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1 KISEP Original Articles 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 Department of Psychiatry, Yonsei University College of Medicine, Seoul, Korea Yong-In Psychiatric Research Institute, Yong-In, Kyunggido 79

2 서론 80

3 대상및방법 1. 연구대상 2. 방법 1) 치료약물투여 2) 임상증상의평가 81

4 3) 혈장 HVA 및 5-HIAA 농도측정 82

5 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 Sexfrequency male 7 female 11 Onset ageyears Duration of illnessyears Number of hospitalizaion Subtype of schizophrenia paranoid type 8 undifferentiated type 10 83

6 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 * HIAAng/ml HVA/5-HIAA ResponsdersN7 HVAng/ml * HIAAng/ml HVA/5-HIAA NonrespondersN11 HVAng/ml HIAAng/ml * HVA/5-HIAA * *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 * * 5-HIAA HVA/5-H IAA monoamine metabolites HVA HIAA * HVA/5-HIAA percent 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 NS Sexfrequency male 2 5 female 5 6 Onset NS Duration of illness years NS No. of hospitalization NS Baseline clinical assessment scores PANSS positive score NS PANSS negative score NS PANSS total score NS CGI severity score NS Each value represent MeanSD or frequency NSp0.05by Mann-Whitney U test p 84

7 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 NS 5-HIAA level ng/ml NS HVA/5-HIAA NS 1 monoamine metabolites HVA HIAA NS HVA/5-HIAA NS 8 monoamine metabolites HVA NS 5-HIAA NS HVA/5-HIAA 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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9 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): 박민철 피상순 이상렬 (1995) : 만성정신분열증환자의 Risperidone 치료효과와안정성. 대한정신약물학회지 6(1):89-99 박순원 정해익 강병조 (1993): 만성정신분열증환자의 Risperidone 치료효과. 신경정신의학 32(5): 우종인 권준수 이상익 (1992): 정신분열병환자에서 Haloperidol 투여에따른치료반응과혈장 Homovanillic Acid 농도및혈장 Haloperidol과 Reduced Haloperidol 농도와의관계에대한연구. 신경정신의학 31 : 전우택 김찬형 전덕인 김광현 민성길 ( 출판중 ) : 정신분열증환자에서기준혈장 Homovanillic Acid가높은군과낮은군간의치료반응비교. 대한정신약물학회지조주연 기백석 박두병 (1996) : 정신분열증환자의혈장 Homovanillic Acid 농도와치료반응과의관계. 신경정신의학 35(3): Alfredsson G, Wiesel FA(1990):Relationships between clinical effects and monoamine metabolites and amino acids in sulpiride-treated schizophrenic patients. Psychopharmacology 101: American Psychiatric Association(1994):Diagnostic and Statistical Manual of Mental Disorders(DSM-Ⅳ). 4th ed, Washington DC, American Psychiatric Association, pp

