KISEP Original Article 대한정신약물학회지 : 제 17 권제 4 호 2006 정신분열병및기타정신증적장애환자의외래유지치료에서 Olanzapine의효과 신희영 1 김성완 1,2 김재현 3 정영철 4 정인원 5 지익성 6 윤보현 7 윤진상 1,2 전남대학교병원임상시험센터, 1 전남대학교의과대학정신과학교실, 2 원광대학교의과대학정신과학교실, 3 전북대학교의과대학정신과학교실, 4 동국대학교의과대학정신과학교실, 5 충남대학교의과대학정신과학교실, 6 국립나주병원 7 ABSTRACT The Effects of Olanzapine in the Maintenance Treatment of Outpatients with Schizophrenia and Other Psychotic Disorders Hee-Young Shin, MD, PhD, 1 Sung-Wan Kim, MD, PhD, 1,2 Jae-Hyun Kim, MD, PhD, 3 Young-Chul Chung, MD, PhD, 4 In-Won Chung, MD, PhD, 5 Ik-Seung Chee, MD, PhD, 6 Bo-Hyun Yoon, MD, PhD 7 and Jin-Sang Yoon, MD, PhD 1,2 1 Clinical Trial Center, Chonnam National University Hospital, Gwangju, 2 Department of Psychiatry, Chonnam National University Medical School, Gwangju, 3 Department of Psychiatry, School of Medicine, Wonkwang University, Iksan, 4 Department of Psychiatry, Chonbuk National University Medical School, Jeonju, 5 Deparment of Psychiatry, College of Medicine, Dongguk University, Gyungju, 6 Department of Psychiatry, College of Medicine, Chungnam National University, Daejon, 7 Naju National Hospital, Naju, Korea Objective:This open multicenter trial examined the effects of olanzapine on profiles of efficacy, safety, and subjective quality of life (QoL) in the maintenance treatment of stable outpatients with schizophrenia or other psychotic disorders. Methods:A total of 47 patients who had completed acute inpatient treatment with olanzapine were recruited from six centers. Information on sociodemographic and clinical characteristics was collected. A variety of measures for efficacy, safety, and QoL were administered at the time of discharge (baseline) and after 12 weeks of maintenance treatment (endpoint). Results:Twenty (43%) patients discontinued olanzapine treatment for various reasons. Twenty-seven patients (57%) completed the study, and in this group, there was a significant additional reduction in overall psychotic symptoms, including negative symptoms. Olanzapine was generally well-tolerated, although substantial weight gain was observed. However, QoL was not improved further during the maintenance treatment. Conclusion:Olanzapine was generally effective and well-tolerated in the maintenance treatment of stable outpatients with schizophrenia and other psychotic disorders. (Korean J Psychopharmacol 2006;17(4):342-348) KEY WORDS:Olanzapine Maintenance treatment Efficacy Safety Quality of life. 접수일자 :2006 년 4 월 13 일 / 심사완료 :2006 년 5 월 23 일본연구는 ( 주 ) 한국릴리의연구비 (FID-KL-S009) 지원을받아수행되었음. 교신저자 : 윤진상, 501-746 광주광역시동구학동 5 전남대학교의과대학정신과학교실전화 :(062) 220-6142 전송 :(062) 225-2351 E-mail:jsyoon@chonnam.ac.kr 342
