항정신병약물 사용 중인 정신분열병 환자에서 올란자판으로의 교체 방법에 관한 연구(II) : Comparison of Safety 안전성 비교

안용민,권용실,권준수,민성호,박두병,양문정,소형석,송종호,신윤식,우행원,유범희,이홍석,정한용,한창환,김용식 大韓神經精神醫學會 2002 신경정신의학 Vol.41 No.5

연구목적: 이 다기관 공동임상연구는 사용 중인 항정신병약물을 ’직접 교체 방법’또는 ’시작-감량 교체 방법’중 한 가지 방법으로 올란자핀으로 교체한 후, 안정성 측면에서 두 교체 방법 간의 비교와 교체후의 변화를 관찰하기 위한 것이다. 방법: 국내 13개 병원의 입원 및 외래에 내원한 환자들 중 ICD-10 지단기준으로 정신분열병에 해당되며, 임상적으로 항정신병약물 교체가 필요한 환자를 대상으로 하였다. 두 가지 교체 방법 중 한 가지를 무작위로 피험자에 적용하였으며, ’직접 교체 방법’에 배정된 경우에는 사용중인 항정신병약물을 일시에 중단하고 10㎎의 올란자핀을 바로 투여하였고, ’시작-감량 교체 방법’에 배정된 경우는 10㎎의 올란자핀 투여하고 2주에 걸쳐서 기존 약물을 감량하여 중단하였다. 올란자핀 사용기간은 총 6주이며, 용량은 5∼20㎎ 범위로 제한하였다. 한정성 평가를 위해서 체중, 생명징후, 자발적인 이상반응 복, 실험실 검사 그리고 Simpson-Angus Scale(SAS), Barnes akathisia rating scale(BARS), Abnormal involuntary movement scale(AIMS). Liverpool University neuroleptic side effect rating scale(LUNSERS)등을 이용하였다. 결과: 총 103명의 정신분열병 환자를 대상으로 하였다. 사용한 올란자핀의 용량, 벤조디아제핀의 병용률, 탈락률과 탈락 사유, 자발적인 이상반응 보고, 생명징후, 실험실 검사 그리고 대부분의 부작용 척도 상에서 임상적으로 의미 있는 차이를 두 교체 방법간에 발견하지 못하였다. 다만 AIMS의 감소는 ’직접 교체 방법’군에서 보다 적었고, 항콜린제의 병용률은 ’시작-감량 교체 방법’군에서 보다 많았다. 기저 상태에서 전체 피험자의 SAS와 BARS 점수는 각각 3.5점과 1.8점이었으며 70% 이상의 피험자가 고프로락틴 혈증을 보였다. 올란자핀으로 교체한 후, SAS, BARS, AIMS 점수의 유의한 감소가 있었으며 고프로락틴 혈증을 보인 피험자 분율도 약 30%이하로 감소하였다. 그러나 교체 방법과 상관없이 올란자핀 교체 후 유의한 체중 증가가 있었다. 결론: 이 연구를 통해 교체 방법에 관계없이 비교적 안전하고 용이하게 올란자핀으로 교체 할 수 있음을 알 수 있었다. 그리고 기존 항정신병약물을 올란자핀으로 교체함으로써 일부 부작용들을 줄일 수 있음을 간접적으로 관찰할 수 있었다. 하지만 이 연구는 여러 제한점과 문제점을 지니고 있기 때문에 보다 체계적인 연구를 통해 검정이 필요하리라 생각된다. Objectives: This multicenter clinical trial involving 13 hospital sites compared the safely of switching to olanzapine between ’direct switching method’ and ’start-tapering switching method’. Method: This study included both inpatients and outpatients who fulfilled the criteria for schizophrenia as defined in the ICD-10, and were in need to be appropriate for switching antipsychotics. Subjects were randomly assigned to one of the two switching methods. For ’direct switching method’group, previous antipsychotics were abruptly discontinued and 10㎎ of olanzapine was administered, and previous antipsychotics was gradually tapered for 2 weeks. Olanzapine was used for 6 weeks and the dose was adjusted within the range of 5-20㎎. The safety of switching to olanzapine was measured with vital sings including body weight, adverse events reported spontaneously, laboratory tests, and various scales such as Simpson-Angus Scale(SAS), Barnes Akathisia Rating Scale(BARS). Abnormal Involuntary Movement Scale(AIMS), and Liverpool University Neuroleptic Side Effect Rating Scale(LUNSERS). Results: 103 patients were switched to olanzapine in this study. The comparison between two switching methods did not show any significant difference in the dosage of olanzapine used, the concomitant use of benzodiazepine, the rate and reasons of drop-out, the adverse events, vital signs, laboratory tests, and most scales for measuring side-effects. However, the decrease in AIMS scores was significantly lower in ’direct switching method’ group, and the concomitant use of anticholinergics was comparatively greater in ’start-tapering switching method’ group. At baseline, SAS and BARS scores were 3.5 and 1.8 points respectively, and more than 70% of the subjects showed hyperprolactinemia. After switching to olanzapine, SAS, BARS, and AIMS scores were significantly decreased and the proportion of the patients with hyperprolactinemia was also decreased to less than 30%. However significant weight gain after the treatment of olanzapine was observed regardless of switching method. Conclusion: This study may suggest that switching to olanzapine can be done with relatively high safety regardless of switching methods and olanzapine can significantly decrease some side-effects induced by other antipsychotics.

