• 한국임상약학회지
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• 제30권2호
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• pp.81-86
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• 2020

Background: The number of patients with dementia continues to increase as the age of aging continues to grow. Psychiatric symptoms caused by senile dementia are controlled using antipsychotics. However, these antipsychotics can lead to Parkinson's disease, and abuse of dopamine derivatives such as levodopa among Parkinsonian drugs can lead to psychosis. Therefore, we evaluated the patterns of prescribed antipsychotics and antiparkinsonian drugs in patients with senile dementia. Methods: We used data from the sample of elderly patients from the Health Insurance Review and Assessment Service (HIRA-APS-2016). We analyzed the patterns of prescribing antipsychotics and antiparkinsonian drugs including prescribed daily dosage, period of prescription, and number of patients with both antipsychotics and antiparkinsonian drugs for senile dementia. Results: Among the 159,391 patients with dementia included in this analysis, 4,963 patients (3.1%) and 16,499 patients (10.4%) were prescribed typical and atypical antipsychotic drugs, respectively. The most frequently prescribed typical antipsychotic was haloperidol (4,351 patients with dementia), whereas the atypical agent was quetiapine (12,719 patients). The most frequently prescribed antiparkinsonian drugs were in the order of levodopa/carbidopa, benztropine, and ropinirole. In addition, 1,103 and 3,508 patients prescribed typical and atypical antipsychotics, respectively, were co-prescribed antiparkinsonian drugs. Conclusions: Atypical antipsychotics were the preferred prescription in patients with senile dementia. The prescription dose was relatively low; however, the average treatment duration was mostly long-term. Selection of antipsychotics and/or antiparkinsonian drugs should be made carefully in senile dementia and the causal relationship of adverse drug reactions needs further study.

• Animal cells and systems
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• 제16권1호
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• pp.20-26
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• 2012

Drug-induced parkinsonism has been associated with an increased risk for Parkinson's disease. Antipsychotic drugs have long been known to cause parkinsonian symptoms. However, it remains unclear whether antipsychotics can directly damage the nigrostriatal pathway. In the present study, we investigated the toxicity mechanism of two typical antipsychotics, perphenazine and trifluoperazine, in a human dopaminergic cell line, SH-SY5Y. Perphenazine and trifluoperazine induced mitochondrial damage as evidenced by fragmentation of mitochondria, activation of Bax, cytochrome c release and a decrease in cellular ATP level. In addition, activation of caspase-3 and apoptotic nuclei were observed following the drug treatment. However, pan-caspase inhibitor did not suppress the cell death induced by the antipsychotics, suggesting that the initiated apoptosis was possibly shifted to necrosis upon caspase inhibition. Damaged mitochondria may have induced oxidative stress since the drug-induced cell death was partially suppressed by an antioxidant. Taken together, our results suggest that perphenazine and trifluoperazine can induce apoptotic cell death in a dopaminergic cell line via mitochondrial damage accompanied by oxidative stress.

• 대한조현병학회지
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• 제22권2호
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• pp.42-50
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• 2019

Objectives: In this preliminary study, we investigated the clinical characteristics of patients who were first diagnosed with psychotic disorder and explored the impact of the adherence to antipsychotics on long-term medical use. Methods: All national health insurance claims related to psychotic disorders including gender, age, income, and drug compliance, from January 1, 2008 to December 31, 2015, were examined. With trend test using Medication Possession Ratio (MPR), we compared the medical use between the compliant group (MRP≥0.8) and the comparative non-compliant group (0.2≤MPR<0.8). Results: Among 28,095 participants in total, 16,239 patients (57.8%) were diagnosed as schizophrenia; the 30s were the most common (n=7,151, 25.5%). Drug compliance was generally low regardless of the diagnosis and was the lowest among 20s with the 40-60% range of income. The compliant group showed lower psychiatric and medical use than the comparative group in the following years (p<0.0001). Conclusion: These findings suggest that patients in the 20s and 30s with the 40-60% range of income, who are diagnosed with schizophrenia at the first psychiatric visit, may need more clinical and political attention. The results also emphasize the importance of initial drug adherence to antipsychotics in reducing long-term psychiatric costs.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제14권1호
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• pp.26-35
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• 2003

