• 대한조현병학회지
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• 제22권1호
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• pp.1-7
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• 2019

Objectives: Clozapine is the drug of choice in treatment-resistant schizophrenia. However, its use is often delayed and a significant proportion of clozapine treated patients fails to respond and experience potentially dangerous side-effects. The aim of this retrospective study was to describe the clinical characteristics of patients started on clozapine and the rate and reason of discontinuation of clozapine. Methods: Medical records of 83 patients started on clozapine during the period of 2012-2016 were reviewed. Results: Clozapine started on patients in chronic phase; the mean age of start was 38.1 years old and the mean number of psychiatric admission was 6.5. A majority (80.7%) of the patients had been subjected to antipsychotic polypharmacy prior to clozapine and most (61.5%) of them were being treated with polypharmacy including clozapine. Overall, 39 (47.0%) subjects had continued clozapine whereas 15 (18.1%) discontinued it; 29 (34.9%) were lost to follow-up. The most common reason for discontinuation was side-effects (n=13) including six life-threatening cases, most of which occurred within 6 months of its start. Conclusion: This study demonstrated that there is some evidence of delays to clozapine use, high rates of polypharmacy and significant rate of discontinuation during the early phase of clozapine treatment.

• 생물정신의학
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• 제13권3호
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• pp.152-161
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• 2006

Objective : The relationship between the total daily dose of clozapine given and the plasma concentrations of clozapine and its metabolites(N-desmethylclozapine and clozapine N-oxide) and the effect of Glu158Lys (wild-type : Glu, 'H' ; variant : Lys, 'h') and Glu308Gly(wild-type : Glu, 'D' ; variant : Lys, 'd') variation in FMO3 gene on plasma concentrations of clozapine and its metabolites was studied in schizophrenic patients. Methods : Trough plasma concentrations of clozapine and its metabolites were measured in 34 schizophrenic patients receiving clozapine. The genetic variation of 'h' and 'd' in FMO3 were analyzed in 21 among 34 patients. Results : A linear relationship between the total daily dose of clozapine given(mg/kg body weight per day) and the plasma concentrations(nM) of clozapine was revealed by regression analysis(p<0.001) in the 23 patients receiving a constant daily dose of clozapine for 8 days. The plasma molar concentration ratios of clozapine N-oxide/clozapine in 8 subjects with 'hh' or 'Hh' alleles were not different from those in 6 subjects with 'HH' alleles and the plasma molar concentration ratios in 6 subjects with 'dd' or 'Dd' alleles were not different from those in 8 subjects with 'DD' alleles. Conclusion : The effect of Glu158Lys and Glu308Gly variation in FMO3 gene on clozapine metabolism could not be shown.

• 생물정신의학
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• 제7권1호
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• pp.80-84
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• 2000

Clozapine의 부작용 중 타액의 과잉분비의 원인을 알아보기 위하여 순천향대학교 천안병원 신경정신과에 입원한 환자 중 정신분열병 환자 21명(남자 12명, 여자 9명)을 대상으로 시행한 본 연구결과는 다음과 같다. 1) 정신분열병 환자에게 clozapine을 투여한 후 타액의 분비는 유의하게 증가하였다. 2) Clozapine을 투여한 후 타액의 과잉분비를 보인 정신분열병 환자에게 clonidine을 투여한 후 타액의 분비는 유의하게 감소하였다. 3) Clozapine에 의한 타액의 과잉분비는 ${\alpha}$-아드레날린성 작용에 의한다는 것을 강하게 시사한다.

• 대한조현병학회지
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• 제24권1호
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• pp.1-7
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• 2021

Clozapine is the first and most effective atypical antipsychotic drug for treatment-resistant schizophrenia (TRS). After withdrawal of clozapine due to concerns of agranulocytosis, clozapine was reintroduced with a comprehensive safety monitoring system, the clozapine patient monitoring system (CPMS). The reintroduction was a response to the pressure from psychiatrists and patients with TRS and their families. Clozapine is still the best single agent for the treatment of TRS. However, approximately 30% of patients with TRS still show psychotic symptoms. In patients with clozapine-resistant schizophrenia (CRS), augmentation of other antipsychotic agents could be considered after a thorough evaluation of proper clozapine treatment. In this review, the status of clozapine in patients with TRS and CRS will be discussed.

• 생물정신의학
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• 제19권4호
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• pp.187-192
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• 2012

Objectives Although antipsychotic drug clozapine has superior efficacy, this is hampered by metabolic side effects such as weight gain and diabetes. Recent studies demonstrate that clozapine induces insulin resistance. However, the identity and location of insulin resistance induced by clozapine has not been clarified. In this study, the effect of clozapine on central insulin response was investigated in rats. Methods Male Sprague-Dawley rats received intraperitoneal injection of clozapine or vehicle, which was followed by intracerebroventricular injection of insulin or its vehicle. The effects of clozapine on insulin-induced changes in blood glucose level and Akt phosphorylation in hypothalamus were investigated. Results Intraperitoneal injection of clozapine (20 mg/kg) increased blood glucose in rats. Intracerebroventricular injection of insulin reduced blood glucose in rats, which was blunted by pretreatment of clozapine. Accompanied with the antagonistic effect of clozapine to central insulin action in terms of blood glucose, clozapine inhibited the insulin-induced phosphorylation of Akt at Ser473 in rat hypothalamus. Conclusion Administration of clozapine inhibited the central insulin-induced changes in blood glucose and Akt phosphorylation in rat hypothalamus. These findings suggest that hypothalamus could be the site of action for the clozapine-induced insulin resistance.