정신분열병 환자에서 가족력, 산과적 합병증 및 신체미세기형의 관련성에 관한 연구

안용민,김용식,정희연,신지용,윤세창,배안,이중서,주은정,이창인 大韓神經精神醫學會 1999 신경정신의학 Vol.38 No.2

연구목적 : 저자들은 태생기 동안에 받는 유전외적 요인, 즉 환경적 요인이 산발성 정신분열병 환자들의 발병에 크게 관여할 것이라고 가정하였다. 이를 검증하기 위하여 형제 중 1인 이상이 발병하여 가족력을 분명히 알 수 있는 정신분열병 환자군(이하 형제 환자군)과 가족력이 없는 산발성 정신분열병 환자군(이하 산발성 환자군) 및 정상대조군을 대상으로 산과적 합병증, 신체미세기형 및 정신분열병의 임상 양상을 비교하였다. 방 법 : 연구 대상은 형제 환자군 43명(남 22명, 여 21명), 산발성 환자군 43명(남 23명, 여 20명), 정상대조군 43명(남 20명, 여 23명)이었다. 산과적 합병증은 Lewis 척도를 이용하여 평가하였고 신체미세기형은 Waldrop 척도를 이용하여 측정하였다. 임상 양상으로서 발병 연령, 병전 기능 수준, 정신병리, 약물에 대한 반응, 회복시의 전반적 기능 수준, 지연성 운동장애의 유무를 평가하였다. 결 과 : 정상대조군과 정신분열병 환자군 전체를 비교하였을 때 산과적 합병증과 신체미세기형의 총점과 각 소항목의 점수에 차이가 없었다. 산발성 환자군과 형제 환자군을 비교하였을 때 산과적 합병증의 전체 점수에서는 유의한 차이가 없었으나, 출생 당시에 태아가 받은 스트레스 항목의 점수가 산발성 환자군에서 유의하게 높았다. 신체미세기형에서는 전체 점수 및 입의 미세기형 점수가 산발성 환자군에서 유의하게 높았다. 신체미세기형의 전체 점수가 4점 이상인 환자수도 산발성 환자군에서 높은 경향성을 보였다. 산과적 합병증과 신체미세기형 사이의 상호 연관성은 찾을 수 없었다. 정신분열병의 임상 양상 중에서는 Krawiecka 척도의 총점 및 양성 증상 점수와 회복시의 전반적 기능 수준만이 형제 환자군에 비해 산발성 환자군에서 유의하게 높았다. 성별에 따라서는 형제 환자군에서 남자 환자의 산과적 합병증이 유의하게 높았다. 결 론 : 본 연구를 통해 산과적 합병증 및 신체미세기형 연구가 정신분열병의 원인을 규명하기 위한 유용한 방법임이 시사되었지만, 가족력, 산과적 합병증 및 신체미세기형의 관련성에 대해서는 분명한 결론을 내리지 못하였다. The authors hypothesized that sporadic schizophrenic patients had more chances of receiving environmental insults during the fetal neural development compared with familial schizophrenics. We tested our hypothesis by comparing obstetric complications(OCs), minor physical anomalies(MPAs) and other clinical features, and examining the correlation between OCs and MPAs in schizophrenic patients who had one or more sibling with schizophrenia(sibling group) and sporadic schizophrenics(sporadic group) and normal controls. OCs were evaluated by the scale of Lewis, and MPAs were measured by the Waldrop scale. There were no significant difference in OCs and MPAs between schizophrenic and control groups. Sporadic group had significantly higher fetal distress, total Waldrop score and Waldrop score for mouth than sibling group. And there was a tendency that the number of subjects having the Waldrop score over 4 points was greater in the sporadic group. No significant correlation was observed between CCs and MPAs. The scores of initial psychopathology and post-treatment functioning were much higher in the sporadic group, but the other clinical feature showed no difference. Although male patients had more OCs than female patients in sibling group, no sex difference were observed as a whole. Our results suggest that, if the methodological weakness were complemented, OCs and MPAs would be useful tools in the search for the cause of schizophrenia.