소아청소년 정신과에서는 정신분열증과 기타 정신증상에 기존 항정신병 약물을 사용하고 있다. 이들 약물은 졸리움, 기립성 저혈압, 추체외로 증상 등의 부작용이 문제가 된다. 성인에서는 최근 비정형 항정신병 약물사용이 기존 약물을 대체해가고 있다. 소아정신과에서도 기존 항정신병 약물과 비슷한 효과를 보이면서도 부작용이 훨씬 적은 비정형 항정신병 약물의 사용을 시도하고 있다. 하지만 소아환자에 대한 장기 사용 자료는 물론 단기 사용 자료도 매우 빈약한 실정이다. 본 논문에서는 소아청소년 환자에서의 비정형 항정신병 약물 사용에 대한 자료를 검토하였다. 그렇게 하므로 써 소아청소년 정신과에서의 비정형 항정신병 약물 사용에 대한 적절한 접근 방법을 제시하고자 한다.

• 생물정신의학
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• 제7권1호
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• pp.14-20
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• 2000

Recently atypical antipsychotics have been used as first line agent in the treatment of schizophrenia, and also played a significant role in the treatment of many kinds of psychiatric disorders. The pharmacokinetic and pharmacodynamic properties of these newer antipsychotics are well known through preclinical and early clinical trials. However, it is important to note the limitations of the results due to its relatively short experience. Clozapine is eliminated principally by the hepatic P450 1A2 and 3A4 cytochrome enzymes. 1A2 inducers such as carbamazepine and smoking can reduce its half-life, while 1A2 inhibitors such as SSRIs, especially fluvoxamine can increase its duration of action. Carbamazepine should be avoided in a patient on clozapine because of carbamazepine's potential effects on bone marrow. Benzodiazepines tend to increase the chances of sedation, delirium and respiratory depression. Risperidone is metabolized to 9-hydroxyriperidone by the hepatic P450 2D6 cytochrome enzymes. Fluoxetine and paroxetine, 2D6 inhibitors interfere with metabolism, but 9-hydroxyrisperidone has similar biological activity as parental drug, so it has little affect on the outcome. Olanzapine shows minimal capacity to inhibit cytochrome P450 isoenzymes and shows minimal chance of drug interaction. It is eliminated principally by the hepatic P450 1A2 and 2D6 cytochrome enzymes.

• The Korean Journal of Pain
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• 제32권1호
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• pp.3-11
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• 2019

Going back to basics prior to mentioning the use of antipsychotics in patients with pain, the International Association for the Study of Pain (IASP) definition of pain can be summarized as an unpleasant experience, composed of sensory experience caused by actual tissue damage and/or emotional experience caused by potential tissue damage. Less used than antidepressants, antipsychotics have also been used for treating this unpleasant experience as adjuvant analgesics without sufficient evidence from research. Because recently developed atypical antipsychotics reduce the adverse reactions of extrapyramidal symptoms, such as acute dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia caused by typical antipsychotics, they are expected to be used more frequently in various painful conditions, while increasing the risk of metabolic syndromes (weight gain, diabetes, and dyslipidemia). Various antipsychotics have different neurotransmitter receptor affinities for dopamine (D), 5-hydroxytryptamine (5-HT), adrenergic (${\alpha}$), histamine (H), and muscarinic (M) receptors. Atypical antipsychotics antagonize transient, weak $D_2$ receptor bindings with strong binding to the $5-HT_{2A}$ receptor, while typical antipsychotics block long-lasting, tight $D_2$ receptor binding. On the contrary, antidepressants in the field of pain management also block the reuptake of similar receptors, mainly on the 5-HT and, next, on the norepinephrine, but rarely on the D receptors. Antipsychotics have been used for treating positive symptoms, such as delusion, hallucination, disorganized thought and behavior, perception disturbance, and inappropriate emotion, rather than the negative, cognitive, and affective symptoms of psychosis. Therefore, an antipsychotic may be prescribed in pain patients with positive symptoms of psychosis during or after controlling all sensory components.

