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Kim, Sin, and Song: Current Status of Intervention Studies on Acupuncture for Parkinson’s Disease

Abstract

Objectives

The purpose of this study was to investigate the effect of acupuncture treatment (AT) in the tendency of increase of the need for AT for the treatment of Parkinson’s disease (PD) worldwide and to investigate the advancements in AT research in Korea and the future directions of research on this topic.

Methods

Until May 2017, the PubMed, Scopus, Medline, and four Korean databases were searched. The searched keywords were “Parkinson’s disease”, “Acupuncture”, and “Intervention study”. The intervention groups from all screened original studies were analyzed and the methods used to determine the effect of AT on PD were examined.

Results

A total of 17 studies were grouped by country on the basis of the first author’s position, of which 10 studies were conducted in China, four in the United States, two in Korea, and one in Brazil. The most common type of intervention was electroacupuncture (nine studies), followed by AT (six studies), and a combination of AT and bee venom AT (two studies). The most frequently used acupoints in AT were Baihui (GV20), Taichong (LR3), Zusanli (ST36), Sanyinjiao (SP6), and Yanglingquan (GB34). The most commonly used tool for evaluation of PD was the Unified Parkinson’s Disease Rating Scale III, which assesses motor functions.

Conclusion

The screened studies reported that there were no adverse effects of AT on drug therapy, and AT reduced the dose of drugs used in PD treatment. Future studies on PD treatment with AT should use the acupoints GV20, LR3, ST36, SP6, and GB34, and the meridians Gallbladder meridian and Governor Vessel. Clinical studies on PD should use CONSORT or STRICTA to ensure the quality of national studies and allow the development of new tools for the assessment of the effect of AT on PD using the above criteria.

초록

목적

본 연구의 목적은 전 세계적으로 파킨슨병 치료를 위한 침술 수요 증가 추세에 침술이 미치는 영향을 조사하고 이를 통하여 파킨슨병에 대한 한국의 침술 연구의 개선을 연구하고 향후 연구자들의 방향을 논의하는 것이다.

방법

총 7개 데이터베이스(Pubmed, Scopus, Medline 및 국내 4개 데이터베이스)에서 '파킨슨 병', '침', '중재 연구'를 키워드로 하여 2017년 5월까지 검색된 문헌을 참고하였다. 그리고 모든 원문의 중재연구 방법을 분석하고 각각의 원문에서 PD에 대한 침술 효과의 평가 방법의 상태를 조사했다.

결과

총 17편의 원문을 1저자 소속을 기준으로 하여 국가별로 분류하였을 때 중국이 10편, 미국이 4편, 한국이 2편, 브라질이 1편 검색되었다. 중재방법으로는 전침이 9편으로 원문 중 가장 많았고, 단독침이 6편, 그 외 침치료와 약침 및 봉약침 등이 결합된 원문이 2편이었다. 침 치료에서 가장 많이 다용된 혈위는 백회(GV20), 태충(LR3), 족삼리(ST36), 삼음교(SP6), 양릉천(GB34) 등이다. 파킨슨병의 평가도구는 UPDRS 중 운동기능 평가항목인 UPDRS Ⅲ가 17편의 원문 중 9편으로 가장 많이 사용되었다.

결론

각 연구에서 약물 치료와 침치료를 병행함으로 발생한 부작용은 없었으며 침술로 인해 약물 복용량도 줄일 수 있었다. 파킨슨병에 대한 향후 침술 연구를 위해 경혈은 GV20, LR3, ST36, SP6, GB34를 추천하고 경락은 족소양담경과 독맥을 권장한다. 향후 파킨슨병 임상 시험에서는 CONSORT 또는 STRICTA를 참고하여 국내 연구의 질을 보장하고 위 기준에 따라 침술 치료가 파킨슨병에 미치는 영향을 반영할 수 있는 새로운 평가 도구를 확립해야한다.