면역방사계수법을 이용한 Thyroglobulin 측정시 항 Thyroglobulin 항체의 존재가 미치는 영향

안병철,배진호,정신영,박호용,김정국,하승우,이재태,김보완,이규보 대한내분비학회 2004 Endocrinology and metabolism Vol.19 No.1

연구배경: 혈청 thyroglobulin (Tg)은 옥소전신스캔과 함께 분화갑상선암환자에서 갑상선암 재발에 대한 추적관찰에 매우 예민하고, 중요한 표지자로 임상에서 널리 이용된다. 그러나 많은 수의 분화갑상선암환자는 Tg 항체인 항 Tg 항체를 가지고 있고, 이는 방사면역검사법 (radioimmunoassay) 및 면역방사계수 검사법(immunoradiometric assay)으로 Tg 측정시 영향을 미칠 수 있다. 이에 연자들은 면역방사계수법으로 Tg를 측정할 경우, 항 Tg항체에 의하여 어떤 영향이 생길수 있는지를 알아보고자 하였다. 방법: 이중위치 고상법 (solid phase two-site)법을 이용하는 ELSA-hTg in vivo test (CIS international, Schering, France) 시약을 이용하여 Tg를 측정하였다. Tg과 항 Tg 항체는 검사시약에 포함된 표준용액을 사용하였으며, Tg는 두 가지 농도 (23.5 ng/mL, 62.5 ng/mL)로, 항 thyroglobulin 항체는 세 가지 농도(25U/mL, 50U/mL, 100U/mL)로 이용하였다. Tg가 높게 나타나는 환자의 혈청에 항 Tg 항체가 높게 나타나는 환자의 혈청을 혼합하여 동일한 방법으로 Tg 검사를 시행하였다. 통계학적 분석은 ANOVA와 Scheffe test 및 Quadratic regression modeling을 시행하였다. 결과: 면역방사계수법을 이용한 Tg 측정시 항 thyroglobulin 항체가 존재하는 경우 그 값이 낮게 측정되었다. Tg 농도가 23.5 ng/mL인 표준용액이 항 Tg 항체의 농도가 0, 25, 50 및 100U/mL 경우, 각각 24.5±1.1, 11.8±0.4, 7.7±0.1 및 4.5±0.4ng/mL로 측정되었으며, Tg 농도가 62.5 ng/mL인 표준용액은 각각 65.9±5.7, 36.3±2.2, 23.7±0.7, 및 14.0±1.0 ng/mL로 측정되었다(ANOVA test, p=0.000). 항 Tg 항체에 의한 Tg 측정값의 저하 정도는 항 Tg 항체의 농도에 비례하는 것으로 나타났다 (Quadratic model regression, SigT=0.000). 결론: 분화갑상선암환자에서 항 Tg 항체의 존재는 면역방사계수법을 이용한 혈청 Tg 측정으로 갑상선암 재발을 파악하는데 방해하는 인자로 작용될 수 있으며, Tg 측정시 항 Tg 항체의 측정이 꼭 필요하며, 항 Tg 항체를 가진 분화갑상선암환자에서 Tg 수치를 해석할 경우 세심한 주의가 요구된다. Background: Serum thyroglobulin (Tg) is a valuable and sensitive tool needed in the follow-up of patients with differentiated thyroid cancer (DTC), but antithyroglobulin antibody (Anti-Tg), common in patients with DTC, can interfere with the assay for Tg. In this study, we evaluated the influence of Anti-Tg on the measurement of Tg using the immunoradiometric assay (IRMA). Methods: In using ELSA-hTg in vivo test (CIS international, Schering, France), a solid phase two-site IRMA was used to measure Tg (23.5 ng/mL, 62.5 ng/mL) under the absence or presence