• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.9 no.1
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• pp.98-104
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• 1998

A 12-year-old girl with a 6 year history of childhood-onset schizophrenia required 2 hospitalizations and long-term clozapine trial due to inadequate responses to combinations of typical neuroleptics and traditional treatments of schizophrenic disorder. On admission, she had continuous auditory and visual hallucinations, persecutory delusion, emotional instability, regression of behaviors including temper tantrums as well as specific developmental delays in learning, language, and motor coordination. The clozapine trial significantly reduced most of the positive symptoms, and facilitated in successful discharge from the hospital. During the 4 year clozapine treatment, no significant adverse reactions were noted, and she returned to a structured school setting with minimal degrees of schizophrenic symptoms. From this clinical experience, we suggest that clozapine might be safe and effective in treating treatment-refractory schizophrenic children.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.9 no.2
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• pp.247-252
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• 1998

Neuroleptic malignant syndrome(NMS) is an acute, potentially fatal, idiosyncratic reaction to neuroleptic medication. Early recognition and intensive care are crucial. An important issue is whether NMS will recur after initial recovery and subsequent use of neuroleptic medication. The authors presented with a male adolescent who had suffered a bipolar disorder manic episode and been taking clozapine after recovering from MNS. He had been admitted into a psychiatric ward once before and similarly diagnosed. On the second admission, he showed muscle rigidity, autonomic instability, mild fever, severe diaphoresis, and altered mental status on the fourth hospital day following a haloperidol injection. He was diagnosed with NMS, according to the clinical signs and laboratory data. After the use of antipsychotics was discontinued, he was moved to intensive care unit and given dantrolene. His condition began to improve about 48 hours after the onset of NMS. Due to manic behavior, he returned to the psychiatric ward. On the 21 st hospital day, clozapine was administered to counter the manic symptoms. The final dose was 350mg and showed good remission signs without further recurrence of NMS.

• Korean Journal of Biological Psychiatry
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• v.6 no.1
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• pp.74-80
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• 1999

This study was performed to investigate the mechanism of the clozapine-induced seizures in partially restrained rats by concomitant treatment with drugs affecting monoaminergic systems. Partially restrained rats treated with acute single doses of 10mg/kg clozapine exhibited myoclonic jerks (MJs). Drugs affecting the monoaminergic systems, including 2mg/kg haloperidol, 5mg/kg propranolol, 2mg/kg ritanserin, 20mg/kg fluoxetine, and 20mg/kg imipramine, were concomitantly treated with clozapine to observe the effects of these drugs on the MJs. The drugs were given intraperitoneally either as acute single doses(haloperidol, propranolol, ritanserin, and fluoxetine) or as chronic doses for 21days(haloperidol, imipramine, ritanserin, and fluoxetine). The effects of the concomitant treatment of other drugs on the clozapine-induced MJs were evaluated by comparison of the total numbers of the MJs between the clozapine-treated and concomitantly treated groups. The results were as follows. 1) Concomitant treatment with acute single doses of haloperidol, propranolol, and fluoxetine reduced the total numbers of the clozapine-induced MJs, while concomitant treatment with ritanserin did not. 2) Concomitant treatment with chronic doses of imipramine and ritanserin increased the total numbers of the MJs, while concomitant treatment with fluoxetine reduced them. Concomitant chronic treatment with haloperidol did not affect the numbers of the MJs. These results suggest that dopamine and serotonin, not noradrenalin may be involved in the clozapine-induced MJs in partially restrained rats. Future research needs to study the function of each subtype of monoaminergic receptors on the mechanism of the clozapine-induced seizure.

• Korean Journal of Psychosomatic Medicine
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• v.14 no.1
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• pp.62-66
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• 2006

Introduction: Unexpected serious and lethal drug interactions can be occurred by polypharmacy for treatment-resistant psychiatric disorders. We report a case who has suspected upper gastrointestinal bleeding after the combination of clozapine and buspirone. Case : A 69-year-old woman with DSM-IV schizophrenia who was admitted to our hospital had no previous medical problems. Findings on physical exam, laboratory values, EEG, and a magnetic reso-nance imaging scans were no abnormality, except for slightly low level of hemoglobin at admission. Because of aggravating anxiety symptom, a trial of buspirone was begun from 15mg, in addition to olanzapine 30mg. And then olanzapine was switched to clozapine due to her treatment-refractory his-tory and poor response on this admission. Moreover, At the admission 11 weeks later, after 4 weeks of starting buspirone and clozapine, she was placed on a regimen of clozapine 300mg and buspirone 60mg. At this point, she started to complaint nonspecific abdominal pain for 4 days and then hematemesis, melena and hypotension were developed suddenly with negative findings in gastroduodenoscopy. After stopping all medication, the suspected upper gastrointestinal bleeding was subsided. After the regimen was switched back to clozapine only, psychotic symptoms were improved without the recurrence of the adverse events. Conclusion : We concluded that the upper gastrointestinal bleeding in this case was attributed to the drug interaction with clozapine and buspirone, although the definite mechanism is not clear. The clini-cians should be very cautious to prescribe the combination of clozapine and buspirone due to a possible lethal adverse effect.

• 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.

• 대한임상약리학회:학술대회논문집
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• 1993.12a
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• pp.50-50
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• 1993

• 대한임상약리학회:학술대회논문집
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• 2006.11a
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• pp.85-85
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• 2006

• Proceedings of the Zoological Society Korea Conference
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• 1997.10b
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• pp.178.1-178
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• 1997

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.1
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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.

• Korean Journal of Clinical Pharmacy
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• v.28 no.3
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• pp.204-215
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• 2018

Background: In this systematic review and meta-analysis, the effect of metformin on weight loss was assessed to determine whether metformin should be recommended for the prevention or treatment of weight gain in patients receiving antipsychotic medication for the treatment of schizophrenia or schizoaffective disorder. Methods: The PubMed, Embase, and Cochrane Library databases were searched for all published randomized controlled trials (RCTs) from inception to June 2018. In addition, the references of relevant articles were also examined. Using Review Manager 5, the pooled estimates of the weighted mean difference (WMD) of the changes in body weight and body mass index (BMI) and the corresponding 95 % confidence intervals (CIs) were calculated. Results: The meta-analysis included 15 RCTs. The pooled analysis showed that compared with placebo, metformin led to significant reductions in body weight (WMD: -2.09, 95% CI: -2.59, -1.60; p<0.00001) and BMI (WMD: -0.90, 95% CI: -1.08, -0.72; p<0.00001). The effect of metformin on weight loss was greater in patients receiving olanzapine than in patients receiving clozapine (body weight, WMD: -2.39, 95% CI: -3.76, -1.02; p=0.0006 for olanzapine; -1.99, 95% C: -3.47, -0.51; p=0.009 for clozapine; BMI, WMD: -1.15, 95% CI: -1.74, -0.57, p=0.0001 for olanzapine; WMD: 0.76, 95% CI: -1.23, -0.28; p=0.002 for clozapine). Conclusion: Metformin can be recommended to manage olanzapine-induced weight gain in patients with schizophrenia or schizoaffective disorder. The magnitude of the reductionss in body weight and BMI implieds that the use of metformin to attenuate olanzapine-induced weight gain can minimize the risk of coronary heart disease.