J Korean Med Obes Res 2018;18(1):1-9 https://doi.org/10.15429/jkomor.2018.18.1.1 pissn 1976-9334, eissn 2288-1522 JKOMOR Original Article 가미태음조위탕과저열량식이를병행한체중감량프로그램에서발생한이상반응분석 윤나라 유영재 김민지 김서영 임영우 임형호 1 박영배 2 누베베한의원, 1 가천대학교한의과대학, 2 누베베미병의학연구소 Analysis of Adverse Events in Weight Loss Program in Combination with Gamitaeeumjowee-Tang and Low-Calorie Diet Na-Ra Yoon, Young-Jae Yoo, Min-ji Kim, Seo-Young Kim, Young-Woo Lim, Hyung Ho Lim 1, Young-Bae Park 2 Nubebe Korean Medical Clinic, 1 College of Korean Medicine, Gachon University, 2 Nubebe Mybou Research Institute Received: April 7, 2018 Revised: May 18, 2018 Accepted: May 31, 2018 Correspondence to: Young-Bae Park Nubebe Mybou Research Institute, Top Building 2F, 10 Seongnam-daero 926beon-gil, Bundang-gu, Seongnam 13506, Korea Tel: +82-31-745-6400 Fax: +82-31-736-2252 E-mail: bmppark@khu.ac.kr Copyright 2018 by The Society of Korean Medicine for Obesity Research Objectives: The objective of this study was to assess the safety of 'Gamitaeeumjowee-tang' by analyzing adverse events in weight loss program in combination with 'Gamitaeeumjoweetang' and low-calorie diet. Methods: A retrospective review of adverse events in weight loss program in combination with 'Gamitaeeumjowee-tang' and low-calorie diet from the electronic medical chart (n=124) between June 2015 and December 2016 was conducted. Three Korean Medicine Doctors (KMDs) reviewed adverse events for two times, during week 2 to 4 and at week 10, after starting weight loss program. Adverse events were evaluated in terms of causality, severity and system-organ classes. Also, agreement among the three KMDs was made through further discussion in case of disagreement after independent review. Results: The overall rate of adverse events was 37.1% during week 2 to 4 and 16.9% at week 10. For causality of adverse events using the World Health Organization-Uppsala Monitoring Centre causality categories, 52.2% were evaluated 'possible' at week 2-4 and 57.1% were evaluated 'unlikely' at week 10. All symptoms were evaluated as 'mild' by LDS scale. Nausea (15, 12.1%) was the most frequent adverse event at week 2-4 and dizziness (6, 4.8%) was the most common at week 10. Conclusions: Adverse events decreased over time. There were no serious adverse events and none of the subjects were dropped due to adverse events. Continuous study is needed to prove the safety of 'Gamitaeeumjowee-tang' for treating obesity. Key Words: Gamitaeeumjowee-tang, Adverse drug event, Safety, Weight loss program, Low-calorie diet 서론 비만은지방이체내에과잉축적된상태로, 제2형당뇨, 심혈관계질환, 골관절염, 담낭질환등의유병률을높이는건강의위협요인이다 1). 