섬망 환자의 치료에서 Haloperidol과 Quetiapine의 효과 비교 : 전향성 개방 연구

이진영(Jinyoung Lee),김상헌(Sang Heon Kim),서유진(Eugene Seo),이준영(Joon Young Lee),심제용(Jaeyong Shim),이양현(Yanghyun Lee) 대한생물치료정신의학회 2006 생물치료정신의학 Vol.12 No.2

본 연구는 섬망 환자를 대상으로 haloperidol 또는 quetiapine으로 치료하였을 때의 치료 효과와 부작용을 비교 평가하였는데, haloperidol군과 quetiapine군 모두에서 치료 후에 섬망 증상의 현저한 호전을 보였고, 환자가 섬망 증상에서 호전되는 데 걸린 기간에서도 차이를 보이지 않았다. 또한 사용한 두 약물을 등가용량으로 비교하였을 경우 quetiapine이 haloperidol 보다 적은 용량으로 섬망의 치료에 효과적이라는 것을 보였다. 대부분의 환자가 심각한 부작용이 없이 섬망에서 호전되었으나, haloperidol을 사용하였던 1명의 환자에서 추체외로계 부작용으로 인해 약물을 중단하였고, quetiapine을 사용하였던 환자에서는 추체외로계 부작용을 호소하는 환자가 없었다. Quetiapine을 사용하였던 2명의 환자에서 진정작용을 호소하였으나 경한 정도였고 약물을 중단하지는 않았다. Quetiapine은 섬망의 치료에서 haloperidol과 동등한 효과를 보이며, 특히 추체외로계 부작용이 적기 때문에 노인 환자의 섬망 치료에서 보다 안전하게 사용할 수 있으리라는 가능성을 보였다. 본 연구는 섬망이 발생한 환자들을 전향성으로 평가하였다는 데 의의가 있겠지만, 향후에 더 많은 수의 환자를 대상으로 한 이중맹검 위약대조군 연구가 필요할 것이다. Objectives:Delirium is a complex psychiatric syndrome with an acute onset and a fluctuating course. Typical antipsychotics, especially haloperidol, have been used as the main tool for pharmacological treatment of delirium. Recently, the newly developed atypical antipsychotics have been used successfully in control of delirium. The purpose of this prospective, open-clinical trial is to compare the clinical efficacy and tolerability of haloperidol and quetiapine for the treatment of delirium. Methods:Between July 2005 and June 2006, 36 patients who were diagnosed as having delirium according to the criteria of the DSM-IV were enrolled in this study from psychiatric practice settings and from consultation department. They were randomly assigned to be treated with a flexible-dose regimen of haloperidol(n=19) or quetiapine (n=17). K-DRS, K-DRS-R-98, CGI, MMSE-K, and ESRS had been assessed repeatedly until the K-DRS score reached 12 or less. We assumed that the patient whose K-DRS score had reached 12 or less was recovered from delirium. Results:Sixteen subjects in haloperidol group and sixteen subjects in quetiapine group completed the study. The mean dosage of antipsychotics for delirium is 2.9mg(SD=1.8) of haloperidol and 39.8mg(SD=28.9) of quetiapine. K-DRS and K-DRS-R-98 scores in both groups were significantly decreased after individual treatments. But there were no significant differences of changing extent of CGI-Improvement, MMSE-K, K-DRS and K-DRSR- 98 scores between the groups. There was no significant difference in duration of treatment and clinical improvement between the groups. Most of the patients were well tolerated to the adverse events of each antipsychotic drug but only one patient who had been treated with haloperidol showed extrapyramidal symptom after the medication. Conclusion:Quetiapine may be more useful than haloperidol in old aged patients with delirium because of its safety and low dose effectiveness. This trial is a prospective, open-label, flexible dose study with a small sample size, so further double-blind placebo-controlled studies with a large sample size will be necessary.

섬망 치료에서 Aripiprazole과 Haloperidol의 효과 : 무작위 개방 연구

이준영(Joonyoung Lee),조현영(Hyunyoung Jo),정운선(Unsun Chung),이병대(Byung Dae Lee),이양현(Yanghyun Lee),정성훈(Sunghoon Jeong) 대한생물치료정신의학회 2007 생물치료정신의학 Vol.13 No.2