신희영등 서론 olanzapine은국내에서 1998년임상사용을허가받은이후현재가장널리사용되고있는비정형항정신병약물중하나로, 정신분열병약물치료에대한한국형알고리듬지침서 1) 에서 1단계약물로추천되고있다. olanzapine 은여러국외임상시험 2-4) 에서유효성과안전성이반복적으로증명되었는데, 음성증상과우울증상은물론이고삶의질 (quality of life, QoL) 에도효과적이었다. 또한정형항정신병약물에비해추체외로계부작용 (extrapyramidal side effect, EPS) 의발생율이낮고혈중프로락틴증가도미약하여우수한안전성을보였다. 단기비교임상연구를연장한연구에서도 olanzapine 의급성기치료효과가유지되고재발율도낮은것으로나타났다. 5) olanzapine 의임상효과를평가한국내연구 6-8) 는많지않으며수행된연구또한대개 6주또는 8주간의치료후유효성과안전성을평가한연구들이었다. 본저자들도 2003년에 94명의정신분열병및기타정신증적장애입원환자를대상으로 12주이내의급성기치료효과에대한연구결과를발표한바있다. 9) 그러나정신분열병은급성기증상이안정된이후에도재발가능성이높은만성적질환이기때문에 10) 항정신병약물의효과를논하기위해서는급성기치료효과뿐아니라유지치료효과에대한평가가필요하다. 하지만국내에서는안정된환자를대상으로한 olanzapine 의유지치료에대한연구는거의없었다. 이에 1차연구 9) 과정을통해입원기간중급성정신증적상태가완화된후외래유지치료를시작하는정신증환자들을대상으로 olanzapine 의유효성, 안전성, QoL 등을포괄적으로평가하는연장연구를진행하였다. 방법 본연구는정신분열병, 정신분열형장애및분열정동장애환자를대상으로 2000년 7월부터 2001년 12월까지 9개병원에서실시되었던 olanzapine 의전향적공개다기관임상시험의연장연구이다. 입원중인정신증환 자들을대상으로한 olanzapine 의급성기치료효과에대한연구결과는저자들이이미보고하였다. 9) 본연구는 1차급성기연구를완료한후퇴원하여외래치료를시작하는환자들을대상으로하였고, 주요평가시점은 1차급성기연구의종료시점인퇴원당시와퇴원후 12주였다. 1. 연구대상 1차급성기연구의포함기준및배제기준은선행논문에기술한바있다. 요약하면 DSM-IV 의진단기준 11) 에따라정신분열병, 정신분열형장애또는분열정동장애로진단된만 18세에서 65세사이의남녀로입원치료기개시시점에서 Positive and Negative Syndrome Scale (PANSS) 12) 점수가 60~120점또는 EPS가 Simpson- Angus Rating Scale(SARS) 13) 에서 3점이상으로서기존의항정신병약물에대한내약성이없는환자였다. 1차연구를완료한 73명의환자중연장연구에동의한 6개기관 47명의환자를대상으로퇴원시점에서연장연구를시작하였다. 2. 약물투여 olanzapine 은하루에한번저녁에투약하며용량은 5~20 mg/day 로하였다. 퇴원시점의약물을외래치료에서도사용하였으며임상적판단에따라용량변경은가능하였다. olanzapine 의평균사용용량은 16.1±4.4 mg이었다. 시험기간에다른항정신병약물은물론일차적으로중추신경계에작용하는타약물의병용은금지하였고, 항콜린성약물은추체외로계부작용이발생한경우 benztropine 등가량 6 mg/day 이하로투여하였다. 또한항불안및진정수면의목적으로는 benzodiazepine (BZD) 계의약물 ( 허용량은 diazepam 등가량 40 mg/day 이하 ) 을임상의의판단에따라서최소한으로사용하도록허용하였다. 3. 평가내용및도구퇴원시점과퇴원후 12 주말의평가는크게다음의세가지내용을포함하였다. 첫째, PANSS, Clinical Global Impression for Severity of Illness(CGI-SI), 14) 수면및주간상태설문지 (Sleep and Daytime Status Questionnaire, SDSQ), 9) Global Assessment of Functioning 343
Olanzapine 과유지치료 Scale(GAF) 등 11) 을이용하여유효성을평가하였다. 둘째, 활력징후, 체중및각종검사실검사, UKU side effect rating scale(uku 척도 ), 15) SARS, Barnes- Akathisia Rating Scale(BARS), 16) Abnormal Involuntary Movement Scale(AIMS) 등 14) 을이용하여안전성을평가하였다. 셋째, General Health Questionnaire/ Quality of Life-12(GHQ/QL-12) 17) 와 Korean Modification of the Scale to Measure Subjective Well- Being under Neuroleptic Treatment의 10문항척도 (KmSWN-10) 18) 을이용하여 QoL 을평가하였다. 4. 