EKAT Appendix 2015 漢方専門医認定機関、日本東洋医学会 | EBM特別委員会

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Evidence Reports of Kampo Treatment (EKAT)

Appendix 2015

漢方治療エビデンスレポート

(EKAT) Appendix 2015

31 March 2017

Task Force for Evidence Reports (ER-TF)

Committee for Evidence-based Medicine (EBM)

The Japan Society for Oriental Medicine (JSOM)

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6 Jun. 2015: Kampo Chiryo Ebidensu Repoto Appendix 2014 (Evidence Reports of Kampo Treatment Appendix 2014) 31 Dec. 2013: Kampo Chiryo Ebidensu Repoto 2013 – 402 no RCT (Evidence Reports of Kampo Treatment 2013: 402

Randomized Controlled Trials)

31 Dec. 2012: Kampo Chiryo Ebidensu Repoto Appendix 2012 (Evidence Reports of Kampo Treatment Appendix 2012) 1 Oct. 2011: Kampo Chiryo Ebidensu Repoto Appendix 2011 (Evidence Reports of Kampo Treatment Appendix 2011) 1 Jun. 2010: Kampo Chiryo Ebidensu Repoto 2010 – 345 no RCT (Evidence Reports of Kampo Treatment 2010: 345

Randomized Controlled Trials)

1 Jun. 2009: Kampo Chiryo Ebidensu Repoto 2009 – 320 no RCT (Evidence Reports of Kampo Treatment 2009: 320 Randomized Controlled Trials)

1 Apr. 2008: Kampo Chiryo Ebidensu Repoto Dai 2-han – RC T wo Shu ni Shite- Chukan Hokoku 2007 ver 1.1 (Evidence Reports of Kampo Treatment 2nd edition - Focusing on RCTs- Interim Report 2007 ver.1.1)

15 Jun. 2007: Kampo Chiryo Ebidensu Repoto Dai 2-han –RC T wo Shu ni Shite- Chukan Hokoku 2007 (Evidence Reports of Kampo Treatment 2nd edition - Focusing on RCTs- Interim Report 2007)

20 Jul. 2005: Kampo Chiryo niokeru Ebidensu Repoto (Evidence Reports of Kampo Treatment) (Nihon Toyo Igaku Zasshi [Kampo Medicine] 2005: 56, EBM supplementary issue)

20 Sept. 2002: Kampo Chiryo niokeru EBM – 2002 nen Chukan Hokoku (EBM in Kampo 2002, Interim Report) (Nihon Toyo

Igaku Zasshi [Japanese Journal of Oriental Medicine] 2002: 53 [5], supplementary issue)

Version/date Title Year of publication

of target references s

2017.3.31

Evidence Reports of Kampo Treatment, Appendix 2015

(EKAT appendix 2015)

From EKAT 2014

2014 545

2) ₄₄₇1), 2) ₁₇₇

2015.6.6

From EKAT 2013

2013 (First half) 513

3) ₄₁₈1), 3) ₁₆₇

2013.12.31 Evidence Reports of Kampo Treatment, 2013

- 402 Randomized Controlled Trials 1986-2012 (First half) 494

4) ₄₀₃1), 4) ₁₅₉

2012.12.31

From EKAT 2011

2011 (First half) 457 379

1), 5) ₁₅₀5)

2011.10.1

From EKAT 2010

2010 (First half) 432 360

1), 6)

-2010.6.1

Evidence Reports of Kampo Treatment, 2010 - 345 Randomized Controlled Trials

(EKAT 2010)

1986-2009 (First half) 416 3461) ₁₃₂

2009.6.1

Evidence Reports of Kampo Treatment, 2009 - 320 Randomized Controlled Trials

(EKAT 2009)

1986-2008 (First half) 385 3211) 111

2008.4.1

Evidence Reports of Kampo Treatment, 2nd edition

- Focusing on RCTs - Interim Report 2007 ver1.1

1999-2005 116 98 32

2007.6.15

Evidence Reports of Kampo Treatment, 2nd edition

- Focusing on RCTs - Interim Report 2007

1999-2005 104 102 42

1) _{Including 1 meta-analysis}

2) _{Total of all references added or removed in EKAT 2013, EKAT Appendix 2014 and EKAT Appendix 2015.}

3) _{Total of all references added or removed in EKAT 2013, EKAT Appendix 2014.}

4)

5) _{Total of all references added or removed in EKAT 2010, EKAT Appendix 2011 and EKAT Appendix 2012.}

6) _{Total of all references added in EKAT 2010 and EKAT Appendix 2011.}

No. of references

No. of structured

abstracts (SAs)

No. of excluded references

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Notes on the current version

The Task Force for Evidence Reports (ER-TF) of the Committee for Evidence-based Medicine (EBM), Japan

Society for Oriental Medicine (JSOM), comprehensively gathers data obtained in randomized controlled trials (RCTs)

of Kampo formulations in Japan, compiles structured abstracts (SAs), and then publishes them as Evidence Reports of

Kampo Treatment (EKAT). The ER-TF started working with the Task Force for Clinical Practice Guidelines in June

2009, because data obtained in RCTs of Kampo formulations were used in the preparation of the Clinical Practice

Guidelines and the two task forces were therefore considered to be closely related. However, for project management

reasons, since June 2014, the ER-TF, consisting of fifth-generation members, has been working as a separate body once

again.

As indicated in the "History of version upgrades" on the previous page, “Evidence Reports of Kampo

Treatment 2013 – 402 RCTs” (EKAT 2013) was published on December 31, 2013. EKAT 2013 states the results of 402

RCTs and a meta-analysis performed between 1986, when the current quality specifications for Kampo formulations for

medical use were established, and the first half of 2012. On June 6, 2015, EKAT Appendix 2014 was published and

additionally states only SAs of RCT reports published for approximately one year after the publication of EKAT 2013.

EKAT Appendix 2015 contains SAs of 31 of the RCT reports published within approximately one year after

the publication of EKAT Appendix 2014 and two revised SAs published before the publication. Even though the

ER-TF website has not been updated since the publication of the EKAT 2013, the Google search engine available on

the website allows users to access all SAs in EKAT 2013, EKAT Appendix 2014, and EKAT Appendix 2015.

To enable the inclusion of the results of all RCTs on Kampo formulations in the EKAT, a wide range of

documents and reports were referred to: even articles about academic societies were referred to, provided that the

articles stated the names of the authors and provided sufficient information to use as basis to prepare SAs. However,

issues of authorship and conflict of interest (COI) in regard to medical reports have gained interest since the 2010s. In

March 2015, the Japanese Association of Medical Sciences and the Japanese Association of Medical Journal Editors

published the Medical Journal Editing Guidelines (http://jams.med.or.jp/guideline), which require that articles written

by journalists regarding RCTs on Kampo formulations should not be included in EKAT Appendix 2014 or subsequent

EKAT appendices, and that SAs based on such articles should be reviewed and complemented by relevant RCT reports

or replaced with new SAs, because the number of subjects and the results of RCTs differed between some articles and

relevant RCT reports, and some RCTs in such articles were not linked to relevant RCT reports. EKAT Appendix 2015

has been reviewed in accordance with the guidelines, and two SAs (two RCT reports) have been deleted. EKAT

Appendix 2015 contains the results of 445 RCTs and two meta-analyses.

Even though the objective of the EKAT and the methods to prepare the EKAT have basically remained the

same since EKAT 2013, the time to carry out a search for RCT reports necessary for EKAT Appendix 2015 has been

changed from November to April, because there were discrepancies in the title of the EKAT and the time of publication.

Although the ER-TF planned to carry out a search for RCT reports necessary for the present EKAT in April 2015, to

prepare SAs of RCT reports published in most medical journals in 2014, and to publish a Japanese version under the

name of “EKAT Appendix 2015” by the end of 2015, the ER-TF actually published it in 2017. However, the ER-TF

will carry out a search for RCT reports in April of each year going forward.