I. Introduction

Parkinson’s disease (PD) is the second-most common chronically progressive neurodegenerative disease worldwide. PD is associated with the degeneration of dopaminergic neurons and is clinically characterized by resting tremor, rigidity, bradykinesia, and postural instability1,2). The cause of PD is multifactorial, including a combination of genetic and environmental factors, but the exact cause is unknown1). Pathologic features include the death of melanin-containing dopaminergic neurons in melancholy densities. Diagnosis of PD is possible only by pathologic examination through autopsy or clinical findings. Treatment with levodopa, a precursor of dopamine, is the most effective treatment for PD to date, although non-pharmacological adjuvant therapies and surgical therapies are available1). However, there is no definitive treatment for PD. Furthermore, the long-term use of levodopa has adverse effects, the surgical outcome is poor, and the outcome of drug therapy has not improved1,3).
Therefore, the interest in complementary and alternative medicine (CAM) for PD therapy in substitution for conventional therapies is increasing. More than 40% of PD patients in the United States and Europe are using CAM, and an even higher percentage is using CAM in Europe and Asia4,5). Acupuncture treatment (AT) is one of the most commonly used treatment modalities for PD patients, and the greatest advantage is the absence of adverse effects and acupuncture does not affect drug response. Despite these advantages, the methodological deficiencies that limit the effectiveness of AT remain unknown because of the lack of objective criteria7). The preclinical studies that demonstrated the effectiveness of AT, including those by Kang et al.8), Liu et al.9), and Wattanathorn et al.10), serve as the basis for clinical research and are useful for the development of new treatment methods. However, the analysis of intervention methods in human studies is essential, to improve the quality of life and promote health11).
The purpose of this study was to investigate the effect of AT in the tendency of increase of the need for AT for the treatment of PD worldwide and to investigate the advancements in AT research in Korea and the future directions of research in this field.

II. Methods

1. Search methods

In this study, the databases PubMed, Scopus, and Medline were searched until May 2017. The studies which described studies conducted in Korea, were searched in the Korean databases DBpia, KISS, RISS, NDSL. The keywords used in the search were “Parkinson’s disease”, “Acupuncture”, and “Intervention study”. The corresponding keywords in the Korean language “pa-kin-seun-byeong”, “chim”, and “jung-jae-yeon-gu”, were searched in the Korean databases. The search strategy was adjusted for each database.

2. Inclusion and exclusion criteria

A total of 55 publications were identified. After the screening of the abstracts, the studies not related to PD and those that did not assess the effect of AT on the symptoms of PD were excluded. Studies conducted before 2015, experimental researches, review articles, and non-articles were also excluded (Fig. 1).

3. Data extraction

The therapies used in the intervention and control groups (AT, electroacupuncture (EA), and scalp acupuncture, among others) and the methods used to evaluate the effect of AT on PD were analyzed in all original studies.

III. Results

1. Publication characteristics

A total of 17 publications were grouped by country on the basis of the first author’s position, of which 10 studies were conducted in China, four in the United States, two in Korea, and one in Brazil (Fig. 2).
The classification of the original studies by type indicated that most studies (N=15) were randomized clinical trials (RCTs), one was a clinical trial, and one was a pilot study (Fig. 3). Fig. 4 classifies the studies by country (Fig. 4).
For proper comparison of all searched original studies, the studies were classified by the duration of PD, sample size, evaluation method, intervention group, and control group, among other parameters (Table 1).

2. Acupuncture treatment

The most common types of Intervention were EA (N=9), AT (N=6), and AT combined with bee venom AT (N=2). Among the nine original studies that used EA, in most studies the frequency was set to 100 Hz for the head and 4 Hz for the region below the elbow and knee (N=5), whereas in the remaining three studies frequency was set to a tolerable range. In AT, several acupoints were included or removed depending on the severity of symptoms, but the most frequently used acupoints were Baihui (GV20), Taichong (LR3), Zusanli (ST36), Sanyinjiao (SP6) and Yanglingquan (GB34) (Fig. 5).
The evaluation of the meridians in the searched studies (in one study, duplication of meridians used for treatment was excluded.), indicated that the most common meridians were Gallbladder meridian (GB) and Governor Vessel (GV). The use of the large intestine meridian (LI), stomach meridian (ST) and liver meridian (LR) was also common (Fig. 6).
In the case of scalp-acupuncture, the same acupoints (MS6, MS4, MS8, MS9, and MS14) were used in three studies (Huang et al.18), Huang et al.23), and Jiang et al.25)).

