ORIGINAL ARTICLE pissn , eissn J of Oriental Neuropsychiatry 2016;27(4): 화병의한의학적치료

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1 ORIGINAL ARTICLE pissn , eissn J of Oriental Neuropsychiatry 2016;27(4): 화병의한의학적치료에대한연구동향 서효원, 최은지, 김상호 *, 김동희, 김락형, 김종우,, 이재혁, 임재환 **, 최우진, 정선용, 경희대학교대학원한방신경정신과, 대구한의대학교포항한방병원신경정신과 *, 동의대학교부속한방병원한방신경정신과, 우석대학교한의과대학한방신경정신과학교실, 경희대학교한의과대학한방신경정신과학교실, 강동경희대학교병원한방신경정신과, 세명대학교한의과대학한방신경정신과학교실, 경희밝은마음한의원 **, 상지대학교한의과대학한방신경정신과학교실 Current Trends in Intervention Studies of in Korean Medicine Hyo-Weon Suh, Eun-Ji Choi, Sang-Ho Kim*, Dong Hee Kim, Lak-Hyung Kim, Jong-Woo Kim,, Jae-Hyok Lee, Jae-Hwan Lim**, Woo-Jin Choi, Sun-Yong Chung, Department of Neuropsychiatry, Graduate School, Kyung Hee University, *Department of Neuropsychiatry, Pohang Oriental Hospital of Daegu Haany University, Department of Oriental Neuropsychiatry, Dongeui Oriental Medical Hospital of Dongeui University, Department of Neuropsychiatry, College of Korean Medicine, Woo-Suk University, Department of Neuropsychiatry, College of Korean Medicine, Kyung Hee University, Department of Korean Neuropsychiatry, Gangdong Kyung Hee University Hospital, Department of Neuropsychiatry, College of Korean Medicine, Semyung University, **Kyung Hee Brightmind Korean Medical Clinic, Department of Neuropsychiatry, College of Korean Medicine, Sangji University Received: November 25, 2016 Revised: December 13, 2016 Accepted: December 21, 2016 Correspondence to Sun-Yong Chung Department of Neuropsychiatry, College of Korean Medicine, Kyung Hee University, Department of Korean Neuropsychiatry, Gangdong Kyung Hee University Hospital, 149, Sangil-dong, Gangdong-gu, Seoul, Korea. Tel: Fax: lovepwr@khu.ac.kr Acknowledgement This was supported by the Traditional Korean Medicine R&D program funded by the Ministry of Health & Welfare through the Korea Health Industry Development Institute (KHIDI) (HB16C0068). Objectives: To determine the general characteristics of clinical studies about and assess their limitations and alternatives. Methods: Clinical studies that examined the effects of traditional Korean medicine intervention on were included in this. A systematic search of English, Chinese, Japanese, and Korean databases was performed. The characteristics of included articles were described and those articles were assessed by Risk of Bias (RoB) tool or Risk of Bias for Nonrandomized Studies (RoBANS) tool. Results: Sixteen articles were selected from 1,826 articles. Most clinical studies about were published in Korea. The number of conducted trials was insufficient. The prevailing design was randomized controlled trial. Traditional Korean medicine intervention used in the trials were acupuncture, herbal medicine, counselling, meditation, emotional freedom technique (EFT), music therapy, art therapy, and multi intervention program. Herbal medicine used placebo as control while non-pharmacological intervention mostly used no treatment as control. Most of the trials were supported by the government. Therefore, financial conflict of interest might not exist for results. We judged that some studies had a high risk of bias. In general, most of the studies with a high risk of bias were non-pharmacological intervention studies, and the risk of bias was mainly due to lack of blinding. Conclusions: More clinical studies of are needed. There are some issues about a suitable comparison and effective blinding strategy for non-pharmacological. Improving methodological quality is required. Key Words:, Anger syndrome, Complementary and alternative medicine, Korean medicine. Copyright 2016 by The Korean Society of Oriental Neuropsychiatry. All rights reserved. CC This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