2016년보건복지부에서시행한국민건강영양조사에의하면체질량지수 25 kg/m 2 이상인 19세이상성인의비만유병률이 1998년 25.8% 에서 2016년 35.5% 로상승하였다 2). 이는우리나라에서도비만 치료의필요성이점차커지고있음을시사한다. 비만의치료방법으로약물요법은운동, 식사, 행동수정요법의보조적인치료수단으로체질량지수가 25 kg/m 2 이상이거나 23 kg/m 2 이상에서고혈압, 당뇨등의합병증이동반된경우일차적으로고려되고있다 3). 약물치료요법으로는위장관계지질분해효소길항제, 세로토닌수용체효현제, 도파민및노르에피네프린재흡수억제제등을사용하며유효성및안전성에대한연구가지속적으 www.jkomor.org 1
로이루어지고있다 4). 비만의한의학적치료에서도침, 약침, 매선요법등의다양한방법이있으나, 그중한약치료에대한연구가가장많이보고된다 5). 한국에서비만에응용되는한약의빈도는사상처방, 체감의이인탕, 방풍통성산순이었으며, 사상처방중에서는태음조위탕이가장많이사용된것으로알려졌다 6). 태음조위탕은이제마의동의수세보원 ( 東醫壽世保元 ) 에수록된처방으로 7) 비록태음인위완수한표한병 ( 胃脘受寒表寒病 ) 에사용되는처방이나, 일반적으로비만인에게서체중감량의효과가입증되어, 임상적으로다용되고있으며 8), 다수연구에서유효성과안전성에대한부분들이보고되었다 9-11). 비만치료에서한약을활용한연구들의대부분이유효성입증을목적으로진행되었으며, 임상에서치료중발생하는이상반응에대한보고들이체계적으로이루어져있지않다. 이에본연구에서는체중감량을목적으로한의원에내원한 124명의환자들을대상으로의무기록을후향적으로검토하여이상반응을체계적으로확인하고, 이를활용하여비만치료에서가미태음조위탕의안전성을제고하고자하였다. 대상및방법 이연구는보건복지부지정공용기관생명윤리위원회 (Institute Review Board, IRB) 의승인을받은연구계획서에따라진행되었다 ( 승인번호 : P 01-201708-21-010). 1. 연구대상 1) 경기소재누베베한의원에초진내원하였고, 처방 배제기준 (Table 1) 12-13) 에해당되지않아다이어트프로그램을진행하였으며, 개인정보제공에동의한만 19세이상의성인 2) 2015년 6월 1일부터 2016년 12월 31일까지가미태음조위탕을 10주동안규정대로복용완료하였으며, 의무기록차트에그기록이존재하는 124명을대상으로함 2. 연구방법 1) 의무기록검토모든의무기록차트는복약기간동안상담을통하여체중및이상반응이기재되었다. 연구대상자선정과정에서 200명의차트를열람하였고, 복용법을지키지않았거나기록이없는경우는배제하였다. 선정된연구대상자의의무기록을토대로, 복약기간동안발생했던이상반응을복약시작후 2~4주차, 10주차 2차례에걸쳐임상 5년차이상 3인의한의사가검토하였다. 2) 투약약물및식이가미태음조위탕의처방구성은 1첩당마황 12-18 g, 의이인, 건율각 12 g, 숙지황 6 g, 오미자, 맥문동, 천문동각 4 g, 생강 3 g, 산조인, 석창포각 2.5 g, 택사 2 g, 용안육, 황금, 갈근, 고본각 1 g으로 15일기준으로 20첩이투약되었으며, 마황의용량은환자의체중및병증에따라조절하여사용하였다. 모든환자들은처방된약물을탕약형태로 1일 3회에걸쳐 10주간복약하였다. 또한다이어트프로그램진행시변비예방상비약으로가미내소산을처방하여필요시복약하게하였다. 모든환자들에게는안내책자를통하여 1일 1,200 kcal 의한식위주의저열량식이를지도하였다. 권장식이의 Table 1. Exclusion Criteria for Prescription 12,13) (1) Heart disease (Heart failure, arrhythmia, myocardial infarction, angina pectoris, etc.), uncontrolled hypertension, past history of stroke or ischemic heart attack (2) Type 2 diabetes, Hypothyroidism, Cushing's syndrome or the other endocrine diseases (3) Anemia (4) Angle close glaucoma, serious neurological or psychological diseases (schizophrenia, epilepsy, alcoholics, drug addiction, anorexia, bulimia nervosa, etc.) (5) Malignant tumor, pulmonary disease, liver failure, renal failure (6) Children, adolescents (7) Pregnant women, breast feeding women, women with a pregnancy plan or disapproval of contraception (8) Past history of surgical treatment for weight loss (9) Patients taking Tuberculosis drugs, asthma drugs, drugs affecting the central nervous system or anti- obesity drugs. (10) Or the other chronic neurological or cardiovascular disease 2 www.jkomor.org
