• 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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• 제2권1호
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• pp.140-143
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• 1995

Tardive dyskinesia(TD), typically appearing as an undesirable side effect of a long term antipsychotic drug treatment has gained increased attention in recent times due to the discovery of many TD variants. This is a single case study of a patient who has undergone more than 8 years of high dosage antipsychotic treatment. After altering the type and dosage of antipsychotic medication 3 months prior to visit, the patient showed relatively abrupt onset symptoms of severe tremor and dystonia. These symptoms, appearing in clear consciousess, got better to a certain degree after 48 hours, worsened for 12 hours, and then improved again. Subsequently there was no continuing movement disorder. Several tests and consultation were carried out. However except for the medication factor, no other possible causes for such disabling symptoms were found. This clinical condition was thought to be akin to tardive tremor, a variant of TD. Furthermore, the course was atypical.

• 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.

• 우울조울병
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• 제16권3호
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• pp.109-122
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• 2018

Objectives : The objective of this study was to revise the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) 2014: Children and Adolescents. Methods : We performed the survey, using a questionnaire comprising 22 questions according to each situation, in children and adolescents with bipolar disorder. Results : First-line pharmacotherapeutic strategies for manic episode in children with bipolar disorder were a combination of mood stabilizer (MS) and an atypical antipsychotics (AAP), monotherapy with an AAP, risperidone, and aripiprazole. Aripiprazole was selected as first-line medication for depressive episode in children with bipolar disorder, and aripiprazole, and risperidone were selected as first-line at high-risk children. First-line pharmacotherapeutic strategies for manic episode in adolescents were a combination of MS and an AAP, monotherapy with an AAP valproate, lithium, risperidone (Treatment of Choice, TOC), aripiprazole, and quetiapine. First-line pharmacotherapeutic strategies for depressive episode in adolescents, were a combination of an atypical antipsychotics and lamotrigine, valproate, aripiprazole (TOC), risperidone, and quetiapine. For depressive episodes in adolescents at high risk for bipolar disorder, valproate, aripiprazole (TOC), and risperidone were selected as first-line medication. Conclusion : We expect that the present KMAP-BP 2018-children and adolescents, is useful for clinicians to treat children and adolescents with bipolar disorder.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제24권6호
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• pp.545-553
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• 2020

Aripiprazole is a quinolinone derivative approved as an atypical antipsychotic drug for the treatment of schizophrenia and bipolar disorder. It acts as with partial agonist activities at the dopamine D2 receptors. Although it is known to be relatively safe for patients with cardiac ailments, less is known about the effect of aripiprazole on voltage-gated ion channels such as transient A-type K⁺ channels, which are important for the repolarization of cardiac and neuronal action potentials. Here, we investigated the effects of aripiprazole on Kv1.4 currents expressed in HEK293 cells using a whole-cell patch-clamp technique. Aripiprazole blocked Kv1.4 channels in a concentration-dependent manner with an IC₅₀ value of 4.4 μM and a Hill coefficient of 2.5. Aripiprazole also accelerated the activation (time-to-peak) and inactivation kinetics. Aripiprazole induced a voltage-dependent (δ = 0.17) inhibition, which was use-dependent with successive pulses on Kv1.4 currents without altering the time course of recovery from inactivation. Dehydroaripiprazole, an active metabolite of aripiprazole, inhibited Kv1.4 with an IC₅₀ value of 6.3 μM (p < 0.05 compared with aripiprazole) with a Hill coefficient of 2.0. Furthermore, aripiprazole inhibited Kv4.3 currents to a similar extent in a concentration-dependent manner with an IC₅₀ value of 4.9 μM and a Hill coefficient of 2.3. Thus, our results indicate that aripiprazole blocked Kv1.4 by preferentially binding to the open state of the channels.

• 생물정신의학
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• 제27권2호
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• pp.58-63
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• 2020

Depressive disorder is a very common disease, clinical manifestations vary, and the mechanism is not clear. Therefore, a pharmacotherapy is very important to achieve sufficient therapeutic effect, but the choice of drug is not easy due to the occurrence of side effects of treatment and confusion with clinical features. It is easy to overlook the side effects of weight gain with antidepressants compared with antipsychotics, but they are frequently observed in clinical settings. The first-generation antidepressants have higher weight gains than selective serotonin reuptake inhibitors. Serotonin norepinephrine reuptake inhibitors are observed to have less weight gain, and dopamine norepinephrine reuptake inhibitors have weight loss effect due to decreased appetite. Mirtazapine, an atypical antidepressant, has a strong histamine H1 blockade, and gains weight gain from short-term use. The effects of desvenlafaxine, vortioxetine, and agomelatin on weight, which have recently been increasing in use, have not been largely identified. For better compliance, studies on weight gain due to the use of antidepressants are needed.

