotic drugs) increased sharply from 1997 to 2004 (Chien et al., 2007). A prevalence study revealed that approximately 30–40% of adults reported experiencing short-term insomnia, and as many as 10–15% experienced chronic insomnia (Roth, 2001). Insomnia is a risk factor for the onset of severe depression; one study demonstrated that MDD at baseline was the strongest predictor of developing insomnia

6

Contain drug

Cinnamomum cassia Presl. ZingiberisRhizomaRecens (Sheng-Jiang), Zingiber officinale Roscoe. AsiniCoriiColla (A-Jiao), Equus asinus L. JujubaeFructus (Da-Zao), Ziziphus jujuba Mill. CannabisFructus (Ma-Zi-Ren), Cannabis sativa L. CannabisFructus (Ma-Zi-Ren), Cannabis sativa L. PaeoniaeRadixAlba (Bai-Shao), Paeonia lactiflora Pall. AurantiiFructusImmaturus (Zhi-Shi), Citrus aurantium L. RheiRadixetRhizoma (Da-Huang), Rheum palmatum L. MagnoliaeOfficinalis Cortex (Hou-Po), Magnolia officinalis Rehder & E.H.Wilson. ArmeniacaeSemen (Xing-Ren), Prunus armeniaca L.

%

1.49

(Ohayon, 2009). Therefore, effective management of insomnia and depression is an important public health concern. The predominance of women in our study was similar to that in another study, which determined that for adults, prevalence of insomnia was estimated to be 17.3–22.3% in men and 20.5–21.5% in women (Doi, 2009). In addition, we observed that insomnia and depression prevalence was higher among patients aged 25–44 years, possibly because these patients experience more psychosocial stress from work. In the current economic environment, stress is constant for many people. Our results suggested that patients who lived in areas with Level 1 and Level 2 urbanization (cities) may experience more stress, and thus have a high prevalence of insomnia and depression. The top two SHs prescribed for sleep disorder during 2007 and 2011 was Ziziphi Spinosae Semen and Polygalae Radix. Ziziphi Spinosae Semen has been used widely in clinics to treat insomnia, anxiety and night sweats. Recent pharmacological studies have shown that Ziziphi Spinosae Semen has multiple active constituents and exerts a number of pharmacological effects including antihyperlipidemia, immunopotentiation, and anxiolytic effects. Fufang Suanzaoren decoction, a TCM preparation, has been used widely for treating insomnia in clinical practice (Fang et al., 2010). One study, in normal rats, has found that the hypnotic effect of jujuboside, one of the active constituents isolated from Ziziphi Spinosae Semen may be influenced by circadian rhythms, and the serotonergic system may enhance the hypnotic effect. In addition, jujuboside may serve as a valuable lead compound for the development of novel hypnotics (Cao et al., 2010). Polygalae Radix is mainly used for treating insomnia, depression, palpitations caused by anxiety, restlessness, and disorientation, as well as to prevent dementia and memory failure. Recent pharmacological studies in animals have demonstrated that constituents of Polygalae Radix can improve cognition and potentially exert antipsychotic, antioxidant, and antiinflammatory effects. (Ling et al., 2013). In the present study, the top two SHs prescribed for MDD in Taiwan from 2007 to 2011 were Polygoni Multiflori Caulis and Polygala Tenuifolia. The sedative-hypnotic effect of a Polygoni Multiflori Caulis decoction has been observed in an animal model (Yang et al., 1990). Polygala Tenuifolia was used to calm the mind, disperse negative energy and alleviate emotional upset, depression, and insomnia (Wing, 2001). A preclinical study in mice has provided evidence that an extract from Polygalae Radix exerts

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313

Table 5 Top 10 of single herbs and herbal formulas for patients with MDD in Taiwan during 2007–2011. No. SHs

%

HFs

7.42 Gan-Mai-Da-Zao-Tang

Number of Contain drug herbs

1

PolygoniMultiflori Caulis (Ye-Jiao-Teng) Polygonum multiflorum Thunb.

3

2

Cortex Albiziae (He-Huan-Pi) Albizia julibrissin 5.01 Jia-Wei-Xiao-Yao-San sensu Baker.

10

3

ZiziphiSpinosae Semen (Suan-Zao-Ren) Ziziphus jujuba Mill.

4.68 Chai-Hu-Chia-LungKu-Mu-Li-Tang

11

4

Curcumae Radix (Yu-Jin) Curcuma aromatica Salisb.