• 한국임상약학회지
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• 제30권2호
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• pp.92-101
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• 2020

Background: Delirium is a neuropsychiatric disorder characterized by sudden impairments in consciousness, attention, and perception. The evidence of successful pharmacological interventions for delirium is limited, and medication recommendations for managing delirium are not standardized. This study aimed to provide evidence of antipsychotics for symptomatic treatment of delirium in cancer patients receiving palliative care. Methods: We retrospectively reviewed adult cancer patients in palliative care who received antipsychotic delirium treatment at Severance Hospital between January 2016 and June 2019. The efficacy was evaluated primarily by resolution rates. The resolution of delirium was defined as neurological changes from drowsiness, confusion, stupor, sedation, or agitation to alertness or significant symptomatic improvements described in the medical records. The safety was studied primarily by adverse drug reaction incidence ratios. Results: Of the 63 enrolled patients, 60 patients were included in the statistical analysis and were divided into three groups based on which antipsychotic medication they were prescribed [quetiapine (n=27), haloperidol (n=25) and co-administration of quetiapine and haloperidol (n=8)]. The resolution ratio showed quetiapine to be more effective than haloperidol (p=0.001). No significant differences were seen in adverse drug reaction rates among the three groups (p=0.332). Conclusions: Quetiapine was considered the most effective medication for delirium, with no significant differences in adverse drug reaction rates. Therefore, quetiapine may be considered a first-line medication for treating delirium in cancer patients receiving palliative care. However, further studies comparing more diverse antipsychotics among larger populations are still needed.

• The Korean Journal of Physiology and Pharmacology
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• 제9권1호
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• pp.17-22
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• 2005

We examined whether the abnormal EEG state by NMDA receptor blocker MK-801 can be reversed by typical and atypical antipsychotics differentially by comparing their spectral profiles after drug treatment in rats. The spectral profiles produced by typical antipsychotics chlorpromazine (5 mg/kg, i.p.) and haloperidol (0.5 mg/kg, i.p.) were differ from that by atypical antipsychotic clozapine (5 mg/kg, i.p.) in the rats treated with or without MK-801 treatment (0.2 mg/kg, i.p.) which produce behavioral abnormalities like hyperlocomotion and stereotypy. The dissimilarity between the states produced by antipsychotics and the control state was examined with the distance of the location of the canonical variables calculated by stepwise discriminant analysis with the relative band powers as input variables. Although clozapine produced more different state from normal state than typical antipsychotics, clozapine could reverse the abnormal schizophrenic state induced by MK-801 to the state closer to the normal state than the typical antipsychotics. The results suggest that atypical anesthetic can reverse the abnormal schizophrenic state with negative symptom to the normal state better than typical antipsychotic. The results indicate that the multivariate discriminant analysis using the spectral parameters can help differentiate the antipsychotics with different actions.

• 대한약학회:학술대회논문집
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• 대한약학회 2005년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.131-132
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• 2005

• 생물정신의학
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• 제10권1호
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• pp.3-19
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• 2003

The use of atypical antipsychotics is limited by occurrence of adverse reactions such as weight gain, despite of their benefits. This article provides a comprehensive review and discussion of the most significant findings regarding obesity-related pathways and integrates these with the known mechanism of atypical antipsychotic action. The focus of this article is primarily on the genetics of obesity related pathways that may be disrupted by atypical antipsychotics. This review also discussed weight gain, hyperglycemia or occurrence of diabetes while being treated with atypical antipsychotics from the point of view of pharmacogenetics. Pharmacogenetic research seeks to uncover genetic factors that will help clinicians identify the best treatment strategies for their patients. It will aid clinically in the prediction of response and side effects, such as antipsychotic-induced weight gain, and minimize the current "trial and error" approach to prescribing in the near future. This article also presents the genetics of both central and peripheral pathways putatively involved in antipsychotic-induced weight gain while providing a comprehensive review of the obesity literature. This article also review obesity related candidate molecules which may be disrupted during atypical antipsychotic drug treatment.