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Committee for Evidence-based Medicine (EBM)

The Japan Society for Oriental Medicine (JSOM)

Organization

Chair and chairperson of Committee for EBM

:

Yoshiharu MOTOO

Department of Medical Oncology, Kanazawa Medical

University

Members (12 persons, order of the Japanese syllabary):

Ichiro ARAI

Department of Pharmaceutical Sciences, Nihon

Pharmaceutical University

Takahisa

USHIROYAMA

Health Science Clinic, Osaka Medical College

Hiroshi KOIKE

Department of General Internal Medicine, Tokyo Saiseikai

Central Hospital

Center for Kampo Medicine, Keio University School of

Medicine

Toshiaki KOGURE

Department of Japanese Oriental Medicine, Gunma Central

General Hospital

Hirozo GOTO

Department of Kampo Medicine

,

Hokusei Hospital

Hiroki TAKUMA

Acupuncture and Physical Therapy Teacher Training School,

University of Tsukuba

Koki TSURUOKA

Graduate School of Social Service Management, Japan

College of Social Work

Hideyuki NAKATA

Kampo Internal Medicine/Health Medical Center, Nerima

General Hospital

Michio FUJISAWA

Division for Health Service Promotion, University of Tokyo

(-2016.2)

Etsuo HOSHINO

Division of Kampo Support, Cancer Institute Ariake Hospital

Miyuki MINARI

Sub Committee to Assess the Efficacy of Kampo

Formulations, Committee on Kampo Formulations for

Prescription, Japan Kampo Medicines Manufacturers

Association

Trustee in charge of Committee for EBM, Japan Society for Oriental Medicine (JSOM):

Shin-ichi

MURAMATSU

Division of Oriental Medicine, Center for Community

Medicine, Jichi Medical University (trustee in charge of

Committee for EBM, JSOM)

Yukio KANEKO

Kaneko Clinic (vice-trustee in charge of Committee for EBM)

Observer of Committee for EBM, Japan Society for Oriental Medicine (JSOM):

Kiichiro TSUTANI

Faculty of Health Sciences, Tokyo Ariake University of

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<<EKAT Appendix 2015: Structured Abstracts describing RCTs and the References Reporting Them>>

Note: Original English titles assigned by authors were used in these lists and the structured abstracts. When

references had no English titles, the Task Force translated the original Japanese titles into English ones (*).

ICD-10 Research Question

Kampo

Formula References

Study Design Source

Page No.

A31.0

To evaluate the effectiveness of hochuekkito (補中益気湯)

as an adjunct to conventional treatment for progressed refractory pulmonary Mycobacterium avium complex (MAC) disease.

hochuekkito (補中益気湯)

Enomoto Y, Hagiwara E, Komatsu S, et al. Pilot quasi-randomized controlled study of herbal medicine hochuekkito as an adjunct to conventional treatment for progressed pulmonary mycobacterium avium complex disease. PLOS ONE 2014; 9: 1-8.

quasi-

RCT C&N 9

E14

To evaluate the efficacy and safety of goshajinkigan (牛車腎気丸) for treatment of

diabetic complications.

goshajinkigan (牛車腎気丸)

Watanabe K, Shimada A, Miyaki K, et al. Long-term effects of goshajinkigan in prevention of diabetic complications: A randomized open-labeled clinical trial. Evidence-Based Complementary and Alternative Medicine 2014: 1-8. doi: 10.1155/2014/128726

RCT C&N 10

E88.9

To evaluate the effects of co-administration of probiotics with bofutsushosan (防風通聖散) on obesity.

bofutsushosan (防風通聖散)

Lee S J, Bose S, Seo J-G, et al. The effects of co-administration of probiotics with herbal medicine on obesity, metabolic endotoxemia and dysbiosis: A randomized double-blind controlled clinical trial. Clinical Nutrition 2014; 33: 973-81.

DB-RCT N 11

F41.1

To evaluate the effectiveness and safety of yokukansan (抑肝散) in preoperative

sedation.

yokukansan (抑肝散)

Arai YC, Kawanishi J, Sakakima Y, et al. The effect of the kampo medicine yokukansan on preoperative anxiety and sedation levels. Evidence-Based Complementary and Alternative Medicine 2014: 1-4. doi: 10.1155/2014/965045

RCT N 12

F43.1

To evaluate the efficacy and safety of saikokeishikankyoto (柴胡桂枝乾姜湯) for

posttraumatic stress disorder (PTSD).

saikokeishikankyoto (柴胡桂枝乾姜湯)

Numata T, Gunfan S, Takayama S, et al. Treatment of posttraumatic stress disorder using the traditional Japanese herbal medicine saikokeishikankyoto: A randomized observer-blinded controlled trial in survivors of the great East Japan earthquake and tsunami. Evidence-Based Complementary and Alternative Medicine 2014: 1-6. doi:10.1155/2014/683293

RCT C&N 13

F45.9

To evaluate the efficacy and safety of kamikihito (加味帰脾湯) and kamishoyosan (加味逍遙散) for

otorhinolaryngological symptoms with a strong psychosomatic element.

kamikihito (加味帰脾湯)

Tanaka H. Problems and approaches to treatment of psychosomatic disease by an otorhinolaryngologist, and Kampo treatment for psychosomatic cases with depressive tendency – Focusing on kamikihito (加味帰脾湯) –. Phil

Kampo 2014; 47: 20-2.

RCT- cross over

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F52.2 To compare the efficacy of LEOPIN ROYAL with that of Kampo medicines for aging in males.

kamishoyosan (加味逍遙散)

hangekobokuto (半夏厚朴湯)

saikokaryukotsuboreito

(柴胡加竜骨牡蛎湯)

gosyajinkigan (牛車腎気丸)

hachimijiogan (八味地黄丸)

Nishimatsu H, Kitamura T, Yamada D, et al. Improvement of symptoms of aging in males by a preparation LEOPIN ROYAL containing aged garlic extract and other five of natural medicines-comparison with traditional herbal medicines (Kampo). Aging male 2014; 17: 112-6.

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G30.1

To evaluate the efficacy and safety of yokukansan (抑肝散) for behavioral and

psychological symptoms of dementia (BPSD).

Teranishi M, Kurita M, Nisiho S, et al. Efficacy and tolerability of risperidone, yokukansan, and fluvoxamine for the treatment of behavioral and psychological symptoms of dementia: A blinded, randomized trial. Journal of Clinical Psychopharmacology 2014; 33: 600-7.

RCT N 16

G62.9

To evaluate the efficacy of the carbonate spring foot bath and goshajinkigan (牛車腎気丸)

for lower-extremity peripheral neuropathy due to cancer chemotherapy.

Kawabata K, Nakano T, Tsutsumi J, et al. Evaluation of alleviation for lower-extremity peripheral neuropathy due to cancer chemotherapy. Effectiveness of the carbonate spring foot bath and goshajinkigan*. Journal of the Japanese Society of Footcare. 2014; 12: 145-50 (in Japanese).

RCT-

envelope I 17

G62.9

To verify the effects of goshajinkigan (牛車腎気丸)

for peripheral neuropathy during chemotherapy for breast cancer.

Abe H, Kawai Y, Mori T, et al. The Kampo medicine goshajinkigan prevents neuropathy in breast cancer patients treated with docetaxel. Asian Pacific Journal of Cancer Prevention 2014; 14: 6351-6.

RCT N 18

H66.9

To evaluate the efficacy and safety of juzentaihoto (十全大補湯) in children with

recurrent otitis media.

juzentaihoto (十全大補湯)

Yoshizaki T. A multicenter, double-blind, randomized controlled trial on the usefulness of juzentaihoto in children with recurrent otitis media* (2009— _{clinical study}— general—007) Chozai to Joho (Dispensing and Information) Health Labour Sciences Research Grant, General Research Program for Practical Application of Medical Technology, 2009, General Research Report in 2011. 2012: 1-23 (in Japanese).

