• 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.

• Korean Journal of Biological Psychiatry
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• v.4 no.2
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• pp.198-210
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• 1997

To examine the double-faced thymoleptic(antidepressant and antimanic) effects of risperidone in mood disorders, this article reviews the psychotropic-induced mania, thymoleptic effects of antipsychotics, therapeutic effects of risperidone and risperidone(RIS)-induced mania(RIM) in mood disorders, risk factors of RIM, possible neurochemical mechanism of these thymoleptic effects, pathophysiological and clinical significance of thymoleptic effects, and suggestive clinical guideline of RIS in mood disorders. RIS appeared effective for bipolar disorder at a lower dose than that recommended for schizophrenia, especially in the cases of maintenance of mood stabilizers, and gradual titration from low doses. Manic induction/exacerbation can occur by chance during RIS treatment in mood disorders, schizoaffective disorders, and schizophrenias. The possible risk factors for RIM are refractory mood disorder, especially in bipolar I disorder with poor initial response ; refractory schizoaffective disorders, especially in bipolar type with poor initial response ; refractory chronic schizophrenias, especially with initial responses ; psychotic features ; higher initial doses ; rapid titration ; combined therapy with antidepressants in refractory depression ; and RIS monotherapy in mania/hypomania. RIS is a drug that preferentially block 5-HT2 receptors. The effects of low dose are due mainly to the blockade of 5-HT2 receptors. There are more gradual increase in D2 blockade with increasing dose and this D2 blocking properties become apparent at higher doses. This may be related to a modulation of dopaminergic transmission by 5-HT2 antagonism at lower doses with the direct action of RIS on DA receptors coming into play at higher dose. The serotonergic antagonistic effect may be important for its effects on depressive symptoms. This, together with adequate blo-ckade of D2 receptors, may not necessarily lead to destabilization of mood disorder, but rather to more therapeutic effects. Therefore, this dose-receptor affinity relationship with both antidepressant and antimanic effects according to treatment duration can explain a continuum of antidepressant effect, antimanic effect, behavioral stimulation, and manic/hypomanic induction/exacerbation. It was the recognition of a useful psychiatric side effects by a thoughtful observer with fertile minds that led to their ultimate utilization as psychotropic drugs, i.e., phenothiazine, MAOI, TCA, and lithium. And, in vivo pharmacological challenge by novel psychotropics, as a neurochemical probe, with more specific actions is a useful tool to select pharmacologically homogeneous subgroup of the same phenotypical(clinical) condition, to further study the unknown underlying pathogenesis of various mental illnesses. Finally, RIS may be a useful alternative or adjunctive drug for patients with mood disorders without psychotic features or refractory to treatment with standard antipsychotic drugs. The more conservative doses(tirated slowly from 1-3 mg/d) of RIS, and maintenance of mood stabilizer in the cases with risk factors of RIM are recommended in mood disorder.

• Korean Journal of Biological Psychiatry
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• v.19 no.4
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• pp.193-198
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• 2012

Objectives Despite the growing research interest in the role of immunological markers in schizophrenia, a few studies, with conflicting results, have focused on the association between high sensitivity C-reactive protein (hs-CRP) levels and clinical characteristics in schizophrenia. The aim of the present study was to examine the association of serum hs-CRP with psychopathology in schizophrenia. Methods Fifty-five inpatients with schizophrenia or schizoaffective disorder were enrolled. Serum levels of hs-CRP were measured, and each patient was assessed with the Korean version of the Positive and Negative Syndrome Scale (PANSS). Results In correlation analysis of hs-CRP with PANSS subscales, positive subscale score has significant positive correlation (r = 0.271, p = 0.046). In independent t-test analysis, subjects with hs-CRP > 0.3 mg/dL (elevated CRP group, n = 43) had significantly higher PANSS positive subscale score (t = -3.273, df = 24.107, p = 0.003) than those with hs-CRP ${\leq}$ 0.3 mg/dL (normal CRP group, n = 12). Conclusions Elevated serum levels of high sensitivity C-reactive protein in schizophrenia are associated with the severity of psychotic symptoms.

• Korean Journal of Biological Psychiatry
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• v.16 no.4
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• pp.256-265
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• 2009

Objectives : The aims of this study were to assess a) the prevalence of trauma and posttraumatic stress disorder(PTSD) in schizophrenic patients and b) the differences in symptomatology and outcome after 1year treatment between those with and without PTSD. Methods : Twenty eight schizophrenia and schizoaffective disorder patients completed the Positive and Negative Syndrome Scale(PANSS), Life Stressor Checklist-Revised(LSCL-R), Clinician-Administered PTSD Scale(CAPS), Dissociative Experiences Scale(DES), Hamilton Psychiatry Rating Scale for Depression(HAM-D), and Rosenberg Self-Esteem Scale(RSE). Results : Twenty six patients(92.9%) had at least one trauma in their life time. Eleven patients(39.3%) were diagnosed with PTSD. PTSD group had significantly higher scores on HAM-D and DES but lower scores on RSE. PTSD group also had significantly lower score in the baseline PANSS Negative score. Higher CAPS scores were significantly correlated with lower baseline PANSS Negative score and greater change after 1year of PANSS Negative score. Conclusion : These results showed that the prevalences of trauma and PTSD are high in schizophrenic patients and suggested that PTSD and trauma-related symptoms affected the symptomatology and treatment outcome. More research is warranted to better understand the effects of PTSD in schizophrenic patients.

