• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.246-252
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• 1999

Objectives : Daytime drowsiness or sedation and changes in night sleep are commonly seen in patients treated with clozapine. There is, however, very limited information on their degree and nature during the course of treatment. The purpose of this study was to understand the sleep patterns in chronic schizophrenic patients with clozapine treatment over a period of 24 weeks. Method : The sleep pattern was evaluated using a set of 5-point scale questionnaire, to record subjective impressions of the night sleep induction, maintenance and quality, and daytime drowsiness and fatigue. In addition, unusual experiences associated with night sleep were recorded. The sleep questionnaire was repeatedly administered at baseline and at 1, 2, 4, 8, 12 and 24 weeks of drug treatment. At present, data on 12 patients has been collected. Results : All the components of night sleep were significantly improved in the 1st through the 12th week after treatment with clozapine. Daytime drowsiness was significantly higher in the 1st to the 2nd week after the treatment and fatigue was also significantly higher in the 1st to the 4th week after the treatment. Eight patients experienced noticeable increases in salivation during night sleep, and of these, one also reported frequent nocturnal urination and even enuresis. However, all these adverse factors did not affect the major sleep patterns. Conclusions : These findings suggest that the beneficial effects of clozapine on night sleep might last much longer than the undesirable effect of daytime drowsiness and fatigue. In other words, tolerance of the hypnotic action of clozapine might develop late and tolerance of the daytime drowsiness and fatigue might be evident earlier.

• Clinical Psychopharmacology and Neuroscience
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• v.16 no.4
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• pp.505-507
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• 2018

Clozapine may be associated with cardiovascular adverse effects including QTc prolongation and, more rarely, with myocarditis and pericarditis. Although rare, these latter cardiovascular adverse effects may be life-threatening and must be immediately recognized and treated. Several cases of clozapine related-pericarditis have been described and often it has a subtle and insidious onset with symptoms that may be often misdiagnosed with psychiatric manifestations (e.g. anxiety, panic or somatization) leading to a delayed correct diagnosis with potential fatal consequences. In the present report we describe the case of a 27-year-old girl with schizoaffective disorder taking long acting aripiprazole and valproate who developed a sudden onset clozapine-related pericarditis during titration phase that resolved with immediate clozapine discontinuation and indomethacin administration. We underline the importance of an early diagnosis of clozapine-related pericarditis and the need to have monitoring protocols to prevent this potentially fatal adverse effect especially when polypharmacy is administered to patients taking clozapine.

• 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 Psychosomatic Medicine
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• v.28 no.1
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• pp.36-41
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• 2020

Objectives : Clozapine has been known to increase the possibility of developing cardio/cerebrovascular diseases, and the platelet activation has been deemed to be related to the occurrence of them. In author's previous study, we observed the increase of platelet activity with short-term clozapine administration. This study was conducted, as a follow-up study, to investigate the effect of clozapine on the platelet activity when administered continuously for long-term period of time of 1 year. Methods : The medical records of the patients with schizophrenia or schizoaffective disorder who were treated with clozapine for 1 year were retrospectively reviewed. The degree of platelet activation was assessed by measuring the mean platelet component. Results : Total of 24 patients were enrolled. 9 of them (37.5%) were male and 15 of them (62.5%) were female. In the Wilcoxon sign-ranks test, no significant change was observed between the mean platelet factor values at the beginning and at the end of one year. Conclusions : No significant changes of mean platelet activity were observed after continued administration of clozapine for 1 year. Considering the author's previous findings that observed a prominent decrease of mean platelet component after short-term clozapine administration, the result of this study suggests the possibility that the activity of the platelet may change depending on the duration of the clozapine administration.

• Animal cells and systems
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• v.4 no.2
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• pp.173-179
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• 2000

Evidence suggested that atypical antipsychotics (APs) such as clozapine show less side effects than those of typical APs such as haloperidol and sulpiride. However, little is known about chronic effects of these drugs on changes in gonadotropin releasing hormone (GnRH) mRNA expression and luteinizing hormone (LH) immunoreactivity. Male rats were divided into water-, haloperidol-, sulpiride-, and clozapine-treated groups, and these drugs were administered orally for 4 weeks. The changes in the expression of GnRH mRNA and the LH immunoreactivity were determined in the hypothalamus and pituitary, respectively, using in situ hybridization and immunohistochemistry. GnRH mRNAs were clearly expressed in the water-treated control vats. This was significantly reduced by the chronic treatments with the typical APs, especially with haloperidol, but not with atypical APs clozapine. Likewise, LH immunoreactivity was clearly stained in the control group. While its immunoreativity was significantly reduced by the chronic APs treatments, clozapine treatment showed only slight attenuation. The results show that the atypical APs clozapine has less side effects in the gonadal function than the typical APs haloperidol and the sulpiride. These results suggest that clozapine is a safer drug than the typical APs, at least in the reproductive system.