자료분석입원치료를마치고퇴원하여외래유지치료에들어간환자중 12주말까지치료를받은환자 ( 완료군 ) 와도중에탈락된환자 ( 탈락군 ) 의기준시점특성비교는독립표본 T 검정 (independent t-test), 카이제곱검정 (χ 2 test), 또는 Fisher의정확한검정 (Fischer s exact test) 가운데적절한방법을사용하였다. 완료군에서 PANSS 총점수및소척도 ( 양성, 음성, 전반적정신병리 ) 점수, SDSQ 총점수및소척도 ( 야간의수면, 주간상태 ) 점수, GAF, CGI-SI, GHQ/QL-12, Km- SWN-10, 체중, 활력징후, UKU 척도범주별 ( 정신적, 신경학적, 자율신경계, 기타 ) 점수, SARS, AIMS 총점수, BARS 1항목전체점수 (global score) 의기준시점과연 구종료시점의차이를대응표본 T 검정 (paired t-test) 으로분석하였다. 또한 Andreasen 등이제시한관해 (remission) 기준 19) 중 PANSS의중증도기준 (P1, P2, P3, N1, N4, N6, G5, G9의 8개항목에서모두 3점이하 ) 을만족하는환자비율의변화를분석하였다. 모든통계분석은 SPSS for Windows 12.0(SPSS Inc, Chicago, USA) 을사용하였고, 통계적유의수준은 p< 0.05 로서양측검정을하였다. 결과 1. 연구대상자의특성급성기연구를마친총 73 명의환자중 6개기관 47 명 ( 정신분열병 38명, 정신분열형장애 8명, 분열정동장애 1명 ) 이연장연구에참여하였다. 참여자가운데연구종료시점인외래치료 12주째까지연구가완료된피험자는 27 명 (57%), 탈락된피험자는 20 명 (43%) 이었다. 파악된연구탈락의이유로는동의철회 (9 명, 45%), 환자의병원방문기피 (8 명, 40%), 연구계획서위반 (3 명, 15%) 등이었다. 연구완료군과탈락군사이에인구사회학적특성및임상적특성은유의한차이가없었다 ( 표 1, 2). 단, 임상적특성가운데삶의질을반영하는 KmSWN-10 과 GHQ/QL-12 가완료군에서더높은경향을나타냈고, 이는통계적유의성에근접하였다 ( 각각 p=0.052, 0.059). Table 1. Comparison of patient's sociodemographic and clinical characteristics at baseline between subjects who completed 12-week trial and those who dropped out Total participants (n=47) Completed (n=27) Dropped out (n=20) Age, mean (SD) years 30.2 (6.9) 29.9 (7.4) 30.8 (6.4) 0.664 Gender, male:female (%) 23:24 (51) 13:14 (52) 10:10 (50) 0.900 Education, mean (SD) years 13.1 (2.9) 13.5 (3.1) 12.6 (2.5) 0.279 Spouse, no:yes (%) 37:10 (21) 20:7 (26) 17:3 (15) 0.481 Occupation, no:yes (%) 38:9 (19) 22:5 (19) 16:4 (20) 1.000 Living area, rural:urban (%) 10:37 (79) 06:21 (78) 04:16 (80) 1.000 Religion, no:have (%) 23:24 (51) 13:14 (52) 10:10 (50) 0.900 Socio-economic status, middle:low (%) 40:7 (15) 23:4 (15) 17:3 (15) 1.000 Diagnosis, SPR:SPF:SA 38:8:1 21:5:1 17:3:0 0.638 Age of psychosis onset, mean (SD) years 26.6 (6.6) 26.9 (6.8) 26.2 (6.4) 0.740 Mean dosage of olanzapine, mean (SD) mg 16.1 (4.4) 16.3 (4.4) 15.8 (4.6) 0.686 Previous hospitalization, mean (SD) frequency 1.23 (1.86) 1.33 (2.06) 1.10 (1.59) 0.675 SPR:Schizophrenia, SPF:Schizophreniform Disorder, SA:Schizoaffective Disorder. a:by t-, chi-square or Fischer s exact tests, as appropriate p a 344 Korean J Psychopharmacol 2006;17(4):342-348
