1. 연구대상 대상및방법 2. 연구방법 1) Fluoxetine 의병합투여 2) 임상반응평가 3) 통계분석 1. 인구학적특성 결 2. 정신병리의변화 3. 추체외로부작용의변화 과

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KISEP Original Articles 생물정신의학 Vol. 4, No. 1, June 1997 Fluoxetine과 Haloperidol의병합투여시정신병리및추체외로증상의변화 이민수 * 한창수 * 김제원 ** 원경식 ** 곽동일 ** Changes of Psychopathology and Extrapyramidal Symptoms When Co-administering Fluoxetine and Haloperidol Min-Soo Lee, M.D.,* Chang-Su Han, M.D.,* Jae-Won Kim, M.D.,** Kyung-Sik Won, M.D.,** Dong-Il Kwak, M.D.** ABSTRACT O bjectivesthe authors have intended to know the drug interaction of fluoxetine and haloperidol when coadministering two drugs to the chronic schizophrenics by assessing the changes of positive, negative symptoms and extrapyramidal symptoms. MethodWe selected 38 patients, the chronic schizophrenics with no physical problems. they are randomly assigned to placebo group and drug group. And then, placebo or fluoxetine 20mg were administered to the subjects of each group during 8 week period. We have assessed their psychopatholgy and extrapyramidal symptoms using Positive and Negative Syndrome ScalePANSS, Clinical Global ImpressionCGI, Simpson-Angus Scale at 0, 2, 4, 6, 8 week during the period. Results38 patients have completed the study during 8 weeks. 1 PANSS, CGIno significant difference between groups and no significant change according to the times. 2 Simpson-Angus Scaleno significant changes. ConclusionWhen co-administering fluoxetine and haloperidol, there were no significant changes of psychopathology and extrapyramidal symptoms. These results suggest that it is safe to coadminister fluoxetine to schizophrenic patients with haloperidol treatmemt. KEY WORDSFluoxetineHaloperidolDrug interaction. 서 Department of Neuropsychiatry, College of Medicine, Korea University, Seoul, Korea Department of Psychiatry, Dong-In Hosptal, Pusan, Korea 론 - 121 -

1. 연구대상 대상및방법 2. 연구방법 1) Fluoxetine 의병합투여 2) 임상반응평가 3) 통계분석 1. 인구학적특성 결 2. 정신병리의변화 3. 추체외로부작용의변화 과 - 122 -

Table 1. Characteristics of the patients entering the study Flouxetine group N19 Control group N19 Sexmalefemale 136 136 NS Ageyears 39.78 7.93 38.57 8.47 NS Dosage of Haloperidol 24.2117.10 25.9220.77 NS Weightkg 60.31 6.64 63.6811.48 NS Heightkg 162.10 6.19 164.00 5.32 NS Blood pressure Systolic 124.7312.18 121.0511.49 NS Diastolic 76.84 8.85 75.26 7.72 NS Pulse rate 92.21 9.99 88.94 9.96 NS Student t-test, two-tailed Each values are expressed as meansd Fig. 1. Comparison of PANSS positive scale value between the groups. Table 2. Comparison of PANSS positive scale score between the groups* Floxetine**N19 16.505.35 15.255.52 16.313.09 16.192.79 16.192.79 Control**N19 14.911.64 13.964.38 15.091.38 15.091.38 15.091.38 *Each values are expressed as meansd **Fluoxetine+Haloperidol group ***Placebo+Haloperidol group Group effectf1.03, df1/36, nonsignificant Time effectf0.29, df4/144, nonsignificnat GroupPANSS positive score interactionf0.32, df4/144, nonsignificant Table 3. Comparison of PANSS negative scale score between the groups* Floxetine**N19 19.314.47 19.734.85 19.214.23 19.054.23 18.314.46 Control***N19 17.685.89 17.475.88 17.685.62 17.475.16 17.264.87 *Each values are expressed as meansd **FluoxetineHaloperidol group ***PlaceboHaloperidol group Group effectf1.05, df1/36, nonsignificant Time effectf1.99, df4/144, nonsignificant GroupPANSS negative score interactionf0.89, df4/144, nonsignificant Table 4. Comparison of PANSS general scale score between the groups* Floxetine**N19 34.156.16 34.106.16 34.216.44 34.157.22 34.107.21 Control***N19 31.687.28 32.317.68 31.847.38 31.788.10 31.527.75 *Each values are expressed as meansd **FluoxetineHaloperidol group ***PlaceboHaloperidol group Group effectf1.03, df1/36, nonsignificant Time effectf0.29, df4/144, nonsignificant GroupPANSS general score interactionf0.32, df4/144, nonsignificant Table 5. Comparison of clinical global impression scale values between the groups* Floxetine**N19 4.311.25 4.471.17 4.471.147 4.471.21 4.471.21 Control***N19 4.421.30 4.421.30 4.421.30 4.421.30 4.471.34 *Each values are expressed as meansd **FluoxetineHaloperidol group ***PlaceboHaloperidol group Group effectf0.00, df1/36, nonsignficant Time effectf0.53, df4/144, nonsignificant GroupCGI score interactionf0.39, df4/144, nonsignificant - 123 -

