• Korean Journal of Biological Psychiatry
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• v.7 no.1
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• pp.34-45
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• 2000

Pharmacotherapy of bipolar disorder is a rapidly evolving field. Mood stabilizers and anticonvulsants have varying biochemical profiles which may predispose them to different adverse effects and drug-drug interactions. Several of the new anticonvulsants appear less likely to have the problems with drug-drug interaction. To provide more effective combination pharmacotherapies, clinicians should be allowed to anticipate and avoid pharmacokinetic and pharmacodynamic drug-drug interactions. We reviewed the role of cytochrome P450 isozymes in the metabolism of the drugs and their interactions. The drug-drug interactions of several classes of drugs which used as mood stabilizers and new anticonvulsants, some of which may have psychotropic profiles, are discussed mainly in this article. Finally, potential pharmacokinetic interactions between the benzodiazepines and other coadministered drugs are discussed briefly.

• Korean Journal of Schizophrenia Research
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• v.24 no.1
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• pp.36-43
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• 2021

Objectives: Despite the high discontinuation rate of clozapine in refractory schizophrenia, there is limited evidence regarding the suggested treatment after clozapine discontinuation. Methods: The medical records of 37 patients who discontinued clozapine were retrospectively reviewed. The prescription patterns of antipsychotics, mood stabilizers, and antidepressants were compared at three points before and after clozapine treatment and at the most recent visit. Results: After clozapine discontinuation, 75.6% of the subjects were receiving antipsychotic polypharmacy, and 32.4% were taking more than 3 antipsychotics. The frequently used antipsychotics were olanzapine (21.5%), quetiapine (21.5%), and paliperidone (12.7%). The rates of augmentation with mood stabilizers and antidepressants were 43.2% and 29.7%, respectively. Furthermore, valproate was the most commonly used mood stabilizer (87.5%). Conclusion: Antipsychotic polypharmacy and augmentation are inevitable in schizophrenia patients for whom clozapine has been discontinued. Further research is required to improve the outcomes of polypharmacy and augmentation in schizophrenia patients.

• Journal of Korean Neuropsychiatric Association
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• v.57 no.4
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• pp.287-300
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• 2018

Of the different phases of bipolar disorder, bipolar depression is more prevailing and is more difficult to treat. However, there is a deficit in systemic research on the pharmacological treatment of acute bipolar depression. Therefore, consensuses on the pharmacological treatment strategies of acute bipolar depression has yet to be made. Currently, there are only three drugs approved by the Food and Drug Administration for acute bipolar depression : quetiapine, olanzapine-fluoxetine complex, and lurasidone. In clinical practice, other drugs such as mood stabilizers (lamotrigine, lithium, valproate) and/or the other atypical antipsychotics (aripiprazole, risperidone, ziprasidone) are frequently prescribed. There remains controversy on the use of antidepressants in bipolar depression. Here, we summarized the evidence of current pharmacological treatment options and reviewed treatment guidelines of acute bipolar depression from recently published studies.

• Korean Journal of Biological Psychiatry
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• v.1 no.1
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• pp.40-59
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• 1994

The introduction of lithium salts for the treatment of mood disorder by Code in 1949 was a major therapeutic breakthrough. Yet it is far from the universal therpeutic agent in the treatment of mood disorders. Indeed, some acutely manic patients do not respond adeqately to lithium and some individuals experience breakthrough affective episodes during lithium maintenance. In the last decode, it has become c1ear that a significant number of patients with more highly recurrent disorders may require alternative or enhanced forms of prophylactic treatment. For these reasons, a variety of other drugs hove been employed for the treatment and prophylaxis of mood disorders. Efforts to develop new pharmacologic strategies for mood disorder hove included a diverse array of medications, ranging from potent benzodiazepines to novel neuroleptics and from anticonvulsants to calcium channel blockers. The anticonvulsants appear particularly useful in cases of dysphoric mania and rapid cycling state, subforms of bipolar disorder that respond quite poorly to conventional treatments. Among all of these new pharmacologic strategy, carbamazepine and sodium valproate have received the broadest clinical applications as maintenance therapies. The data documenting the short-term antimanic effectiveness of the calcium channel blocker verapamil and benzodiazepins such as clonazepam and lorazepam appear also promising. A number of other theoretically interesting, as well as clinically relevant therapies, which are not presently employed routinly, hove also been studied, including 2 blocker clonidine, atypical antipsychotic clozapine, cholinomimetics, 5-HT enhancers, thyroid and magnesium preparations. Now prophylaxis in mood disorder remains a considerable therapeutic challenge. Controlled testing of the prophylactic efficacy of compounds such as carbamazepine, valproic acid, and the calcium channel blockers represent important next step in the clinical trials for mood disorder.

• 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.20 no.4
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• pp.159-165
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• 2013

Objectives Mechanisms of clinical synergistic effects, induced by co-treatments of lithium and valproate, are unclear. Extracellular signal-regulated kinase (ERK) has been suggested to play important roles in mechanisms of the action of mood stabilizers. In this study, effects of co-treatments of lithium and valproate on the ERK1/2 signal pathway and its down-stream transcription factors, ELK1 and C-FOS, were investigated in vitro. Methods PC12 cells, human pheochromocytoma cells, were treated with lithium chloride (30 mM), valproate (1 mM) or lithium chloride + valproate. The phosphorylation of ERK1/2 was analyzed with immunoblot analysis. Transcriptional activities of ELK1 and C-FOS were analyzed with reporter gene assay. Results Single treatment of lithium and valproate increased the phosphorylation of ERK and transcriptional activities of ELK1 and C-FOS, respectively. Combined treatments of lithium and valproate induced more robust increase in the phosphorylation of ERK1/2 and transcriptional activities of ELK1 and C-FOS, compared to those in response to single treatment of lithium or valproate. Conclusions Co-treatments of lithium and valproate induced synergistic increase in the phosphorylation of ERK1/2 and transcriptional activities of its down-stream transcription factors, ELK1 and C-FOS, compared to effects of single treatment. The findings might suggest potentiating effects of lithium and valproate augmentation treatment strategy.