신희영등 2. 유효성 완료군은연구종료시점에서기준시점에비해 PANSS 의총점수, 양성증상, 음성증상, 전반적정신병리의소척도점수가유의하게감소하였다. 또한 GAF 와 CGI-SI 의점수도유의한호전을보였으나 SDSQ 점수는유의한변화가없었다 ( 표 3). Andreasen 등이제시한관해의정의에의하면 6개월동안그기준을충족해야하지만, 본연구는분석시점인 3개월째까지 PANSS 의관해기준을만족하는환자를분석하였다. 연장연구참여자 47명중 36명인 77% 가기저시점에서 PANSS 의관해기준을만족하였는데, 완료환자 27 명중 23 명인 85% 가 PANSS 의관해기준을만족하였다. 이를세부적으로분석하여보면, 완료환자 27 명가운데 22 명 (81%) 이연장연구시작시점인퇴원시이 Table 2. Comparison of baseline scores on clinical measures between subjects who completed 12-week trial and those who dropped out Completed (n=27) Efficacy measures, mean (SD) scores Dropped out (n=20) PANSS, total 54.90 (13.9) 57.3 (16.5)0 0.592 Positive 12.20 (03.2) 12.1 (04.1)0 0.927 Negative 13.30 (04.5) 15.1 (04.6)0 0.176 General 29.40 (07.7) 30.1 (09.0)0 0.789 SDSQ, total 04.70 (04.2) 4.8 (04.7)0 0.940 Daytime 00.10 (01.7) -0.1 (01.7)0 0.864 Nighttime 04.70 (03.7) 4.9 (03.8)0 0.868 GAF 60.50 (11.1) 59.5 (14.7)0 0.793 CGI-SI 02.60 (00.9) 2.9 (00.9)0 0.325 Quality-of-life measures, mean (SD) scores GHQ/QL-12 19.50 (05.5) 16.3 (05.8)0 0.059 KmSWN-10 40.00 (09.5) 34.6 (07.0)0 0.052 Safety measures, mean (SD) scores SARS, total (10 items) 00.30 (00.54) 0.50 (01.60) 0.541 BARS, global (1 item) 00.22 (00.58) 0.10 (00.31) 0.395 AIMS, total (7 items) 00.07 (00.39) 0.15 (00.49) 0.554 PANSS:Positive and Negative Symptom Scale, SDSQ: Sleep and Daytime Status Questionnaire, GAFS:Global Assessment of Functioning Scale, CGI-SI:Clinical Global Impression for Severity of Illness, GHQ/QL-12:General Health Questionnaire/Quality of Life-12, KmSWN-10: Korean Modification of the Scale to Measure Subjective Well-Being under Neuroleptic Treatment-10. a:by paired t-test p a 미 PANSS 의관해기준을만족하였는데, 이들중 3개월째까지관해를유지한환자는 20 명으로 91% 가관해상태를지속하였다. 퇴원시관해상태가아닌 5명의환자중약물을 3개월간유지한후새롭게 PANSS 의관해기준을만족하게된환자는 3명 (60%) 이었다. 3. 안전성 1) 활력징후, 체중, 검사실검사 종료시점에서좌위및앙와위수축기와이완기혈압, 맥박, 체온등은기준시점에비해유의한변화는없었으나, 체중및체질량지수는유의하게증가하였다 ( 표 4). 2) 이상반응 연구기간에약물관련의이상반응으로약물을중단한경우는없었으며, 약물과관련된이상반응은 5명에서총 8건이보고되었다. 이가운데변비 2건, 정좌불능증, 발기부전, 체중증가, 졸음 ( 진정 ), 간기능효소수치증가, 혈당증가가각각 1건있었다. UKU 척도는신경학적증상의소척도점수에서만기준시점에비해종료시점에서유의 Table 3. Data on efficacy and quality-of-life measures at baseline and endpoint in completers (n=27) Baseline Endpoint p a Efficacy measures, mean (SD) scores PANSS, total 54.9 (13.9) 47.6 (13.2) <0.001 Positive 12.2 (03.2) 10.3 (02.6) <0.001 Negative 13.3 (04.5) 11.6 (03.8) 0.001 General 29.4 (07.7) 25.6 (07.3) <0.001 SDSQ, total 04.7 (04.2) 04.5 (03.9) 0.797 Daytime 00.1 (01.7) -0.2 (01.7) 0.434 Nighttime 04.6 (03.7) 04.8 (03.5) 0.790 GAFS 60.5 (11.1) 66.5 (10.5) 0.004 CGI-SI 02.6 (00.9) 02.1 (01.3) 0.020 Quality-of-life measures, mean (SD) scores GHQ/QL-12 19.5 (05.5) 18.4 (06.7) 0.368 KmSWN-10 40.0 (09.5) 37.3 (10.5) 0.366 PANSS:Positive and Negative Symptom Scale, SDSQ: Sleep and Daytime Status Questionnaire, GAFS:Global Assessment of Functioning Scale, CGI-SI:Clinical Global Impression for Severity of Illness, GHQ/QL-12:General Health Questionnaire/Quality of Life-12, KmSWN-10: Korean Modification of the Scale to Measure Subjective Well-Being under Neuroleptic Treatment-10. a:by paired t-test 345
