• Korean Journal of Biological Psychiatry
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• v.3 no.1
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• pp.22-29
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• 1996

The introduction of chlorpromazine in the 1950's revolutionized the treatment of schizophrenia and ultimately led to the development of selective $D_2$ antagonists such as haloperidol, a goal in keeping with the prevalent theories at that time. However, limitations in the efficacy of these agents, a growing awareness of their side effects, and theoretical shifts in our understanding of schizophrenia have encouraged ongoing efforts to develop better 'atypical' antipsychotics. Clozapine, and subsequently risperidone, represent examples of these novel compounds, both of which incorporate shared serotonin-dopamine antagonism(SDA). The next years will be dominated by further development of SDA compounds, although a number of other lines of investigation are also being pursued.

• Korean Journal of Biological Psychiatry
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• v.14 no.1
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• pp.68-71
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• 2007

Quetiapine is an atypical antipsychotic drug with a benign side effect profile. However, recent studies have reported that thyroid dysfunction is associated with quetiapine treatment. The authors report a patient with DSM-IV bipolar I disorder who developed subclinical hypothyroidism during quetiapine treatment. The patient showed no significant clinical symptoms, but only abnormal thyroid function test findings including antithyroglobulin antibody. The abnormal thyroid function test findings were normalized after discontinuation of quetiapine. The subclinical hypothyroidism developed during quetiapine treatment may be associated with autoimmune process.

• Clinical Psychopharmacology and Neuroscience
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• v.16 no.4
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• pp.501-504
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• 2018

Autoimmune hemolytic anemia is a disease characterized with destruction of erythrocytes as a result of antibody produce against patient's own erythrocytes and anemia. Autoimmune hemolytic anemia can be roughly stratified into two groups according to serological features and secondary causes including drugs induced hemolytic anemia. Drugs induced autoimmune hemolytic anemia is very rare in pediatric patients. Even though hematological side effects such as leucopenia, agranulocytosis, eosinophilia, thrombocytopenic purpura and aplastic anemia might occur due to psychotropic drug use; to the best of our knowledge there is no autoimmune hemolytic anemia case due to quetiapine, an atypical antipsychotics, in literature. We hereby describe the first child case of autoimmune hemolytic anemia during quetiapine treatment.We also are pointing out that one should keep in mind serious hematological side effects with atypical antipsychotic drug use with this case report.

• BMB Reports
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• v.55 no.6
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• pp.293-298
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• 2022

Antipsychotics have been widely accepted as a treatment of choice for psychiatric illnesses such as schizophrenia. While atypical antipsychotics such as aripiprazole are not associated with obesity and diabetes, olanzapine is still widely used based on the anticipation that it is more effective in treating severe schizophrenia than aripiprazole, despite its metabolic side effects. To address metabolic problems, metformin is widely prescribed. Hypothalamic proopiomelanocortin (POMC) neurons have been identified as the main regulator of metabolism and energy expenditure. Although the relation between POMC neurons and metabolic disorders is well established, little is known about the effects of olanzapine and metformin on hypothalamic POMC neurons. In the present study, we investigated the effect of olanzapine and metformin on the hypothalamic POMC neurons in female mice. Olanzapine administration for 5 days significantly decreased Pomc mRNA expression, POMC neuron numbers, POMC projections, and induced leptin resistance before the onset of obesity. It was also observed that coadministration of metformin with olanzapine not only increased POMC neuron numbers and projections but also improved the leptin response of POMC neurons in the olanzapine-treated female mice. These findings suggest that olanzapine-induced hypothalamic POMC neuron abnormality and leptin resistance, which can be ameliorated by metformin administration, are the possible causes of subsequent hyperphagia.