10 Andreasen NC, Olsen SA(1982):Negative vs positive schizophrenia:definition and validation. Arch Gen Psychiatry 39: Bacopoulos NG, Hattox SE, Roth RH(1979):3-4-Dihydroxyphenylacetic acid and homovanillic acid in rat plasma: possible indicators of central dopaminergic activity. Eur J Pharmacol 56: Berger PA, Faull K, Kilkowski J, Anderson PG, Kraemer H, Davis KL, Barchas JD(1980):CSF monoamine metabolites in depression and schizophrenia. Am J Psychiatry 137: Borison RL, Pathiraja AP, Diamond BI, Meibach RC(1992): Risperidone:clinical safety and efficacy in schizophrenia. Psychopharmacol Bull 28: Bowers MB Jr, Heninger GR(1981):Cerebrospinal fluid homovanillic acid patterns during neuroleptic treatment. Psychiatry Res 4: Bowers MB, Swigar ME, Jatlow PI, Goicoechea N(1984): Plasma catecholamine metabolites and early response to haloperidol. J Clin Psychiatry 45: Bower MB, Swigar ME, Jatlow PI(1987):Early neuroleptic response:clinical profiles and catecholamine metabolites. J Clin Psychopharmacol 7:83-36 Bowers MB, Swigar ME, Jatlow PI, Hoffman FJ(1989):Plasma catecholamine metabolites and treatment response at neuroleptic steady state. Biol Psychiatry 25: Chang WH, Chen TY, Lee CF, Hung JC, Hu WH, Yeh EK (1988):Plasma homovanillic acid levels and subtyping of schizophrenia. Psychiatry Res 23: Chang WH, Chen TY, Lin SK, Lung FW, Lin WL, Hu WH, Yeh EK(1990):Plasma catecholamine metabolites in schizophrenics:evidence for the two-subtype concept. Biol Psychiatry 27: Chouninard G, Jones B, Remington G, Bloom D, Addington D, MacEwan GW, Labelle A, Beauclair L, Arnott W (1993):Canadian multicenter placebo-controlled study of fixed dose of resperidone and haloperidol in the treatment of chronic schizophrenic patients. J Clin Psychopharmacol 13:25-40 Chouninard G, Ross-Chouninard A, Annable L, Jones BD (1980):The extrapyramidal symptoms rating scale. Can J Neurol Sci 7:233 Claus A, Bollen J, De Cuyper H, Eneman M, Malifroid M, Peuskens J, Heylen S(1992):Risperidone versus haloperidol in the treatment of schizophrenia in patients:a multicentre double-blind comparative study. Acta Psychiatr Scand 85: Coward DM(1992):General pharmacology of clozapine. Br J Psychiatry 160(suppl 17):5-11 Davidson M, Losonczy MF, Mohs RC, Lesser JC, Powchik P, Freed LB, Davis BM, Mykytyn VV, Davis KL(1987): Effects of debrisoquin and haloperidol on plasma homovanillic acid concentration in schizophrenic patients. Neuropsychopharmacology 1:17-23 Davila R, Manero E, Zumarraga M, Andia I, Schweitzer JW, Friedhaff AJ(1988):Plasma homovanilic acid as predictor of response to neuroleptics. Arch Gen Psychiatry 45: Davis JM, Schaffer CB, Killian GA, Kinard C, Chan C(1980): Important issues in the drug treatment of schizophrenia. Schizophr Bull 6:70-87 Davis JM, Erickson SE, Hurt S, Chang SS, Javaid JL, Dekirmenjian H, Casper R(1985):Haloperidol plasma levels and clinical response:basic concepts and clinical data. Psychopharmacol Bull 21:48-51 Degrell I, Nagy E(1990):Correlation between cisternal CSF and plasma concentrations of HVA, MHPG, 5-HIAA, DA, and NA. Biol Psychiatry 27: Guy W(1976):ECDEU Assessment Manual for Psychopharmacology. Rockville, MD, US Department of Health Education and Welfare, pp Hsiao JK, Colison J, Barko JJ, Doran AR, Konicki PE, M, Potter MZ, Pickar D(1993):Monoamine neurotransmitter interactions in drug-free and neuroleptic-treated schizophrenics. Arch Gen Psychiatry 50: Janssen PAJ, Niemegeers CJE, Awouters F, Schellekens KHL, Megens AHP, Meert TF(1988):Pharmacology of risperidone(r ), a new antipsychotic with serotonin- S2 and dopamine D2 antagonistic properties. J Pharmacol Exp Ther 244(2): Kahn RS, Davidson M(1993):On the value of measuring dopamine, norepinephrine and their metabolites in schizophrenia. Neuropsychopharmacology 8:93-95 Kahn RS, Davidson M, Knott P, Stern RG, Apter S, Davis K(1993):Effect of neuroleptic medication on cerebrospinal fluid monoamine metabolite concentrations in schizophrenia. Arch Gen Psychiatry 50: Kane JM(1989):The current status of neuroleptic therapy. J Clin Psychiatry 50: Kay SR, Fiszbein A, Opler LA(1987):The Positive and Negative Syndrome Scale(PANSS) for schizophrenia. Schizophr Bull 13:55-70 Kendler KS, Davis KL(1984):Acute and chronic effects of neuroleptic drugs on plasma and brain homovanillic acid in the rat. Psychiatry Res 13:51-58 Koreen AR, Lieberman J, Alvir J, Mayerhoff D, Loebel A, Chakos M, Amin F, Cooper T(1994):Plasma homovanillic acid levels in firstepisode schizophrenia:psychopathology and treatment response. Arch Gen Psychiatry 51: Leysen JE, Gommeren W, Eens A, De Chaffoy de Courcelles D, Stoof JC, Janssen PAJ(1988):The biochemical profile of risperidone, a new antipsychotic. J Pharmacol Exp Ther 247(2): Lieberman JA(1994):Clinical biological studies of atypical antipsychotics:focus on the serotonin/dopamine systems. J Clin Psychiatry Monograph 12(2):24-28 Marder SR, Meibach RC(1994):Risperidone in the treatment of schizophrenia. Am J Psychiatry 151: Mass JW, Contreras SA, Miller AL, Berman N, Bowden CL, Javors MA, Seleshi E, Weintraub S(1993):Studies of catecholamine metabolism in schizophrenia/psychosis-i. Neuropsychopharmacology 8: Mazure CM, Nelson CJ, Jatlow PI(1991):Plasma free homovanillic acid as a predictor of clinical response in acute psychosis. Biol Psychiatry 30: Meltzer HY(1989):Clinical studies on the mechanism of action of clozapine:the dopamine-serotonin hypothesis of schizophrenia. Psychopharmacology 99(suppl):S18-S27 Pickar D(1988):Perspectives on a time-dependent model of neuroleptic action. Schiziphr Bull 14: Pickar D, Labarca R, Linnoila M, Roy A, Hommer D, Ever- 88