Objectives:Delirium is a common condition frequently seen in consultation-liaison psychiatry. Antipsychotic drugs are the primary treatment for symptoms of delirium. Typical antipsychotics, especially haloperidol, have been used as the mainstay of pharmacological treatment of delirium. With the introduction of atypical antipsychotics, the clinical usefulness of these medication has also been investigated for delirious patients. The purpose of this randomized, open-clinical trial is to compare the clinical efficacy and tolerability of haloperidol and aripiprazole for the treatment of delirium. Method:45 patients with a diagnosis of delirium were enrolled between July 2005 and May 2007 in this study. They were randomly assigned to be treated with a flexible-dose regimen of haloperidol or aripiprazole. The Korean version of Delirium Rating Scale(K-DRS) and other measures related with delirium had been used repeatedly until the K-DRS score reached 12 or less which we defined as the criteria for recovery from delirium. 22 subjects in haloperidol group and 19 in aripiprazole group completed the study. Results:The mean dosage of antipsychotics for delirium was 3.0±1.6㎎ of haloperidol and 5.5±1.5㎎ of aripiprazole which was relevant to 150.5±83.6㎎ and 73.7±20.9㎎ of chlorpromazine respectively. Aripiprazole was effective to subside the delirium symptoms at less dosages than haloperidol. There were no significant group differences in the score of K-DRS, K-DRS-R-98 and MMSE-K at baseline as well as final assessments. There was no significant difference in duration of treatment and clinical improvement between the groups. Most of the patients were well tolerated to the adverse events of each antipsychotic drug but only two patients in haloperidol group showed extrapyramidal symptom. Conclusion:Aripiprazole may be more useful than haloperidol in patients with delirium because of its safety and low dose effectiveness, especially in aged patients. Further double-blind placebo-controlled studies with a large sample size will be necessary.

젊은 성인에서 아이오와 도박과제와 주사위게임과제를 이용한 의사결정능력의 평가

서유진(Eugene Seo),이양현(Yanghyun Lee),조현진(Hyun-Jin Cho),김양태(Yang-Tae Kim) 대한생물치료정신의학회 2007 생물치료정신의학 Vol.13 No.2

Objectives:Decision-making ability is one of the most important human functions to maintain everyday life. Two commonly used decision-making tools, the Iowa Gambling Task(IGT) and the Game of Dice Task(GDT) has been drawing attention because two tasks may reflect distinctive aspects of decision-making;the IGT for affective and the GDT for cognitive aspect of decision-making. This study examined the demographic and neuropsychological factors affecting the performance of the IGT and the GDT and any relationship between the two tasks. Methods:Eighty seven healthy young adults(female=41) underwent intelligence test, computerized versions of the IGT, the GDT and the Wisconsin Card Sorting Test(WCST). Results:The performances on both tasks had no relationships with sex, intelligence, and working memory. There was a significant yet moderate correlation between emotional decision-making tested by the IGT and cognitive decision-making by the GDT. In a subanalysis dividing subjects into‘non-impaired’ and‘impaired’ group according to the performance on the IGT, subjects in impaired group were more likely to make riskier choices than those in non-impaired group were. Conclusion:These results suggest that both decision-making tasks are relatively independent to sex, intelligence and working memory, and common factors shared by both tasks should be considered when it comes to interpret the performance on the IGT and the GDT together. The reason for this correlation between two decisionmaking tasks was explained by the perspectives of risk taking, hypersensitivity to rewards, and impulsivity.

정신분열병 환자에서 아이오와도박과제를 이용한 의사결정능력의 평가

서유진(Eugene Seo),김양태(Yang-Tae Kim),이양현(Yanghyun Lee),박옥태(Oaktae Park),정성훈(Sung-Hun Jeong),김상헌(Sang Heon Kim),이승재(SeungJae Lee),조경아(Gyung Ah Cho),곽경필(Kyung-Phil Kwak),이상희(Sanghee Lee) 대한생물치료정신의학회 2005 생물치료정신의학 Vol.11 No.2

Objectives: The purpose of this study was to examine the performance of schizophrenic patients on the Iowa Gambling Task(lGT). In addition, it was aimed to test whether the performance on IGT is related to working memory within schizophrenic group. Methods: Twenty-three stable schizophrenic patients and twenty-eight control subjects underwent computerized versions of the IGT and the Wisconsin Card Sorting Test(WCST). Results: Schizophrenic patients performed poorly on IGT relative to normal controls. On WCST performance, schizophrenic patients completed significantly fewer categories and made more errors than controls did. There was no significant relationship between IGT and WCST performance. Conclusion: It was suggested that schizophrenic patients have impaired decision-making and the performance on IGT is separable from cognitive functions considered to be related to dorsolateral prefrontal cortex.

한국에서 11년간 Clozapine 투여에 의한 무과립구증과 호중구감소증

조만제(Man-Je Cho),오정태(Jung-Tae Oh),강병조(Byung-Jo Kang),이양현(Yanghyun Lee) 대한생물치료정신의학회 2004 생물치료정신의학 Vol.10 No.2

