KISEP Original Articles 8 1 1997 Korean J Psychopharmacol Vol 8, No 1 정신분열증환자에서 Risperidone 의치료반응과혈장 Homovanillic Acid 및 5-Hydroxyindoleacetic Acid 농도와의관계 * 김찬형 ** 김지웅 ** 이홍식 ** 김광현 *** Relationship between Risperidone-Induced Therapeutic Responses and Plasma Homovanillic Acid and 5-Hydroxyindoleacetic Acid Levels in Patients with Schizophrenia* Chan-Hyung Kim, M.D., Ph.D.,** Ji-Woong Kim, M.D.,** Hong-Shick Lee, M.D., Ph.D.,** Kwang Hyeon Kim, M.A.*** ObjectivesThis study was purposed to examine the changes of plasma homovanillic acidhva, 5-hydroxyindoleacetic acid5-hiaa, and HVA/5-HIAA ratio during an 8-week risperidone trial and to investigate the relationship between the plasma monoamine metabolites and risperidone-induced treatment resposes. MethodEighteen schizophrenic patients were treated for 8 weeks with risperidone. The psychopathology was assessed at baseline just before risperidone trial and then at 1st week, 2nd week, 4th week, and 8th week using the Positive and Negative Syndrome ScalePANSS and the Clinical Global Impression scalecgi. The plasma HVA and 5- HIAA levels were measured using high performance liquid chromatography with electrochemical detection method. Results39% of the patients treated with risperidone was categorized as responders, who showed at least a 20% decrease in PANSS total score at the end point of the study. At the end point of the 1st week, there was significant difference in the percent change of plasma HVA between responders39% increment and nonresponders9% increment. But no significant differences in the percent change of plasma 5-HIAA and the percent change of plasma HVA/5-HIAA ratio between responders and nonresponders were observed. ConclusionThese results suggest that the magnitude of the early increase of plasma HVA may be associated with risperidone-induced treatment response in schizophrenia. Key wordsschizophrenia Risperidone Plasma HVA Plasma 5-HIAA Plasma HVA/5-HIAA. This study was supported by a Yonsei university faculty research grant for 1996. Department of Psychiatry, Yonsei University College of Medicine, Seoul, Korea Yong-In Psychiatric Research Institute, Yong-In, Kyunggido 79
서론 80
대상및방법 1. 연구대상 2. 방법 1) 치료약물투여 2) 임상증상의평가 81
3) 혈장 HVA 및 5-HIAA 농도측정 82
4) 자료분석 1. 인구사회학적자료 결 과 2. Risperidone 치료에따른혈장 HVA 농도, 5-HIAA 농도및 HVA/5-HIAA 농도비의변화 3. Risperidone 치료에따른혈장대사물의변화율과치료반응과의상관관계 Table 1. Demographic data and schizophrenic subtypesn18 Variables Ageyears Value 30.836.65 Sexfrequency male 7 female 11 Onset ageyears 22.334.92 Duration of illnessyears 8.50 6.37 Number of hospitalizaion 3.25 1.88 Subtype of schizophrenia paranoid type 8 undifferentiated type 10 83
Table 2. Changes of plasma monoamine metabolite levels during an 8-week risperidone treatment in schizophrenia Duration of risperidone treatmentweek Total subjectn18 baseline 1st week 2nd week 4th week 8th week HVAng/ml 8.342.15 10.052.98* 8.872.70 7.992.59 7.691.93 5-HIAAng/ml 11.605.21 12.413.31 13.253.73 13.534.56 12.472.56 HVA/5-HIAA 0.830.35 0.860.32 0.680.18 0.620.19 0.630.15 ResponsdersN7 HVAng/ml 8.061.23 11.212.13* 9.211.90 7.551.34 7.081.61 5-HIAAng/ml 12.856.33 12.842.06 13.763.54 13.433.54 12.482.18 HVA/5-HIAA 0.770.38 0.890.24 0.710.23 0.590.18 0.580.14 NonrespondersN11 HVAng/ml 8.522.62 9.313.30 8.633.23 8.313.23 8.122.09 5-HIAAng/ml 10.804.51 12.143.98 12.904.00 13.605.36* 12.462.91 HVA/5-HIAA 0.870.34 0.840.37 0.670.15 0.640.21* 0.670.16 *p0.05, compared to baseline levelsby Wilcoxon Signedranks test Table 3. Correlation between the change of plasma metabolites levels and the change of PANSS subscale scores during the