• 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.23 no.6
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• pp.467-474
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• 2019

Exposure to lead during pregnancy is a risk factor for the development of psychiatric disorders in the offspring. In this study, we investigated whether exposure to low levels of lead acetate (0.2%) in drinking water during pregnancy and lactation causes behavioral impairment and affects the expression of proteins associated with neurodevelopment. Lead exposure altered several parameters in rat offspring compared with those unexposed in open-field, social interaction, and pre-pulse inhibition tests. These parameters were restored to normal levels after clozapine treatment. Western blot and immunohistochemical analyses of the hippocampus revealed that several neurodevelopmental proteins were downregulated in lead-exposed rats. The expression was normalized after clozapine treatment (5 mg/kg/day, postnatal day 35-56). These findings demonstrate that downregulation of several proteins in lead-exposed rats affected subsequent behavioral changes. Our results suggest that lead exposure in early life may induce psychiatric disorders and treatment with antipsychotics such as clozapine may reduce their incidence.

• Korean Journal of Psychosomatic Medicine
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• v.26 no.2
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• pp.188-193
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• 2018

Objectives : Clozapine is a widely prescribed antipsychotic drug for schizophrenia and is known to increase the risk of cardiovascular disease due to its metabolic side effects. However, little is known about the effect of clozapine on the platelet activation, another important factor in the development of cardiovascular disease. In this study, we tried to investigate the effect of clozapine on platelet activity in patients with schizophrenia by comparing the mean platelet component (MPC) values before and after the clozapine administration. Methods : A retrospective review of medical records of patients with schizophrenia, who newly started clozapine treatment from September 1st, 2003 to April 30th, 2007 at the Department of Psychiatry, Konyang University Hospital in Republic of Korea was performed. The final statistical analysis included 14 participants. Bayer ADVIA $120^{(R)}$ system was used to measure MPC. Results : Among the 14 participants, five subjects were males (28.60%), and ten subjects were females (71.40%). The mean age of participants was $37.50{\pm}11.64years$. Average of duration of illness was $91.00{\pm}93.96months$, with the mean dosage of clozapine taken by participants at the time of the last blood test was $337.50{\pm}109.52mg$. The mean MPC measurement before and after receiving clozapine was $26.12{\pm}2.22g/dL$ and $25.14{\pm}2.08g/dL$ respectively. Wilcoxon signed rank test showed that there was a statistically significant decrease in MPC levels after clozapine administration (V=16, p=0.024). Conclusions : Decreased MPC levels after clozapine administration implies that clozapine may increase platelet activation which could have an adverse effect on the occurrence of thromboembolic disease. Our findings also suggest that careful monitoring of the risk factors of cardiovascular diseases, such as platelets activity, is necessary when administering clozapine.

• Bulletin of the Korean Chemical Society
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• v.30 no.7
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• pp.1445-1451
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• 2009

New benzotriazoles (5-8) or dibenzodiazepine derivatives (11-18) were synthesized starting from 3-[(2-amino- 4,5-disubstitutedphenyl)amino]-5,5-disubstitutedcyclohex-2-enones (1-4) through internal coupling of their diazonium salts or internal Mannich reaction in the presence of aromatic aldehydes. Pharmacological evaluation of benzotriazole and dibenzodiazepine derivatives for their clozapine-like properties revealed that dibenzodiazepine 11 bearing 4-bromophenyl group exhibited the same antipsychotic activity as the reference drug clozapine while the activity of benzotriazole 7 was 25% lesser than that of clozapine. Moreover, compounds 7 and 11 did not show significant CNS depressant activity as well as no or slight neurotoxicity on contrast to clozapine when tested in mice using forced swim, rotarod and horizontal screen tests.

• Analytical Science and Technology
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• v.35 no.1
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• pp.24-31
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• 2022

Herein, we present a simple, precise, accurate, and ultra-sensitive spectrofluorimetric method for estimation of clozapine (CLZ) in tablets and human plasma was developed and then validated. A highly fluorescent brown-yellowish fluorophore was formed (λ_ex=469 nm, λ_emi=540 nm) as a nucleophilic substitution reaction occurred between CLZ and 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) in alkaline mcllavine buffer (pH 9.0). Optimum values of experimental parameters were carefully determined and optimized. The calibration curve was rectilinear over the concentration range of 80-900 ng mL^-1 with a linear correlation coefficient (r=0.9984). The LOD and LOQ were determined to be 14 ng mL^-1 and 42 ng mL^-1, respectively. The proposed approach has been used successfully to quantification of Clozapine in its commercial formulations and human plasma.