• Journal of The Korean Society of Clinical Toxicology
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• v.18 no.2
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• pp.66-77
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• 2020

Purpose: The aims of the present study were twofold. First, the research investigated the effect of an individual's risk factors and the prevalence of psychotropic drugs on QTc prolongation, TdP (torsades de pointes), and death. Second, the study compared the risk scoring systems (the Mayo Pro-QT risk score and the Tisadale risk score) on QTc prolongation. Methods: The medical records of intoxicated patients who visited the emergency department between March 2010 and February 2019 were reviewed retrospectively. Among 733 patients, the present study included 426 psychotropic drug-intoxicated patients. The patients were categorized according to the QTc value. The known risk factors of QTc prolongation were examined, and the Mayo Pro-QT risk score and the Tisadale risk score were calculated. The analysis was performed using multiple logistic regression, Spearman correlation, and ROC (receiver operating characteristic). Results: The numbers in the mild to moderate group (male: 470≤QTc<500 ms, female: 480≤QTc<500 ms) and severe group (QTc≥500 ms or increase of QTc at least 60ms from baseline, both sex) were 68 and 95, respectively. TdP did not occur, and the only cause of death was aspiration pneumonia. The statically significant risk factors were multidrug intoxications of TCA (tricyclic antidepressant), atypical antipsychotics, an atypical antidepressant, panic disorder, and hypokalemia. The Tisadale risk score was larger than the Mayo Pro-QT risk score. Conclusion: Multiple psychotropic drugs intoxication (TCA, an atypical antidepressant, and atypical antipsychotics), panic disorder, and hypokalemia have been proven to be the main risk factors of QTc prolongation, which require enhanced attention. The present study showed that the Tisadale score had a stronger correlation and predictive accuracy for QTc prolongation than the Mayo Pro-QT score. As a result, the Tisadale risk score is a crucial assessment tool for psychotropic drug-intoxicated patients in a clinical setting.

• Korean Journal of Biological Psychiatry
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• v.8 no.1
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• pp.140-146
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• 2001

In clinical setting, treatment-refractoriness, medication induced tardive dyskinesia and amenorrhea in chronic schizophrenia are frequently problematic. However, there are few guideline solving these problem available to clinicians. The goal of this study was collecting clinical data on clinical effectiveness and predictors of response of switching to olanzapine. We attempted to switch to olanzapine from risperidone and clozapine in chronic 31(risperidone 17, clozapine 14) schizophrenia and schizoaffective disorder patients suffering from sustained symptoms, weekly blood monitoring, medication induced tardive dyskinesia and amenorrhea. Previous antipsychotics dosage was gradually decreased for 2 or 3weeks, at the same time olanzapine dosage was gradually increased. At baseline, after 1 week, after 2 weeks and after 4 weeks we checked Brief Psychiatric Rating Scale, Clinical Global Impression Scale, Sympson-Angus Rating Scale, Barnes Akathisia Rating Scale and followed up after 12 months. Successful switch after 4 weeks was achieved in 25 patients(clozapine 9(64.2%), risperidone 16(94.1%)). Overall, mean BPRS and CGI scores increased significantly. Successful maintenance after 12 months was achieved in 17 patients(clozapine 5(35.7%), risperidone 12(70.5%)). Overall, mean BPRS and CGI scores increased significantly too. Switching to olanzapine from other atypical antipsychotics is recommendable in chronic schizophrenia with treatment refractoriness and drug induced side effect.

• Korean Journal of Biological Psychiatry
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• v.3 no.1
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• pp.115-120
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• 1996

To investigate characteristic drug effects on the genetic basis, the authors administered haloperidol- the $D_2$ antagonist- and clozapine -the atypical antipsychotics with few extra- pyramidal side effects- to the rats. Then, we edobtain brain specimen from the striatum, prefrontal cortex, and cortical region and compared the degree of c-fos expression. The results are 1) haloperidol was found to produce a rapid and transient induction of dos mRNA expression in striatum as compared with cortex and prefrontal area. 2) clozapine was found to produce rapid induction of c-fos mRNA in striatum and prefrontal area. From these data, we can concluded that the mechanism of action of haloperidol is different from the mechanism of clozapine in gene expression.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.2
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• pp.71-78
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• 2009