윤나라외 : 가미태음조위탕과저열량식이를통한체중감량시발생한이상반응분석 구성은 1,200 kcal 중탄수화물 50~55%, 단백질 20~25%, 지방 20~25% 로구성되었다 14). 3. 평가방법보고된이상반응의인과성은 World Health Organization- Uppsala Monitoring Centre (WHO-UMC) 평가지표 15,16) 를, 중증도는 LDS scale 17-19) 을사용하여각각 3인의한의사가이를평가하였다. 또한인체기관계별분류 (system organ classes, SOC) 에따라이상반응의빈도를분석하였다. 평가자 3인의결과가일치되지않는경우논의를거쳐다수결의원칙에따라 3인중 2인이상의평가결과가동일할경우채택하였다. 1) 인과성평가 WHO-UMC 평가지표 15,16) 는약물이상반응 (adverse drug reaction) 의인과성을평가하는지표로시간적인과관계, Table 2. World Health Organization-Uppsala Monitoring Centre (WHO-UMC) Causality Categories 15,16) 1. Certain Event or laboratory test abnormality, with plausible time relationship to drug intake Cannot be explained by disease or other drugs Response to withdrawal plausible (pharmacologically, pathologically) Event definitive pharmacologically or phenomenologically (i.e. an objective and specific medical disorder or a recognised pharmacological phenomenon) Rechallenge satisfactory, if necessary 2. Probable/Likely Event or laboratory test abnormality, with reasonable time relationship to drug intake Unlikely to be attributed to disease or other drugs Response to withdrawal clinically reasonable Rechallenge not required 3. Possible Event or laboratory test abnormality, with reasonable time relationship to drug intake, could also be explained by disease or other drugs Information on drug withdrawal may be lacking or unclear 4. Unlikely Event or laboratory test abnormality, with a time to drug intake that makes a relationship improbable (but not impossible) Disease or other drugs provide plausible explanations 5. Conditional/Unclassified Event or laboratory test abnormality, more data for proper assessment needed, or additional data under examination 6. Unassessable/Unclassifiable Report suggesting an adverse reaction Cannot be judged because information is insufficient or contradictory Data cannot be supplemented or verified Table 3. LDS Scale Categories 17-19) Question Yes No Unknown Did the adverse drug reaction impair the patient's quality of life? 1-1 0 Was the (immediate) discontinuation of the drug necessary or recommended? 1 0 0 Was the use of a different drug or other therapy necessary or recommended? 1 0 0 Did the adverse drug reaction prolong treatment or lead to hospitalization? 1 0 0 Did the adverse drug reaction cause temporary malfunctioning of an organ (system)? 