2 262 Current Trends in Intervention Studies of in Korean Medicine I. 서론 화병은울화병의준말로, 분노와같은부정적인감정이해소되지못하여화의양상으로폭발하는증상이있는증후군으로정의된다 1). 화병은가슴의답답함, 열감, 치밀어오름, 목이나명치에덩어리가뭉쳐있는느낌, 억울하고분한감정, 마음의응어리나한을핵심증상으로하여구건ㆍ구갈, 두통ㆍ현훈, 입면난또는빈각, 심계ㆍ정충이관련신체증상으로나타나고사소한일에도화가나거나분노가치밂, 삶이허무하게느껴지거나자신이초라하고불쌍하게느껴짐, 두렵거나깜짝깜짝놀람등이관련심리증상으로나타날수있다. 이러한증상들이명확하게스트레스와관련되어있을때화병으로진단할수있다 2). 화병은한국의문화특수성을지닌질환으로, 1603 년조선왕조실록에서부터화병에대한기록을찾을수있으나한의학의서에서는화병의개념을정확히찾아보기는어렵고 3), 1994 년미국정신의학회가발간한정신장애의진단및통계편람제 4판 (Diagnostic and statistical manual of mental disorders-4th edition, DSM-IV) 에서도화병은한국의문화관련증후군으로등재되어있다 4). 2000년대에이르러화병의진단에대한연구가본격적으로시작되어김종우등에의해 2003년에최초로화병의진단기준이정립되었다 5). 이후의학계에서는화병증상에대한 Paroxetine 의효과를보고한임상시험이발표되었으나후속연구가수행되지않고있어화병에대한표준치료는확립되어있지않다 6). 반면, 한의계에서는보건복지부보건산업진흥원한의약연구개발사업한의임상진료지침개발사업 ( 과제번호 B080009) 의일환으로전문가의견과선행연구결과등을종합하여 2013년화병임상진료지침이개발되었으며최근보건복지부한의표준임상진료지침개발대상질환으로선정되어예비개정안이출간된상태이다. 한의표준임상진료지침개발사업은제3차한의약육성발전종합계획에따라한의약의표준화및과학화를위해추진되는사업으로화병의경우 2018 년까지임상연구를추진하고최종개정안을개발하게된다. 따라서본연구에서는현재까지이루어진화병의한의학적치료에대한연구동향을분석하여임상연구의설계및수행과임상진료지침개발에도움이되고자하였다. 이에논문출판현황을파악하고, 개별연구의연구대상및방법 을검토하여일반적인연구특성을정리하였다. 뿐만아니라, 임상시험심사위원회 (Institutional Review Board, IRB) 승인및이해상충여부, 연구자금출처등연구윤리와관련된요소를분석하여최근떠오르고있는윤리적쟁점들에대해평가하였다. 마지막으로, 화병임상연구논문의비뚤림위험도를평가하여지금까지수행되었던화병임상연구의한계및그에대한해결방안을제시하고, 앞으로의임상연구수행및결과보고에대한발전방향을제안하고자한다. II. 연구대상및방법 1. 선정기준화병또는관련질환및증후군을대상으로한의학적치료를중재로사용한임상연구를포함하였다. 화병을대상으로하지않거나중재개입이없는경우, 화병에대한평가지표가없거나정량적결과를보고하지않은연구는배제하였다. 연구설계상임상연구가아닌경우 (in vivo 또는 in vitro 연구 ), 원저가아닌경우 ( 종설이나체계적문헌고찰 ), 증례보고는배제하였다. 2. 정보원및검색전략국외 DB에서 CENTRAL, PubMed, EMBASE, AMED 와 CNKI, J-STAGE 를선정하였으며, 국내 DB에서학술연구정보서비스 (RISS), 과학기술정보통합서비스 (NDSL), 한국한의학연구원의전통의학정보보털 (OASIS), 한국전통지식포탈, KoreaMed 를선정하였다 년 8월 31일까지선정된 DB에등록된모든문헌에대해언어및기간제한없이검색을시행하였다. 추가로체계적문헌고찰이나종설에서인용한참고문헌을수기검색하였다. 화병으로진단을받거나화병과관련이있는질환및증후군을대상으로하여, 다음과같은검색어를포함하여검색하였다 (Table 1). 3. 문헌선택문헌선택과정에 8인의연구자가참여하였으며, 중복배제, 제목및초록확인후배제, 원문확인후배제의순서로진행하였다. 1차로제목과초록수준에서화병과관련없거나중재연구가아닌문헌을배제하고, 원문을검토하여선정기준에맞지않는문헌을추가로배제하였다. 동일문헌

3 HW Suh, EJ Choi, SH Kim, DH Kim, LH Kim, JW Kim, JH Lee, JH Lim, WJ Choi, SY Chung 263 Table 1. Database Search Terms Korean terms English terms Chinese terms 화병 홧병 울화병 Hwa-byung Hwabyeong Hwa-byeong Fire disease Fire disorder Fire syndrome Fire illness 火病 분노증후군 분노장애 Anger disease Anger disorder Anger syndrome Anger illness 문화관련증후군 Culture bound syndrome Culture related syndrome Culture bound disorder Culture related disorder 愤怒综合征 愤怒障碍 愤怒疾病 文化相关精神综合征 文化相关精神障碍 文化相关精神疾病 있다 7). RoBANS는비무작위연구의비뚤림위험평가를위해 2009 년개발된도구로비무작위연구의체크리스트도구중타당도가입증된유일한도구이다. RoB 도구와유사하게체크리스트방식과영역평가방식이결합된형태를갖추고있다. 비뚤림을분류하여기본영역으로설정하였으며, 비무작위연구에서발생할수있는비뚤림위험의평가영역을정의하고, 이에대한세부기술과평가방식을제시하였다. RoB 와마찬가지로비뚤림위험을높음, 낮음, 불확실로판단하도록되어있다 8). III. 결과 1. 문헌선택 에대해 2인의연구자가독립적으로선정여부를판단한뒤연구자간일치여부를확인하였으며, 의견이불일치할경우해당문헌을검토하지않은제3의연구자의자문을구하여최종포함여부를결정하였다. 4. 