Fig. 2. Comparison of PANSS negative scale value between the groups. Fig. 4. Comparison of clinical global impression scale values between the groups. Fig. 3. Comparison of PANSS general scale value between the group. Fig. 5. Comparison of simpson-angus scale value between the groups. Table 6. Comparison of simpson-angus scale values between the groups* Floxetine**N19 4.685.03 4.735.07 4.735.17 3.835.74 4.476.05 Control***N19 3.004.42 3.365.02 3.155.25 2.425.04 2.475.12 *Each values are expressed as meansd **FluoxetineHaloperidol group ***PlaceboHaloperidol group Group effectf0.98, df1/36, nonsignificant Time effectf2.06, df4/144, nonsignificant GroupSimpson-Anugs scale score interactionf0.22, df4/144, nonisngnificant 고찰 - 124 -

요 중심단어 : 참고문헌 유영운 김승현 이민수 (1994): 정신분열증환자에서 Sertraline 병합투여시혈중 Haloperidol 농도에미치는영향. 신경정신의학 43:544-552 정한용 이민수 곽동일 (1994): 정신분열증환자에서 fluoxetine 투여에따른임상반응과혈청 Haloperidol, Reduced Haloperidol 및 5-Hydroxyindoleacetic Acid 농도의변화에대한연구. 고대논문집. 31:377-392 한창수 이민수 김표한 (1996): 만성정신분열증환자에서 paroxetine 과 haloperidol 병합투여시정신병리증상과 haloperidol, reduced haloperidol 혈중농도의변화. 생물정신의학 3: 251-257 American Psychiatric Association(1987):Diagnostic and Statistical 약 - 125 -