Olanzapine 과유지치료 Table 4. Data on physical examinations and safety measures at baseline and endpoint in completers (n= 27) 하게감소하였다 ( 표 4). 346 3) 추체외로계증상 기준시점과종료시점에서 SARS, BARS, AIMS 각척도의점수는평균 1점미만으로 EPS 의심도는경미한수준이었으며, SARS 점수에서만기준시점에비해유의한감소를보였다 ( 표 4). 4. QoL GHQ/QL-12 과 KmSWN-10 점수는기준시점에비해종료시점에서유의한변화가없었다 ( 표 3). 고 Baseline Endpoint p a Physical examinations, mean (SD) scores Blood pressure, mmhg Sitting, Systolic 120.0 (16.5) 119.4 (13.6) 0.798 Diastolic 78.0 (13.6) 80.0 (12.1) 0.408 Lying, Systolic 120.7 (17.3) 120.0 (14.1) 0.752 Diastolic 77.9 (14.8) 76.8 (12.0) 0.640 Pulse rate, per minute 86.0 (07.9) 86.3 (10.6) 0.890 Body temperature, 36.5 (00.3) 36.4 (00.2) 0.953 Body weight, kg 65.6 (10.4) 69.2 (11.4) <0.001 Body mass index, kg/m 2 24.6 (02.7) 25.8 (03.1) <0.001 Safety measures, mean (SD) scores UKU, category Psychic 2.26 (2.11) 1.78 (02.12) 0.374 Neurologic 0.30 (0.61) 0.04 (00.19) 0.017 Autonomic 0.59 (1.08) 0.26 (00.59) 0.142 Others 1.46 (1.88) 1.81 (02.26) 0.314 SARS, total (10 items) 0.30 (0.54) 0.04 (00.19) 0.032 BARS, global (1 item) 0.22 (0.58) 0.11 (00.42) 0.265 AIMS, total (7 items) 0.07 (0.39) 0.00 (00.00) 0.327 UKU:Udvalg for Klinske Undersogelser side effect rating scale, AIMS:Abnormal Involuntary Movements Scale, BARS:Barnes-Akathisia Rating Scale, SARS:Simpson- Angus Rating Scale. a:by paired t-test 본연구는 12주이내의 olanzapine 급성기입원치료를마친상태에서안정된상태를유지하고재발을막기위 찰 한외래유지치료에들어간 47명의정신분열병및기타정신병환자를대상으로이루어진연구이다. olanzapine 의유효성과안전성에관한국내임상연구 6-9) 는많지않으며대부분이단기급성기치료의효과를본연구들이었다. 그러나정신분열병은급성기증상이안정된이후에도재발가능성이높은만성적질환이므로항정신병약물의효과를논하기위해서는급성기단기치료효과뿐아니라안정기유지치료효과에대한검증이필요하다. 하지만현재까지이러한국내연구는이루어지지않았다. 본연구는급성기입원치료를마치고외래유지치료에들어간환자를대상으로 12 주동안재발방지, 정신병적증상의추가적호전, 지연되어나타나는부작용발생및삶의질개선에관해평가하였다는점에서그의의를둘수있다. 1차급성기연구 9) 에서 olanzapine의입원치료에 94명이참여하여 73명이연구를종료하고 21명 (22%) 이중도에탈락되었던반면, 본연장연구에서는입원치료를마치고외래유지치료에들어간 47명가운데 27명이연구를종료하고 20명 (43%) 이탈락하여더높은탈락률을보였다. 이는외국의 6주단기연구들 4,20,21) 에서보인 27~ 45% 와비교하면높은탈락률은아니지만, 28주이중맹검연구 22,23) 에서보인 40~42% 와비교하면연구의방법과기간등을고려할때상대적으로높은탈락률이라고할수있다. 1차급성기연구에서탈락의가장주된이유는불충분한약물반응 (38%) 이었던것 9) 에반해, 연장연구에서는탈락의주이유가동의철회와외래방문중단이었다. 또한탈락군과연구종료군간에인구사회학적및임상적특징의차이가발견되지않았는데, 이러한점들을고려하면본연구의탈락률은 olanzapine 의약리학적특성이아닌환경적요인에의해더큰영향을받았음을시사한다. 다만, 비록통계적유의성에이르지는못했지만, 급성기치료종료시점에서약물치료와관련한주관적만족감과삶의질이낮은환자일수록외래방문중단을포함한탈락률이높은경향을보여정신분열병의유지치료에환자의주관적만족감및삶의질이영향을미칠가능성에대해서도고려할수있다. 외래유지치료기간동안유효성을평가하는대부분의척도에서유의한호전을보여, PANSS의총점수, 양성증상, 음성증상, 및전반적정신병리의소척도점수가유의 Korean J Psychopharmacol 2006;17(4):342-348