• 생물정신의학
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• 제12권2호
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• pp.151-158
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• 2005

Background:Clozapine is a unique atypical antipsychotic medication. It is considered to be superior, even amongst the newer agents, in treatment-resistant schizophrenia. However, de novo emergence or exacerbation of obsessive-compulsive(OC) symptoms during treatment with clozapine has been reported. We prospectively evaluated 19 cases which newly developed OC symptoms during clozapine treatment and discussed the treatment of OC symptoms induced by it. Methods:We recruited 19 patients(8 males, 11 females) with a DSM-IV diagnosis of schizophrenia and schizoaffective disorder who had developed OC symptoms during clozapine treatment. OC symptoms were assessed using the Padua-ICMA and YBOCS on a monthly basis over three months. Results:Eleven female and eight male patients were enrolled and the average age of patients was 32.8 years. At baseline, no patients showed OC symptoms. Moderate to severe OC symptoms appeared with mean daily dose of 298.68 mg of clozapine. There were no significant differences in improving OC symptoms between the clozapine dose reduction group and the OC treatment group. Conclusion:We noticed the possibility that the appearance of OC symptoms is connected with the effect of clozapine. The clozapine-induced OC symptoms were improved both by reducing clozapine daily doses, and by adding OC treatment drugs. With other atypical antipsychotics now available, to know and treat the side effects of clozapine would be of considerable value, offering clinical guidance in making a decision on treatment-resistant schizophrenia.

• 대한조현병학회지
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• 제24권2호
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• pp.52-59
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• 2021

Objectives: Recent studies have reported that delayed initiation of clozapine can affect clinical response in patients with treatment-resistant schizophrenia (TRS). This study aimed to explore the relationship between delayed initiation of clozapine and acute treatment response. Methods: Sixty-five inpatients with TRS who started clozapine for the first time were included through a retrospective chart review. Acute treatment response was defined as a 30% reduction in the Positive and Negative Syndrome Scale score or a Clinical Global Impression of Improvement score of 1 (very much improved) or 2 (much improved) at 4 weeks after initiating clozapine. Results: After meeting the TRS criteria, the mean delay for initiating clozapine was approximately 13.8 months. The delay was shorter in patients who showed a better response to clozapine in logistic regression analysis (p=0.037). Conclusion: Our findings suggest that reducing the delay in initiating clozapine increases the effectiveness of clozapine in patients with TRS.

• 대한조현병학회지
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• 제24권1호
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• pp.36-43
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• 2021

Objectives: Despite the high discontinuation rate of clozapine in refractory schizophrenia, there is limited evidence regarding the suggested treatment after clozapine discontinuation. Methods: The medical records of 37 patients who discontinued clozapine were retrospectively reviewed. The prescription patterns of antipsychotics, mood stabilizers, and antidepressants were compared at three points before and after clozapine treatment and at the most recent visit. Results: After clozapine discontinuation, 75.6% of the subjects were receiving antipsychotic polypharmacy, and 32.4% were taking more than 3 antipsychotics. The frequently used antipsychotics were olanzapine (21.5%), quetiapine (21.5%), and paliperidone (12.7%). The rates of augmentation with mood stabilizers and antidepressants were 43.2% and 29.7%, respectively. Furthermore, valproate was the most commonly used mood stabilizer (87.5%). Conclusion: Antipsychotic polypharmacy and augmentation are inevitable in schizophrenia patients for whom clozapine has been discontinued. Further research is required to improve the outcomes of polypharmacy and augmentation in schizophrenia patients.

• 생물정신의학
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• 제28권2호
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• pp.50-57
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• 2021