11 ett D, Paul SM(1984):Neuroleptic-induced decrease in plasma homovanilic acid and antipsychotic activity in schizophrenic patients. Science 225: Pickar D, Owen RR, Litman RE, Konicki E, Gutierrez R, Rapaport MH(1992):Clinical and biologic response to clozapine in patients with schizophrenia:crossover comparison with fluphenazine. Arch Gen Psychiatry 49: Richelson E(1984):Neuroleptic affinities for human brain receptors and their use in predicting adverse effects. J Clin Psychiatry 45: Rimon R, Roos BE, Rakkolainen V, Alanen Y(1971):The content of 5-hydroxyindoleacetic acid and homovanillic acid in the cerebrospinal fluid of patients with acute schizophrenia. J Psychosom Res 15: Seegal RF, Brosch KO, Bush B(1986):High-performance liquid chromatography of biogenic amines and metabolites in brain, cerebrospinal fluid, urine and plasma. J Chromatography 377: Sharma R, Javaid JI, Janicak P, Faull K, Comaty J, Davis JM (1989):Plasma and CSF HVA before and after pharmacological treatment. Psychiatry Res 28: Szymanski S, Lieberman J, Pollack S, Munne R, Safferman A, Kane J, Kronig M, Cooper T(1993):The dopamineserotonin relationship in clozapine response. Psychopharmacology 112(suppl):85-89 Van putten T, Marder S, Aravagiri M(1989):Plasma homovanillic acid as a predictor of response to fluphenazine treatment. Psychopharmaco Bull 1:

1. 연구대상 대상및방법 2. 연구방법 1) 치료약물투여 61

1. 연구대상 대상및방법 2. 연구방법 1) 치료약물투여 61 KISEP Original Articles 8 1 1997 Korean J Psychopharmacol Vol 8, No 1 치료저항만성정신분열증환자의 Risperidone 효과 이홍식 * 전지용 * 김찬형 * 송동호 * 육기환 * 김병천 * 손석한 * 구민성 * Efficacy of Risperidone in Treatment-Resistant Patients