3. Evaluation methods

The tool used by most original studies (9 out of 17) for the evaluation of PD was the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III, which assesses motor functions. Six studies used the total efficacy score and comprehensively assessed the patient’s condition, and three studies used the Parkinson’s Disease Quality of Life Questionnaire (PDQL) and the shorter version of PDQL (PDQ-39) (Fig. 7).

4. Comparison with the control group

Among the 17 original studies, most studies (N=11) used drug monotherapy for the control groups, including Madopar (N=9), and levodopa (N=1). One study did not specify the active ingredient or drug name. In addition, four studies evaluated sham AT and one study did not evaluate any treatment.

IV. Discussion

PD is the second most common neurodegenerative disease after Alzheimer’s disease. The most common clinical symptoms are motor symptoms, including bradykinesia, rest tremor, rigidity, and postural and gait impairment. Non-motor symptoms include neuropsychiatric features, dysautonomia, sleep disorders, sensory dysfunction, pain, and fatigue, and the prevalence of these symptoms is increasing29). At present, drug therapy based on levodopa, a precursor of dopamine, is the treatment of choice for PD. However, the amount of levodopa or dopamine agonist usually is increased during therapy as PD advances because the disease is progressive and levodopa does not prevent disease progression. Symptoms such as non-motor wearing-off and motor fluctuations may occur with the long-term use of levodopa. Dopamine agonists may cause adverse effects such as nausea, vomiting, orthostatic hypotension, leg swelling, anorexia, and sleepiness1).
Although AT is one of the most commonly used alternative therapies for PD, few studies evaluated the effects of AT in PD patients6). Park et al30) and Kang et al31) reported that AT prevented 6-hydroxydopamine-induced neuronal death and inhibited microglial activation in PD animal models. Bee venom AT was also associated with neuroprotection32,33). In addition, Jia et al34) reported that AT improved the motor symptoms of PD by normalizing GABA levels in the midbrain. Other studies demonstrated the effect of AT on PD in animal models. However, Lee et al7) and Baek et al35) found no evidence of the effectiveness of AT, EA, and scalp acupuncture on PD. In fact, few studies evaluated the effectiveness of AT in PD patients6,19).
Of the screened original studies, ten were conducted in China, including nine RCTs and one clinical trial, in which AT was used and the control group was screened; 3 RCTs, 1 pilot study, were conducted in the United States, two RCTs were from Korea, and one RCT was from Brazil. Few intervention studies from Korea evaluated the effectiveness of AT in PD treatment. The retrieved articles were classified by the duration of PD, sample size, evaluation methods, intervention group, and control group. The most common interventions were EA (N=9) and, in these cases, the frequency was set to 4 Hz or 100 Hz or to a frequency that the patient could withstand. In 12 of the 17 original studies, AT was combined with drug therapy using Madopar or levodopa, and no adverse effects were observed in the evaluated studies. In this context, Ren et al20) suggested that AT might be effective in reducing the dosage of drugs used in PD treatment. Six original studies used AT alone and two studies used pharmacoacupuncture. Liu et al13) injected kakkonein extract into Fengchi (GB20) in combination with drug therapy to improve patient’s behavior, emotion, and activities of daily living, and observed short-term and long-term benefits. Moreover, Cho et al16) reported that bee venom AT was a promising adjunctive therapy for PD by injecting 0.1 mL of bee venom (0.001%) into acupoints Fengchi (GB20), Quchi (LI11), Yanglingquan (GB34), Zusanli (ST36), and Taichong (LR3).
The most commonly used acupoints and meridians in the intervention groups were GV20 (7 studies), followed by LR3, ST36, SP6, and GB34. GB and GV were the most commonly used meridians (8 studies). These acupoints and meridians should be used as a criterion for the selection of high-quality studies on AT for PD patients.
The UPDRS36) is the most widely used scale to assess the effect of clinical interventions on PD. It has four sections (I to VI), and section III evaluates motor functions37). UPDRS III is used most often because the total UPDRS score is inefficient in many cases. Although it was used in most screened studies (9 out of 17), UPDRS III does not evaluate the effect of AT on PD, and thus a new standard should be developed38,39). Some studies reported that the evaluation of the effect of AT on PD is limited by the sample size7,35,40). In addition, the effectiveness of AT could be assessed because the quality of the studies was poor. Therefore, high-quality clinical studies are necessary to evaluate the effectiveness of AT and thus provide valuable information to physicians and patients. The methodological deficiencies can be overcome by using Consolidated Standards of Reporting Trials (CONSORT)41) and Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA)42) to ensure the quality of research.