DB-RCT N 19

I63.9

To evaluate the effectiveness of saireito (柴苓湯) for acute

ischemic stroke.

saireito (柴苓湯)

Nakae Y. Effectiveness of saireito in acute ischemic stroke. Kampo to Saishin Chiryo (Kampo & the Newest Therapy) 2013; 22: 329-32.

RCT I&N 20

J00

To evaluate the efficacy of Kakkonto (葛根湯) for

alleviating early cold symptoms.

kakkonto (葛根湯)

Okabayashi S, Goto M, Kawamura T, et al. Non-superiority of Kakkonto, a Japanese herbal medicine, to a representative multiple cold medicine with respect to anti-aggravation effects on the common cold: a randomized controlled trial. Internal Medicine 2014; 53: 949-56.

RCT N 21

J00

To evaluate the efficacy and safety of shimpito (神秘湯)

for treatment of cough associated with cold syndrome.

shimpito (神秘湯)

Itagaki K, Efficacy of shimpito for treatment of cough associated with cold syndrome.* Igaku to Yakugaku (Japanese Journal of Medicine and Pharmaceutical Science) 2013; 70: 813-6 (in Japanese).

quasi- RCT

I&N 22

J10.1

To evaluate the long-term effects of juzentaihoto (十全大補湯) on maintenance of

the anti-influenza antibody titer in elderly people after influenza vaccination.

juzentaihoto (十全大補湯)

Saiki I, Koizumi K, Goto H, et al. The long-term effects of a Kampo medicine, juzentaihoto, on maintenance of antibody titer in elderly people after influenza vaccination. Evidence-Based Complementary and Alternative Medicine 2013: 1-8. doi: 10.1155/2013/568074.

RCT N 23

K12.1

To evaluate the efficacy of hangeshashinto (半夏瀉心湯)

for gastric cancer chemotherapy-induced oral mucositis.

hangeshashinto (半夏瀉心湯)

Aoyama T, Nishikawa K, Takiguchi N, et al. Double-blind, placebo-controlled, randomized phase II study of TJ-14 (hangeshashinto) for gastric cancer chemotherapy-induced oral mucositis. Cancer Chemotherapy and Pharmacology 2014; 73: 1047-54.

DB-RCT C&N 24

K21.9

To evaluate the efficacy and safety of rikkunshito (六君子湯) for proton-pump inhibitor

(PPI)-refractory laryngopharyngeal reflux (LPR).

rikkunshito (六君子湯)

Tokashiki R, Okamoto I, Funato N, et al. Rikkunshito improves globus sensation in patients with proton-pump inhibitor-refractory laryngopharyngeal reflux. World Journal of Gastroenterology 2013; 19: 5118-24.

RCT N 25

K21.9

To evaluate the efficacy and safety of rikkunshito (六君子湯) for proton pump

inhibitor-refractory non-erosive reflux disease.

Tominaga K, Kato M, Takeda H, et al. A randomized, placebo-controlled, double-blind clinical trial of rikkunshito for patients with non-erosive reflux disease refractory to proton-pump inhibitor: the G-PRIDE study. Journal of Gastroenterology 2014; 49: 1392-405.

DB-RCT

N 26 Sakata Y, Tominaga K, Kato M, et al. Clinical characteristics

of elderly patients with proton pump inhibitor-refractory non-erosive reflux disease from the G-PRIDE study who responded to rikkunshito. BMC Gastroenterology 2014; 14: 116.

RCT

K30.0

To evaluate the treatment effects of rikkunshito (六君子湯) on functional dyspepsia.

Suzuki H, Matsuzaki J, Fukushima Y, et al. Randomized clinical trial: rikkunshito in the treatment of functional dyspepsia - a multicenter, double-blind, randomized, placebo-controlled study. Neurogastroenterology and Motility 2014; 26: 950-61.

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K30.0

To evaluate the efficacy of rikkunshito (六君子湯) for

gastrointestinal symptoms following endoscopic submucosal dissection (ESD) of early gastric cancer.

Uehara R, Isomoto H, Minami H, et al. Characteristics of gastrointestinal symptoms and function following endoscopic submucosal dissection and treatment of the gastrointestinal symptoms using rikkunshito. Experimental and Therapeutic Medicine 2013; 6: 1083-8.

RCT N 28

K59.0

To evaluate the efficacy and safety of daikenchuto (大建中湯) as treatment for functional

constipation in poststroke patients.

daikenchuto (大建中湯)

Numata T, Takayama S, Tobita M, et al. Traditional Japanese medicine daikenchuto improves functional constipation in poststroke patients. Evidence-Based Complementary and Alternative Medicine 2014: 1-8. doi: 10.1155/2014/231258

RCT C&N 29

K73.9

To evaluate whether use of Kampo medicines (Shimbuto [真武湯] and Ninjinto [人参湯]) in combination with pegylated interferon α plus

ribavirin promotes therapeutic responses in patients with chronic hepatitis C.

shimbuto (真武湯)

ninjinto (人参湯)

Kainuma M, Furusyo N, Murata M, et al. The effectiveness of traditional Japanese medicine (Kampo), in combination with

pegylated interferon α plus ribavirin for patients with chronic

hepatitis C: A pilot study. Journal of Traditional Medicines 2013; 30: 132-9.

RCT I 30

M79.2

To evaluate the efficacy of maobushisaishinto (麻黄附子細辛湯) for treatment of

occipital neuralgia.

maobushisaishinto (麻黄附子細辛湯)

Nakajima K, Sato H, Ooyama K, Is maobushisaishinto effective for neuropathic pain? Effect of maobushisaishinto on occipital neuralgia* Itami to Kampo (Pain and Kampo Medicine) 2014: 24: 31-7 (in Japanese with English abstract).

RCT-

envelope I&N 31

N95.1

To evaluate clinical effects of porcine placental extract on climacteric symptoms in peri-postmenopausal women.

tokisyakuyakusan (当帰芍薬散)

Koike K, Yamamoto Y, Suzuki N, et al. Efficacy of porcine placental extract on climacteric symptoms in peri- and postmenopausal women. Climacteric 2013; 16: 28-35.

RCT N 32

R13

To evaluate the nutrition improvement effects of hochuekkito (補中益気湯) in

patients with tube feeding.

Sasaki S, Oumi A, Kumeda M, et al. Evaluation of nutrition improvement effects of hochuekkito (補中益気湯) in patients

with tube feeding. Science of Kampo Medicine 2014 (in Japanese), 38: 263-6.

RCT I 33

T67.8

To evaluate the efficacy of Kampo therapy in patients with heat illness requiring hospitalization.

Nimura T, Yamada S, Ohwaki T, et al. Evaluation of the efficacy of Kampo therapy in patients with heat illness requiring hospitalization*. Kampo Igaku (Kampo Medicine) 2014: 38; 178-81 (in Japanese).

quasi-

RCT I&N 34

T67.8

To evaluate the effect of Kampo extract preparations as an adjunct to the standard therapy to shorten the symptom resolution time in patients with heat illness.

shakuyakukanzoto (芍薬甘草湯)

Takamura M, Effectiveness of Kampo extract preparations for the treatment of heat illness.* Kampo to Saishinchiryo (Kampo & the Newest Therapy) 2014; 23: 121-4 (in Japanese).

RCT N 35

T88.8

To evaluate pre-and post-operative analgesic effects of shakuyakukanzoto (芍薬甘草湯) for treatment of

pain after hemorrhoidectomy.

shakuyakukanzoto (芍薬甘草湯)

Fukuda Y, Azuma M, Novel pain reliever shakuyaku-kanzo-to after hemorrhoidectomy, Journal of the Japan Society of Coloproctology, 2014; 67: 324-9.

