• Korean Journal of Biological Psychiatry
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• v.7 no.2
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• pp.198-205
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• 2000

Objectives : Risperidone and clozapine belong to a new generation of antipsychotics that are reportedly more effective and better tolerated than conventional neuroleptics. However, each of these agents costs far more per unit than conventional neuroleptics. The purpose of our retrospective study was to ascertain the total cost and effectiveness of treatment before and after administration of risperidone and clozapine in "revolving door" schizophrenia patients. Method : Data collected on revolving door schizophrenics for 2 years before clozapine and risperidone treatment and for at least 2 years after clozapine and risperidone treatment. Direct cost of inpatient and outpatient treatment was measured. Effectiveness was scaled as "years of mild disability gained". Result : Both risperidone and cloazpine result in higher costs and additional benefits to patients, for example, increased mild disability, reduced number of relapse, and reduced hospital length-of-stay. An ICER of risperidone was less than Rc and ICER of clozapine was greater than Rc. According to decision-analytic this model, risperidone had favorable cost-effectiveness ratios relative to clozapine. Conclusion : We have assumed that risperidone is more cost-effective than clozapine.

• Korean Journal of Biological Psychiatry
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• v.2 no.1
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• pp.131-139
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• 1995

Clozapine, on atypical antipsychotic drug, has been estimated to be a major improvement in the treatment-refractory schizophrenic patients. We evaluated the clozapine efficacy in the treatment of schizophrenic patients who are refractory to classic neuroleptics. The patients were assigned in a prospective, open, comparative trial for 12 weeks. Following an dose titration, 33 inpatients with treatment-refractory schizophrenia diagnosed according to DSM-III-R were given a clozapine(N=17, approximate 300-600mg/day) or haloperidol(N=16, approximate 20-30 mg/day) for 12 weeks. The clinical state was assessed before treatment, and 1st, 4th, 8th and 12th week during treatment using Brief Psychiatric Rating Scale(BPRS) and Positive and Negative Syndrome Scale(PANSS). Assessment of side effects were mode weekly using Simpson-Angus Scale for Extrapyramidal Side Effects and Adverse Events-Somatic Symptoms. Clozapine produces significant improvement than haloperidol on the BPRS and PANSS scores. 77% (13/17) of the clozapine-treated patients were categorized as responders, who showed at least 20% decrease in total BPRS scores, compared with 31% (5/16) of haloperidol-treated patients. Extrapyramidal side effects occurred in only one patient in clozapine group, but nine patients in haloperidol group. Salivation, sleepiness, constipation and hypotension were most frequent adverse effects observed in clozapine group. There was no significant changes in total WBC and neutrophil during clozapine treatment. These findings suggest that clozapine is on effective antipsychotic drug for the Korean treatment-refractory schizophrenic patients, who are nonresponsive to or unable to tolerate classcal antipsychotic drugs due to extrapyramidal side effects.

• Korean Journal of Biological Psychiatry
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• v.3 no.2
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• pp.262-268
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• 1996

It has been known that clozapine is more selective mesolimbic dopamin $D_2$ receptor antagonist and related to 5-HT receptor. In this study, we wxamined the plasma homovanillic acid(HVA), serotonin(5-HT), and 5-hydroxyindoleacetic acid(5-HIM) levels in refractory schizophrenics during clozapine treatment. And we assessed the effects of clozapine on these plasma monoamine metabolites and their association with psychopathology and treatment response. Eight refractory schizophrenic patients(DSM-IV) have entered the study for 3 months during clozapine treatment. Patients were admitted to the inpatient sevice and withdrawn from all neuroleptics for 7-14 days but exceptionally occasional doses of lorazepam was given if needed for behavioral control. The dose of clozapine was titrated as tolerated to 800mg/day. The plasma HVA. 5-HIM and 5-HT levels were measured before treatment and following 2nd week, 4th week, 8th week, and 12th during treatment. Psychopathology was assessed with Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Synrome Scale(PANSS) before and during clozapine treatment. During clozapine treatment, no statistically significant changes were found in plasma HVA, 5-HIM, 5-HT levels, and HVA/5-HIM ratio between baseline and following 2nd week, 4th week, 8th week, 12th week. However, the change in plasma 5-HIAA/5-HT ratio from baseline to 4th week was statistically significant. Generally, changes of plasma HVA, 5-HIAA, 5-HT levels and HVA/5-HIAA ratio were not associated with psychopathology but 5-HIAA was associated with in positive symptoms and general psychopathology of PANSS. These results suggest that clozapine has been found to have relatively weak dopaminergic blokade and stronger serotonergic antagonism.

• Korean Journal of Biological Psychiatry
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• v.19 no.3
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• pp.146-151
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• 2012

Clozapine is an atypical antipsychotic agent that is more effective than the typical neuroleptics in the treatment of refractory schizophrenia. Recently, there has been an increased recognition of the association of clozapine with myocarditis and cardiomyopathy. Commonly used diagnostic tests have limited sensitivity in diagnosing this potentially life-threatening complication. Here we report a case of 36-year-old male patient who developed fever, tachycardia, and dyspnea after introduction of clozapine. By clinical evaluation and laboratory test we diagnosed the patient with myocarditis and treated him successfully. To our knowledge this is the first case report of clozapine-induced myocarditis in Korea.

• Korean Journal of Biological Psychiatry
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• v.6 no.1
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• pp.135-140
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• 1999

The authors described a case of male schizophrenia who developed myoclonic jerk repeatedly and one episode of convulsive seizure during the treatment of clozapine. According to literatures and reported cases, myoclonic jerks induced in a small amount of clozapine may precede and predict the development of a convulsive seizure. Therefore clinicians have to pay attention to the development of a myoclonic jerk during the administration of clozapine. They may decrease the dosage of clozapine step by step at first in the convulsive state, and observe EEG changes of patients frequently.