of three concentrations of Anti-Tg (25U/mL, 50U/mL, 100U/mL). We also performed Tg measurement using patients serum that was mixed with patients serum containing high Anti-Tg. ANOVA and Scheffe tests were performed to evaluate the effect of Anti-Tg on Tg IRMA, and an inverse regression was made to calculate the level of Tg from measured Tg and used Anti-Tg levels and also to assess the degree of effect of anti-Tg on Tg IRMA. Results: In measuring Tg using the standard solution, the presence of Anti-Tg resulted in a falsely suppressed Tg value. The IRMAs for 23.5ng/mL of the standard Tg solution resulted in 24.5±1.1 ng/mL under no Anti-Tg, 11.8±0.4 ng/mL under 25U/mL of Anti-Tg, 7.7±0.1 ng/mL under 50U/mL of Anti-Tg, and 4.5±0.4 ng/mL under 100U/mL of Anti-Tg. IRMAs 62.5 ng/mL of the standard Tg solution resulted in 65.9±5.7 ng/mL under no Anti-Tg, 36.3±2.2 ng/mL under 25U/mL of Anti-Tg, 23.7±0.7 ng/mL under 50U/mL of Anti-Tg, and 14.0±1.0 ng/mL under 100U/mL of Anti-Tg. (ANOVA test, p=0.000). The degree of suppression of the measured Tg value was positively correlated with the Anti-Tg level (Quadratic model regression, Sig T=0.000). The presence of Anti-Tg also resulted in a falsely suppressed Tg value for the Tg measurement using patient's serum. 2004). Conclusion: The presence of Anti-Tg could consist of the use of Tg as a tumor, therefore Anti-Tg should be measured in all patients diagnosed with DTC. The interpretation of the Tg level must be performed with extreme caution in patients with Anti-Tg (J Kor Soc Endocrinol 19:42∼47, 2004)

A Comparison of Lyophilized Amniotic Membrane with Cryopreserved Amniotic Membrane for the Reconstruction of Rabbit Corneal Epithelium

Ahn Jae-Il,Jang In-Keun,Lee Doo-Hoon,Seo Young-Kwon,Yoon Hee-Hoon,Shin Youn-Ho,Kim Jae-Chan,Song Kye-Yong,Lee Hee-Gu,Yang Eun-Kyung,Kim Ki-Ho,Park Jung-Keung The Korean Society for Biotechnology and Bioengine 2005 Biotechnology and Bioprocess Engineering Vol.10 No.3