• 생물정신의학
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• 제11권2호
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• pp.127-135
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• 2004

본 연구는 비전형적 항정신병약물이 체중과 혈당에 미치는 영향을 알아보고 그에 관계되는 여러 변인들의 관련성을 알아보고자 하였으며 이를 위해 비전형적 항정신병약물인 risperidone과 clozapine을 쓰는 환자 각각 20명, 대조군으로 전형적 항정신병약물인 haloperidol을 쓰는 환자 20명을 대상으로 입원 후 4주, 8주, 12주째 체중과 공복 시 혈당을 입원 초기 체중 및 혈당과 비교하였으며 각 약물군 간의 차이를 조사하여 다음과 같은 결과를 얻었다. 첫째, 연구 대상 환자의 초기 특성 상 clozapine군이 haloperidol과 risperidone군에 비하여 입원 시 체중이 높은 상태였는데 이는 clozapine을 복용하는 환자들이 이전에 haloperidol과 risperidone을 포함한 여러 가지 항정신병약물을 복용했던 경험이 있고 이로 인해 이미 어느 정도의 체중 증가가 있었던 것으로 생각해볼 수 있다. 둘째, 체중 변화는 risperidone과 clozapine군 모두 haloperidol을 쓴 군과 유의한 차이가 없었다. 셋째, 혈당 변화도 비전형적 항정신병약물인 risperidone과 clozapine군이 haloperidol군에 비해 의미 있는 차이가 없었다. 넷째, 몇 가지 변수들이 체중과 혈당의 변화에 연관성을 가지고 있었으나 그 정도는 크지 않았고 그 인과관계를 증명할 수는 없었다. 위의 결과들에서 볼 때 유병 기간이 길고 이전에 여러가지 항정신병약물을 복용한 경험이 있는 환자, 약물 복용에 따른 증상의 호전 정도가 두드러지지 않는 만성적인 정신분열병 환자들에서는 비전형적 항정신병약물이 전형적 항정신병약물에 비해 체중 변화와 혈당의 수치를 변화시키는 경향이 크지 않다는 점을 알 수 있었다.

• Journal of Hospice and Palliative Care
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• 제19권3호
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• pp.201-210
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• 2016

섬망은 완화치료를 받는 말기암환자에서 흔히 나타나는 증상으로 임종기에 접어들수록 빈도는 증가한다. 섬망은 환자와 가족의 삶의 질에 부정적인 영향을 줄 뿐 아니라, 높은 사망률과 관련되어 있으나 실제 임상에서 의료진들이 적절히 인지하지 못하고 있다는 연구들이 보고되고 있다. 이는 우울이나 치매와 같은 정신질환과의 중복되는 특성, 섬망에 대한 평가 및 진단에 대한 지식의 부족 등이 원인으로 생각되고 있다. 이를 개선하기 위해 현재까지 알려진 섬망 선별검사를 통해 섬망환자를 정확히 인지하고, 진단하는 것이 완화의료 영역에서 섬망 증상 관리에 우선되어야 할 분야로 생각된다. 섬망이 진단되었을 때는 유발요인을 확인하고 약물이나 탈수, 감염 등의 가역적인 원인에 대해서는 이를 교정하는 것이 섬망을 조절에 가장 중요한 부분이다. 이와 함께 소음을 줄이거나, 적절한 조명을 유지하는 등의 환자의 주변 환경을 안정적으로 유지하는 등의 비약물적 치료가 병행되어야 한다. 비약물적 치료로 효과가 없거나, 증상이 심한 경우에 항정신병 약물과 벤조디아제핀과 같은 진정효과가 있는 약물을 사용할 수 있으며, 현재까지는 저용량의 할로페리돌 투여가 가장 효과적인 치료 약제로 인정되고 있다. 비정형적 항정신병 약물로는 Olanzapine, Quetiapine, Risperidone 등이 있으며 현재까지 보고된 바로는 할로페리돌과 비교하여 섬망 개선 효과는 비슷하나 추체외로 증상이 드물고 진정 효과가 있어 경구 섭취가 가능한 경우 고려해 볼 수 있는 약제로 생각된다. 현재까지 완화의료 영역에서의 섬망에 사용할 수 있는 약물에 대한 연구 결과는 근거가 충분하지 않은 상태이며, 이로 인해 임상에서 활용할 수 있는 임상진료 지침 또한 부족한 상태이다. 현재까지는 중환자실, 노인 환자에서의 연구 결과를 바탕으로 한 결과를 토대로 완화의료 영역에서의 섬망 치료에 이용하였지만 추후 말기암환자에서의 섬망에 대한 연구를 바탕으로 한 임상진료지침의 개발도 필요할 것으로 생각된다.

• 대한불안의학회지
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• 제4권1호
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• pp.42-48
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• 2008

현재 PTSD와 관련한 여러 병태생리 기전들이 밝혀지고 있으며 이에 초점을 둔 다양한 약물치료가 행해지고 있다. 본 연구에서는 일 대학병원에서 PTSD로 진단된 환자들의 의무기록을 검토하여 약물치료의 경향에 대해 알아보았다.1998년 1월부터 2007년 12월까지 DSM-IV에 의해 PTSD로 진단된 입원 환자 75명이 대상군이 되었으며, 이들의 인구학적 요인들, 입원기간, 외상의 종류, 외상 후 경과시간 및 정신과적 공존병리 및 처방 받은 약물을 조사하였다. 조사 결과, 75명 중 남자는 33명, 여자는 42명이었다. 정신과적 공존병리는 총 50명(66.7%)에서 존재하였으며, 우울장애, 인지장애, 정신장애 및 불안장애 순이었다.73명(97%)의 대상군은 항우울제를 처방 받았으며, 그 중 paroxetine이 54.7%로 가장 많았고 두 가지 이상의 항우울제를 처방 받은 경우도 24%였다. 또 거의 대부분의 환자에서 비정형 항정신병약물(33.3%), 기분안정제(17.3%),항불안제(94.7%)가 항우울제와 병용 처방된 것으로 조사되었다. 여러 제한점에도 불구하고 본 연구에서 얻어진 약물 처방 경향은 향후 국내 실정에 맞는 치료 지침을 수립하는 데에 하나의 근거 자료가 될 수 있을 것이다.