• Korean Journal of Biological Psychiatry
• /
• v.28 no.2
• /
• pp.50-57
• /
• 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.

• Korean Journal of Biological Psychiatry
• /
• v.2 no.1
• /
• pp.140-143
• /
• 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.

• Korean Journal of Schizophrenia Research
• /
• v.24 no.1
• /
• pp.1-7
• /
• 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.

• Mood & Emotion
• /
• v.16 no.3
• /
• pp.109-122
• /
• 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.

• Korean Journal of Biological Psychiatry
• /
• v.12 no.2
• /
• pp.151-158
• /
• 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
• /
• v.24 no.6
• /
• pp.545-553
• /
• 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.

• Korean Journal of Biological Psychiatry
• /
• v.27 no.2
• /
• pp.58-63
• /
• 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.

• Korean Journal of Biological Psychiatry
• /
• v.11 no.2
• /
• pp.127-135
• /
• 2004

Object:The goal of this study was to examine the changes in body weight and glucose levels of the patients treated with risperidone, clozapine or haloperidol in order to compare the effect of risperidone or clozapine with that of haloperidol. Methods:For nine months(January to September, 2003), a prospective study was performed in 60 patients with chronic schizophrenia who were in Seoul National Hospital. Two-week period was required for a drug wash-out. The patients were randomly assigned to risperidone, clozapine and haloperidol groups. They were given risperidone(n=20), clozapine(n=20) and haloperidol(n=20), respectively, everyday for 12 weeks. To examine the effects of these drugs on body weight and fasting glucose levels, we measured body weight and glucose levels of all the patients first without the drug treatment and at each end of 4, 8, and 12-week periods with the treatment. And we examined the differences among three groups in the changes of body weight and fasting glucose levels. Results:There were no significant differences in the changes of the body weight and fasting glucose levels between the atypical antipsychotics(risperidone or clozapine) and the typical antipsychotics(haloperidol). Conclusion:The study in the patients with chronic schizophrenia suggests that risperidone or clozapine do not cause any additional effects on body weight or glucose levels compared to haloperidol.

• Journal of Hospice and Palliative Care
• /
• v.19 no.3
• /
• pp.201-210
• /
• 2016

Delirium is a common symptom in patients with terminal cancer. The prevalence increases in the dying phase. Delirium causes negative effects on quality of life for both patients and their families, and is associated with higher mortality. However, some studies reported that it tends to remain unrecognized in palliative care setting. That may be related with difficulties to distinguish the symptom from others with overlapping characteristics such as depression and dementia, and a lack of knowledge regarding assessment and diagnostic tools. We suggest that accurate recognition with validated tools and early diagnosis of the symptom should be highly prioritized in delirium management in palliative care setting. After diagnosing delirium, it is important to identify and address reversible precipitants such as medication, dehydration, and infection. Non-pharmacological interventions including comfortable environment for the patient and family education are also essential in the management strategy. If such interventions prove ineffective or insufficient to control hyperactive symptoms, pharmacologic interventions with antipsychotics and benzodiazepine can be considered. Until now, low levels of haloperidol remains the standard treatment despite a lack of evidence. Atypical antipsychotics such as olanzapine, quetiapine and risperidone reportedly have similar efficacy with a stronger sedating property and less adverse effect compared to haloperidol. Currently, delirium medications that can be used in palliative care setting require more clinical trials, and thus, clinical guidelines are not sufficiently available. We suggest that it is warranted to develop clinical guidelines based on well-designed clinical studies for palliative care patients.

• Anxiety and mood
• /
• v.4 no.1
• /
• pp.42-48
• /
• 2008

Objective : Due to a better understanding of the pathophysiology of posttraumatic stress disorder (PTSD) and the relative limitations in the treatment of patients with PTSD, a variety of medications and treatment algorithms for PTSD have been investigated. This study was conducted to investigate the trends in the pharmacotherapy used in the treatment of inpatients with PTSD at a single university hospital in Korea. Methods : Data from 75 patients diagnosed with PTSD according to the DSM-IV criteria from January 1998 to December 2007 were collected. Demographic data and clinical data, including medications prescribed, were investigated. Results : Thirty-three of the 75 subjects included in this study were male, and 42 were female. Considering psychiatric comorbidity, depressive disorder, cognitive disorder, psychotic disorder and anxiety disorder were reported in order. Approximately 97% of the subjects were treated with antidepressants, including paroxetine in 54.7%, and 24% of the subjects were treated with two different kinds of antidepressants. In addition, atypical antipsychotics were prescribed in 33.3% of patients, mood stabilizers in 17.3%, and anxiolytics in 94.7% of the subjects. Conclusion : In our study, various kinds of antidepressants were prescribed for most patients with PTSD. Antipsychotics and mood stabilizers were added to the treatment regimens of some subjects, and anxiolytics were added to the treatment regimens of most subjects. Despite its many limitations, this study shows the prescription pattern and trends in PTSD treatment in Korea. We hope that these preliminary data would be helpful for the development and integration of a practical guideline for the treatment of PTSD in Korea.