RCT I&N 36

Z01.0

To evaluate the ability of tokishakuyakusan (当帰芍薬散) to increase ocular blood

flow.

tokishakuyakusan (当帰芍薬散)

keishibukuryogan (桂枝茯苓丸)

hachimijiogan (八味地黄丸)

Takayama S, Shiga Y, Kokubun T, et al. The traditional kampo medicine Tokishakuyakusan increases ocular blood flow in healthy subjects. Evidence-Based Complementary and Alternative Medicine 2014: 1-8. doi: 10.1155/2014/586857

RCT cross- over

C&N 37

Z04.8

To isolate the indicator ingredients of Kampo medicines and evaluate their equivalence with extract and decoction.

kakkonto (葛根湯)

Horii C, Okonogi A, Okubo T, et al. Studies on bioequivalence of kakkonto decoction and its extract preparation (I)*. Shoyakugaku zasshi 2014; 68: 9-12 (in Japanese).

RCT cross-

over

N 38

Z04.8

To evaluate the

bioequivalence of shoseiryuto (小青竜湯) extract and its

decoction.

shoseiryuto (小青竜湯)

Horii C, Okonogi A, Studies on bioequivalence of shoseiryuto decoction and its extract preparation (I), Shoyakugaku zasshi (Journal of Natural Medicines) 2014; 68: 65-9.

RCT cross-

over

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ICD-10

Question Formula References Design Source No.

J00

To compare the efficacy of treatment (Kampo medicine vs. Western medicine) for upper airway inflammation in children.

group of Kampo formulations

（maoto[麻黄湯],

keimakakuhanto[桂麻各半湯]etc.）

Abe K. Outcomes of treatment for upper airway inflammation in children with Kampo medicine and Western medicine*. Dai 10-kai Nihon Shoni Toyo Igaku Kenkyukai Koen Kiroku (Proceedings of the 10th meeting of the Japan Pediatric

Society for Oriental Medicine) 1993; 10: 19–23 (in Japanese). quasi-RCT N 40 Abe K, Takagi K, Comparison of treatment results between

Kampo medicine-treated group and Western medicine-treated group for upper respiratory tract inflammation in children, Kampo medicine 1993; 43: 509-15.

K59.8

To evaluate the effectiveness of daikenchuto (大建中湯)

for perioperative intestinal paralysis following laparoscopic colon cancer surgery.

Yaegashi M, Otsuka K, Itabashi T, et al. Applying a Kampo medication to lower gastrointestinal tract surgery*. Shokaki Geka (Gastroenterological Surgery) 2013; 36: 1315-24.

RCT

N 41 Yaegashi M, Otsuka K, Itabashi T, et al. Daikenchuto

stimulates colonic motility after laparoscopic -associated colectomy. Hepato-Gastroenterology 2014; 61: 85-9.

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9 140001e 1. Infections (including Viral Hepatitis)

Reference

Enomoto Y, Hagiwara E, Komatsu S, et al. Pilot quasi-randomized controlled study of herbal medicine hochuekkito as an adjunct to conventional treatment for progressed pulmonary mycobacterium avium complex disease. PLOS ONE 2014; 9: 1-8. CENTRAL ID: CN- 00998327, Pubmed ID: 25093868

1. Objectives

To evaluate the effectiveness of hochuekkito (補中益気湯) as an adjunct to conventional treatment for

progressed refractory pulmonary Mycobacterium avium complex (MAC) disease.

2. Design

Quasi-randomized controlled trial (quasi-RCT).

3. Setting

One hospital, Japan.

4. Participants

Eighteen pulmonary MAC disease patients aged 20 years or older who were treated for at least one year but persistently culture-positive, or who were difficult to treat with antibiotics due to drug allergy.

5. Intervention

Prior treatment: Combination of rifampicin, ethambutol, clarithromycin, levofloxacin, kanamycin, and streptomycin or no treatment.

Arm 1: Hochuekkito (補中益気湯) (manufacturer unknown) administered orally 2.5 g b.i.d. or 2.5 g t.i.d.

+ prior treatment for up to 24 weeks (n=9) (one subject untreated). Arm 2: Prior treatment (n=9) (one subject untreated).

6. Main outcome measures

Sputum conversion rate at 24 weeks and number of MAC colonies. Change in shadow size in the lungs at 24 weeks.

Chronic obstructive pulmonary disease assessment test (CAT) scores and serum albumin level, serum C-reactive protein (CRP) level, and erythrocyte segmentation rate (ESR).

7. Main results

The sputum of all subjects remained positive for bacteria throughout the study. The number of colonies from baseline to 24 weeks remained essentially unchanged in Arm 1 or 2. Chest X-ray revealed improvement or no change in 8 subjects in Arm 1, and 3 subjects in Arm 2, showing that the MAC disease had a significantly more favorable course in the hochuekkito arm. CAT scores and ESR and CRP levels were worsened in most subjects in the two arms, but body weight and serum albumin level tended to increase in Arm 1. Interestingly, body weight increased in all subjects with radiographic improvement and decreased in most subjects with radiographic progression.

8. Conclusions

Although patients in the hochuekkito group had higher baseline ESR level and lower baseline blood albumin level, they showed chest radiographic improvement and increased body weight. Thus hochuekkito is useful as a therapeutic drug for pulmonary MAC disease.

9. From Kampo medicine perspective

Hochuekkito is indicated for patients in poor general condition.

10. Safety assessment in the article No serious adverse events were noted.

11. Abstractor’s comments

This RCT selected study subjects from a group of 155 patients with pulmonary MAC disease. These days, the number of pulmonary MAC disease patients is increasing. Since patients are not always responsive to general treatment, this study treatment seems meaningful. Establishing true outcome measures will improve the quality of evidence in a future RCT. Further development of this research is anticipated.

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140002e 4. Metabolism and Endocrine Diseases

Reference

Watanabe K, Shimada A, Miyaki K, et al. Long-term effects of goshajinkigan in prevention of diabetic complications: A randomized open-labeled clinical trial. Evidence-Based Complementary and Alternative

Medicine 2014: 1-8. doi: 10.1155/2014/128726 CENTRAL ID: CN-00993596, Pubmed ID: 24812564

1. Objectives

To evaluate the efficacy and safety of goshajinkigan (牛車腎気丸) for treatment of diabetic complications.

2. Design

Randomized controlled trial (RCT). 3. Setting

Nine hospitals, Japan. 4. Participants

A total of 149 type 2 diabetic patients with HbA1c of ≥6.5%, aged 40 to 75 years. Exclusion criteria were macroangiopathies including cerebral infarction, myocardial infarction, angina pectoris, leg gangrene, and arteriosclerosis obliterans; nephropathy associated with microalbuminuria or serum creatinine of 1.0 mg/dL; and proliferative or pre-proliferative retinopathy. Other exclusion criteria were related to sho (証,

pattern) for goshajinkigan and included BMI of 30 kg/m2 or more; two or more digestive system symptoms including gastrointestinal weakness, anorexia, nausea, and diarrhea; and three or more symptoms or activities indicative of sensitivity to heat such as a preference for dressing lightly, sweating upwards from the neck, a tendency to drink cold water, flushed face, congestion of the eyeballs, and a high body temperature of 36.7°C or higher.

5. Intervention

Arm 1: TSUMURA Goshajinkigan (牛車腎気丸) Extract Granules administered orally at 2.5 g t.i.d.

(n=100).

Arm 2: No treatment (n=49). 6. Main outcome measures

The primary outcome measures were occurrence of nonfatal myocardial infarction or cerebral infarction and frequency of diabetic nephropathy or retinopathy; the progression of diabetic nephropathy as indicated by a new onset of renal failure or an increase in urinary protein; and the progression of diabetic retinopathy as evaluated by fundus photography performed annually by ophthalmologists. Secondary outcome measures were body weight, blood pressure, fasting blood glucose, glycosylated hemoglobin, blood insulin, diabetic neuropathy, etc. Diabetic neuropathy was evaluated on the basis of characteristic symptoms: ankle reflex, lightheadedness, abnormal sweating, occurrence of constipation or diarrhea, etc. 7. Main results

A total of 116 subjects, i.e., 149 subjects minus 33 subjects who stopped visiting the hospital, were included in the analysis (74 subjects in the goshajinkigan arm; 42 subjects in the no treatment arm). The mean observation period was 28 months in Arm 1, and 15 months in Arm 2. No macroangiopathies such as myocardial infarction and cerebral infarction occurred in the two arms. The occurrence of diabetic nephropathy and retinopathy was not significantly different between arms. The deterioration of ankle reflex was significantly more frequent in Arm 2 than in Arm 1 (P=0.04). Glycosylated hemoglobin level was significantly lower in Arm 1 than in Arm 2 at 60 months (P<0.05). The fasting blood glucose level was significantly decreased from baseline in Arm 1 at 36 months (P<0.05).