• Journal of Pharmacopuncture
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• v.22 no.3
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• pp.147-153
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• 2019

Objectives: Many studies have been reported the efficacy of intravenous lipid emulsion (ILE) as an antidote on acute lipophilic drug toxicity. Clozapine, highly lipophilic dibenzodiazepine neuroleptics, is an important medication in the schizophrenia therapy regimen. Acute intoxication with antipsychotics is one of the main reasons for the referral of poisoned patients to the hospital. We expected that ILE could be used for the therapy of acute clozapine intoxicated patients. Methods: We used two groups of consisting of six male rats. Both groups received a toxic dose of clozapine (40 mg/kg) intravenously, via the tail vein. After 15 minutes, they were treated with intravenous infusion of 18.6 mg/kg normal saline (NS group), or 18.6 mg/kg ILE 20% (ILE group). We evaluated blood pressure (BP) and heart rate by power lab apparatus through the tail artery, ataxia by a rat rotary circle, seizure scores and death in multiple times after starting clozapine administration. For biochemical and pathological evaluations the samples of tissue and blood were taken. Results: Our results demonstrated that ILE 20% could return hypotension-induced clozapine better than normal saline. Furthermore, ataxia and seizure have rectified more rapidly and deaths reduced. Clozapine administration causes pancreatitis and lung injury but fat emulsion did not show an optimal effect on tissue damages caused by clozapine toxicity. Conclusion: In conclusion, ILE can remove toxic signs of clozapine same as other lipophilic medicines, however, clinical uses of ILE for this intention requires more appraisement to determine the precise implication and safety.

• Korean Journal of Biological Psychiatry
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• v.1 no.1
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• pp.109-116
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• 1994

It is not known whether negative symptoms and cognitive functions are dissociable or improvements in symptoms are reflected in improvements in cognitive functions in chronic schizophrenic patients. We administered clozapine to evaluate its effect on cognitive functions in chronic schizophrenic patients and to show correlations between improvement in psychotic symptoms and in cognitive functions. Neuropsychological tests such as Wisconsin Card Sorting Test, Digit Span test and Judgment of Line Orientation Test were applied to 16 chronic schizophrenic patients at baseline and after 9 months of treatment with clozapine. Using BPRS we assessed psychopathology before initiation of clozapine and at 9 months. Clozapine improved both positive and negative symptoms in chronic schizophrenic patients significantly. After nine months of clozapine treatment, significant improvements occurred in attention, short-term memory and visual perception ability. And interestingly we noted the trend of improvement in executive functions even though they were not statistical significant. Any significant correlations between the clinical improvement and change in congnitive functions were not observed. Long-term treatment with clozapine improved parts of cognitive functions of chronic schizophrenics. The results of the study suggest that deficits in simple cognitive functions as well as psychotic symptoms are improved after 3 month period of short-term treatment, but executive functions requiring more sophisticated processing of information could be improved after more than 9 months of long-term treatment.

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

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.4
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• pp.277-285
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• 2022

To investigate the adverse effects of clozapine on cardiovascular ion channels, we examined the inhibitory effect of clozapine on voltage-dependent K⁺ (Kv) channels in rabbit coronary arterial smooth muscle cells. Clozapine-induced inhibition of Kv channels occurred in a concentration-dependent manner with an half-inhibitory concentration value of 7.84 ± 4.86 µM and a Hill coefficient of 0.47 ± 0.06. Clozapine did not shift the steady-state activation or inactivation curves, suggesting that it inhibited Kv channels regardless of gating properties. Application of train pulses (1 and 2 Hz) progressively augmented the clozapine-induced inhibition of Kv channels in the presence of the drug. Furthermore, the recovery time constant from inactivation was increased in the presence of clozapine, suggesting that clozapine-induced inhibition of Kv channels is use (state)-dependent. Pretreatment of a Kv1.5 subtype inhibitor decreased the Kv current amplitudes, but additional application of clozapine did not further inhibit the Kv current. Pretreatment with Kv2.1 or Kv7 subtype inhibitors partially blocked the inhibitory effect of clozapine. Based on these results, we conclude that clozapine inhibits arterial Kv channels in a concentration-and use (state)-dependent manner. Kv1.5 is the major subtype involved in clozapine-induced inhibition of Kv channels, and Kv2.1 and Kv7 subtypes are partially involved.

• Korean Journal of Psychosomatic Medicine
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• v.30 no.2
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• pp.66-72
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• 2022

Clozapine is accepted as the "gold standard" antipsychotics for treatment-resistant schizophrenia. Clozapine rarely causes extrapyramidal syndrome and tardive dyskinesia, which are common with other antipsychotics, and only a transient elevation of hyperprolactinemia has been reported. Despite such clinical usefulness, there are limitations to the use of clozapine due to adverse drug reactions (ADR). Fever is a common in adverse drug reactions associated with clozapine. At initiation of clozapine most fatal ADR such as agranulocytosis and neuroleptic malignant syndrome associated with fever, in which case clozapine should be discontinued immediately. However, as benign causes of fever are much more frequent than life-threatening ADR, clozapine should not be discontinued unconditionally in the event of fever during clozapine initiation. In addition, fever may occur at any time during the maintenance of clozapine treatment. In particular, since the risk of pneumonia does not decrease over time, and clozapine has a higher risk of pneumonia than other antipsychotic drugs, it is recommended to adjust clozapine dosage through therapeutic drug monitoring.