Many researchers have employed cryopreserved amniotic membrane (CAM) in the treatment of a severely damaged cornea, using corneal epithelial cells cultured on an amniotic membrane (AM). In this study, two Teflon rings were made for culturing the cells on the LAM and CAM, and were then used to support the AM, which is referred to in this paper as an Ahn's AM supporter. The primary corneal epithelial cells were obtained from the limbus, using an ex-plantation method. The corneal epithelium could be reconstructed by culturing the third­passage corneal epithelial cells on the AM. A lyophilized amniotic membrane (LAM) has a higher rate of graft take, a longer shelf life, is easier to store, and safer, due to gamma irradiation, than a (AM. The corneal epithelium reconstructed on the LAM and (AM, supported by the two­Teflon rings, was similar to normal corneal epithelium. However, the advantages of the LAM over that of the (AM make the former more useful. The reconstruction model of the corneal epithelium, using AM, is considered as a good in vitro model for transplantation of cornel epithelium into patients with a severely damaged cornea.

Golgi 염색 기법에 대한 연구

안병권,박매자,김은희,배용철,홍해숙,조희중,주강 慶北大學校 醫科大學 1990 慶北醫大誌 Vol.31 No.4

여러 Golgi methods 중에서 본 실험실 환경에 적합한 방법을 확립하기 위해서, Golgi Method, Golgi-Kopsch modification, silver-chromate Golgi method 그리고 Rapid Golgi method의 네가지 방법을 실제로 실시했는데 그 중 Adam의 silver-chromate Golgi method에서 가장 좋은 결과를 얻었는데 그 결과는 다음과 같다. 1) 착색에 소요되는 시간이 약 7일 정도였다. 2) 대뇌피질, 시상하부, 뇌간의 모든부위 등 실험을 실시한 거의 모든 부위에서 착색된 신경세포를 관찰할 수 있었다. 3) 착색된 신경세포는 세포체 뿐만 아니라 축삭돌기, 수상돌기 그리고 수상돌기소극 등의 미세구조도 잘 관찰되었으며, 규칙적인 분포를 하였다. 4) 착색된 신경교세포와 혈관은 저밀도로 관찰되었다. Four modifications of the Golgi method, i. e. Golgi method, method, Golgi-Kopsch modification, silver-chromate Golgi method and rapid Golgi method were tested to find out most reliable method. Compared to another 3 modifications, Adams' silver chromate Golgi method was found to have several advantages as follows. 1) It took 7 days for impregnation procedure. 2) Neurons were well impregnated and their axons, dendrites and spines could be identified very clearly. 3) Impregnated neurons formed few clusters. 4) Glias and vessels showed very minimal impregnations.

제조에 對한 文獻的 考察

안태규,최병렬,송기철,이용연,유화승,서상훈,최우진,조정효,이연월,손창규,조종관 대전대학교 한방병원 2001 惠和醫學 Vol.10 No.1

In the literatual study on Holotrichia, the results were obtained as follows ; 1. Holotrichia is larva of Holotrichia diomphalia Bates etc. powder or liquor of Holotrichia is used medically. 2. Appearance of Holotrichia is shape of kidney, yellowish color. 3. The oriental characters of Holotrichia is warm, toxicant, salty. 4. The significant efficancy of Holotrichia is breaking the stagnant blood. 5. Holotrichia can be applied to the diseases related to thrombosis, and recover the demage of liver. 6. Holotrichia avails Liver diseases such as Hepatitis, Liver cirrhosis, Hepatosplenomegaly, Hepatoma etc.