신희영등 하게감소하고 GAF 와 CGI-SI 의점수도유의한호전을보였다. 이는 olanzapine 의급성기치료효과가유지치료기간에도유지되었다고보고한외국의연구들 5,22,23) 의결과와일치하는것이다. 한편, 선행연구에서유의한호전을보였던야간의수면상태와주간의피로와졸음을반영하는 SDSQ 점수는유의한변화가없었다. olanzapine 은진정효과가높아서야간수면에는유익하지만, 주간에는오히려졸음이나피로를야기하는부정적인측면을가지고있어서졸음은가장흔한이상반응으로보고되어있으나 24) 본연구에서는졸음을약물관련이상반응으로보고한경우가 1례에불과하였고유지치료기간동안야간수면과주간수면에유의한영향을주지는않았다. 6개월이라는관해기준의요건이충족되지는않았지만, 올란자핀을 3개월간유지한환자군에서관해기준을지속한비율은 91% 였고, 새롭게관해를획득한비율은 60% 였다. 비록상대적으로높은탈락률로인해이결과에는제한점이있지만, 적어도일정기간 olanzapine 을유지해간경우 olanzapine 이정신분열병의관해유지에효과적일수있음을시사한다. olanzapine 외래유지치료의안전성과관련하여종료시점에서혈압, 맥박, 체온등은기준시점에비해유의한변화는없었다. UKU 척도에서는정신증적증상, 자율신경계증상, 기타증상등에서는변화가없었지만신경학적증상의소척도점수는유의하게감소하였다. EPS 와관련하여 BARS 와 AIMS 점수에서는유의한변화가없었으나 SARS 점수에서는오히려기준시점에비해종료시점에서유의한감소를보였다. 이는 olanzapine 의급성 EPS 발생율이 haloperidol 보다유의하게낮고 (18% vs. 47%), 25) 위약과차이가없다는 (8% vs. 12%) 3) 선행연구결과들과같은맥락이라할수있다. 그러나체중은유의하게증가하여외래유지치료 12주동안약 3.6 kg이증가하였다. 1차급성기연구에서입원치료기간동안 2.6 kg 체중증가가유지치료기간에도계속되었음을의미한다. 이러한체중증가는외국의 12주연구 26) 에서의 5.4 kg, 28주연구 22) 에서의 4.1 kg과유사하였다. 체중증가는 olanzapine 을포함한다른비정형약물에서도문제점으로인식되고있어, 27) 약물치료의선택시체중증가에대한인식과관리가필요하다. 28) 항정신병약물치료의궁극적치료목표가운데하나는 환자의 QoL 향상이라할수있다. 환자의 QoL 향상에는비정형항정신병약물이정형약물보다더우수하다는보고들이있어왔다. 29,30) 1차급성기연구에서 GHQ/QL- 12과 KmSWN-10을통해평가한 QoL은 olanzapine 급성기입원치료동안개선되었으나, 본연구의외래유지치료기간동안에추가적으로나타나지는않았다. 1차급성기연구에서 QoL 변화와독립적인연관성을갖는변인으로서야간수면의개선이파악되었는데본연구에서는야간수면의추가적인개선과 QoL 의추가적인개선모두없었다. 본연구는다음과같은몇가지제한점을가지고있다. 첫째, 무작위배정비교연구가아니었고맹검법을시행하지않은개방시험이었다. 그러므로본연구를통해위약또는다른항정신병약물과비교한 olanzapine 의효과를알아볼수는없었다. 둘째, 외래유지치료기간이 12주로비교적짧아 olanzapine 의장기유지치료효과를평가하기는어려웠다. 셋째, 연구탈락률이 43% 로비교적높았다. 그럼에도불구하고본연구는여러기관이공동으로참여함으로써환자군의대표성을확보할수있었고, 처음으로유효성, 안전성및 QoL 관련영역의포괄적인평가가급성기입원치료후 12주간의외래유지치료기간동안이루어졌다는점에서그의의가있다. 장기유지치료연구는새로운항정신병약물의치료효과를입증하기위하여필수적이며재발률및운동장애의발생률등을알기위해서도필요하다. 향후에는이와같은정보를제공해줄수있는무작위배정비교장기연구가국내에서도이루어져서 olanzapine 의장기유지치료에대한객관적인임상정보가제공되기를기대한다. 중심단어 : Olanzapine 유지치료 유효성 안전성 삶의질. 참고문헌 1) Korean Medication Algorithm for the Treatment with Schizophrenic Patients 한국형정신분열병 양극성장애약물치료알고리듬개발위원회. 정신분열병약물치료에대한한국형알고리듬지침서. 서울 : 중앙문화사 ;2001. 2) Beasley CM, Tollefson G, Tran P, Satterlee W, Sanger T, Hamilton S. Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. Neuropsychopharmacology 1996;14:111-124. 3) Beasley CM, Sanger T, Satterlee W, Tollefson G, Tran P, Hamilton S. Olanzapine versus placebo: results of a double-blind, 347