1 0 0 Did the adverse drug reaction cause permanent malfunctioning of an organ (system)? 2 0 0 Did the adverse drug reaction lead to permanent inability to work? 1 0 0 Was the adverse drug reaction potentially dangerous? 1 0 0 Was the adverse drug reaction (potentially) life-threatening? 2 0 0 Was the adverse drug reaction fatal? 3 0 0 The severity of the adverse drug reactions is classified according to the total score. A score of 1 4 indicates a mild reaction, a score of 5 8 a moderate reaction, and a score of 9 a severe adverse drug reaction. www.jkomor.org 3
약물외타요인의개연성, 투여중단여부및재투여후환자의반응에따라약물과이상반응의인과성을확실함 (certain), 상당히확실함 (probable/likely), 가능함 (possible), 가능성적음 (unlikely), 평가곤란 (conditional/unclassified), 또는평가불가 (unassessable/unclassified) 로분류한다 (Table 2) 15,16). 2) 중증도평가 LDS scale 17)-19) 은약물이상반응을삶의질저하여부, 입원치료의필요성, 일시적또는영구적장애발생여부등총 10개항목에따라점수를부여하고, 총점이 9점이상일경우중증 (severe), 5-8점이면중등증 (moderate), 4점이하면경증 (mild) 으로평가한다 (Table 3) 17-19). 3) 인체기관계별분류이상반응을인체기관계별로분류하기위해 WHO-Adverse Reaction Terminology (WHO-ART) 092 버전의분류를사용하였다. WHO-ART 분류는인체기관계별분류 (SOC), 상위용어 (high level terms, HLT), 우선순위용어 (preferred terms, PT), 하위포함용어 (included terms, IT) 의 4단계로이루어지는데 20), 본연구에서는파악된이상반응을 WHO-ART 의우선순위용어 (PT) 에따라나누고, 각우선순위용어 (PT) 의상위분류인인체기관계별분류 (SOC) 에따른발생빈도를분석하였다. Table 4. Characteristics of Baselines Characteristic Total (N=124) Female, n (%) 110 (88.8) Age, n (%) 20 s 24 (19.4) 30 s 51 (41.1) 40 s 38 (30.6) 50 s 11 (8.9) 60 s 0 (0) Mean age (SD) 36.9 (8.5) Weight, mean (SD), kg 78.3 (12.7) Body mass index, mean (SD), kg/m2 29.1 (3.8) Prescription drugs, n (%) 15 (12.0) Dietary supplements, n (%) 26 (20.9) SD: standard deviation. 4) 통계분석모든통계분석은 PASW Statistics ver. 18.0 (IBM Co., Armonk, NY, USA) 으로수행하였으며, 이상반응의인과성, 중증도, SOC 분류에따라빈도분석을시행하였다. 또한연구자간의일치도를파악하기위해평가자간급내상관계수 (intra-class correlation, ICC) 분석을시행하였다. 모든연속형변수에대한측정치는 Mean±standard deviation 으로나타내었으며범주형자료의경우는빈도 (n, %) 로표시하였다. 통계적유의수준은 P<0.05로검증하였다. 결과 1. 인구학적특성연구대상자 124명중 110명이여성으로 88.8% 를차지하였고, 평균연령은 36.9±8.5세였다. 124명중 15명 (12%) 이다른양약을복용중이었으며, 26명 (20.9%) 이건강보 Fig 1. Change in percentage of adverse events for 10 weeks. The overall rate of adverse events was 37.1% during week 2 to 4 and 16.9% at week 10. 조식품을복용하고있었다 (Table 4). 이중현병력이있는자는총 34명 (27.4%) 이었으며, 과거력이있는자는 21명 (16.9%) 이었다 (Table 5). 10주간다이어트프로그램을진행후, 연구대상자의체중이평균 7.8±3.3 kg 감량되어유의하였다 (P<0.05) (Table 6). 2. 이상반응평가 이상반응의발현비율은 2~4주차에 37.1% (46명), 10 주차에 16.9% (21명) 로감소하였다 (Fig. 1). WHO-UMC 지표로이상반응의인과성을평가한결과, 2~4주차에는이상반응이발생한 46명중 24명이 possible ( 가능함 ) 로 4 www.jkomor.org