자발성 기흉을 동반한 폐림프관평활근종증 1예

안용환,정종훈,김소영,김휘정,김학렬,양세훈,최순호,문형배,조향정,정은택 圓光大學校 醫科學硏究所 2005 圓光醫科學 Vol.20 No.1

Reconstruction of Rabbit Corneal Epithelium on Lyophilized Amniotic Membrane Using the Tilting Dynamic Culture Method

Ahn, Jae-Il,Lee, Doo-Hoon,Ryu, Yang-Hwan,Jang, In-Keun,Yoon, Mun-Young,Shin, Youn Ho,Seo, Young-Kwon,Yoon, Hee-Hoon,Kim, Jae-Chan,Song, Kye-Yong,Yang, Eun-Kyung,Kim, Ki-Ho,Park, Jung-Keug Blackwell Publishing Inc 2007 Artificial Organs Vol.31 No.9

<P>Abstract: </P><P>Rabbit corneal epithelium was reconstructed using tilting dynamic culture with a self-manufactured, amniotic membrane (AM) supporter and a lyophilized amniotic membrane (LAM). Rabbit corneal epithelial (RCE) cells were cultured and cryopreserved after isolation from the limbus. The second- and third-passage RCE cells were plated onto the epithelial side of the LAM of Ahn's AM supporter. Two days later, the air–liquid interface culture was maintained with third-passage RCE cells for 6 days and second-passage corneal epithelial cells for 9 days. The average viability of thawed RCE cells, assessed using trypan blue dye exclusion, was 77.42%. The reconstructed corneal epithelium was characterized by histological (hematoxylin and eosin) and immunohistochemical staining (proliferating cell nuclear antigen) for light microscopy, and by reverse transcriptase-polymerase chain reaction, glucose assay, and transmission electron microscopy. The basal layer of the reconstructed corneal epithelium was well formed, and the epithelium was tightly constructed due to the increase in cell proliferation and differentiation caused by the tilting dynamic culture, as opposed to static culture. Tilting dynamic culture was useful for the reconstruction of the epithelium using easily damaged epithelial cells and resulted in more stratum cell layers. Moreover, cytokeratin (CK3) mRNA expression in tilting dynamic cultured third-passage RCE cells seeded onto AM was greater than in static cultured third-passage RCE cells. The morphology of the reconstructed corneal epithelium on LAM by tilting dynamic culture for 9 days resembled that of the skin epidermis. This was thought to be because the tilting dynamic culture not only accelerated the proliferation and differentiation of cells by physical or mechanical stimulation, but also ensured that the supply of medium was delivered to the basal cells more efficiently. Thus, the reconstruction of the corneal epithelium using LAM and tilting dynamic culture was considered to be a good in vitro model for autologous or allogeneic transplantation of corneal epithelium and skin epidermis in patients with damaged epithelia. </P>