Olanzapine 과유지치료 fixed-dose olanzapine trial. Psychopharmacology 1996;124: 159-167. 4) Tollefson GD, Beasley CM Jr, Tran PV, Street JS, Krueger JA, Tamura RN, et al. Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial. Am J Psychiatry 1997;154:457-465. 5) Tran PV, Dellva MA, Tollefson GD, Wentley AL, Beasley CM. Oral olanzapine versus oral haloperidol in the maintenance treatment of schizophrenia and related psychoses. Br J Psychiatry 1998;172:499-505. 6) Cho BH, Jung IK, Paik JW. Switch to olanzapine from clozapine or risperidone and 12-months follow up. J Korean Soc Biol Psychiatry 2001;8:140-146. 7) Ahn YM, Kang DY, Kwon JS, Kim CY, Kim CE, Bahn GH. Efficacy and safety of olanzapine in the treatment of Korean patients with schizophrenia and schizophreniform disorder. J Korean Neuropsychiatr Assoc 2001;40:693-707. 8) Kim CW, Lee TG, Kang SH, Cho JH, Lee SJ, Cho DH, et al. A comparative effectiveness study of risperidone and olanzapine in the treatment of inpatient of schizophrenia or schizophreniform disorder: 6 weeks, open-labelled, prospective study. J Korean Soc Biol Ther Psychiatry 2003;9:160-168. 9) Shin IS, Kim JM, Kim DI, Kim SH, Kim JH, Shin MS, et al. The effects of olanzapine in the treatment of inpatients with schizophrenia and other psychotic disorders: efficacy, safety and quality of life. Korean J Psychopharmacol 2003;14:48-62. 10) Lieberman J, Jody D, Geisler S, Alvir J, Loebel A, Szymanski S, et al. Time course and biological correlates of treatment response in first-episode schizophrenia. Arch Gen Psychiatry 1993;50:369-376. 11) American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed, Washington DC, American Psychiatric Association;1994. 12) Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome (PANSS) for schizophrenia. Schizophr Bull 1987;13: 261-276. 13) Simpson GM, Angus JWS. A rating scale for extrapyramidal side effect. Acta Psychiatr Scand (suppl) 1970;212:11-19. 14) Guy W. Early Clinical Drug Evaluation (ECDEU) Assessment Manual for Psychopharmacology. Rev ed. Bethesda, MD: US Department of Health, Education and Welfare;1976. 15) Lingjarde O, Ahlfors UG, Bech P, Dencker S, Elgen K. The UKU side effect rating scale: A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand (supple) 1987;334:1-100. 16) Barnes TR. A rating scale for drug induced akathisia. Br J Psychiatry 1989;154:672-676. 17) Bech P. Rating scales for psychopathology health status and quality of life. A compendium on documentation in accordance with the DSM-III-R and WHO Systems. Berlin, Heidelberg, Springer-Verlag;1993. p.402-404. 