자료추출임상연구의특징을분석하기위해연구수행연도, 수행국가, 의료환경및연구기관수, 연구설계, 대상, 중재및대조군, 연구기간, 결과변수, IRB 승인및이해상충여부, 연구자금출처에대해자료를추출하였다. 5. 비뚤림위험도평가선정된논문들은연구설계에따라무작위대조군연구및비무작위대조군연구는 RoB (Risk of Bias), 관찰연구는 RoBANS (Risk of Bias Assessment tool for Non-randomised Study) 로비뚤림위험도를평가하였다. RoB 는코크란그룹에서개발한무작위배정대조군연구의비뚤림위험평가도구로, 체크리스트방식과영역평가방식이결합된형태를갖추고있으며, 문항을단순화한반면에같은문항에대한주관적이거나자의적인답변의가능성을최소화하고평가자의연구방법론에대한이해도와숙련도에따른평가결과의변동을최소화하기위한노력을기울여만들어진도구이다. 각영역에대하여비뚤림위험을 높음 (high risk of bias, +, 낮음 (low risk of bias, -, 또는 불확실 (unclear risk of bias,? 로판단하도록하고 국내외 DB에서중복된문헌을제외하고총 1,826 편의문헌이검색되어독립된 8인의연구자가 1차로제목과초록을보고화병에대한한의학중재연구와관련없는문헌을배제하여 366편의문헌을선정하였다. 1차선정된논문에대하여 3인의연구자가독립적으로본문을검토하면서선정기준을만족하지않는논문을제외하였다. 2차선정에서 25 편의논문이포함되었고, 최종선정과정에서화병치료와관련이있지만화병으로진단받은대상자가아닌연구, 화병평가지표가없는연구, 정량적결과를보고하지않은 9편의연구를배제하였다 (Table 2). 따라서최종적으로 16편의논문이선정되었다 9-24). 2. 출판현황 1) 출판연도화병임상연구논문을출판연도별로살펴보면 2004 년과 2006년에 1편씩발표되고, 2007년에 2편, 2011년에 1 편이발표되어 2012 년이전까지는매년발표되는연구가없거나출판되는문헌수가 1 2편에불과했다 년에는논문수가급증하여 5편의연구가발표되었으나 2013년, 2014년에는 1편씩만발표되었고 2015년에다시 4편으로증가하였다 (Fig. 1). 2) 출판저널선정된문헌 16편중학위논문은 5편, 학술논문은 11편

4 264 Current Trends in Intervention Studies of in Korean Medicine Table 2. Excluded Articles with Reasons Study design* Participant characteristics (Diagnosis standard) 2003 Seo 25) RCT HB patients (Unvalidated questionnaire) 2007 Choi 26) CCT Self reporting of current or past suffering from symptoms of 2010 Hwang 27) RCT Highly stressed adults 2013 Hwang 28) RCT Highly stressed adults 2013 Cho 29) Qualitative HB patients ( ) 2014 Bae 30) RCT HB patients with insomnia (, ISI) 2014 Song 31) Qualitative HB patients ( ) 2015 Choi 32) RCT HB patients (HBDIS) 2015 Jeong 33) Beforeafter Healthy adults Intervention External Gigong+ Korean hand acupuncture Psychiatric nursing program Brief qigong-based stress reduction program Brief qigong-based stress reduction program Group Loving-Kindness meditation Acupuncture at Shigu, Ahnmyun, BL62, and KI6 Comparison Korean hand acupuncture Number of (Intervention/ Comparison) 24 (12/12) No treatment 26 (15/11) No treatment 50 (25/25) No treatment 50 (25/25) - 9 (9/-) No treatment 37 (19/18) Group EFT - 13 (13/-) Sa-am acupuncture (Simpojeonggyeok) Placebo (superficial insertion at nonacupoint) 50 (25/25) Maum meditation (120/-) Duration (Length of follow-up) 1 day 4 weeks 4 weeks 4 weeks 8 weeks 2 weeks (2 weeks) 4 weeks (4 weeks) 2 weeks (2 weeks) 8 days Outcome Meridian Cardiac CMP change SCL-90-R TCI, PSS, HB scale, STAI, WHOQOL-BREF PSS, STAI, HB scale, WHOQOL-BREF, salivary cortisol Qualitative data BVP, RR, BT, Skin conductance, EMG Qualitative data BP, RR, BT Modified HBDIS, VAS, SCL-90-R, MCS Reasons for exclusion Ineligible outcomes Ineligible Ineligible Ineligible and duplicates No quantitative data Ineligible outcomes No quantitative data Ineligible outcomes Ineligible *RCT: Randomized controlled trial, CCT: Controlled Clinical Trial. BP: Blood Pressure, BT: Body Temperature, BVP: Blood volume pulse, EFT: Emotional Freedom Techniques, EMG: Electromyography, F/U: Follow-up, HB:, HBDIS: Hwa-Byung Diagnostic Interview Schedule, ISI: Insomnia Severity Index, MCS: Multidimensional Coping Scale, PSS: Perceived Stress Scale, RR: Respiration Rate, : Structured Clinical Interview for DSM, STAI: State-Trait Anxiety Inventory, SCL-90-R: Symptom Checklist-90-Revised, TCI: Temperature and Character Inventory, VAS: Visual Analogue Scale, WHOQOL-BREF: The World Health Organization Quality of Life Scale-BREF. 이었다. 학술논문의경우국내학술지에 10편, 해외학술지에 1편이발표되었다. 3. 연구특성 16편의논문을분석하여임상연구에대한정보를추출하였다 (Table 3). 1) 연구수행연도 Fig. 1. Numbers of published articles about ( ). 환자모집시기를기준으로화병임상연구의수행연도를분석하였을때, 화병임상연구는 2003 년부터시작되어 2010