연작업자들에서의 δ -aminolevulinic acid dehydratase 유전형질의 다형성이 신기능에 미치는 영향

안익수,황보영,김용배,리갑수,이성수,장봉기,함정오,안규동,이병국 순천향대학교 산업의학연구소 2001 순천향산업의학 Vol.7 No.1

δ-aminolevulinic acid hehydratase (ALAD) is a polymorphic enzyme that has two alleles, ALAD1 (ALAD1-1 as phenotype) and ALAD2 (ALAD1-2 or ALAD2-2 as phenotype). ALAD genotype has been reported to modify the toxicokinetics of lead. To investigate the influence of ALAD genotype polymorphism on renal function in lead workers, author studied 1022 male lead workers and 149 non lead workers in the same industries. For the cross-sectional renal function indices, blood urea nitrogen (BUN), serum creatinine, uric acid and total protein were selected. Blood lead and blood zinc protoporphyrin were also measured as indices of lead exposure. Information on weight, age, job duration, smoking & drinking history were collected. Following results are as follows: 1. Whereas the mean (standard deviation) of blood lead and blood ZPP of lead workers were 27.2±12.5 ㎍/㎗ and 57.7±37.8 ㎍/㎗, those of non-lead workers in the same premises were 14.9±6.5 ㎍/㎗ and 44.6± 15.8 ㎍/㎗ respectively. The difference of mean blood lead and blood ZPP between two groups were statistically significant. 2. Whereas the prevalence of the variant allele, ALAD2 in 1022 lead workers was 10.2 %, the prevalence of that in 149 non-lead workers was 7.4 %. But there was no difference of prevalence between two groups. 3. The mean±standard deviation of blood lead of subjects with ALAD1 was 25.5± 12.7 ㎍/㎗ and was slightly lower than that of subjects with ALAD2 (26.5±10.9 ㎍/㎗), and the mean±standard deviation of blood ZPP of subjects with ALAD1 was slightly higher than that of subjects with ALAD2 (56.7±37.3 ㎍/㎗ vs 48.9±18.6 ㎍/㎗). But the differences of blood lead and blood ZPP between two genotypes were not statistically significant. 4. There were no differences of cross-sectional renal function indices (BUN, serum creatinine, uric acid and total protein) either by lead workers and non-lead workers or two genotypes. 5. In multiple regression analysis of ALAD genotype on BUN after controlling for possible confounders (sex, weight, job duration, smoking and drinking status), the mean of BUN in ALAD2 subjects was 0.629 ㎎/㎗ lower than ALAD1 subjects with a weak statistical significance (p=0.07). But in logistic analysis of ALAD genotype on median value of BUN revcaled that subjects of ALAD2 genotype were 32% less likely to have median value or more of BUN than subjects of ALAD1 with odd ratio of 0.618 (95% confidence interval 0.411-0.920). 6. In multiple regression analysis of ALAD genotype on serum creatinine after controlling for possible confounders (sex, weight, job duration, smoking and drinking status), the mean of serum creatinine in ALAD2 subjects was 0.0271 ㎎/㎗ lower than ALAD1 subjects with statistical significance (p=0.02). On the other hand, in logistic analysis of ALAD genotype on median value of serum creatinine revealed that subjects of ALAD2 genotype were 30% less likely to have median value or more of scrum creatinine than subjects of ALAD1 with odd ratio of 0.700 (95% confidence interval 0.442-1.080). With the above results, it was found that the variant allcle, ALAD2 appeared to modify the association of lead and renal function and ALAD2 genotype may be supportive for the protective effect of lead.

정신분열병 및 정신분열형 장애에 대한 올란자핀의 효과와 안전성

안용민,강대엽,권준수,김창윤,김철응,반건호,신영민,이기철,이동우,이중서,조현상,채정호,김용식 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.4