윤나라외 : 가미태음조위탕과저열량식이를통한체중감량시발생한이상반응분석 Table 5. Medical Records of 124 Patients N (number) Diagnosis (n) Present illness (N=124) Cardiovascular system 11 Hyperlipidemia (3), Hypertension (8) Musculoskeletal system 5 Lumbar disc herniation (3), Ankle sprain (1), Spinal stenosis (1) Urogenital system 2 Nephrolithiasis (1), Polycystic ovarian disease (1) Hepatobiliary system 2 Fatty liver (2) Digestive system 3 Gastritis (1), Reflux esophagitis (1), Enteritis (1) Nervous system 1 Vertigo (1) Integumentary system 3 Eczema (1), Atopy (1), Hyperhidrosis (1) ENT system 4 Otitis (1), Vestibular neuritis (1), Rhinitis (1), Sinusitis (1) Etc 3 Common cold (1), Breast calcification (1), Varicose vein (1) Total, n (%) 34 (27.4) Past history (N=124) Musculoskeletal system 2 Cervical/ lumbar disc herniation (1), Rhabdomyolysis (1) Urogenital system 6 Tubotubectomy (1), Nephritis (1), Hysteromyoma (2), Ectopic pregnancy (1), Hysterectomy (1) Hepatobiliary system 2 Cholecystotomy (1), Cholelithiasis (1) Digestive system 6 Appendicitis (3), Anemia (2), Enterotomy (1) Nervous system 1 Facial palsy (1) Endocrine system 3 Hypothyroidism (1), Hyperthyroidism (1), Gestational diabetes (1) Integumentary system 1 Sunlight allergy (1) Total, n (%) 21 (16.9) ENT: ear nose and throat. Table 6. Change of Weight and Body Mass Index for 10 Weeks N=124 Before After 10 weeks P-value Weight (kg) 78.25±12.79 70.48±11.79 P<0.001 Body mass index (kg/m 2 ) 29.05±3.82 26.2±3.49 P<0.001 Values are presented as mean ± standard deviation unless otherwise indicated. Table 7. Scores of World Health Organization Uppsala Monitoring Centre (WHO-UMC) Causality Categories and LDS Scale Total patients (N=124) 2-4 weeks, n (%) 10 weeks, n (%) WHO-UMC Possible 24 (52.2) 6 (28.6) Unlikely 17 (36.9) 12 (57.1) Conditional / unclassified 5 (10.9) 3 (14.3) Total 46 (100) 21 (100) LDS-scale Mild 46 (100) 21 (100) Moderate 0 (0) 0 (0) Severe 0 (0) 0 (0) Total 46 (100) 21 (100) 가장많은빈도를보였으며 (52.2%), 10주차에는이상반응이발생한 21명중 unlikely ( 가능성적음 ) 가 12명 (57.1%) 으로가장많은빈도를보였다. LDS scale에따라중증도를평가한결과, 2~4주, 10주차이상반응은모두경증이었다 (Table 7). 세연구자간의 ICC는 2~4주차 0.961 (0.936~ 0.977), 10주차 0.939 (0.873~0.973) 이었다. 인체기관계별분류로볼때, 2~4주차에는위장관계이상반응중오심 (12.1%) 이가장많이보고되었으며, 10주차에서는신경계이상반응중어지러움 (4.8%) 이가장많이보고되었다. 10주차에보고된이상반응은 2~4주차에비해전체기관계에걸쳐발생비율이줄어드는양상을보였으며, 혈관계증상중수족부위냉감만이 2~4주차에는발생하지않았다가 10주차에서만보고되었다 (1.6%) (Table 8). www.jkomor.org 5