5 HW Suh, EJ Choi, SH Kim, DH Kim, LH Kim, JW Kim, JH Lee, JH Lim, WJ Choi, SY Chung 265 Table 3. Characteristics of Included Studies Enrollment (from) Study design* 2004 Park 9) 2003 Beforeafter 2006 Bae 10) 2004 Beforeafter 2007 Park 11) 2006 Beforeafter Diagnosis standard HBDIS HBDIS 2007 Jung 12) 2006 RCT Intervention control program Yuldahanso-tang (Reduohanshaotang) Comparison Number of (Intervention/ Comparison) - 16 (16/-) - 37 (37/-) HBDIS Music-listening - 9 (9/-) Sa-am acupuncture (Simseunggyeok) 2011 Choi 13) 2010 RCT HBDIS Sa-am acupuncture (Simpojeonggyeok) 2012 Kim 14) 2008 RCT 2012 Song 15) 2011 Beforeafter 2012 Lee 16) 2010 RCT, ISI 2012 Jung 17) 2010 Beforeafter 2012 Hong 18) 2012 Beforeafter 2013 Kim 19) 2012 RCT Modified 2014 You 20) 2010, unclear Bunsimgi-eum (Fenxinqiyun) Placebo (superficial insertion at nonacupoint) Placebo (superficial insertion at nonacupoint) 26 (13/13) 50 (25/25) Placebo 144 (73/71) Group MBSR - 10 (10/-) Acupuncture at Shigu, Ahnmyun, BL62, and KI6 Acupuncture at HT7, SP6, Indang (EX-HN3), and CV17 Forest healing program Group art therapy No treatment 37 (19/18) - 15 (15/-) - 20 (20/-) No treatment RCT HB-S Group MBSR No treatment 14 (7/7) 22 (11/11) 2015 Suh 21) 2013 RCT Group EFT Group PMR 27 (15/12) 2015 Kim 22) 2015 CCT HB-S Group ACT No 24 treatment (12/12) Duration (Length of follow-up) 4 weeks (1 months) 2 weeks 15 days (6 weeks) 2 weeks (2 weeks) 2 weeks (2 weeks) 8 weeks (4 weeks) 8 weeks 2 weeks (2 weeks) days Outcome STAXI, BDI, STAI, modified HB scale, pressure pain threshold Modified HB scale, STAXI, STAI, BDI HB-M, STAXI, STAI, BDI, HRV HB-M, HB scale, STAXI, STAI, BDI VAS for chest discomfort, HB-M, STAXI, STAI, BDI HB scale, STAXI, HAD, MAAS, DERS, SCS, AAQ ISI, PSQI, HB-M, HB scale, STAXI, STAI, BDI HRV, modified HBDIS, STAI, BDI, VAS 3 days HB-E, BDI, STAI, STAXI, HOQOL-BREF, HRV 7 weeks 8 weeks 4 weeks (5 weeks) 8 weeks (only intervention group, 8 weeks) Modified HB scale, CES-D, STAI, SRI, MAAS, AAQ, SCL-90-R HB scale, STAXI, STAI, SCL-90-R HB scale, STAXI, VLQ, PWBS

6 266 Current Trends in Intervention Studies of in Korean Medicine Table 3. Continued Enrollment (from) Study design* Diagnosis standard Intervention Comparison 2015 Lee 23) 2014 CCT HB-S Group ACT No treatment 2015 Choi 24) 2011 RCT (Multicenter trial), HAM-A Sihogayonggolmoryeotang (Chaihujialonggumulitang) Number of (Intervention/ Comparison) 19 (13/6) Placebo 152 (75/77) Duration (Length of follow-up) 8 weeks (only intervention group, 4 weeks) 8 weeks Outcome HB scale, STAXI, AAQ-II HAMA, HB-I, HB-M, BDI, STAI, STAXI, WHOQOL-BREF, RSE, GSES *RCT: Randomized controlled trial, CCT: Controlled Clinical Trial. AAQ: Acceptance-Action Questionnaire, ACT: Acceptance-Commitment Therapy, BDI: Beck Depression Invention, CES-D: the Center for Epidemiologic Studies- Depression Scale, DERS: Difficulties in Emotional Regulation Scale, EFT: Emotional Freedom