8. Conclusions

Goshajinkigan inhibits worsening of ankle reflex and improves glycosylated hemoglobin and fasting blood glucose levels.

To evaluate patients with sho (証, pattern) for goshajinkigan, patients with obesity, gastrointestinal

weakness, and sensitivity to heat were excluded from the study. 10. Safety assessment in the article

No dropouts due to adverse reactions to goshajinkigan were noted. 11. Abstractor’s comments

This is an interesting clinical study planned to elucidate the long-term effects of goshajinkigan, which is frequently used for treatment of diabetes mellitus. As stated by the authors, however, the desired number of subjects could not be included in the study and the available macroangiopathies occurrence data were inadequate. On the other hand, there were data suggesting that goshajinkigan was effective. Future studies with more subjects are anticipated.

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11 140003e 4. Metabolism and Endocrine Diseases

Reference

Lee S J, Bose S, Seo J-G, et al. The effects of co-administration of probiotics with herbal medicine on obesity, metabolic endotoxemia and dysbiosis: A randomized double-blind controlled clinical trial.

Clinical Nutrition 2014; 33: 973-81. Pubmed ID: 24411490

1. Objectives

To evaluate the effects of co-administration of probiotics with bofutsushosan (防風通聖散) on obesity.

2. Design

Double-blind, randomized controlled trial (DB-RCT). 3. Setting

One university hospital in Seoul, the Republic of Korea. 4. Participants

Fifty females aged 19 to 65 years with BMI of >25 kg/m2 and waist circumference of >85 cm. Exclusion criteria were hypothyroidism, Cushing's syndrome, heart diseases, cancer, lung diseases, severe renal dysfunction (Cr >2.0 mg/dL), hepatic dysfunction, non-insulin dependent diabetes mellitus (fasting blood sugar level [FBS] >140 mg/dL), eating disorders, pregnancy, breast feeding, and body weight decrease by 10% within 6 months of the study.

5. Intervention

Arm 1: TSUMURA Bofutsushosan (防風通聖散) Extract Granules 3 g b.i.d. + probiotics twice daily

(Duolac7 capsules) for 8 weeks (n=25).

Arm 2: TSUMURA Bofutsushosan (防風通聖散) Extract Granules 3 g b.i.d. + placebo twice daily

(identical to Duolac7 capsules) for 8 weeks (n=25). 6. Main outcome measures

The main outcome measures were body weight and gut permeability. The secondary outcome measures were BMI, blood pressure, blood parameters (e.g., lipid levels), fecal bacteria count, endotoxin level, body fat level (as measured by bioelectrical impedance), and quality of life (as measured using the Korean version of obesity-related quality of life [KOQOL] scale). In the article, parameters including body weight, waist circumference, BMI, and body fat level (bioelectrical impedance) were termed “body composition parameters,” while other parameters including blood parameters, fecal bacteria count, and endotoxin level were termed “metabolic biomarkers.”

7. Main results

Although body weight and waist circumference were significantly decreased in both arms (P=0.000), no inter-arm difference in the body composition parameters or metabolic biomarkers were found. Correlation analysis revealed that change in body composition was positively correlated with endotoxin level (γ=0.441, P<0.05 for body weight; γ=0.350, P<0.05 for fat mass) and lactic acid bacteria count (γ=0.425,

P<0.05 for body weight; γ=0.407, P<0.05 for BMI). The body composition parameters, waist circumference and total cholesterol level were positively correlated with Gram negative bacteria count (γ=0.359 and γ=0.393, respectively; P<0.05 for both) and Bifidobacterium breve count was negatively correlated with endotoxin level (γ=−0.350, P<0.05).

8. Conclusions

Correlation between gut microbiota and change in body composition shows that probiotics affect energy metabolism in obese subjects. Correlation between endotoxin level and body weight decrease suggests that probiotics play a role in preventing the growth of endotoxin-producing bacteria in gut microbiota that promote obesity-associated dysbiosis.

9. From Kampo medicine perspective None.

10. Safety assessment in the article Not mentioned.

This DB-RCT was conducted in the Republic of Korea and evaluated the effects of co-administration of bofutsushosan and probiotics on obesity. This study was a registered clinical trial of the Korean National Institute of Health (NIH) and seems to be a well-designed study. Although body weight was decreased in both arms, the body weight decrease was not significantly different between arms. Therefore, the efficacy of adding bofutsushosan to probiotics remains unknown. In the article, the authors focused mainly on the results of correlation analyses rather than the effectiveness of probiotics. Research questions posed at the time of the study’s design seem to remain unanswered. The significance and effects of co-administration of bofutsushosan were poorly described. More explanation is needed. Further development of this research is anticipated.

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12 140004e 5. Psychiatric/Behavioral Disorders

Reference

Arai YC, Kawanishi J, Sakakima Y, et al. The effect of the kampo medicine yokukansan on preoperative anxiety and sedation levels. Evidence-Based Complementary and Alternative Medicine 2014: 1-4. doi: 10.1155/2014/965045 Pubmed ID: 24799947

1. Objectives

To evaluate the effectiveness and safety of yokukansan (抑肝散) in preoperative sedation.

2. Design

Single facility (hospital surgery department). 4. Participants

Seventy patients whose physical status was rated I or II (American Society of Anesthesiologists) before hemicolectomy (ages: 30-85; 23 females and 47 males).

5. Intervention

Arm 1: TSUMURA Yokukansan (抑肝散) extract granules (2.5 g) taken orally 1.5 hours before general

anesthetic (n=36).

Arm 2: Diazepam (5 mg) taken orally 1.5 hours before general anesthetic (n=34). 6. Main outcome measures

Intensity of anxiety immediately prior to anesthesia, using a verbal rating scale (VRS); Level of sedation using the modified Observer’s Assessment of Alertness/Sedation Scale (OAA/S).

7. Main results

There was no significant difference between arms 1 and 2 in the intensity of anxiety on the VRS. The levels of sedation on the OAA/S showed statistically significant sedation in arm 2 compared to arm 1 (P<0.05).

8. Conclusions

Compared to diazepam, yokukansan does not excessively sedate patients. 9. From Kampo medicine perspective

None.

10. Safety assessment in the article

There were no adverse drug reactions in either the yokukansan group or the diazepam group. 11. Abstractor’s comments

This clinical trial evaluated the significance of using yokukansan in sedation prior to hemicolectomy. The authors concluded that sedation with yokukansan prior to surgery under general anesthesia is not excessive. However, because the trial was not designed as a non-inferiority study, it does not clarify whether diazepam and yokukansan have the same level of effectiveness in suppressing anxiety. Hopefully the authors will conduct a trial that indicates non-inferiority by comparing yokukansan administration with diazepam administration for the suppression of anxiety prior to surgery under general anesthesia, and indicates the effectiveness of yokukansan administration for the suppression of anxiety prior to surgery under general anesthesia in comparison with the use of placebo or no preoperative drugs prior to surgery, as the next stage of their research.