risperidone treatment in schizophrenia 8 PANSS subscale scores Total score 1 monoamine metabolites Positive score Negative score HVA 0.680.00* 0.230.360.590.01* 5-HIAA 0.040.87 0.250.31 0.160.54 HVA/5-H IAA 0.050.85 0.100.710.320.19 8 monoamine metabolites HVA 0.300.24 0.210.41 0.320.21 5-HIAA 0.140.60 0.130.630.590.01* HVA/5-HIAA 0.080.77 0.170.51 0.170.51 1percent changebaseline level-1th week level/ baseline level100 8percent changebaseline level-8th week level/ baseline level100 Each valvue represent correlation coefficientp value *p0.05by Spearman correlation test 4. 치료반응군과치료비반응군간의인구사회학적자료및기준임상변수의비교 Table 4. Comparison between responders and nonresponders in demographic data and baseline clinical assessment scores Variables Demographic data Responder N7 Nonresponder N11 Age 29.43 3.55 31.73 8.09 NS Sexfrequency male 2 5 female 5 6 Onset 21.57 5.50 22.82 4.73 NS Duration of illness years 7.86 6.52 8.91 6.56 NS No. of hospitalization 2.71 2.22 3.67 1.58 NS Baseline clinical assessment scores PANSS positive score 21.72 8.28 22.18 4.33 NS PANSS negative score 22.57 6.75 19.45 6.99 NS PANSS total score 84.5718.43 86.2715.88 NS CGI severity score 3.86 1.46 3.91 1.04 NS Each value represent MeanSD or frequency NSp0.05by Mann-Whitney U test p 84
Table 5. Comparison between responders and nonresponders in plasma baseline monoamine metabolites levels and the change of monoamine metabolite levels Variables Baseline metabolites levels Responders N7 Nonresponders N11 HVA levelng/ml 7.91 1.48 8.66 3.14 NS 5-HIAA level ng/ml 12.85 6.33 10.80 4.51 NS HVA/5-HIAA 0.77 0.38 0.87 0.34 NS 1 monoamine metabolites HVA 39.4120.37 8.6811.10 0.01 5-HIAA 24.2022.74 28.5819.80 NS HVA/5-HIAA 51.0339.73 4.2414.73 NS 8 monoamine metabolites HVA 9.8110.83 0.82 6.40 NS 5-HIAA 21.8626.52 35.8123.12 NS HVA/5-HIAA 7.8817.36 14.3920.13 NS 1percent changebaseline level-1th week level/ baseline level100 8percent changebaseline level-8th week level/ baseline level100 Each valvue represent means.d. *p valueby Mann-Whitney U test NSp0.05by Mann-Whitney U test 5. 치료반응군과치료비반응군간의 risperidone 투여전기준대사물농도와 risperidone 투여 1주후및 8주후대사물농도변화율의비교 p* 고찰 85
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목적 : 요약 방법 : 결과 : 결론 : 중심단어 : 참고문헌 강대엽 이충순 최진숙 김형섭 한광수 황태연 김융희 이정식 (1996) : 만성정신분열증환자에대한리스페리돈과할로페리돌의효과및안전성비교시험. 용인정신의학보 3(1):61-77 구자일 오동열 양병환 (1992) : 정신분열증환자의임상반응에따른혈장 Homovanillic Acid와혈장할로페리돌의변화. 김승현 이민수 곽동일 (1995) : 정신분열증환자에서 Haloperidol 투여에따른임상효과와혈장 Homovanillic Acid의농도및혈장 5-Hydroxyindoleacetic Acid 농도와의관계. 생물정신의학 2:77-90 김찬형 (1995) : 만성정신분열증환자에서 Clozapine의치료반응과혈장 Homovanillic acid 및 5-Hydroxyindoleacetic acid 농도와의관계 ( 박사학위 ). 연세대학교대학원민성길 이충순 김철응 강대엽 (1994) : 만성정신분열증환자치료에있어 Risperidone과 Haloperidol의이중맹비교. 대한정신약물학회지 5(1):156-167 박민철 피상순 이상렬 (1995) : 만성정신분열증환자의 Risperidone 치료효과와안정성. 대한정신약물학회지 6(1):89-99 박순원 정해익 강병조 (1993): 만성정신분열증환자의 Risperidone 치료효과. 신경정신의학 32(5):744-757 우종인 권준수 이상익 (1992): 정신분열병환자에서 Haloperidol 투여에따른치료반응과혈장 Homovanillic Acid 농도및혈장 Haloperidol과 Reduced Haloperidol 농도와의관계에대한연구. 신경정신의학 31 : 443-456 전우택 김찬형 전덕인 김광현 민성길 ( 출판중 ) : 정신분열증환자에서기준혈장 Homovanillic Acid가높은군과낮은군간의치료반응비교. 대한정신약물학회지조주연 기백석 박두병 (1996) : 정신분열증환자의혈장 Homovanillic Acid 농도와치료반응과의관계. 신경정신의학 35(3):529-535 Alfredsson G, Wiesel FA(1990):Relationships between clinical effects and monoamine metabolites and amino acids in sulpiride-treated schizophrenic patients. Psychopharmacology 101:324-331 American Psychiatric Association(1994):Diagnostic and Statistical Manual of Mental Disorders(DSM-Ⅳ). 4th ed, Washington DC, American Psychiatric Association, pp273-290 87
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