• Biomolecules & Therapeutics
• /
• v.1 no.1
• /
• pp.121-124
• /
• 1993

To elucidate the effect of antipsychotics and antidepressants on phosphoinositide(Pl) second massenger system, we studied the dose-dependent inhibition of the phosphoinositide-specific phospholipase C(PLC) isozymes, ${\beta}_1,\;{\gamma}_1$ and${\delta}_1,$ by fluphenazine and haloperidol as antipsychotics, and amitriptyline, maprotiline and mianserin as antidepressants. All the antipsychotics and antidepressants tested showed inhibition on at least one of the PLC isozymes with $IC_{50}$ at the concentration between 25 and $250 {\mu}M.$ Maprotiline, mianserin and amitriptyline inhibited 80 to 90% of the activities of all three PLC isozymes at the concentration of $250{\mu}M,$ while haloperidol and fluphenazine inhibited PLC ${\beta}_1$ and${\gamma}_1$ But baclofen didn't inhibit any PLC isozyme. These results suggested that PLC isozymes are inhibited by antipsychotics and antidepessants even though the concentration is high, and these drugs may affect PI signal transduction system by direct inhibition of PLC isozymes.

• Korean Journal of Biological Psychiatry
• /
• v.5 no.2
• /
• pp.263-277
• /
• 1998

Conventional high-dose antipsychotics tend to result in more side effects, negative symptoms and dysphoria, and at the same time lower the cognitive function which is already impaired in most schizophrenics. Florid psychotic symptoms, negative symptoms and cognitive impairment greatly impede psychosocial performance and eventual reintegration into society. The reduction of symptom and the improvement of cognitive funtions and social skills are therefore central to the psychiatric rehabilitation process. The purpose of this study was to evaluate the dose-reduction effects of antipsychotics on chronic schizophrenics prescribed conventional high-dose antipsychotics more than 1,500mg equivalent of chlorpromazine. Fifty-one chronic schizophrenics who maintained high-dose antipsychotics for more than three months were randomly assigned to two groups : 20 patients comprised the dose-maintaining group and 31 patients made the dose-reduction group. Over a sixteen weekperiod Positive and Negative Syndrome Scale(PANSS), Extrapyramidal Symptom(EPS), Nurses' Observation Scale for Inpatient Evaluation(NOSIE-30), Continuous Performance Test(CPT), Quality of Life(QOL), and haloperidol/reduced haloperidol blood levels were determined at the base line and after 2, 4, 6, 8, 12, 16 weeks to evaluate the dose reduction effects of high-dose antipsychotics. The results were as follows : 1) Dose-reduction is highly effective in reducing positive and negative symptoms, and general psychopathology. Effects were most prominent at 8, 12, 16 weeks. Among the dose reduction group, positive symptoms in positive symptom group and negative symptoms in negative symptom group were more reduced. 2 Extrapyramidal symptoms showed no significant difference between two groups. But the EPS was reduced time after time within two groups. 3) Hit rates of Continuous Performance Test, which indicate attentional capacity, increased significantly after dose reduction. 4) Haloperidol and reduced haloperidol blood levels decreased until the 4th week, after which they were constant. 5) Total scores of Nurses' Observation Scale for Inpatient Evaluation were unchanged between the two groups. But among the indices, social interest and personal neatness were improved in the dose-reduction group and retardation was aggrevated in the dose-maintaining group. 6) Total quality of life scores were unchanged between two groups. But in the dose maintaining group, satisfaction scores of attention, autonomy, and interpersonal relationship decreased progressively. These findings suggest that the dose reduction of antipsychotics for chronic schizophrenics on programs of high-dose antipsychotics were effective. Dose reduction should therefore be implemanted to spread the rehabilitation and improve quality of life for chronic schizophrenics.

• Korean Journal of Biological Psychiatry
• /
• v.7 no.2
• /
• pp.159-163
• /
• 2000

Background : Dopamine receptors are strong candidates for involvement in schizophrenia and are target of a wide variety of antipsychotics. Dopamine $D_5$ receptor(DRD5) gene polymorphisms may be associated with various treatment response. The purpose of our study was define to what significance can be held as a predictor of treatment response in this polymorphism. Method : The total number of 116 Korean chronic schizophrenic patients was assessed after 48 weeks treatment. The Positive and Negative Syndrome Scale(PANSS) was rated for the clinical response to various antipsychotics. With the use of polymerase chain reaction amplification, we assessed this dopamine $D_5$ receptor polymorphism in schizophrenic patients who had been treated with antipsychotics, and related genotype with treatment response, to test the hypothesis that DRD5 polymorphism may lead to varying response to antipsychotics. Result : DRD5 polymorphism was not associated with treatment response to a variety of antipsychotics in chronic schizophrenic patients. Conclusion : Genetic variation of $D_5$ receptors do not predict treatment response to antispychotics.

• Korean Journal of Biological Psychiatry
• /
• v.10 no.1
• /
• pp.3-19
• /
• 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.