V. Conclusions

The purpose of this study was to provide directions for research on AT in PD patients in Korea by reviewing national and international intervention studies.
  1. AT for PD improves all aspects of daily life functions, including motor and neurological symptoms.

  2. The screened studies reported that there were no adverse effects of AT on drug therapy, and AT reduced the dose of drugs used during PD treatment.

  3. Future studies on AT for PD should use acupoints Baihui (GV20), Taichong (LR3), Zusanli (ST36), Sanyinjiao (SP6), and Yanglingquan (GB34) and meridians GB and GV.

  4. Clinical studies on PD should use CONSORT or STRICTA to ensure the quality of national studies and allow the development of new tools to evaluate the effect of AT on PD using the above criteria.

Fig. 1
Flowchart of the study selection process
acup-34-3-13f1.tif
Fig. 2
Number of original studies by country
acup-34-3-13f2.tif
Fig. 3
Number of original studies screened by type
acup-34-3-13f3.tif
Fig. 4
Number of studies screened by country
acup-34-3-13f4.tif
Fig. 5
Number of acupoints used in the screened studies
acup-34-3-13f5.tif
Fig. 6
Number of meridians used in the screened studies
acup-34-3-13f6.tif
Fig. 7
Evaluation methods used in the screened studies
acup-34-3-13f7.tif
Table 1
Summary of intervention studies on Parkinson’s disease
Ref. Duration of PD(y) (sample size) Hoehn & Yahr scale Evaluation methods Intervention group Control group
Aroxa et al12) n.r. (11/11)
HY 1–3(avg. n.r.)
(1) PDSS
(2) Total efficacy
(A) AT+medication (LR3, SP6, LI4, TE5, HT7, PC6, LI11, GB20 once a week for 8 weeks, 30 min) (B) Medication (n.r.)
Liu et al13) (A) 5.8 (B) 6.4 (C) 6.0 (45/45/45)
HY 1–3(avg. 2.8)
(1) UPDRS III
(2) Total efficacy
(A) PA+medication (GB20 kakkonein extract 1 mℓ, once every days for 8 weeks, n.r.) (B) AT (GB20 once every days for 8 weeks, n.r.)
(C) Medication (Madopar)
Toosizadeh et al14) n.r. (10/5)
HY n.r.
(1) UPDRS (I, II, III)
(2) Postural balance assessment
(A) EA (GV20, GV14, ST36, LI4, GB34, LR3, KI3, SP6, BL40 once a week for 3 weeks, 4 or 100 Hz, 30 min) (B) Sham treatment
Xia et al15) n.r. (30/30)
HY n.r.
(1) HAMD (A) EA+medication (GV20, EX-HN3, EX-HN1, LR3, SP6 every other day for 3 months, frequency within tolerable range, 30 min) (B) Medication (Madopar)
Cho et al16) (A) 5.0 (B) 6.0 (C) 5.0 (15/14/14)
HY 1–3(avg. n.r.)
(1) Total UPDRS (2) PDQL
(3) BDI (4) BBS
(5) 30 m gait speed(s)
(A) BVA (GB20, LI11, GB34, ST36, LR3 0.005% 0.1 mℓ, twice a week for 8 weeks)
(B) AT (GB20, LI11, GB34, ST36, LR3 twice a week for 8 weeks, 20 min)
(C) None
Chen et al17) (A) 5.4 (B) 6.4 (30/30)
HY 1–3(avg. 2.1)
(1) UPDRS III (A) EA+medication (GV20, EX-HN1, EX-HN3 once every days for 6 weeks, frequency within tolerable range, 1 hr) (B) Medication (Madopar, tolterodine)
Huang et al18) (A) 5.4 (B) 6.04 (5/5)