연구목적 : 본 다기관 공동임상연구는 국내 환자를 대상으로 새로운 항정신병약물인 올라자핀의 치료 효과와 안전성을 확인하고자 시행되었다. 방 법 : 1999년 7월부터 2000년 3월까지 국내 10개 병원에 방문한 정신분열병 및 정신분열형 장애 105명을 대상으로 비대조 개방 임상연구를 시행하였다. 중등도 이상의 정신병 증상을 지니거나, 부작용으로 약물교체가 필요한 경우 또는 기분장애 증상의 치료가 필요한 환자를 대상으로 하였다. 2∼7일간의 약물 배설기간 후에 1일 10mg의 올란자핀을 투여하였고, 이후로 3∼7일 간격으로 용량을 조절하여 총 8주간 투여하였다. 치료 효과는 PANSS(Positive and Negative Syndrome Scale), BPRS(Brief Psychiatric Rating Scale), CGI(Clinical Global Impression-Severity), MADRS(Montgomery-Asberg Depression Rating Scale), HAM-A(Hamilton Rating Scale for Anxiety)로 판정하였다. 안전성 평가는 자발적인 이상반응 보고, 활력징후와 혈액 검사 및 SAS(Simpson-Angus Scale), BARS(Barnes Akathisia Rating Scale), AIMS(Abnormal Involuntary Movement Scale)척도를 이용하였다. 결 과 : 105명중에서 85.7%인 90명이 8주간의 치료를 완료하였다. 평균 최빈 용량은 일일 16.1(±4.7)mg이었고, 종료시점에서의 BPRS전체 점수가 기저 상태에 비해 40%이상 감소된 반응군은 69.5%이었다. PANSS의 양성 증후군과 일반정신병리 뿐만 아니라 음성 증후군 소척도에서도 유의한 감소를 보였으며, 이 감소들은 치료 초기부터 나타나서 8주간 지속되었다. 43.8%의 피험자가 중등도 이상의 우울증상을 같이 지니고 있었으며, 올란자핀에 의해 MADRS와 HAM-A가 유의하게 감소하였다. 치료 기간 동안에 활력징후에는 뚜렷한 변화가 없었으나 체중은 8주간 지속적으로 증가하였다. SAS와 AIMS는 감소하였으며, 정좌불능증을 제외한 나머지 추체외로 증상의 발생비율도 낮았다. 임상적인 증상이나 징후를 동반하지 않는 ALT/SGPT의 상승을 보였지만 프로락틴을 포함하는 대부분의 혈액 검사상 뚜렷한 이상 변화는 없었다. 결 론 ; 비록 본 임상연구가 비대조 개방 임상연구로서 많은 제한점을 가지고 있지만, 올란자핀이 기존 약물에 내약성을 보이거나 기분증상을 동반하는 정신병에 치료 효과가 있었다. 그리고 기존 항정신병약물 치료시에 문제가 되었던 추체외로 증상과 고프르로락틴 혈증을 포함하는 대부분의 부작용면에서 안전성을 보여 주었다. Objective : This multicenter clinical trial was carried out to investigate the efficacy and the safety of olanzpine for the treatment of Korean patients. Mothod : 105 patients with schizophrenia and schizophreniform disorder, visited at 10 mental or university hospitals, had received an open and non-comparative treatment with olanzapine for 8 weeks. Patients had psychotic or depressive symptoms with the severity above moderate degree or intolerable side effects to previous antipsychotics. After a wash-out period of 2-7 days, 10mg olanzapine was prescribed initially to all the patients, and then the dosage could be adjusted within the range of 5-20mg/day of olanzapine by 3-7 days. Results : 90(85.7%) of 105 patients completed the 8-weeks trial and the mean modal dose of olanzapine was 16.1(±4.7%)mg/day. At the end of the trial, 73 patients(69.5%) were classified as responder, which was defined as 40% or more improvement in BPRS(Brief Psychiatric Rating Scale) score comparing to baseline. There was a significant reduction in the scores of PANSS(Positive and Negative Syndrome Scale)and subscales including negative symptom scores and CGI. Also weekly analysis showed that the reductions in scores were kept on for the whole period of the trial. 43.8% of all the patients had depressive symptoms at the baseline and total scores of MADRS(Montgomery-Asberg Depression Rating Scale) and HAM-A(Hamilton Rating Scale for Anxiety) were also reduced after the trials. Vital signs revealed no clinically significant changes but continuous weight gain was observed during the treatment with olanzapine. The scores of SAS(Simpson-Angus Scale) and AIMS(Abnormal Involuntary Movement Scale) for assessing the EPS(extrapyramidal symptoms)and tardive dyskinesia respectively were significantly decreased and only a few patients reported EPS as adverse events. Although mild and clinically non-significant of ALT/SGPT was observed, most laboratory parameters including plasma prolactin level showed to significant changes during the trial. Conclusions : Although this trial had many limitations because it was a non-comparative and open study, olanzapine showed high efficacy on the positive, negative and depressive symptoms in schizophrenia and schizophreniform disorder.In addition to that, olanzapine showed a substantially favorable safety profile, such as low incidence of EPS and hyperprolactinemia.