Table 8. Adverse Events According to System Organ Classes System-organ classes Symptom 2-4 weeks N (%) 10 weeks N (%) Gastro-intestinal system disorders Nausea 15 (12.1) 3 (2.4) Constipation 8 (6.5) 4 (3.2) Heartburn 2 (1.6) 1 (0.8) Vomiting 2 (1.6) 0 (0) Diarrhea 1 (0.8) 0 (0) Dry mouth 1 (0.8) 0 (0) Sub-total 29 (23.3) 8 (6.4) Central & peripheral nervous system disorders Dizziness 8 (6.5) 6 (4.8) Headache 2 (1.6) 1 (0.8) Hyperhidrosis 1 (0.8) 1 (0.8) Shakiness 1 (0.8) 0 (0) Sub-total 12 (9.6) 8 (6.4) Vascular disorders Peripheral coldness 0 (0) 2 (1.6) Psychiatric disorders Insomnia 11 (8.8) 2 (1.6) Autonomic nervous system disorders Palpitation 2 (1.6) 0 (0) Hypotension postural 1 (0.8) 0 (0) Sub-total 3 (2.4) 0 (0) Musculo-skeletal system disorders Muscle cramp 2 (1.6) 1 (0.8) Hearing and vestibular disorders Tinnitus 1 (0.8) 1 (0.8) Skin and appendages disorders Alopecia 1 (0.8) 0 (0) Vision disorders Vision decreased 1 (0.8) 0 (0) 고찰 한방비만치료에있어태음조위탕은빈용되는처방으로 6), 현재까지유효성과안전성을증명하기위한연구들이지속적으로수행되고있다 8-11). 그러나대부분의연구가유효성을중심으로진행되었으며 9,10), 안전성이나이상반응에관한연구는상대적으로적었을뿐만아니라이상반응에대한보고도단순보고에그치는등 21-23), 대규모인원을대상으로이상반응을체계적으로조사한연구는찾아보기어려웠다, 이에저자들은가미태음조위탕의안전성을종합적으로평가하고자가미태음조위탕과저열량식이를병행한다이어트프로그램을진행한환자 124 명을대상으로, 후향적차트분석을시행하였다. 본연구에서는가미태음조위탕복약시점부터 2~4주차, 10주차 2차례에걸쳐나타난이상반응을후향적으로분석하였다. 구성약재중마황복용시 2주정도의시점이이상반응의발현과약화에중요한시기이기에 24) 2~4 주차를 1차연구시점으로선정하였고, 복약완료시점인 10주차를 2차연구시점으로선정하였다. 태음조위탕의구성약재중마황은항비만효과를나타내는대표적인약재로, 비만치료에서단일약재및복합처방으로가장많이사용되는약재이다 6). 마황의주성분은 L-ephedrine, pseudoephedrine, norephedrine 등의알칼로이드로 25), 이중 ephedrine이총 alkaloid의 30~90% 로가장많다 12). 에페드린은교감신경계흥분작용이있어식욕을억제하고, 열생산및대사량을높여, 유의한체중감소효과가있는것으로보고된다 26,27). 그러나 2004년미국 Food and Drug Administration (FDA) 에서마황을식품으로사용하는것을금지한후마황및에페드린에대한안전성문제가논란이되었고 25), 이후한의학계에서는안전한마황사용을위한지침이제시되어왔다 12,13). 마황은교감신경활성과정에서불면, 심계항진, 발한과다, 위장불편감등의부작용을발생시키기도한다 12). 현재까지마황을포함한한약을비만환자에게투여한연구에서대표적인이상반응으로심계항진, 불면, 두통과같은교감신경활성에따른증상또는오심, 구역, 구토와 6 www.jkomor.org
윤나라외 : 가미태음조위탕과저열량식이를통한체중감량시발생한이상반응분석 같은위장관계증상들이보고되었는데 9,23), 본연구에서나타난이상반응의범주또한마황의이상반응으로보고된범주와일치하는것을확인할수있었다. 마황에포함된에페드린은장기사용시부작용이초기에비해줄어드는반면, 체중감량의치료효과는지속된다고보고되는데 6,24,28), 본연구결과에서도이상반응의발생비율이 2~4주차 37.1% 에서 10주차 16.9% 로감소되고, 인과성평가에서 10주차가 2~4주차에비해 unlikely ( 가능성적음 ) 의빈도가높아진부분을확인할수있었다. 연구대상자선정과정에서 200명의차트를열람한결과, 20명이복약기간과용량을지키지않아제외되었으며, 56명이복약후10주차의기록이없어제외되었다. 배제된대상자들에서도복용을중단할만한중증의이상반응은없었으며, 연구대상자 124명에게발생한이상반응또한모두경증으로평가되었는데, 이는기존마황포함한약제제및태음조위탕연구에서중증의이상반응이보고되지않았던것과같은맥락을가진다 9,10,13). 인체기관계별분류에서위장관계이상반응은 2~4주차에 23.3% 로가장많이보고되었으며, 10주차에6.4% 로감소하였다. 이는가미태음조위탕내마황의교감신경활성작용에따른이상반응으로도볼수있으나, 약물과함께병행한저열량식이 (1,200 kcal) 로인한영향일가능성을배제할수없다. 