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140005e 5. Psychiatric/Behavioral Disorders

Reference

Numata T, Gunfan S, Takayama S, et al. Treatment of posttraumatic stress disorder using the traditional Japanese herbal medicine saikokeishikankyoto: A randomized observer-blinded controlled trial in survivors of the great East Japan earthquake and tsunami. Evidence-Based Complementary and

Alternative Medicine 2014: 1-6. doi:10.1155/2014/683293 CENTRAL ID: CN-00988474, Pubmed ID:

24790634 1. Objectives

To evaluate the efficacy and safety of saikokeishikankyoto (柴胡桂枝乾姜湯) for posttraumatic stress

disorder (PTSD). 2. Design

One hospital, Japan. 4. Participants

Forty-three patients aged 20 years or older who survived the Great East Japan Earthquake and tsunami and had a diagnosis of PTSD according to the Diagnostic and Statistical Manual of Mental Disorders fourth edition (text revision) (DSM-IV TR), with an Impact of Event Scale-Revised Questionnaire (IES-R) score of ≥25. The patients meeting any of the following four criteria were excluded from the study: 1) major medical illness such as neoplastic disease, acute inflammation, and any other disease precluding successful completion of the study; 2) psychosis due to other disorders such as schizophrenia, depression, and dementia; 3) delirium due to drugs, alcohol; and 4) use of neuroleptics, antianxiety drugs, antiepileptic drugs, antidepressants, or herbal remedies during the past 2 months.

5. Intervention

Arm 1: TSUMURA Saikokeishikankyoto (柴胡桂枝乾姜湯) Extract Granules 2.5 g t.i.d. for 2 weeks

orally (n=21).

Arm 2: No administration (n=22). 6. Main outcome measures

The primary outcome measure was severity of PTSD as measured on the total IES-R scale. The secondary outcome measures were scores on three IES-R subscales: the intrusion subscale of 8 items, Questions 1, 2, 3, 6, 9, 14, 16, and 20; the avoidance subscale of 8 items, Questions 5, 7, 8, 11, 12, 13, 17, and 22; and the hyperarousal subscale of 6 items, Questions 4, 10, 15, 18, 19, and 21.

7. Main results

Twenty-one subjects in Arm 1 and 22 subjects in Arm 2 were included in the analysis. One subject in Arm 1 dropped out of the study due to cough on Day 3. Changes in total IES-R scores were significantly different between the two arms (P<0.001). Total IES-R scores were significantly improved from baseline to the completion of the study in Arm 1 (P<0.001) but not in Arm 2. The between-arm differences in all three subscales were significant (P=0.025 for avoidance subscale; P=0.005 for hyperarousal subscale;

P<0.001 for intrusion subscale). From baseline to the completion of the study, there was a significant

improvement in three subscale scores in Arm 1 (P=0.003 for avoidance sub-scale; P<0.001 for hyperarousal subscale; P<0.001 for intrusion sub-scale) and a significant improvement in one subscale score in Arm 2 (P=0.032 for avoidance subscale). There were significant inter-arm differences in the scores on Questions 1, 3, 6, 14, 19, 20, and 21 (P<0.001 for Question 1; P=0.005 for Question 3; P<0.001 for Question 6; P=0.003 for Question 14; P=0.001 for Question 19; P=0.002 for Question 20; P=0.001 for Question 21).

8. Conclusions

Saikokeishikankyoto is effective for alleviation of PTSD. 9. From Kampo medicine perspective

None.

One subject in the saikokeishikankyoto arm was withdrawn from the study on Day 3 due to mild cough. 11. Abstractor’s comments

This was an innovative clinical study evaluating the efficacy of a Kampo product for treatment of post-disaster PTSD, and a valuable study given the rarity of this type of disaster. However, as mentioned by the authors, the small number of subjects, the influence of placebo effect, and the absence of control drugs for comparison seems to preclude adequate evaluation of the efficacy. Although there are many limitations to the conduct of this type of study, based on this study’s findings, further development of clinical studies with longer follow-up and inclusion of positive and negative controls for comparison is anticipated.

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Reference

Tanaka H. Problems and approaches to treatment of psychosomatic disease by an otorhinolaryngologist, and Kampo treatment for psychosomatic cases with depressive tendency – Focusing on kamikihito (加味帰脾湯) –. Phil Kampo 2014; 47: 20-2. Ichushi Web ID: 2014238207

1. Objectives

To evaluate the efficacy and safety of kamikihito (加味帰脾湯) and kamishoyosan (加味逍遙散) for

otorhinolaryngological symptoms with a strong psychosomatic element. 2. Design

Quasi-randomized controlled trial (quasi-RCT). 3. Setting

Single facility (hospital otorhinolaryngology department). 4. Participants

Thirty patients who presented at the otorhinolaryngology department with dizziness, tinnitus or hypopharyngeal globus sensation; who scored at least 11 points on the Toho University Self-Rating Questionnaire for Depression, SRQ-D; and whose psychosomatic factors appeared to aggravate symptoms. 5. Intervention

Arm 1: Kamikihito (加味帰脾湯) (manufacturer and dose unknown) taken for four weeks then

kamishoyosan (加味逍遙散) (manufacturer and dose unknown) taken for four weeks (n=15).

Arm 2: Kamishoyosan (加味逍遙散) (manufacturer and dose unknown) taken for four weeks then

kamikihito (加味帰脾湯) (manufacturer and dose unknown) taken for four weeks (n=15).

Change in chief complaint following the change of Kampo medication. 7. Main results

Efficacy was relatively high in 6.7% and low in 33.3% of patients in arm 1 after the change of Kampo medication. Efficacy was not high in any and it was low in 50.0% of the 10 patients who scored 16 or more on the SRQ-D, which is an indicator of possible depression. Of the 5 patients who scored 11-15 on the SRQ-D, which is on the borderline of depression, efficacy was high in 20.0% and it was not low in any patient. In arm 2, efficacy was high in 26.7% and low in 6.7% of patients. Of the 10 patients who scored 16 or more on the SRQ-D, efficacy was high in 40.0% and it was not low in any patient. Of the 5 patients who scored 11-15 on the SRQ-D, efficacy was not high in any and it was low in 20.0%.

8. Conclusions

Kamikihito was more effective than kamishoyosan for dizziness, tinnitus and hypopharyngeal globus sensation aggravated by psychosomatic factors in patients with an SRQ-D score of 16 or more and kamishoyosan was more effective than kamikihito in patients with an SRQ-D score of 11-15.

Kamikihito appears to be more appropriate than kamishoyosan for patients with severe depressive tendency.

No adverse effect induced by kamishoyosan or kamikihito was observed. 11. Abstractor’s comments

This study was a cross-over comparison to evaluate whether kamikihito or kamishoyosan is more effective for otorhinolaryngological symptoms in which psychosomatic factors exist. The study suggests that kamikihito is effective for patients with severe depression and that kamishoyosan is effective for patients with slightly mild depression. It suggests that the SRQ-D could be a tool when selecting these two prescriptions. However, this study alone does not conclusively prove that kamikihito and kamishoyosan are effective for otorhinolaryngological symptoms. As the next stage of research to clarify which patient group responds to kamikihito and kamishoyosan, the author should prospectively study in a randomized controlled trial whether kamikihito is effective for patients with severely depressive otorhinolaryngological symptoms and whether kamishoyosan is effective for patients with mild depressive otorhinolaryngological symptoms.

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Reference

Nishimatsu H, Kitamura T, Yamada D, et al. Improvement of symptoms of aging in males by a preparation LEOPIN ROYAL containing aged garlic extract and other five of natural medicines-comparison with traditional herbal medicines (Kampo). Aging male 2014; 17: 112-6. CENTRAL ID: CN-00992899, Pubmed ID: 24844765

1. Objectives

To compare the efficacy of LEOPIN ROYAL with that of Kampo medicines for aging in males. 2. Design

One department of urology in a university hospital and one department of urology in a hospital, Japan. 4. Participants

Forty-nine males who complained of aging symptoms and underwent physical examinations at the Department of Urology, Faculty of Medicine, University of Tokyo.

5. Intervention

Arm 1: LEOPIN ROYAL for 6 months (n=24).

Arm 2: Kamishoyosan (加味逍遙散) (n=20), hangekobokuto (半夏厚朴湯) (n=1), saikokaryukotsuboreito

(柴胡加竜骨牡蛎湯) (n=1), hochuekkito (補中益気湯) (n=1), goshajinkigan (牛車腎気丸) (n=1),

and hachimijiogan (八味地黄丸) for 6 months (n=1) (manufacturers unknown).