Objectives Clozapine is the most effective atypical antipsychotic agent for the treatment-resistant schizophrenia (TRS), however, only 40%-70% of TRS patients respond to clozapine. Moreover, TRS encompasses various symptom dimensions. Therefore, augmentation with other medications for clozapine is frequently applied. However, the prescription pattern of clozapine and combined medications in Korea is yet to be examined. This study aims to investigate the maintenance treatment pattern of clozapine and augmentation agents in one Korean tertiary hospital. Methods The patients with schizophrenia spectrum disorders under clozapine maintenance, defined as one-year clozapine continuation, were subjected for analysis. Medication data at one-year time-point after clozapine initiation was extracted and analyzed. Results Among total 2897 patients having clozapine prescription experience from January 2000 to December 2018, 1011 patients were on clozapine maintenance. The mean age of clozapine initiation was 30.2 ± 11.3 years, and the maintenance dose of clozapine was 217.8 ± 124.3 mg/day. Combination rate of antipsychotics, mood stabilizers, and antidepressants were 43.5%, 25.3%, 38.6%, respectively. Most frequently prescribed drugs in each category were aripiprazole, valproate, and sertraline. Olanzapine equivalent dose of combined antipsychotics was 10.4 ± 7.7 mg/day. Male patients were prescribed higher dose of combined antipsychotics and higher rate of antidepressants. Female patients had later onset of clozapine prescription. Patients with two or more combined antipsychotics were prescribed higher dose of clozapine and higher rate of antidepressants compared to patients with one combined antipsychotic. Conclusions Taken together, among the patients taking clozapine, a substantial rate of patients were under polypharmacy. The present findings based on the real-world prescription pattern could provide the valuable clinical information on the treatment of TRS-related conditions.

• 생물정신의학
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• 제4권1호
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• pp.84-94
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• 1997

본 연구는 27명의 만성 정신분열증 환자들을 대상으로 비정형적 항정신병 약물인 clozapine을 8주간 투여하여 임상증상 치료반응(PANSS와 CGI 척도 이용)과 혈장 대사물(혈장 HVA 농도, 5-HIAA 농도 및 HVA/5-HIAA 농도비 측정) 변화와의 상관관계를 알아보고, 아울러 clozapine 치료 반응군과 치료 비반응군간의 약물투여전 기준 혈장 대사물과 clozapine투여 8주후 대사물의 변화율을 비교하여 혈장 대사물 농도가 clozapine 치료의 예측인자로서 가능성이 있는 가를 알아 보기 위하여 시행되었다. 전체 연구대상군에서 clozapine 투여기간에 따른 혈장 HVA 농도, 5-HIAA 농도는 각각 유의한 감소가 있었으나, 혈장 HVA/5-HIAA 농도비는 유의한 변화가 없었다. 전체 연구대상군에서 clozapine 투여 8주 후 혈장 HVA 농도변화율, 혈장 5-HIAA 농도변화율, 혈장 HVA/5-HIAA 농도비 변화율 각각과 8주후 정신병리(PANSS 양성척도점수, 음성척도점수, 일반정신병리척도 점수, 전체점수) 변화율과의 상관분석결과 혈장 HVA 변화율은 PANSS 양성척도점수 변화율, 일반정신병리척도 점수 변화율, 그리고 전체점수의 변화율과 각각 유의한 정 상관성이 있었으며, 반면 혈장 5-HIAA 농도 변화율은 PANSS 음성척도점수 변화율과 유의한 정 상관성이 있었다. 전체 연구대상군에서 clozapine 투여 8주 후 혈장 HVA 농도변화율은 PANSS 양성척도 항목중 특히 망상 및 환각행동 항목점수의 변화율과 각각 유의한 정 상관성이 있었으며, PANSS 음성척도 항목중에서는 대화흐름 및 자발성 결여 항목점수의 변화율과 유의한 정 상관성이 있었다. 혈장 5-HIAA 농도 변화율은 PANSS 음성척도 항목 중 둔마된 정동, 빈약한 신뢰감 항목 점수의 변화율과 각각 유의한 정 상관성이 있었다. Clozapine 투여 8주 후 PANSS 전체점수가 20% 이상 감소되고 CGI 심도점수가 경도 이하인 경우를 치료반응의 기준으로 정의했을 때, 전체 27명의 대상환자 중 48%(13명)가 치료반응군이었다. Clozapine 치료 반응군(N=13명)과 치료 비반응군(N=14명)의 비교에서 약물투여 전 기준 혈장 HVA 농도와 기준 혈장 HVA/5-HIAA 농도비는 치료 반응군이 유의하게 높았으며, 기준 혈장 5-HIAA 농도는 양 군 간의 유의한 차이가 없었다. Clozapine 치료반응군의 경우 약물투여 8주 후 혈장 HVA 농도가 40.3% 감소하고, 치료 비반응군은 혈장 HVA 농도가 3.1% 증가하여 양군 간의 유의한 차이를 보였다. Clozapine 투여 8주 후 혈장 5-HIAA 농도변화율과 혈장 HVA/5-HIAA 농도비 변화율은 치료반응군과 비반응군 간에 각각 유의한 차이가 없었다. 이상의 연구결과는 만성 정신분열증 환자에서 clozapine의 항정신병효과 중 양성증상은 도파민 길항효과와 관련이 있고, 음성증상은 세로토닌 길항효과와 관련이 있음을 시사하였다. 또한 만성 정신분열증 환자에서 약물투여 전 혈장 HVA 농도와 약물투여 후 혈장 HVA 농도변화가 각각 clozapine의 치료반응 예측인자로서 이용 가능성이 있음을 시사하였다.