Techniques, F/U: Follow-up, GSES: General Self-Efficacy Scale, HAD: Hospital Anxiety Scale, HAMA: Hamilton Anxiety Rating Scale, HB:, HB-E: the Instrument of Oriental Medical Evaluation for Hwa-Byung, HB-I: the Instrument of Pattern Identification for Hwa-byung, HB-M: Likert scale for major symptom of HB, HB-S: Symptom Scale, HBDIS: Hwa-Byung Diagnostic Interview Schedule, HRV: Heart Rate Variability, ISI: Insomnia Severity Index, MAAS: Mindfulness Attention Awareness Scale, MBSR: Mindfulness-Based Stress Reduction program, PMR: Progressive Muscle Relaxation, PSQI: Pittsburgh Sleep Quality Index, PWBS: Psychological Well-Being Scale, RSE: Rosenberg Self-Esteem inventory, : Structured Clinical Interview for DSM, SCL-90-R: Symptom Checklist-90-Revised, SCS: Self-Compassion Scale, SRI: Stress Response Index, STAI: State-Trait Anxiety Inventory, STAXI: State-Trait Anger Expression Inventory, VAS: Visual Analogue Scale, VLQ: Valued Living Questionnaire, WHOQOL-BREF: The World Health Organization Quality of Life Scale-BREF. 년에급증하였다가점차적으로감소하는경향을보이고있어논문출판현황과는다소차이를보이고있다 (Fig. 2). 2) 수행국가, 의료환경및연구기관수 화병임상연구는모두우리나라에서국내연구자들에의해수행되었으며 16건의임상연구중병원외래환경에서수행된연구가대부분이었고 (n=11), 상담센터또는심리치료기관등환경이명확하지는않지만편안한공간에서상담및심리치료를실시한연구가일부있었으며 (n=4), 휴양림에서수행된연구가 1편있었다. 시호가용골모려탕의효과를본무작위배정대조군연구 1건만다기관임상연구로수행되었다. 3) 연구설계무작위배정대조군연구가가장높은빈도를차지했고 (n=8), 다음으로단일군을대상으로한의학적치료효과를본전후연구 (n=6), 무작위배정을하지않은대조군연구 (n=2) 순으로나타났다. 무작위배정대조군연구와비무작위대조군연구는모두 2-arm parallel design 으로설계되었다. 연구대상자수는 9명에서 152명으로다양했다. Fig. 2. Numbers of clinical studies for ( ). 4) 대상자선정기준 (1) 포함기준화병임상연구는모두 세성인화병환자를대상으로하였으며, 화병진단도구는화병진단을위한구조적면담도구 (Structured Clinical Interview for DSM, ), 화병면담검사 ( Diagnostic Interview Schedule, HBDIS), 화병증상척도가사용되었다. 그중화병 가가장많이이용되었고 (n=9), 이외에 HBDIS (n=4), 화병증상척도 (n=3) 가사용되었다. 연구목적에따라일부임상연구에서는 Insomnia Severity Index (ISI), Hamilton Anxiety

7 HW Suh, EJ Choi, SH Kim, DH Kim, LH Kim, JW Kim, JH Lee, JH Lim, WJ Choi, SY Chung 267 Rating Scale (HAMA) 등의척도평가를통해불면이나불안이동반된화병환자들만 (ISI 8, HAMA 17) 대상자로포함하기도하였다. (2) 배제기준대부분의임상연구에서는망상, 환각등의정신증적양상이있거나과거력이있는경우, 조증삽화, 경조증삽화, 혼재성삽화가한번이라도있었던경우, 알코올또는다른물질남용 / 의존이있거나과거력이있는경우, 증상유발에영향을줄것으로판단되는물질을지속적으로투여하여야하는경우 ( 스테로이드등 ), 현재증상유발에영향을줄것으로판단되는의학적상태에있는경우 ( 갑상성기능항진증, 갑상선종, 뇌의기질적질환등 ), 간암또는간경변증, 만성신부전, 울혈성심부전등으로치료중인경우, 임신부, 수유부또는적절한피임방법을사용하지않는가임기여성, 기타임상시험을수행하기어렵다고판단되는경우배제하였다. 연구에따라서는증상지속기간이 6개월미만인경우 (n=3) 또는향정신약물을복용중인경우 (n=2) 배제하기도하였다. 반면, 6편의연구에서는배제기준을구체적으로설정하지않았다. 5) 중재및대조군 16건의임상연구에서총 9개의중재가사용되었는데, 침연구가 4건, 한약연구가 3건, 상담, 명상이각각 2건, Emotional Freedom Techniques (EFT), 음악치료, 미술치료, 화병관리프로그램과산림치유프로그램연구가각각 1건씩존재하였다. (1) 침침임상연구에사용된침구처방을살펴보면화병핵심증상에대해사암침심승격과심포정격, 화병환자의불면에대해시구 ( 視區 ), 안면 ( 安眠 ), 신맥사조해보를사용하였으며, 불안을동반한화병환자에대해신문, 삼음교, 인당, 전중을사용한연구가있었다. 총 4편의침임상연구중 3편이무작위배정대조군연구, 1편이단일군전후연구로수행되었다. 무작위배정대조군연구에서는비경혈부위에천자하는방식으로대조군을설정하거나 (n=2) 시험군과동일한시간동안복와위자세는유지하되어떠한시술이나조작을일체시행하지않는무처치군을대조군으로설정하였으며 (n=1) 2주동안치료하고 2 주후경과관찰을시행하였다. 전후연구에서는 3 4일간 격으로 4회침치료를시행하였고경과관찰은시행하지않았다. (2) 한약한약임상연구에서는분심기음, 시호가용골모려탕, 열다한소탕처방이사용되었다. 총 3편의임상연구중 2편이무작위배정대조군연구, 1편이단일군전후연구였다. 무작위배정대조군연구에서는성상과제형이동일한위약을대조군으로설정하고 8주동안치료하였으며 1편의연구에서는 4주후경과관찰하였고다른 1편의연구에서는경과관찰하지않았다. 전후연구에서는한약을 2주동안복용토록하고경과관찰은시행하지않았다. (3) 상담상담을활용한임상연구에서는수용전념상담이중재로사용되었다. 총 2편의비무작위대조군연구가있었고수용전념집단상담에대해무처치대기군을대조군으로설정하였다. 집단상담을 8주동안실시하고 4주동안경과관찰하였다. 대기군에대해서는경과관찰을시행하지않았다. (4) 명상명상을중재로한임상연구에서는마음챙김단체명상이사용되었다. 총 2건의임상연구중 1건 (You 2014) 은무작위배정대조군연구였으며 1건 (Song 2012) 은전후연구였다. 무작위배정대조군연구에서는마음챙김명상에대해대기군을대조군으로설정하였다. 마음챙김명상은 8주동안진행되었으며두연구모두경과관찰은시행하지않았다. (5) EFT EFT를사용한임상연구는무작위배정대조군연구 1편이었고, 점진적근육이완법을활성대조군으로사용하였다. 총 4주동안치료를시행하고치료종료후 5주까지경과관찰하였다. (6) 음악치료음악치료에대한임상연구는전후연구로설계되었다. 음악청취중재로 5 10 분내외의 6곡이사용되었는데화병환자들에게 Gluck 의 Melodie, Vitali 의 Chaconne, Shostakovich 의 Jazz suite No.2 Waltz, Mozart 의 Clarinet Concerto, Mascani의 Cavalleria Rusticana - Intermezzo Sinfonico, Elgar 의 Salut da'mour 순서대로감상하도록하