Aging Males' Symptoms (AMS) scale; International Index of Erectile Function with 5 questions (IIEF-5); Androgen Deficiency in the Aging Male (ADAM) score; Self-Rating Questionnaire for Depression (SRQ-D) score; and serum levels of the following hormones: total testosterone, free testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and estradiol (E2).

7. Main results

In the LEOPIN ROYAL arm compared to the Kampo arm, somatic and phycological subscores and the total score in the AMS scale were significantly lower (P<0.01 for somatic sub-score; P<0.01 for phycological subscore; P<0.01 for total score), and the AMS somatic score and IIEF-5 score were significantly improved (P<0.01 for somatic subscore; P=0.019 for IIEF-5 score). Blood levels of total testosterone, free testosterone, FSH, LH, PRL, or E2 remained unchanged in the two arms.

8. Conclusions

LEOPIN ROYAL is more effective than kamishoyosan for symptoms of aging in males. 9. From Kampo medicine perspective

None.

10. Safety assessment in the article No special problems were noted. 11. Abstractor’s comments

In this study, kamishoyosan was the control for LEOPIN ROYAL, but hangekobokuto, saikokaryukotsuboreito, hochuekkito, goshajinkigan, and hachimijiogan were also used as controls in one subject each, depending on their symptoms. For symptoms such as decreased libido, hachimijiogan was presumably more effective than LEOPIN ROYAL; therefore, presenting in this article information about each Kampo formulation, rather than information about the group of Kampo formulations, would have been more valuable.

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16 140008e 6. Nervous System Diseases (including Alzheimer's Disease)

Reference

Teranishi M, Kurita M, Nisiho S, et al. Efficacy and tolerability of risperidone, yokukansan, and fluvoxamine for the treatment of behavioral and psychological symptoms of dementia: A blinded, randomized trial. Journal of Clinical Psychopharmacology 2014; 33: 600-7. Pubmed ID: 23948783

1. Objectives

To evaluate the efficacy and safety of yokukansan (抑肝散) for behavioral and psychological symptoms of

dementia (BPSD). 2. Design

One psychiatric hospital, Japan. 4. Participants

Eighty-two patients who met the diagnostic criteria of dementia according to the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV) with total score on the Mini-Mental State Examination (MMSE) of <19 and at least one symptom score of >4 in the Neuropsychiatric Inventory- Nursing Home Version (NPI-NH). Patients meeting any of the following criteria were excluded from the study: participation in any other drug study within 4 weeks of the study; hypersensitivity to risperidone, yokukansan, or fluvoxamine; evidence of chronic and/or severe disease that could interfere with the study. 5. Intervention

Arm 1: Yokukansan (抑肝散) (manufacturer unknown) 2.5 to 7.5 g/day for 8 weeks (n=27).

Arm 2: Risperidone 0.5 to 2.0 g/day for 8 weeks (n=27). Arm 3: Fluvoxamine 25 to 200 mg/day for 8 weeks (n=28).

The study was initiated after a 1-week washout of drugs used for treatment of BPSD. The dose of each drug was adjusted at the discretion of the investigator and based on his/her analysis of NPI-NH subscales. 6. Main outcome measures

At baseline and Weeks 2, 4, 6, and 8, an assessment was made of neuropsychiatric symptoms using the NPI-NH, cognitive function using the MMSE, and daily life function using the Functional Independence Measure (FIM). To evaluate drug tolerability, blood and other tests and the Drug-induced Extra-pyramidal Symptoms Scale (DIEPSS) were performed.

7. Main results

Of the 82 subjects, 76 were included in the analysis. NPI-NH scores were significantly improved from baseline to Week 8 in all arms (P=0.034 in Arm 1; P=0.022 in Arm 2; P<0.001 in Arm 3), but with no significant difference among the three arms. MMSE and FIM scores did not change significantly in the three arms.

8. Conclusions

Yokukansan is as effective as risperidone and fluvoxamine for BPSD but safer to use than risperidone. 9. From Kampo medicine perspective

None.

DIEPSS scores were similar between the yokukansan and fluvoxamine arms, but significantly higher in the risperidone arm than in the yokukansan and fluvoxamine arms. One subject in the risperidone arm died suddenly during the study.

BPSDs are important symptoms to treat, but there are no good drugs for BPSD treatment at this time. This clinically meaningful study evaluated the efficacy and safety of risperidone and yokukansan, which are frequently used in clinical settings, and fluvoxamine used by the authors. However, as acknowledged by the authors, no placebo was used in this study; the investigator’s assessment might have been affected by this omission. In addition, since hospitalized patients were included in this study, care by staff members might have improved NPI-NH scores in all arms. However, the intent of this study was to improve the state of current treatment. It is anticipated that similar future studies will be conducted to establish the guidelines for treatment of BPSD with Kampo medicines.

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Reference

Kawabata K, Nakano T, Tsutsumi J, et al. Evaluation of alleviation for lower-extremity peripheral neuropathy due to cancer chemotherapy. Effectiveness of the carbonate spring foot bath and goshajinkigan*. Journal of the Japanese Society of Footcare. 2014; 12: 145-50 (in Japanese). Ichushi Web ID: 2015126257

1. Objectives

To evaluate the efficacy of the carbonate spring foot bath and goshajinkigan (牛車腎気丸) for

lower-extremity peripheral neuropathy due to cancer chemotherapy. 2. Design

Randomized controlled trial using envelopes for allocation (RCT-envelope). 3. Setting

One university hospital, Japan. 4. Participants

Eighteen females with breast cancer aged <75 years who were to receive preoperative chemotherapy with paclitaxel (80 mg/m2 once weekly, infused for 12 consecutive weeks).

5. Intervention

Arm 1: Spring foot bath with Kao carbonated tablets (炭酸足浴剤) diluted in 6 L of warm water

maintained at 38°C to 40°C and administered for 15 minutes daily at a convenient time for 12 weeks (n=8).

Arm 2: TSUMURA Goshajinkigan (牛車腎気丸) Extract Granules orally administered at 2.5 g t.i.d. for 12

weeks (n=4). Arm 3: No treatment (n=6). 6. Main outcome measures

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), peripheral neuropathy (i.e., numbness measured on the CTC-AE version 4.0 grading scale), and foot skin temperature (measured by thermography) at Weeks 4, 8, and 12.

7. Main results

Peripheral neuropathy in the lower extremity (all grade 2 or less) occurred in 11 of the 18 subjects (61%). In the carbonate spring foot bath arm (n=8), the 4 subjects with no numbness compared to the remaining 4 subjects with numbness had higher median skin temperature (34.8°C vs. 31.1°C) and higher percent change in foot skin temperature over time. At Week 12 of paclitaxel chemotherapy, 4 subjects in the carbonate spring foot bath arm, 0 subjects in the goshajinkigan arm, and 3 subjects in the control arm had no numbness, and 2 subjects in the carbonate spring foot bath arm had no numbness for 12 consecutive weeks.

8. Conclusions

Lower-extremity numbness caused by preoperative once-weekly paclitaxel chemotherapy may be alleviated by bathing in carbonate spring foot bath; however, the number of subjects in this study was too small to draw clear conclusions.

10. Safety assessment in the article Not mentioned.

This was a unique study evaluating the effects of carbonate spring foot bath on vasodilation, such as increased muscle blood flow, increased skin temperature, and alleviation of numbness. Presented only at the convention of the Japanese Society of Footcare, the study suggested that carbonate spring foot bath was effective for numbness in patients with non-small-cell lung cancer (NSCLC). Although there were 2 control arms (a goshajinkigan arm and no treatment arm), the number of subjects in each arm was small and no statistical analysis was mentioned in the article. Skin temperature should have been measured at baseline. Although the authors valued that the severity of peripheral neuropathy at the completion of the scheduled 12-week treatment was Grade 2 or lower in all subjects, it was not mentioned whether the treatment could be effective without dose reduction of paclitaxel. In addition, the description of the carbonate spring foot bath arm was mistakenly replaced by the description of the goshajinkigan arm in the third line of the Results section, and the number of subjects in the carbonate spring foot bath arm should be 8 instead of 6 in Table 4. It is anticipated that statistical evaluation of the efficacy of the carbonate spring foot bath will be possible once the number of subjects is increased.