실제로, 저열량및초저열량식이관련무작위대조연구 29) 에서, 8주간저열량식이를진행했을때, 위장관계이상반응으로오심이 9.4%, 변비가 41.7%, 속쓰림 4.2%, 구토 4.2%, 설사 7.3% 가보고되었는데, 오심을제외한나머지이상반응의발생비율은해당연구가본연구보다높았다. 오심의발생비율이본연구에서 2~4주차 12.1% 였고, 10주차에 2.4% 로감소하는추세인것을감안했을때저열량식이로유발된위장관계이상반응보다본연구에서발생한위장관계이상반응의발생비율이높다고판단하기는어려웠다. 변비의경우저열량식이연구에서보다 29) 본연구에서적게보고되었는데 (2~4주차 6.5%, 10주차 3.2%) 이는변비예방차원에서상비약으로본원에서투여한가미내소산의복용이영향을미쳤을것으로보인다. 본연구에서나타난어지러움, 두통과같은신경계이상반응과근육경련, 탈모또한저열량식이의이상반응에서도유사하게보고되었으나, 발생비율은본연구에서현저히낮은경향을보였다 29). 불면역시저열량식이에서나타날수있는이상반응으 로보고되었는데 (6.3%), 본연구 (2~4주차 8.8%, 10주차 1.6%) 와큰차이는없었다. 저탄수화물식이와저지방식이를비교한무작위대조연구 30) 에서도저탄수화물식이군에서변비 68%, 두통 60%, 구취 38%, 근육경련 35%, 설사 23%, 기력저하 25%, 발진이 13% 에게발생했는데, 증상이본연구에서발생한이상반응과겹치며, 발생비율은본연구보다높았다. 이는식이의제한및영양소의제한으로도이상반응이나타날수있기에, 본연구에서발생한이상반응의원인을가미태음조위탕의단독효과로단정짓기어렵다는점을시사한다. 본연구에서체중감량효과는유의하게나타났고, 이상반응의빈도가시간이경과함에따라감소했으며, 복약을중단할만한심각한이상반응은없었음을확인할수있었다. 이는가미태음조위탕이비만치료에있어효과적이고, 안전한처방이될수있음을암시한다. 본연구는실험연구가아닌후향적연구이기에연구대상자의환경을통제하기어려웠으며, 복약전후의혈청학적검사가이루어지지않아안전성을완전히증명하는데한계가있었다. 이는후속연구를통해보완되어야할부분으로보인다. 하지만실제의무기록을바탕으로가미태음조위탕을복약하며체중감량을진행할때나타날수있는이상반응을직접적이고, 체계적으로분석하였기에, 가미태음조위탕의임상적활용가치를높이는데기여하였다고판단된다. 결론 본연구에서는가미태음조위탕의안전성을평가하기위하여, 10주간가미태음조위탕과저열량식이를병행한체중감량프로그램에서나타난이상반응을분석하였다. 1. 10주간다이어트프로그램을진행한연구대상자 124명의감량평균은 7.8±3.3 kg으로유의하였다 (P<0.001). 2. 이상반응의발현비율은 2~4주차에 37.1% (46명), 10주차에 16.9% (21명) 로나타났다. 3. WHO-UMC에따라이상반응의인과성을평가한결과 2~4주차에는 possible ( 가능함 ) 이 52.2%, 10주차에는 unlikely ( 가능성적음 ) 가 57.1% 로가장많은빈도를보였다. 4. LDS scale에따라중증도를평가한결과, 2~4주, 10 www.jkomor.org 7
주차이상반응은모두경증이었으며, 복용을중단할만한심각한이상반응은보이지않았다. 5. 인체기관계별분류로볼때, 2~4주차에서는위장관계불편감중오심 (12.1%) 이가장많이보고되었으며, 10주차에서는신경계불편감중어지러움 (4.8%) 이가장많이보고되었다. References 1. Korean Society for the Study of Obesity. Clinical bariatrics. 3rd ed. Seoul : Korea Medical Book. 2008 : 143. 2. Ministry of Health and Welfare. Korea Centers for Disease Control and Prevention. Korea Health Statistics 2016: Korea National Health Statistics and Nutrition Examination Survey (KNHANESⅦ-1) [Internet]. Seoul (KR): KCDC; 2016 [cited 2018 Jan 4]. Available from: URL: https://knhanes.cdc.go.kr/knhanes/sub04/sub04_03. do?classtype=7. 3. Korean Society for Health Promotion and Disease Prevention. Korean Society for Health Promotion and Disease Prevention 2012 spring academic conference. Seoul : Korean Society for Health Promotion and Disease Prevention. 2012 : 163-8. 4. Kim KK. Safety of anti-obesity drugs approved for long-term use. Korean J Obes. 2015 ; 24(1) : 17-27. 5. Jeong JW, Cho SW. Trend research of the human body-oriented obesity studies on Korean medicine. J Korean Med Rehab. 