• Korean Journal of Biological Psychiatry
• /
• v.1 no.1
• /
• pp.124-128
• /
• 1994

We report a case of antipsychotics induced torsade de pointes in a 42-year-old female schizophrenic patient. The patient had taken perphenazine 20 mg/day, chlorpromazine 100 mg/day, and trifluoperazine 15 mg/day irregularly for about 8 years. She experienced syncope and a few difficulties in breathing. On EKG(electrocardiography), QT interval was delayed and polymorphic QRS complexes and ventricular tachycardia were observed. Following a switch of the antipsychotics to haloperidol, known to have fewest effects on the cardiac rhythms among antipsychotics, the arhythymias disappeared. However after discharge, as dose of haloperidol was increased, the symptoms such as chest discomforts and syncopes reappeared. We concluded that the torsade de pointes was developed by antipsychotics. The most common cause of sudden death in patients receiving antipsychotic treatment appears to be ventricular tochycardia. Therefore, clinician should be well aware of the possible side effects of antipsychotics and be cautious in prescribing such drugs to their patients.

• Korean Journal of Psychosomatic Medicine
• /
• v.27 no.2
• /
• pp.111-118
• /
• 2019

Objectives : The purpose of this study was to investigate the clinical characteristics of antipsychotic medication prescription for the symptom control in patients with delirium. Methods : One hundred and eighty-five patients referred to consultation-liaison psychiatric services for delirium due to general medical condition were included in this study. All subjects were divided into two groups (antipsychotics users vs. antipsychotics nonusers), and comparison analyses on their clinical characteristics were performed. Results : One hundred and twenty nine patients (66.5%) used antipsychotics for their delirium, and 56 patients (30.3%) did not use antipsychotics. The history of psychotropic medication was more frequently observed in antipsychotic users (5.4% vs. 18.6%, χ²=5.498, p=0.022). Especially, the history of benzodiazepine use was significantly high in antipsychotics users. The total score and sub-items of delirium rating scale-severity items except for the psychomotor retardation item showed higher scores in antipsychotic users than in nonusers (all p<0.05). The total score of the delirium rating scale-diagnosis items was higher in antipsychotic users than in the nonusers (p=0.010). Conclusions : Delirium patients with more severe delirium symptoms and with more history of benzodiazepine use were treated with antipsychotics more frequently than those without. These findings imply that benzodiazepine may not only exacerbate delirium but be associated with aggression or psychomotor agitation that need immediate intervention. Clinicians may need to pay attention not only these external symptoms but also to hypoactive symptoms that may lead to misdiagnosis and undertreatment.

• Animal cells and systems
• /
• v.16 no.1
• /
• pp.20-26
• /
• 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.

• Korean Journal of Biological Psychiatry
• /
• v.10 no.2
• /
• pp.186-196
• /
• 2003

Objects:The authors devebped a behavioral modification program for oveweight outpatients with schi-zophrenia and bipolar disorder will had teen treated with atypical antipsychotics, and evaluated the applicability of this program to outpatients Methods:Two men and nine women who had been treated with atypical antipsychotics and will had gained at least 5 percent of their pre-treatment body weight for 10 weeks, attended a behavioral modification program. The patients' weight, body mass index and the diet-activity scale were assessed and were compared with those of a matched comparison group will dd not attend the behavioral modification program Results:The body weight of patients who attended the behavioral modification program reduced with statistical significance, The treatment group showed significant improvement in diet-related items but not in activity-related items of the diet-activity scale Conclusions:This study suggested the applicability of a eehavioral mcdification program on weight reduction to overweight patients taking atypical antipsychotics for the frrst time in Korea Additional large scale studies are needed to validate the effectiveness of this program.

• Korean Journal of Biological Psychiatry
• /
• v.11 no.1
• /
• pp.49-53
• /
• 2004

Objective:A Comparison of QTc prolongation for various antipsychotics and an analysis of QTc prolongation for the various types of serotonin transporter polymorphism were performed. Method:EKG was checked, followed by QTc measurement as Bazett's correction, and the serotonin transporter polymorphism was examined in 110 chronic schizophrenia patients were performed EKG before 24 weeks ago. We defiened QTc prolongation as over 450ms. The risk factor of sudden cardiac death were defiend as QTc prolongation and or 60ms in delta value. Result:The prevalence of QTc prolongation in this study was 7.3%, and the prevalence of over 60ms was 4.5%. Patients who had the risk factors were 10(9.1%). 6/52 who prescribed atypical antipsychotics and 2/58 who prescribed haloperidol showed QTc prolongation. The prevalence who had the risk factor of sudden cardiac death were 16% in atypical antipsychotics group, 3.4% in haloperidol group. QTc prolongation were observed more frequently in l/l type than s/s type. l allele frequency were 50% in QTc prolongated group, 19% in not prolongated group. l allele had an association with QTc prolongation(p<0.01). Conclusion:The prevalence of QTc prolongatin was frequent in chronic schizophrenia patients who were prescribed atypical antipsychotics. It has strong association with l allele of 5-HTTLPR.

• Journal of the Korea Convergence Society
• /
• v.9 no.12
• /
• pp.207-216
• /
• 2018

In Korea, there has been no national research on the use of antipsychotics for people with intellectual disabilities(I.D); therefore, it is difficult to identify the problems or to find solutions for problems in using antipsychotics. So, the purpose of this study analyze research findings on the use of antipsychotics for people with I.D in Japan. This research method compared and analyzed the results of research published in the journal J-STAGE and Medical Online and studied a cohort results using data. The results of the analysis are as follows. First, many antipsychotic drugs are prescribed to people with I.D, but it is difficult to accurately assess the effectiveness of the treatments. Second, it is not easy to detect side effects. Third, the potential side effects of drug interactions have been raised. The results was emphasized the need of research that accurately evaluate the drugs in survey of actual situation to ensure more safe use of antipsychotics to peoples with I.D in Korea.