4.60 Tian-Wang-Bu-ShinDan

13

Gl ycyrrhizae Radix (Gan-Cao), Glycyrrhiza uralensis Fisch. Semen Tritici Levis (Xiao-Mai), Triticum aestivum L. FructusJujubae (Da Zao), Ziziphus jujuba Mill. AngelicaeSinensisRadix (Dang-Gui), Angelica sinensis (Oliv.) Diels PaeoniaeRadixAlba (Bai-Shao), Paeonia lactiflora Pall. BupleuriRadix (Chai-Hu), Bupleurum abchasicum Manden. SclerotiumPoriaeCocos (Fu-Ling), Poria cocos (Schw.) Wolf. AtractylodisMacrocephalaeRhizoma (Bai-Zhu), Atractylodes macrocephala Koidz. GlycyrrhizaeRadix (Gan-Cao), Glycyrrhiza uralensis Fisch. MoutanCortex (Mu-Dan-Pi), Moutan officinalis (L.) Lindl. & Paxton. ZingiberisRhizomaTostum (Wei-Jiang), Zingiber officinale Roscoe. MenthaeHerba (Bo-He), Mentha haplocalyx Briq. GardeniaeFructus (Zhi-Zi), Gardenia jasminoides J.Ellis BupleuriRadix (Chai-Hu), Bupleurum abchasicum Manden. ZingiberisRhizomaRecens (Sheng-Jiang), Zingiber officinale Roscoe Scutellariae Radix (Huang-Qin), Scutellaria baicalensis Georgi. JujubaeFructus (Da-Zao), Ziziphus jujuba Mill. SclerotiumPoriaeCocos (Fu-Ling), Poria cocos (Schw.) Wolf. GinsengRadix (Ren-Shen), Talinum paniculatum (Jacq.) Gaertn. RheiRadixetRhizoma (Da-Huang) Rheum palmatum L. RhizomaPinelliaePreparata (Zhi-Ban-Xia), Pinellia ternata (Thunb.) Makino. OstreaeTesta (Mu-Li (Duan)), Ostrea gigas Thunb. RamulusCinnamomi (Gui-Zhi), Cinnamomum cassia Presl. OsDraconis (FossiliaOssiaMastodi) (long gu) Fossilia Ossia Mastodi RehmanniaeRadix (Sheng-Di-Huang), Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & C.A. Mey. AngelicaeSinensisRadix (Dang-Gui), Angelica sinensis (Oliv.) Diels ZiziphiSpinosiSemen (Suan-Zao-Ren), Ziziphus jujuba Mill. Ophiopogonis Radix (Mai-Men-Dong), Ophiopogon japonicus (Thunb.) Ker Gawl. PolygalaeRadix (Yuan-Zhi), Polygala tenuifolia Willd. AsparagiRadix (Tian-Men-Dong), Asparagus cochinchinensis (Lour.) Merr. PlatycladiSemen (Bai-Zi-Ren), Platycladus orientalis (L.) Franco. SchisandraeFructus (Wu-Wei-Zi), Schisandra chinensis (Turcz.) Baill. SclerotiumPoriaeCocos (Fu-Ling), Poria cocos (Schw.) Wolf. PlatycodonisRadix (Jie-Geng), Platycodon grandiflorus (Jacq.) A. DC. GinsengRadix (Ren-Shen), Talinum paniculatum (Jacq.) Gaertn. SalviaeMiltiorrhizaeRadix (Dan-Shen), Salvia miltiorrhiza Bunge. ScrophulariaeRadix (Xuan-Shen), Scrophularia ningpoensis Hemsl.

%

11.71

11.12

7.68

6.93

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Table 5 (continued ) No. SHs

%

HFs

Number of Contain drug herbs

5

AcoriGramineiRhizoma (Sh-Chang-Pu) Acorus gramineus Aiton.

4.06 Wen-Dan-Tang

8

6

Polygalae Radix (Yuan-Zhi) Polygala tenuifolia Willd.

3.94 Suan-Zao-Ren-Tang

5

7

CyperiRhizoma (Xiang-Fu) Cyperus rotundus L. 2.49 Ban-Xia-Hou-Po-Tang

8

OstreaeTesta (Mu-Li (Duan)) Ostrea gigas Thunb.

2.07 Xin-Yi-Qing-Fei-Tang

10

9

SalviaeMiltiorrhizae Radix (Dan-Shen) Salvia miltiorrhiza Bunge.