8 268 Current Trends in Intervention Studies of in Korean Medicine 였다. 집중적인중재기간은 15일이었으며이후에도환자들이스스로음악을듣도록교육하고 6주후경과관찰하였다. (7) 미술치료미술치료에대한임상연구는무작위배정대조군연구로진행되었다. 집단미술치료에대해무처치군을대조군으로설정하고주 1 2 회빈도로총 10회기에걸쳐 7주동안연구가진행되었다. (8) 복합중재프로그램복합중재프로그램으로서화병관리프로그램과산림치유프로그램에대한전후연구가 1편씩있었다. 화병관리프로그램은인지변화유도, 지지체계구성및이완등의요소로구성되고 1회기마다 2시간 30분 3시간씩총 4회기에걸쳐진행되었다. 산림치유프로그램은약선음식, 약차, 음악치료, 기공, 족욕, 향기요법, 화병교육등다양한활동으로구성되며 2박 3일에걸쳐삼림욕장에서진행되었다. 6) 결과변수 (1) 화병평가지표화병평가지표로는화병척도가가장많이사용되었고 (n=9), 이외에화병의진단기준에해당하는증상을평가문항으로활용한연구가많았는데화병 의핵심증상에대해 5점리커트척도로평가하도록한연구도있었고 (n=5) 화병 를변형하거나 (n=2) HBDIS를변형하여사용하기도하였다 (n=1). 일부논문에서는 Visual Analogue Scale (VAS) 을평가지표로사용하였으며 (n=2), 화병변증도구와한의평가도구를평가항목으로사용한연구도각각 1편씩있었다. (2) 동반증상평가지표화병환자의분노정도를평가할때는공통적으로 State-Trait Anger Expression Inventory (STAXI) 가사용되었다 (n=12). 불안정도를평가할때는 State-Trait Anxiety Inventory (STAI), HAMA, Hospital Anxiety Scale (HAD) 등이사용되었는데, 그중에서 STAI 가가장많이사용되었고 (n=11), HAMA (n=1) 와 HAD (n=1) 를사용한연구는일부였다. 우울평가를위해서는 Beck Depression Invention (BDI) 가가장많이사용되었으며 (n=9), the Center for Epidemiologic Studies-Depression Scale (CES-D) 을사용한연구도있었다 (n=1). 드물게부정적인정서뿐만아니라감정조절, 감정스트레스에대한반응, 받아들임, 자기 애및자존감, 자기효능감을평가하기위해 Difficulties in Emotional Regulation Scale (DERS), Stress Response Index (SRI), Mindfulness Attention Awareness Scale (MAAS), Acceptance-Action Questionnaire (AAQ), Self- Compassion Scale (SCS), Rosenberg Self-Esteem inventory (RSE), General Self-Efficacy Scale (GSES) 와같은평가지표가활용되기도하였으며, 화병환자의통증민감도를평가하기위해압통역치를측정하기도하였다. 한편, 불면증상이있는화병환자들을대상으로진행된연구에서는 ISI, Pittsburgh Sleep Quality Index (PSQI) 를사용하여특이적으로불면에대한한의학적치료의효과를평가하였다 (n=1). (3) 삶의질평가지표삶의질에대한측정도구로는 The World Health Organization Quality of Life Scale-BREF (WHOQOL- BREF), Valued Living Questionnaire (VLQ), Psychological Well-Being Scale (PWBS) 등이활용되었는데 WHOQOL- BREF 를사용한논문이 2편, VLQ 와 PWBS를사용한논문이각각 1편씩으로화병임상연구에서삶의질을평가한논문은총 4편에불과하였다. (4) 객관적생체지표이차평가변수로써자율신경계에대한한의학적치료의영향을평가하기위해 Heart Rate Variability (HRV) 를측정한연구들이있었다 (n=3). 4. 연구윤리 16건의임상연구에대해 IRB 승인및이해상충여부, 연구자금출처에대한정보를추출하였다 (Table 4). 전체연구중 IRB 의심의를통과한연구는 9건 (56.25%) 이었으며병원환경에서수행되고대상자수가많은연구가심의를받은경우가많았다. 전체연구중에서이해상충을언급한연구는단 1편뿐이었으며이해상충은없는것으로서술하였다. 화병임상연구에대한연구자금출처를보면 7건이보건복지부, 2건이한국연구재단 ( 구한국학술진흥재단 ), 한국한의학연구원, 산림청이각 1건씩으로정부기관이나준정부기관의지원을받아수행된연구가많았다.

9 HW Suh, EJ Choi, SH Kim, DH Kim, LH Kim, JW Kim, JH Lee, JH Lim, WJ Choi, SY Chung 269 Table 4. Factors Related to Research Ethics in Included Studies Setting Number of (Intervention/ Comparison) 2004 Park 9) Hospital 16 (16/-) 2006 Bae 10) Hospital 37 (37/-) 2007 Park 11) Hospital 9 (9/-) 2007 Jung 12) Hospital 26 (13/13) 2011 Choi 13) Hospital 50 (25/25) 2012 Kim 14) Hospital 144 (73/71) 2012 Song 15) Hospital 19 (10/9) 2012 Lee 16) Hospital 37 (19/18) 2012 Jung 17) Hospital 15 (15/-) 2012 Hong 18) Forest Park 20 (20/-) 2013 Kim 19) Counselling center, 14 unclear (7/7) 