2016 ; 26(1) : 49-61. 6. Hwang MJ, Shin HD, Song MY. Literature review of herbal medicines on treatment of obesity since 2000; mainly about Ephedra Herba. J Korean Med Obes Res. 2007; 7(1) : 39-54. 7. Lee JM. Longevity and life preservation in Eastern medicine. 2nd. Seoul : Hanglimsa. 1993 : 19-24, 137-41. 8. Park KM, Song YK, Lim HH, Lee JA, Ko HY, Park JH, et al. Review on the research relative to Taeeumjowui-tang (Taiyintiaowei-tang). J Korean Med Obes Res. 2009 ; 9(1) : 23-36. 9. Lee JE, Song YK, Lim HH. Clinical trial of Taeeumjowui-tang (Taiyintiaowei-tang) on obese patients: randomized, double blind, placebo-controlled study. J Oriental Rehab Med. 2010 ; 20(4) : 197-213. 10. Park SJ, Won N, Cheon C, Park JS, Jang BH, Shin Y, et al. Efficacy and safety of taeeumjowi-tang in obese Korean adults: a double-blind, randomized, and placebo-controlled pilot trial. Evid Based Complement Alternat Med. 2013 ; 2013 : 498935. doi: 10.1155/2013/498935. Epub 2013 Aug 26. 11. Seo NJ, Nam DW, Lee EO, Sim BS, Ahn KS, Kim SH. Clinical study of Gamitaeeumjowi-tang for obese patients. Korean J Oriental Physiology & Pathology. 2008 ; 22(2) : 446-52. 12. Song MY, Kim HJ, Lee MJ. The safety guidelines for use of Ma-huang in obesity treatment. J Korean Med Obes Res. 2006; 6(2) : 17-27. 13. Korea Institute of Oriental Medicine. KMCPG-obesity. 1st ed. Seoul : Elsevier Korea. 2016 : 84-9. 14. Korean Society for the Study of Obesity. Clinical Practice Guidelines for Obesity 2012. 1st ed. Seoul : KOSSO. 2012 : 61-71. 15. World Health Organization Uppsala Monitoring Centre (WHO-UMC). Causality categories [Internet]. Uppsala (Sweden): World Health Organization Uppsala Monitoring Centre (WHO-UMC); 2018. [cited 2012 Oct 22]. Available from: https://who-umc.org/media/164200/who-umc-causality-assessment_new-logo.pdf. 16. Korea Institute of Drug Safety & Risk Management. Adverse Drug Reaction Assessment Report. 1st ed. Seoul : Korea Institute of Drug Safety & Risk Management. 2013 : 60-3. 17. Kim M, Han CH. Analysis of herbal-drug-associated adverse drug reactions using data from spontaneous reporting system in electronic medical records. J Korean Med. 2015 ; 36(1) : 45-60. 18. Kyung EJ, Ryu JH, Kim EY. Evaluation of adverse reactions to contrast media in the hospital. Br J Radiol. 2013 ; 86(1032) : 20130418. 19. Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP. Adverse drug events in hospitalized patients. Excess 8 www.jkomor.org
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