1.95 Zhu-Ru-Wen-DanTang

13

5

RhizomaPinelliaePreparata (Zhi-Ban-Xia), Pinellia ternata (Thunb.) Makino. Caulis Bambusae In Taeniis (Zhu-Ru), Bambusa tuldoides Munro. FructusAurantiiImmaturus (Zhi Shi), Citrus aurantium L. PericarpiumCitriReticulatae (Chen-Pi), Citrus reticulata Blanco. SclerotiumPoriaeCocos (Fu-Ling), Poria cocos (Schw.) Wolf. Glycyrrhizae Radix (Gan-Cao), Glycyrrhiza uralensis Fisch. ZingiberisRhizomaRecens (Sheng-Jiang), Zingiber officinale Roscoe. JujubaeFructus (Da-Zao) Ziziphus jujuba Mill. ZizyphiSpinosae Semen (Suan-Zao-Ren), Ziziphus jujuba Mill. SclerotiumPoriaeCocos (Fu-Ling), Poria cocos (Schw.) Wolf. RhizomaAnemarrhenae (Zhi-Mu), Anemarrhena asphodeloides Bge. Radix LigusticiWallichii (Chuan-Xiong), Laserpitium striatum Wall. Glycyrrhizae Radix (Gan-Cao), Glycyrrhiza uralensis Fisch. RhizomaPinelliaeTernatae (Ban-Xia), Pinellia ternata (Thunb.) Makino. Cortex MagnoliaeOfficinalis (Hou-Po), Magnolia officinalis Rehder & E.H.Wilson. SclerotiumPoriaeCocos (Fu-Ling), Poria cocos (Schw.) Wolf. RhizomaZingiberisRecens (Sheng-Jiang), Zingiber officinale Roscoe. Folium PerillaeFrutescentis (Zi-Su-Ye), Perilla frutescens (L.) Britton. Scutellariae Radix (Huang-Qin), Scutellaria baicalensis Georgi FructusGardeniae (Zhi-Zi), Gardenia jasminoides J.Ellis Ophiopogonis Radix (Mai-Men-Dong), Ophiopogon japonicus (Thunb.) Ker Gawl. BulbusLilii (Bai-He), Smilacina racemosa (L.) Desf. Gypsum Fibrosum (Shi-Gao), Gypsum Fibrosum. RhizomaAnemarrhenae (Zhi-Mu), Anemarrhena asphodeloides Bunge. Folium Eriobotryae (Pi-Pa-Ye), Eriobotrya japonica (Thunb.) Lindl. Glycyrrhizae Radix (Gan-Cao), Glycyrrhiza uralensis Fisch. RhizomaCimicifugae (Sheng-Ma), Actaea asiatica H.Hara FlosMagnoliae (Xin-Yi-Hua), Magnolia liliflora var. taliensis (W.W. Sm.) Pamp. BupleuriRadix (Chai-Hu), Bupleurum abchasicum Manden. GinsengRadix (Ren-Shen), Talinum paniculatum (Jacq.) Gaertn. Ophiopogonis Radix (Mai-Men-Dong), Ophiopogon japonicus (Thunb.) Ker Gawl. RhizomaCoptidis (Huang-Lian), Pistacia chinensis Bunge. Cyperus Rhizome (Xiang-Fu), Cyperus rotundus L RhizomaPinelliaePreparata (Zhi-Ban-Xia) Pinellia ternata (Thunb.) Makino. Caulis Bambusae In Taeniis (Zhu-Ru), Bambusa tuldoides Munro. FructusAurantiiImmaturus (Zhi Shi), Citrus aurantium L. PericarpiumCitriReticulatae (Chen-Pi), Citrus reticulata Blanco. SclerotiumPoriaeCocos (Fu-Ling),

%

3.55

3.17

2.15

1.93

1.61

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315

Table 5 (continued ) No. SHs

10

%

Platycladi Semen (Bai-Zi-Ren) Platycladus orientalis (L.) Franco.

HFs

1.78 Qing-Zao-Jiao-Fei-Tang

Number of Contain drug herbs

9

%

Poria cocos (Schw.) Wolf. Glycyrrhizae Radix (Gan-Cao), Glycyrrhiza uralensis Fisch. ZingiberisRhizomaRecens (Sheng-Jiang), Zingiber officinale Roscoe. JujubaeFructus (Da-Zao), Ziziphus jujuba Mill. Folium Mori Albae (Sang-Ye), Morus alba L. GinsengRadix (Ren-Shen), Talinum paniculatum (Jacq.) Gaertn. Ophiopogonis Radix (Mai-Men-Dong), Ophiopogon japonicus (Thunb.) Ker Gawl. AsiniCoriiColla (A-Jiao), Equus asinus L. Folium Eriobotryae (Pi-Pa-Ye), Eriobotrya japonica (Thunb.) Lindl. Gypsum Fibrosum (Shi-Gao), Gypsum Fibrosum. Glycyrrhizae Radix (Gan-Cao), Glycyrrhiza uralensis Fisch. Black Semen Sesame Indici (Hei-Zhi-Ma), Linum usitatissimum L. Semen PruniArmeniacae (Xing-Ren), Prunus armeniaca L.