목적 : Clozapine은 치료저항성 정신분열병환자의 치료에 많이 사용되고 있지만 생명을 위협하는 혈액학적 부작용 때문에 사용에 많은 제한이 따른다. 본 연구자들은 한국에서 장기간의 clozapine 투여에 의한 무과립구증과 호중구감소증의 전체 발생률과 투여 기간에 따른 발생률의 변화를 알아보고자 한다. 방법 : 1993년 2우러부터 2004년까지 11년간 Clozaril Patient Monitoring System(CPMS)에 등록된 7367명 중 분석 기준에 합당한 6,782명의 자료를 분석하였다. 결과 : 조사 대상 6,782명 중 54명에서 무과립구증, 697명에서 호중구감소증이 발생하였다. 따라서 11년간 무과립구증의 일반발생률은 0.8%였고, 호중구감소증의 일반발생률은 1028%였다. 무과립구증이 발생한 환자들 중 53.7%가 18주 이내에 발생하였고, 위험률은 2,3개월째 각각 0.0014, 0.0025로 가장 높았다. 또한 최종 누적발생률은 1.64%였다. 호중구감소증이 발생한 환자들 중 52.4%가 18주 이내 나타났고 위험률은 3개월 이내에 가장 높았다. 무과립구증의 발생에 있어서 성별이나 연령에 따른 유의한 차이는 관찰되지 않았다. 결론 : Clozapine에 의한 혈액학적 부작용은 18주 이내에 많이 나타나고, 무과립구증의 발생률은 외국과 유사한 수준을 보였다. 수 년 이상 장기간의 clozapine 투여 후에도 무과립구증이 발생하였기 때문에 지속적인 혈액학적 감시가 필요할 것으로 판단된다. 향후, 혈액검사의 빈도를 줄일 수 있을 지에 대한 연구가 필요하며, “일시적인 무과립구증(transient agranulocytosis)”이 존재할 가능성도 고려되어야 할 것으로 사료된다. Objectives : Clozapine is effective in treating patients with treatment-resistant schizophrenia. Because of producing a potentially fatal agranulocytosis, the use of clozapine is restricted to patients who are resistant to, or intolerant of, conventional antipsychotic medication. This study documents the incidence of agranulocytosis and neutropenia, and pattern of variation in incidence of these side effects in a long-term clozapine treatment. Methods : An analysis was made of the hematological, demographic, and other characteristics data from Clozaril Patient Monitoring System(CPMS) data on 6782 patients on clozapine over about 11 years in South Korea. Results : During the study period, agranulocytosis developed in 54 patients with 29(53.7%) cases within 18 weeks. The cumulative incidence of agranulocytosis was 1.64% at 6 to 11 years and the crude incidence was 0.8%, with the hazard rates peaking at the 3rd month(0.0025) and 2nd month(0.0014). Neutropenia occurred in 697 patients, and 365(52.4%) cases developed within 18 weeks. The cumulative incidence of this blood abnormality was 19.8% at 8 to 11 years, the crude incidence was 10.3%, and the hazard rates peaked at the 2nd month(0.0188). Conclusions : These results showed that the incidence of agranulocytosis in South Korea is similar to that in the rest of the world. Because of agranulocytosis that occurred after several years of clozapine use, long-term monitoring of patients' white blood cell counts is necessary. In the future, studies of reducing the frequency of hematologic monitoring are needed, and the concept of "transient agranulocytosis'' should be taken into consideration.

한국판 섬망 평가 척도의 표준화

이양현,류지안,김휘중,이상희 대한생물치료정신의학회 2003 생물치료정신의학 Vol.9 No.2

Objectives : Delirium s a highly prevalent disease that occurs in about 1 5 2 0 % of all general admissions to hospital but there is no standardized rating scale that identifies and assesses the symptom severity for delirium in Korea. The Deliruim Rating Scale (DRS) is a widely used delirium rating instrument that specifically, sensitively, and reliably measures delirium symptoms. This study addresses the reliability and validity of Korean version of Delirium Rating Scale(K-DRS) in Korea. Methods : 28 patients with delirium, 28 patients with dementia, 27 patients with schizophrenia, and 21 patients with other mental disorder by DSM-IV entered this study All patients received a structured psychopathology assessment including K-DRS Korean version of Mini-Mental Status Examination (MMSE-K) Clinical Global Impression scale(CG1) and in addition schizophrenia group had done Brief Psychiatric Rating Scale (BPRSI Each instrument scores were compared among the four diagnostic groups by one-way analysis of variance with post hoc comparisons to determine where the difference lie K-DRS scores were compared with 'after usual treatment' scores in a subset of delirious subjects Cutoff scores for K-DRS were determined by using receiver-operator Characteristic (ROC) analyses to determine acceptable levels of sensitivity and specificity Inter-subtest Pearson's correlations, Cronbach's alpha coefficient to assess internal consistency and inter-rater reliability were used for the assessment of reliability of K-DRS. Results : The mean K-DRS score was significantly higher in the delirium group compared with each of the other groups, But mean MMSE-K score was not significantly different between delirium and dementia group Area under curve of K-DRS was 0 998K E=0.002) and its optimal cutoff point for delirium was estimated as 16 5 KDRS score after usual treatment improved from a mean(S.D) of 23 5(3.2) to 3.1(1.7) indicating an ability to measure the severity of delirium K-DRS was found to have significantly high internal consistency(Cronbach's alpha coefficient=0.88) inter-rater reliability (r=0.98 p<0.0001) Conclusion : We confirmed that K-DRS is a reliable valid, and useful diagnostic instrument for delirium.