18) Yoon JS, Kook SH, Lee HY, Lee C, Paik IH. The development of a Korean modification of the Scale to measure Subjective Well-Being under Neuroleptic Treatment (KmSWN). J Korean Neuropsychiatr Assoc 2000;39:987-998. 19) Andreasen NC, Carpenter WT Jr, Kane JM, Lasser RA, Marder SR, Weinberger DR. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry 2005; 162:441-449. 20) Sanger TM, Lieberman JA, Tohen M, Grundy S, Beasley CM, Tollefson GD. Olanzapine versus haloperidol treatment in firstepisode psychosis. Am J Psychiatry 1999;156:79-87. 21) Tran PV, Tollefson GD, Sanger TM, Lu Y, Berg PH, Beasley CM. Olanzapine versus haloperidol in the treatment of schizoaffective disorder: acute and long-term therapy. Br J Psychiatry 1999;174:15-22. 22) Tran PV, Hamilton SH, Kuntz AJ, Potvin JH, Andersen SW, Beasley CM, et al. Double-blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders. J Clin Psychopharmacol 1997;17:407-418. 23) Breier A, Berg PH, Thakore JH, Naber D, Gattaz WF, Cavazzoni P, et al. Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia. Am J Psychiatry 2005;162:1879-1887. 24) Zyprexa package insert. Indianapolis: Eli Lilly and company; 1996. 25) Tran PV, Dellva MA, Tollefson GD, Beasley CM, Potvin JH, Kiesler GM. Extrapyramidal symptoms and tolerability of olanzapine versus haloperidol in the acute treatment of schizophrenia. J Clin Psychiatry 1997;58:205-211. 26) Ossler D, Najarian DI, Berman L. Olanzapine increases weight and triglycerides. Poster presented at 151st American Psychiatric Association Conference, Toronto, Canada, 1-4 June 1998. 27) Allison DB, Casey DE. Antipsychotic-induced weight gain: A review of the literature. J Clin Psychiatry (suppl) 2001;62: 22-31. 28) Gothelf D, Falk B, Singer P, Kairi M, Phillip M, Zigel L, et al. Weight gain associated with increased food intake and low habitual activity levels in male adolescent schizophenic inpatients treated with olanzapine. Am J Psychiatry 2002;159: 1055-1057. 29) Voruganti L, Cortese L, Oyewumi L, Cernovsky Z, Zirul S, Awad A. Comparative evaluation of conventional and novel antipsychotic drugs with reference to their subjective tolerability, side-effect profile and impact on quality of life. Schizophr Res 2000;43:135-145. 30) Karow A, Naber D. Subjective well-being and quality of life under atypical antipsychotic treatment. Psychopharmacology 2002;162:3-10. 348 Korean J Psychopharmacol 2006;17(4):342-348