1.61

MDD: Major depressive disorder. Table 6 Top 3 SHs and HFs for patients with sleep disorder combined with MDD in Taiwan during 2007–2011. No.

1 2 3

Sleep disorder combined with MDD SHs

%

HFs

%

ZiziphiSpinosae Semen (Suan-Zao-Ren) Ziziphus jujuba Mill. PolygoniMultiflori Caulis (Ye-Jiao-Teng) Polygonum multiflorum Thunb. Polygalae Radix Polygalae Radix(Yuan-Zhi) Polygala tenuifolia Willd.

4.69 3.69 3.49

Jia Wei Xiao Yao San Suan Zao Ren Tang Chai Hu Chia Lung Ku Mu LiI Tang

12.41 8.36 5.74

rapid-onset antidepressant effects by modulating glutamatergic synapses in critical brain circuits involved in depression and warrants further evaluation as a potentially safe antidepressant drug (Shin et al., 2014). The top three HFs for sleep disorder prescribed during 2007 to 2011 were Jia-Wei-Xiao-Yao-San, Suan-Zao-Ren-Tang, and ChaiHu-Chia-Lung-Ku-Mu-Li-Tang. This result is similar to that in another study, which indicated that Suan-Zao-Ren-Tang was the most commonly prescribed HF for patients with insomnia, followed by Jia-Wei-Xiao-Yao-San; other frequently prescribed HFs were Tian-Wang-Bu-Shin-Dan, GMDZ-Tang, and Chai-Hu-ChiaLung-Ku-Mu-Li-Tang. These HFs have a long history of use in Taiwan and are frequently prescribed by TCM practitioners to alleviate sleep disturbances (Chen et al., 2011). Another clinical trial demonstrated that the two most commonly prescribed CHPs for patients with insomnia were Jia-Wei-Xiao-Yao-San and SuanZao-Ren-Tang, both effectively improving sleep quality (Wu et al., 2011; Yeh et al., 2011). A systematic review on the efficacy, safety and types of Chinese herbal medicine for depression has concluded that CHM including Chai-Hu-Chia-Lung-Ku-Mu-Li-Tang and Jia-Wei-Xiao-Yao-San was more effective than placebo and as effective as antidepressants in the treatment of depression (Yeung et al., 2014). Our study showed that the top three HFs prescribed for MDD in Taiwan from 2007 to 2011 were GMDZ-Tang, Jia-Wei-Xiao-YaoSan, and Chai-Hu-Chia-Lung-Ku-Mu-Li-Tang. GMDZ-Tang has been shown to inhibit the hyperexcitability of neuronal membranes and may have sedative effects (Chen et al., 2011). GMDZ-Tang can reduce stress by affecting the various taches of the hypothalamus– pituitary–adrenal gland axle and altering stress behaviors (Tong et al., 2005).

The most commonly prescribed HFs for patients with sleep disorder and MDD were Jia-Wei-Xiao-Yao-San and Chai-Hu-ChiaLung-Ku-Mu-Li-Tang. These two HFs share the ingredient Bupleurum falcatum (BFM), which is used widely in TCM. Regarding using BFM to treat depression, some researchers have reported that a few decoctions in which BFM is a major ingredient ameliorate a chronic stressinduced depressive state (Mizoguchi et al., 2003; Pennington et al., 2009). In addition, BFM is one of the major ingredients used to treat psychosomatic disorders in TCM (Zhang et al., 1994).

5. Conclusion Chinese herbal products including SHs and HFs, are widely prescribed for patients with sleep disorder and MDD. However, the safety and efficacy of CHPs for sleep disorder and MDD need to be further evaluated.

Study limitations There are some limitations in our study. First, the estimated top 10 single herbs and herbal formulas were searched from the National Health Insurance database records according to the patient’s main symptoms and secondary symptoms, may be ruled out form the secondary symptoms rather than the main symptoms. Second, the use of these drugs for treatment of sleep disorder and MDD, the dose-response relationship and efficacy was unknown.

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Prescription patterns of Chinese herbal products for patients with sleep disorder and major depressive disorder in Taiwan.

Chinese herbal products (CHPs) are commonly prescribed for sleep disorder and major depressive disorder (MDD). The aim of this study was to investigat...
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