2014 You 20) Counselling center, 22 unclear (11/11) 2015 Suh 21) Hospital 27 (15/12) 2015 Kim 22) Counselling center, 24 unclear (12/12) 2015 Lee 23) Counselling center, 19 unclear (13/6) 2015 Choi 24) Hospital 152 (75/77) *N/R: Not Reported. IRB COI* Source of funding N/R N/R National Research Foundation of Korea (KRF E00257) N/R N/R None N/R N/R None Approved N/R Korea Institute of Oriental Medicine (K06070) Approved N/R Ministry of Health and Welfare (B080009) Approved N/R Ministry of Health and Welfare (B070057) Approved N/R Ministry of Health and Welfare (B080009) Approved N/R Ministry of Health and Welfare (B080009) Approved N/R Ministry of Health and Welfare (B080009) Approved N/R Korea Forest Service (S111010L040100) N/R N/R None N/R N/R None Approved None Ministry of Health and Welfare (KHIDI: HI12C ) N/R N/R None N/R N/R None Approved N/R Ministry of Health and Welfare (B080009), National Research Foundation of Korea (2013R1A1A ) 5. 비뚤림위험도 1) 무작위배정대조군연구무작위배정대조군연구에서는무작위로배정하였다는언급은있으나구체적인무작위방법이나배정순서은폐방법에대한설명이없는연구가많아해당영역에서의비뚤림위험이대부분불확실하였다. 한약임상연구는연구참여자및연구자에대한눈가림이시행되어비뚤림위험이낮은것으로판단하였으나비약물요법임상연구에서는연구자에대한눈가림이불가능하여비뚤림위험이높은것으 로판단하였다. 또한, 화병임상연구에서는자가보고식평가척도를결과변수로사용하기때문에연구참여자눈가림이시행되어결과에영향을미치지않았을것으로판단되는경우평가자눈가림에대한비뚤림위험이낮다고평가하였고, 연구참여자눈가림이불완전하거나불가능한경우평가자눈가림에대한비뚤림위험이높다고판단하였다. 불충분한결과자료및선택적보고에대해적절한언급이있어해당영역에서의비뚤림위험은대부분낮은것으로평가하였으나, 측정하였다고한결과를모두보고하지않은 1편 (You 2014) 과중간보고에서보고하였던 HRV 를최종보고에서보고하지않은 1편 (Kim 2012) 에대해서는선택적보고비뚤

10 270 Current Trends in Intervention Studies of in Korean Medicine 림위험이높다고판단하였다 (Fig. 3). 2) 비무작위대조군연구무작위대조군연구에서는시험군과대조군을분류할때무작위화를시행하지않았으므로무작위배정순서생성, 배정순서은폐영역에서모두비뚤림위험이높았다. 포함된 2편의연구모두집단상담치료를중재로하고대기군을대조군으로설정하였으며, 자가보고식평가척도를사용하였기때문에연구참여자, 연구자, 결과평가에대한눈가림이수행되지않았다. 1편 (Kim 2015) 의연구에서는치료군에서 2명이개인사유로인해불참하게되어통제집단에서무작위로 2명을제외한뒤프로토콜기반분석 (per-protocol analysis, PP) 을시행하였기때문에불충분한결과자료영역에서비뚤림위험이높은것으로판단하였다 (Fig. 4). 향을미치지않았을것으로판단하여교란변수영역의비뚤림위험이낮은것으로평가하였다. 포함된연구들은모두화병환자를대상으로한의학적치료를시행한뒤전후상태를비교하였으므로중재측정에비뚤림위험이낮다고판단하였다. 반면, 대조군연구에서와마찬가지로자가보고식평가척도를결과변수로사용하였기때문에모든연구에서결과평가에대한눈가림은수행되지않았다. 또한, 대부분의전후연구에서연구참여자의수가적고탈락자가발생하였기때문에불완전한자료에대한비뚤림위험이높은 3) 전후연구전후연구에서는대상군을연속적으로모집하고자료를전향적으로수집하였으므로대상군선정영역에대해비뚤림위험이낮은것으로판단하였다. 화병의질환특성상만성적인경과를보이기때문에연구결과에자연경과가영 Fig. 4. Risk of bias summary of 2 CCTs. Fig. 3. Risk of bias summary of 8 RCTs. Fig. 5. Risk of bias summary of 6 before and after studies.

11 HW Suh, EJ Choi, SH Kim, DH Kim, LH Kim, JW Kim, JH Lee, JH Lim, WJ Choi, SY Chung 271 경우가많았다. 또한화병연구에서보고될것으로예상되는결과변수에대한언급이없는연구가많아선택적결과보고영역에서비뚤림위험이대부분불확실하였다 (Fig. 5). IV. 고찰 화병은뚜렷한스트레스사건과관련되어있으며, 원인사건에대한적응이실패한경우억울하고분한감정을오래억눌러서발병하는것으로알려져있다. 앞서언급한것처럼현재의학계에서는화병에대한표준치료가정립되어있지않으나, 한의계에서는화병임상연구를토대로임상진료지침을개발하는등화병의진단및치료를표준화하기위한노력을기울이고있다. 이에본연구에서는앞으로의화병임상연구수행및임상진료지침개발에앞서지금까지수행되었던화병임상연구를평가하고앞으로의발전방향을제안하고자화병의한의학적치료에대한연구동향을분석하였다. 화병은국내에서 화병, 홧병, 울화병 등다양한병명으로불리기때문에국내 DB를검색할때는이와같은검색어를모두사용하였다. 한편, 한국표준질병사인분류 (Korean Standard Classification of Diseases, KCD) 6차에서는화병을 fire disease 라고번역하였고 DSM-IV 에서는화병을문화관련증후군의범주에포함시켜 anger syndrome 이라고번역하였기때문에 fire disease, culture-bound syndrome, anger syndrome 을주요검색어로포함하였다. 이처럼포괄적인검색을통해 1,826 편을검색하여최종적으로 16편의논문을선정하고검토하였다. 화병임상연구의출판현황을보면, 매년발표되는문헌수가극히적고국내학술지또는국내학위논문위주로출판되고있다. 또한임상연구가국내에서만이루어지고있고연구가꾸준히이루어지지못하고있는점도한계로지적될수있다. 화병임상연구의중재는침, 한약, 상담, 명상, EFT, 음악치료, 미술치료, 화병관리프로그램및산림치유프로그램으로, 임상현장에서다빈도로활용되고있는약침, 뜸, 부항에대한연구가부족하였다. 