Manual of Mental disorders. revised 3rd ed, Washington, American Psychiatric Association Ames D, Wirshing WL, Marder SR, Yuwiler A, Brammer GL, Midha KK, Van Putten T(1993):Adjunctive fluoxetine in haloperidol-stabilized schizophrenics(abstract). Presented at the first International Congress on Hormones, Brain and Neuropsycho-pharmacology, Rhodes, Greece, September 13-17 Arnaow RB, Hudson JI, Pope HG, Grade TA, Laage TA, Bell IR, Cole JO(1989):Elevated antidepressant plasma levels after addition of fluoxetine. Am J Psychiatry 146:911-913 Bacher NM, Ruskin P(1991):Addition of fluoxetine to treatment of schizophrenic patients. Am J Psychiatry 148:274-275 Bernstein JG(1995):Handbook of Drug Therapy in Psychiatry, 3rd ed, Mosby, St. louis, Baltimore Black B, Uhde TW(1992):Acute dystonia and fluoxetine[case report]. J Clin Psychiatry 53:327 Bouchard RH, Pourcher EP, Vincent P(1989):Fluoxetine and extrapyramidal side effects.[case report] Am J Psychiatry 146: 1352-1353 Chouinard G, Jones B, Remington G, Bloom D, Addington D (1993):A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. J Clin Psycopharmacol 13:25-40 Ciraulo DA, Shader RI(1990):Fluoxetine Drug-Drug Interactions: I. antidepressants and antipsychotics. J Clin Psychopharmacol 10:48-50 Coulter DM, Pillans PI(1995):Fluoxetine and side effects. Am J Psychiatry 152:122-125 Fallon BA, Liebowitz MR(1989):Fluoxetine and extrapyramidal symtpoms in CNS lupus.[case report] J Clin Psychopharmacol 11:147-148 Gaddun JH, Hameed KA(1954):Drugs which antagonize 5-hydroxytryptamine. Br J Pharmacol 7:365-435 Goff DC, Brotman AW, Waites M, McCormick S(1990):Trial of fluoxetine added to neuroleptics for treatment-resistant schizophrenic patients. Am J Psychiatry 147:492-494 Goff DC, Midha KK, Brotman AW, Waites M, Baldessarini RJ (1991):Elevation of plasma concentrations of haloperidol after the addition of fluoxetine. Am J Psychiatry 148:790-792 Goldman MB, Janecek HM(1990):Adjunctive fluoxetine improves global function in chronic schizophrenia. J Neuropsychiatry 2: 429-431 Grimsley SR, Jann MW, Carter JG(1991):Increased carbamazepine concentrations after fluoxetine coadministration. Clin Pharmacol Ther 50:10-15 Johnson AM(1991):The comparative pharmacological properties of selective serotonin reuptake inhibitors in animals, In:Perspectives in psychiatry, vol 1. Ed by Feighner JP and Boyer WF, Chichester, John Willey, pp37-70 Kaplan HI, Sadock BJ(1991):Fluoxetine, biological therapies, in Synopsis of Psychiatry, 6th ed, Baltimore, Wiliams and Wilkins, pp649-650 Kay SR, Olper LA, Fiszbein A:Positive and negative syndrome sclae(panss) rating menual. Albert Einstein College of Medicine/ Montefior Medical center, New York Lemberger L, Rowe H, Bosomworth JC(1988):The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam. Clin Pharmacol Ther 43:412-419 Lipinski JF, Mallya G, zimmerman P, Pope HG(1989):Fluoxetineinduced akathisia:clinical and theoriticl implications. J Clin Psychiatry 50:339-342 Melzter HY(1989):Clinical studies on the mechanism of action of clozapine:the dopamine-serotonin hypothesis of schizophrenia. Psychopharmacol 99:S18-S27 Pearson HJ(1990):Interaction of fluoxetine with carbamazepine. J Clin Psychiatry 51:126 Preskorn SH, Barke MJ, Fast GA(1993):Therapeutic drug monitoring. Psychiatr Clin North Am 16:611-646 Reccoppa L, Welch WA, Ware MR(1990):Acute dystonia and fluoxetine[case report]. J Clin Psychiatry 51:487-488 Simpson GM, Angus JWS(1970):A rating scale for extrapyramidal side effects. Acta Psychiatr Scand(suppl) 212:11-19 Sovner R, Davis JM(1991):A potential drug interaction between fluoxetine and valproic acid. J Clin Psychopharmacol 11:389 Stahl SM, Uhr SB and Berger PA(1985):Pilot study on the effects on fenfluramine on negative symptoms in twelve schizophrenic inpatients. Biol Psychiatry 20:1098-1102 Sternbach H(1991):Fluoxetine-associated potentiation of calciumchannel blockers. J Clin Psychopharmacol 11:390 Tate JL(1989):Extrapyramidal symptoms in a patient taking haloperidol and fluoxetine[case report]. Am J Psychiatry 146:399-400 Wong DT, Bymaster FP, Horng JS(1975):A new selective inhibitor for uptake of serotonin into synaptosome of rat brain 3-(P-trifluoromethylphenomy)-N-methyl-phenyl prophylamine. J Pharmacol Exp Ther 193:804-811 - 126 -