• Anxiety and mood
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• v.4 no.1
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• pp.42-48
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• 2008

Objective : Due to a better understanding of the pathophysiology of posttraumatic stress disorder (PTSD) and the relative limitations in the treatment of patients with PTSD, a variety of medications and treatment algorithms for PTSD have been investigated. This study was conducted to investigate the trends in the pharmacotherapy used in the treatment of inpatients with PTSD at a single university hospital in Korea. Methods : Data from 75 patients diagnosed with PTSD according to the DSM-IV criteria from January 1998 to December 2007 were collected. Demographic data and clinical data, including medications prescribed, were investigated. Results : Thirty-three of the 75 subjects included in this study were male, and 42 were female. Considering psychiatric comorbidity, depressive disorder, cognitive disorder, psychotic disorder and anxiety disorder were reported in order. Approximately 97% of the subjects were treated with antidepressants, including paroxetine in 54.7%, and 24% of the subjects were treated with two different kinds of antidepressants. In addition, atypical antipsychotics were prescribed in 33.3% of patients, mood stabilizers in 17.3%, and anxiolytics in 94.7% of the subjects. Conclusion : In our study, various kinds of antidepressants were prescribed for most patients with PTSD. Antipsychotics and mood stabilizers were added to the treatment regimens of some subjects, and anxiolytics were added to the treatment regimens of most subjects. Despite its many limitations, this study shows the prescription pattern and trends in PTSD treatment in Korea. We hope that these preliminary data would be helpful for the development and integration of a practical guideline for the treatment of PTSD in Korea.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.25 no.1
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• pp.14-19
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• 2014

Objectives : This study was conducted in order to describe prescribing practices in treatment of pediatric bipolar disorder in a Korean inpatient sample. Methods : We performed a retrospective chart review of 66 youths who had been hospitalized and diagnosed with bipolar disorder according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria. Demographics, clinical characteristics, medications used, doses, and related adverse events were examined. Results : Mood stabilizers and/or atypical antipsychotic medications were the primary treatment. Risperidone, valproate, and lithium were the most commonly used. Thirty seven patients (58.1%) were treated with combination therapy of an atypical antipsychotic and mood stabilizer for improvement of manic/mixed symptoms. Conclusion : Combination pharmacotherapy was necessary for most patients in this admission sample group. Conduct of further studies will be needed for evaluation of treatment response according to the clinical characteristics, and the safety and efficacy of treatment for child and adolescent bipolar disorder.

• Anxiety and mood
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• v.6 no.2
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• pp.109-114
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• 2010

Objective : Being overweight or obesity impairs quality of life and often causes treatment noncompliance in patients with bipolar disorder. This preliminary study evaluated the prevalence of overweight and obesity in inpatients with bipolar mania. Methods : Inpatients with bipolar mania, who were treated with adequate medications at least 4 weeks were included in a retrospective study. The body weight of each patient was measured and the body mass index (BMI) was calculated. Results : Of the 80 patients, 16.4% (N=13) were overweight, and 35.0% (N=28) were obese at discharge. Female patients had higher prevalence rates of overweight and obesity. Being overweight or obesity was associated with the number of previous episodes of depression and combination treatment with atypical antipsychotics and mood stabilizers. Conclusions : Being overweight or obesity is highly prevalent in patients with bipolar mania. Clinicians should pay more attention to weight gain and obesity when prescribing combination therapies. More research is required to identify the impact of specific risk factors for overweight and obesity in patients with bipolar mania.

• Korean Journal of Biological Psychiatry
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• v.23 no.4
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• pp.185-192
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• 2016

Objectives Treatment response of bipolar disorders (BDs) to long-term mood stabilizers maintenance has not been well explored because of complicated clinical and treatment courses. This study aims at investigating long-term clinical response of BDs to lithium and/or valproate in a naturalistic setting of a tertiary-care university-affiliated hospital. Methods Subjects were 65 patients with bipolar I (BD-I) disorders who had been treated with lithium and/or valproate for more than two years at single bipolar disorder clinic. Long-term response to the best treatment based on treatment algorithms and the current clinical standard of care was retrospectively evaluated using the Alda Scale and the Clinical Global Impression Scale for use in bi-polar illness (CGI-BP). Patients were classified into full responder and partial/non responder groups based on the total score of the Alda Scale with the cut-off score generated from the frequentist mixture analysis of the authors' previous study. Results The mean duration of treatment with the index medication was 69.2 months. Baseline demographic and clinical characteristics were not different among three mood stabilizer groups (valproate, lithium, and combination groups). Twenty-one subjects were classified into full responder group (32.3%). Treatment response assessed by the Alda Scale and CGI-BP scores was not different between lithium and valproate groups. The Alda Scale scores were well correlated with the CGI-BP scores (p < 0.05). Conclusions One third of the patients showed a full response to the long-term lithium and/or valproate treatment in BD-I. The degree of response was similar between lithium and valproate groups.