(S)-Carbamic acid 2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-1-phenyl-ethyl ester hydrochloride (YKP1447) is a novel "atypical" antipsychotic drug which selectively binds to serotonin (5-$HT_{2A}$, Ki=0.61 nM, 5-$HT_{2C}$, Ki=20.7 nM) and dopamine ($D_2$, Ki=45.9 nM, $D_3$, Ki=42.1 nM) receptors with over $10\sim100$-fold selectivity over the various receptors which exist in the brain. In the behavioral studies using mice, YKP1447 antagonized the apomorphine-induced cage climbing ($ED_{50}$=0.93 mg/kg) and DOI-induced head twitch ($ED_{50}$=0.18 mg/kg) behavior. In the dextroamphetamine-induced hyperactivity and conditioned avoidance response (CAR) paradigm in rats, YKP1447 inhibited the hyperactivity induced by amphetamine ($ED_{50}$=0.54 mg/kg) and the avoidance response ($ED_{50}$=0.48 mg/kg); however, unlike other antipsychotic drugs, catalepsy was observed only at much higher dose ($ED_{50}$=68.6 mg/kg). Based on the CAR and catalepsy results, the therapeutic index (TI) value for YKP1447 is over 100 (i.p.). These results indicate that YKP1447 has an atypical profile and less undesirable side effects than currently available drugs.

• Archives of Pharmacal Research
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• v.26 no.11
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• pp.951-959
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• 2003

A series of typical (chlorpromazine, haloperidol and thioridazine) and atypical (risperidone, quetiapine, clozapine and olanzapine) antipsychotics were tested for effects on integrated bioenergetic functions of isolated rat liver mitochondria. Polarographic measurement of oxygen consumption in freshly isolated mitochondria showed that electron transfer activity at respiratory complex I is inhibited by chlorpromazine, haloperidol, risperidone, and quetiapine, but not by clozapine, olanzapine, or thioridazine. Chlorpromazine and thioridazine act as modest uncouplers of oxidative phosphorylation. The typical neuroleptics inhibited NADH-coenzyme Q reductase in freeze-thawed mitochondria, which is a direct measure of complex I enzyme activity. The inhibition of NADH-coenzyme Q reductase activity by the atypicals risperidone and quetiapine was 2-4 fold less than that for the typical neuroleptics. Clozapine and olanzapine had only slight effects on NADH-coenzyme Q reductase activity, even at 200 $\mu$ M. The relative potencies of these neuroleptic drugs as inhibitors of mitochondrial bioenergetic function is similar to their relative potencies as risk factors in the reported incidence of extrapyramidal symptoms, including tardive dyskinesia (TD). This suggests that compromised bioenergetic function may be involved in the cellular pathology underlying TD.

• Korean Journal of Biological Psychiatry
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• v.7 no.1
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• pp.74-79
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• 2000

Objectives : The dopamine-blocking effects and the associated side effects(amenorrhea, lactation, sexual dysfunction) of classical antipsychotics in schizophrenic patients have been studied for a long time. The purpose of this study was to find out these effects of new antipsychotics(risperidone, olanzapine) in schizophrenic patients treated with clinically relevant doses. Method : Plasma levels of both prolactin and testosterone were measured in 91 schizophrenic patients(28 taking haloperidol, 4-20mg/day ; 31 taking risperidone, 2-6mg/day ; 32 taking olanzapine, 5-20mg/day). Results : In male schizophrenic patients, the prolactin levels of risperidone group($76.44{\pm}38.85ng/ml$) and haloperidol group($60.26{\pm}20.74ng/ml$) had no significant difference, but were significantly higher than that of olanzapine($26.90{\pm}5.36ng/ml$). In female, the prolactin level of olanzapine group($36.66{\pm}17.55$) was significantly lower than those of risperidone($121.7{\pm}48.33$) and haloperidol group($161.66{\pm}37.53$). And prolactin level of risperidone group was lower than that of haloperidol group. While the testosterone plasma level of risperidone, haloperidol and olanzapine in both male and female schizophrenic patients had no significant difference. Conclusions : At doses known to be effective in popular clinical setting, prolactin level in patients taking risperidone was higher than that of haloperidol, while olanzapine showed no significant difference in terms of prolactin plasma level from haloperidol. New antipsychotics may not influence the testosterone plasma level.