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Reference

Abe H, Kawai Y, Mori T, et al. The Kampo medicine goshajinkigan prevents neuropathy in breast cancer patients treated with docetaxel. Asian Pacific Journal of Cancer Prevention 2014; 14: 6351-6. Pubmed ID: 24377531

1. Objectives

To verify the effects of goshajinkigan (牛車腎気丸) for peripheral neuropathy during chemotherapy for

breast cancer. 2. Design

Single facility (hospital). 4. Participants

Sixty women aged 20-70 who were receiving chemotherapy with docetaxel for invasive breast cancer. 5. Intervention

Arm 1: GJG group: TSUMURA Goshajinkigan Extract Granules (7.5 g divided in two to three doses per day) taken either before or between meals (n=33).

Arm 2: B12 group: Mecobalamin (1500µg/day) taken after meals (n=27). 6. Main outcome measures

Assessment of the frequency of peripheral neuropathy (Neurotoxicity Criteria of Debiopharm [DEB-NTC], Common Terminology Criteria for Adverse Events [CTC-AE], and Visual analogue scale [VAS]).

7. Main results

The incidence of chemotherapy-induced peripheral neuropathy in the GJG group was 39.3% compared to 88.9% in the B12 group, which was significantly (P<0.01) lower. Twelve patients in the B12 group were assessed as DEB-NTC grade 3, a severe assessment, while 5 patients in the GJG group received that assessment, which was a significant difference (P<0.01). Similarly, 12 patients were assessed as CTC-AE grade 2 and 1 as grade 3 in the B12 group, while 6 patients in the GJG group were assessed as grade 2 and none as grade 3, which was a significant difference (P<0.01). The VAS scores for subjective symptom assessment were also significantly lower (P<0.01) in the GJG group (2.7±2.2) compared to the B12 group (4.9±2.4). Taking goshajinkigan during chemotherapy with docetaxel significantly reduced not only the occurrence of peripheral neuropathy but also the severity of subjective symptoms.

8. Conclusions

Preventive oral administration of goshajinkigan suppresses the occurrence of peripheral neuropathy and even when such neuropathy does occur, it reduces symptom severity, during chemotherapy with docetaxel for invasive breast cancer in female patients.

There was no clinically problematic adverse effect. 11. Abstractor’s comments

This study confirmed the preventive effects of goshajinkigan for peripheral neuropathy, an inevitable adverse effect of chemotherapy for invasive breast cancer. It has great significance in clinical medicine and is a valuable study. Confirmation of this significant effect through a randomized trial, not based on the

zuisho (随証, patterns) of Kampo medicine, means the results are worthy of being included in the

guidelines for Western medical treatment. Hopefully the authors will conduct a robust study of its clinical effects under protocols including goshajinkigan’s zuisho (随証, pattern), or at least whether jinkyo (腎虚,

kidney deficiency ) is present or not. Further research is anticipated. 12. Abstractor and date

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19 120015e 8. Ear Diseases

Reference

Yoshizaki T. A multicenter, double-blind, randomized controlled trial on the usefulness of juzentaihoto in children with recurrent otitis media* (2009—_{clinical study}—_{general—007) Chozai to Joho (Dispensing and}

Information) Health Labour Sciences Research Grant, General Research Program for Practical Application

of Medical Technology, 2009, General Research Report in 2011. 2012: 1-23 (in Japanese). 1. Objectives

To evaluate the efficacy and safety of juzentaihoto (十全大補湯) in children with recurrent otitis media.

2. Design

Seven university hospitals, 8 hospitals, and 11 otorhinolaryngological clinics, Japan. 4. Participants

Eighty-seven children aged ≥six months and <4 years with otitis media, recurrences of otitis media that were difficult to treat with standard therapy, a diagnosis of recurrent otitis media "acute otitis media occurring three times or more within the past 6 months, or four times or more within the past 12 months," and any of the following symptoms: a decrease in physical strength, fatigue and malaise, anorexia, night sweat, cold extremities, or anemia.

5. Intervention

Arm 1: Juzentaihoto (十全大補湯) (manufacturer unknown) administered orally at 0.05 to 0.125 g/kg b.i.d

and standard therapy for 3 months (n=39).

Arm 2: Standard therapy alone (n=48). 6. Main outcome measures

The mean number of recurrences with acute otitis media per month during the study, and the difference in mean number of recurrences with acute otitis media per month between baseline and endpoint of the study, mean number of recurrences with coryza per month, mean frequency of antibiotic use per month, number of subjects treated by eardrum ventilation tube insertion during the study, general condition including nutritional status (e.g., albumin level at the completion of the study, Kaup's index), and anemia improvement (yes or no).

7. Main results

A total of 70 subjects were included in the analysis: 31 subjects in the juzentaihoto arm and 39 subjects in the standard therapy alone arm. Compared with Arm-2 patients, Arm-1 patients had decreased mean number of recurrence with acute otitis media per month (time/month) and coryza per month, and decreased mean frequency of antibiotic use per month. However, there was no significant inter-arm difference in nutritional status or anemia improvement.

8. Conclusions

Juzentaihoto decreases the incidence of recurrent otitis media in children. 9. From Kampo medicine perspective

None.

One subject in the juzentaihoto arm experienced skin rash, leading to suspension of treatment. No significant inter-arm difference in blood chemistry was found throughout the study.

This clinical study, which evaluated the efficacy of juzentaihoto in pediatric patients with recurrent otitis media, a widely prevalent and refractory disease, is highly valuable with regard to clinical significance, setting, and study methods. However, this study was published as a report, many details of the results were not mentioned. A more detailed presentation of the results should be published. As stated by the authors, more evidence of juzentaihoto’s efficacy in the treatment of childhood recurrent otitis media is desired and will be sought in the future.

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20 130013e 9. Cardiovascular Diseases

Reference

Nakae Y. Effectiveness of saireito in acute ischemic stroke. Kampo to Saishin Chiryo (Kampo & the

Newest Therapy) 2013; 22: 329-32. Ichushi Web ID: 2014077192

1. Objectives

To evaluate the effectiveness of saireito (柴苓湯) for acute ischemic stroke.

2. Design

Single facility (hospital neurology department). 4. Participants

Ninety-nine patients who gave verbal consent out of the acute ischemic stroke patients hospitalized between December 2010 and December 2011.

5. Intervention

Arm 1: Saireito administration group: TSUMURA Saireito (柴苓湯) Extract Granules (3g t.i.d.)

administered after each meal for two weeks (n=43). Arm 2: Non-administration group (n=56)

NIHSS (National Institutes of Health Stroke Scale) and mRS (modified Rankin Scale) comparison. 7. Main results

The results of a questionnaire taken after the first week of hospitalization showed that symptoms had been significantly alleviated in the saireito administration group. The NIHSS scores showed significant improvement in the saireito administration group compared to the non-administration group after the second week of hospitalization (P=0.020). The mRS scores showed significant improvement in the saireito administration group compared to the non-administration group after the first week (P=0.020) and the second week (P=0.011) of hospitalization.

8. Conclusions

Saireito is effective for acute ischemic stroke. 9. From Kampo medicine perspective

None.

10. Safety assessment in the article None.

This study used the NIHSS and the mRS to evaluate the effectiveness of saireito in acute ischemic stroke. It showed that saireito has a certain effect on symptoms after stroke. Much of saireito’s mechanism of action has not been elucidated, so comparing the scores for each item may provide clues to its mechanism of action, such as whether it is more effective for lower or upper limb symptoms.