또한, 한의임상현실에서는복합적인중재가개입되나임상연구설계에서는중재별로결과에미친영향이명확하지않으므로단일중재에대한연구가진행되는것이바람직하다는의견이있어앞으로의임상연구 계획시고려가필요할것으로생각된다 34). 연구설계는무작위배정대조군연구가 8건, 전후연구가 6건, 비무작위대조군연구가 2건으로대부분무작위배정대조군연구와전후연구로설계되며모두전향적연구로수행되었다. 대조군은중재에따라차이를보이는데한약에대해서는위약이대조군으로통일되어있는경향을보였으나침, 상담, 명상, EFT 등의비약물요법에대해서는표준적인대조군이부재한실정이었다. 비약물요법연구에서는무처치군을대조군으로설정한경우가가장많았고 (n=3) 드문경우로침연구에서비경혈부위에천자하는것을대조군으로설정하거나 (n=1) EFT를활성대조군인점진적근육이완법과비교하기도하였다 (n=1). 한방의료행위중침치료의비율이높고, 화병치료에서정신요법이중요하게생각되므로앞으로화병임상연구에서비약물요법에대한연구가더욱활발해질것으로예상되나, 비약물요법연구에서는표준대조군이정립되어있지않기때문에표준대조군설정및연구설계에대한지속적인고민이필요할것으로생각된다. 결과변수는화병척도, STAXI, STAI, BDI가많이사용되었고화병 의핵심증상에대해 5점리커트척도로평가하거나화병 나 HBDIS 를변형하여척도로사용한연구도있었다. 이외화병심리증상에대한다양한평가지표들이사용되었으나, 화병의신체증상에대한평가도구는상대적으로부족한실정이었다. 화병은정신ㆍ심리적문제가원인이되어신체증상이나타난다는특징을가지고있음에도불구하고현재까지진행된연구에서는심리증상위주로만평가되었다. 따라서가슴의답답함, 열감, 치밀어오름, 목이나명치에덩어리가뭉쳐있는느낌뿐만아니라구건ㆍ구갈, 두통ㆍ현훈, 입면난또는빈각, 심계ㆍ정충등의화병신체증상에대한평가가필요할것으로생각된다. 나아가삶의질이나객관적생체지표를측정하는결과변수에대한고려도필요하다. 최근에는임상연구를수행할때연구윤리의측면이점차강조되고있는데, 우리나라에서는 2013 년에 생명윤리및안전에관한법률 이개정되면서 IRB의구성및운영등에관한사항의규정을의무화하고있다 35). 16건의화병임상연구중 IRB의승인을받고실시한연구는총 9건 (56.25%) 이었다. 이해상충은오직 1편의연구에서만이해상충이없다는

12 272 Current Trends in Intervention Studies of in Korean Medicine 서술이있었고나머지연구에서는전혀언급이없었다. 정신과영역에서는신체질환에비해객관적인평가지표가부족하기때문에연구자의임상적판단이연구결과에영향을미칠수있으므로이해상충문제가특히중요하다고할수있다 36). 또한, 정신과영역에서는재정적이해상충뿐만아니라지지하는정신요법에대한충성효과 (allegiance effect) 가있는것으로알려져있어비재정적이해상충에대한주의도필요하다 37). 이러한문제를방지하기위해연구계획단계에서부터서로다른의견을가진연구자가협력하는것이필요하며 38) 연구자의의도가결과에영향을미칠수없도록무작위배정순서생성및배정순서은폐방법과눈가림법을잘설계해야할필요가있을것으로생각된다. 연구자금출처는보건복지부 (n=7), 한국연구재단 (n=2), 한국한의학연구원 (n=1), 산림청 (n=1) 등정부기관및준정부기관으로부터연구비를지원받아연구자주도임상연구로수행되는경우가대부분이었다. 세계적인학술지에보고되는임상연구의경우, 20년간영향력지수 (IF) 상위 5위에해당하는학술지에실린논문들중 500개의표본을뽑아분석한결과제약회사지원으로수행된연구는 181 건 (36%) 이었으며연도별로분석해보면제약회사로부터지원을받은연구의비율이점차증가한것으로나타났다 39). 즉, 화병임상연구는이에비해재정적이해상충의가능성이적고공익적측면에서연구가이루어진다고평가할수있다. 비뚤림위험도를연구설계에따라살펴보면, 무작위배정대조군연구의경우는무작위배정순서생성방법과배정순서은폐방법이논문에언급되어있지않다는점, 비약물요법을중재로하는경우연구참여자및연구자의눈가림이불가능하다는점등이연구의내적타당성의한계로지적될수있으며비약물요법연구에서발생되는눈가림문제는비무작위대조군연구, 전후연구에서도동일하게나타난다. 추가적으로전후연구에서는중도탈락이많아불충분한결과를보고하는연구의비율이높고화병임상연구에서당연히분석되었을것으로예상되는핵심결과를결과변수로설정하지않은연구가많아불충분한결과자료, 선택적보고영역에서비뚤림위험의가능성이있었다. V. 결론 화병의한의학적치료에대한연구동향을분석한결과 다음과같은결론을얻었다. 첫째, 화병임상연구는국내에주로보고되었으며 2012 년이전까지는매년발표되는연구가없거나출판되는문헌수가 1 2 편에불과했다 년논문수가급증하여 5편의연구가발표되었으나이후출판문헌의증가와감소가반복되어향후지속적인증가를위한노력이필요할것으로생각된다. 둘째, 화병임상연구는주로무작위배정대조군연구와전후연구로수행되었고, 연구설계상비약물요법의대조군설정과눈가림의문제가제기된다. 셋째, 연구윤리의측면에서전체화병임상연구중약 56% 에해당하는연구가 IRB 의승인을받고실시되었다. 이해상충은오직 1편의연구에서만이해상충이없다는서술이있었고연구자금은대부분정부기관및준정부기관으로부터지원을받은것으로분석되었다 년부터 IRB 승인이의무화되었으며정신과영역에서이해상충에대한주의가필요한것으로나타나향후지속적인관심이필요하다. 넷째, 무작위배정대조군연구의경우무작위배정순서생성방법과배정순서은폐방법이언급되어있지않은논문이많다는점에서해당영역의비뚤림위험도가불확실하였고, 특히비약물요법을중재로하는경우연구참여자및연구자의눈가림이불가능하다는점등이문제로지적될수있다. 전후연구에서는중도탈락이많아불충분한결과를보고하는연구의비율이높고화병임상연구에서당연히분석되었을것으로예상되는핵심결과를결과변수로설정하지않은연구가많아불충분한결과자료, 선택적보고영역에서비뚤림위험의가능성이있었다. 이러한비뚤림위험은연구설계상의한계점과관련이있었다. REFERENCES 1. National Oriental Medical College Neuropsychology Textbook Compilation Committee. Korean Neuropsychology. Seoul : Jipmoondang. 2016: Kim JW, Kwon JH, Lee MS, Park DG. Development of Hwa-Byung Diagnostic Interview Schedule (HBDIS) and Its Validity Test. The Korean Journal of Health Psychology. 2004;9(2): Kim JW, Hyun KC, Whang WW. A Study on the Origin of (Fire Syndrome). Journal of oriental neuropsychiatry. 1999;10(1): American Psychiatric Association. Diagnostic and stat-

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