• 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.

• Korean Journal of Biological Psychiatry
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• v.22 no.4
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• pp.155-162
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• 2015

Objectives Second-generation antipsychotics (SGAs) are frequently used in the treatment of bipolar disorder. However, there is still no consensus on their risk of tardive movement syndromes especially for first-generation antipsychotics (FGAs)-naïve patients. This study aimed to investigate the prevalence and associated factors of SGAs-related tardive dyskinesia and tardive dystonia in patients with bipolar disorder, in a naturalistic out-patient clinical setting. Methods The authors assessed 78 non-elderly patients with bipolar (n = 71) or schizoaffective disorder (n = 7) who received SGAs with a combined use of mood stabilizers for more than three months without previous exposure to FGAs. Multiple direct assessments were performed and hospital records longer than one recent year describing any observed tardive movement symptoms were also reviewed. Results The prevalence rates of tardive dyskinesia and tardive dystonia were 7.7% and 6.4%, respectively. These patients were being treated with ziprasidone, risperidone, olanzapine, quetiapine, or paliperidone at the time of the onset of the movement symptoms. Tardive dyskinesia was mostly observed in the orolingual area, and tardive dystonia was most frequently detected in oromandibular area. A past history of acute dystonia was significantly associated with presence of both tardive movement syndromes. Conclusions Our findings suggest that SGAs-related tardive movement syndromes occur in a substantial portion of bipolar disorder patients. Acute dystonia, a reported risk factor of tardive movement syndromes in the era of FGAs is confirmed as a risk factor of both tardive dyskinesia and tardive dystonia that were induced-by SGAs.

• 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.12 no.2
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• pp.151-158
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• 2005

Background:Clozapine is a unique atypical antipsychotic medication. It is considered to be superior, even amongst the newer agents, in treatment-resistant schizophrenia. However, de novo emergence or exacerbation of obsessive-compulsive(OC) symptoms during treatment with clozapine has been reported. We prospectively evaluated 19 cases which newly developed OC symptoms during clozapine treatment and discussed the treatment of OC symptoms induced by it. Methods:We recruited 19 patients(8 males, 11 females) with a DSM-IV diagnosis of schizophrenia and schizoaffective disorder who had developed OC symptoms during clozapine treatment. OC symptoms were assessed using the Padua-ICMA and YBOCS on a monthly basis over three months. Results:Eleven female and eight male patients were enrolled and the average age of patients was 32.8 years. At baseline, no patients showed OC symptoms. Moderate to severe OC symptoms appeared with mean daily dose of 298.68 mg of clozapine. There were no significant differences in improving OC symptoms between the clozapine dose reduction group and the OC treatment group. Conclusion:We noticed the possibility that the appearance of OC symptoms is connected with the effect of clozapine. The clozapine-induced OC symptoms were improved both by reducing clozapine daily doses, and by adding OC treatment drugs. With other atypical antipsychotics now available, to know and treat the side effects of clozapine would be of considerable value, offering clinical guidance in making a decision on treatment-resistant schizophrenia.

• 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.7 no.2
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• pp.191-197
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• 2000

Objectives : Risperidone is a new antipsychotic drug developed to overcome the therapeutic limitation of conventional antipsychotics. It responses to negative as well as positive symptoms by blocking both dopaminergic and serotonergic receptors, causing no significant side effects such as agranulocytosis and seizure. It is, however, not known whether it induces any serious cardiovascular side effects as evoked by other conventional antipsychotic drugs. The aims of this study were to evaluate the effect of risperidone on cardiovascular function, and to discuss the factors affecting the cardiovascular function. Methods : For 42 patients(22 males and 20 females) diagnosed as schizophrenia, schizophreniform disorder or schizoaffective disorder according to the DSM-IV classification, the cardiovascular fuctions such as heart rate, systolic and diastolic blood pressure, PR interval, QRS interval and QT interval were successively checked before and after 2 weeks and 4 weeks risperidone administration. Furthermore, variables such as body weight, Brief Psychiatric Rating Scale(BPRS), Clinical Global Impression(CGI), Extrapyramidal Symptom Rating Scale(ESRS), Anticholinergic Rating Scale(ARS), serum cholesterol level, serum triglyceride level, serum high-density-lipoprotein level, serum WBC, serum Hb, serum platelet level, prothrombin time and partial thromboplastin time were also analyzed before and after 2 weeks and 4 weeks risperidone administration. Results : 1) Risperidone treatment resulted in a significantly decreased heart rate and increased QT interval after 4 weeks administration(p<0.005 respectively). 2) The scores of BPRS and CGI were significantly decreased after 2 weeks and 4 weeks risperidone administration as compared with baseline(p<0.001 respectively). The scores of ESRS and ASRS were significantly increased after 2 weeks and 4 weeks risperidone administration as compared with baseline(p<0.001 respectively). 3) There were positive correlations between heart rate after 4 weeks and total dose(P<0.05). Blood pressure was significantly(p<0.05) correlated with sex(higher in male) and significantly(p<0.05) positive correlated with body weight. QT interval was significantly(p<0.05) correlated with sex(longer in female) and smoking history(shorter in smokers). Conclusions : Risperidone could induce significant change in heart rate and Q-T interval. Therefore, the cardiovascular safety for risperidone should be reconsidered according to the duration and dosage increase.