HY 1.5–3(avg. 2.0)
(1) SPECT (A) Scalp EA+medication (MS6, MS4, MS8, MS9, MS14 once every days for 5 weeks, 50 Hz, 30 min) (B) Medication (levodopa)
Chae et al19) (A),(B),(C) 3.0 (10/10/10)
HY avg. 1.6
(1) fMRI (A) AT (GB34 inserting to 10 mm depth, 3 min) (B) Covert placebo (GB34 non-penetrating, 3 min)
(C) Overt placebo
Ren et al20) n.r. (50/30)
HY n.r.
(1) Total efficacy (A) AT+medication (TE14, TE2, PC2, PC7 once every 3–5 days, 10 courses each, 30 min) (B) Medication (Madopar)
Chang et al21) (A) 3.4, (B) 3.6 (30/30)
HY 2–3(avg. n.r.)
(1) Total UPDRS
(2) Total efficacy
(A) AT+medication (GV24, GV20, EX-HN1 once every days for 30 days, 30 min) (B) Medication (Madopar)
Chen et al22) (A) 4.85, (B) 4.65 (30/30)
HY n.r.
(1) Webster scale
(2) Total efficacy
(A) AT+medication (CV12, CV10, CV6, CV4, KI13, KI17, ST24 once every days for 10 days, 30 min) (B) Medication (Madopar)
Huang et al23) (A) 5.4 (B) 6.4 (5/5)
HY 1–3(avg. 2.0)
(1) SPECT (A) Scalp EA+medication (MS6, MS4, MS8, MS9, MS14 once every days for 5 weeks, 100 Hz, 30 min) (B) Medication (Madopar)
Wang et al24) (A) 2.6 (B) 2.2 (37/39)
HY 2–3(avg. n.r.)
(1) Measuring of SOD, LPO (A) Scalp EA+medication (EX-HN1, GB6, GV21, GB5, GV17, GV16, BL9, BL10, GB19, GB20 once every days for 30 days, frequency within tolerable range, 30 min (B) Medication (Madopar)
Jiang et al25) (A) 5.4, (B) 6.4 (15/15)
HY 1.5–3(avg. 2.2)
(1) Webster scale
(2) UPDRS III
(3) Total efficacy
(A) Scalp EA+medication (MS6, MS4, MS8, MS9, MS14 5 times weekly for 6 weeks, 100 Hz, 30 min) (B) Medication (Madopar)
Cristian et al26) n.r. (7/7)
HY 2–3(avg. n.r.)
(1) UPDRS III (2) PDQ-39
(3) GDS
(A) EA (KI3, KI10, BL60, LR3, ST41, ST36, GB34, LI4, GV20 inserting into muscle, 4 Hz, 20 min) (B) Sham EA (nonacupoint, inserting just under the skin, 4 Hz, 20 min)
Kluger et al27) n.r. (47/47)
HY 1–4(avg. 2.3)
(1) MFIS (2) UPDRS III
(3) PDQ-39
(A) AT (GV20, GV24, CV6, LI10, HT7, ST36, SP6 biweekly for 6 weeks, 30 min) (B) Sham AT (nonacupoint)
Lei et al28) (A) 6.2 (B) 5.2 (10/5)
HY avg. 2.9
(1) UPDRS (I, II, III)
(2) Gait evaluation
(A) EA+medication (GV20, GV14, LI4, ST36, GB34, BL40, SP6, KI3, LR3 once a week for 3 weeks, 4 or 100 Hz, 30 min) (B) Sham EA (nonacupoint, inserting just under the skin, 0 or 4 or 100 Hz, 30 min)

n.r.=Not reported, AT=Acupuncture treatment, HY=Hoehn and Yahr scale, avg.=average, BVA=Bee venom acupuncture, PA=Pharmacoacupunctre, EA=Electroacupuncture, UPDRS=Unified Parkinson’s Disease Rating Scale, BBS=Berg Balance Scale, PDQL=Parkinson’s Disease Quality of Life Questionnaire, BDI=Beck Depression Inventory. SPECT=Single Photon Emission Computed Tomography.

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Review of Clinical Studies on Acupuncture for Shoulder-hand syndrome  2016 December;33(4)
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