• Mood & Emotion
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• v.16 no.3
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• pp.123-128
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• 2018

Objectives : The fourth revision of Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was performed to provide more proper guidelines for clinicians. In this study, we evaluated treatment strategies of elderly patients with bipolar disorders of KMAP-BP 2018. Methods : Sixty-one psychiatrists of the review committee with vast clinical experiences in treating bipolar disorders, completed the survey. An expert consensus was obtained, on pharmacological treatment strategies for elderly patients with bipolar disorder. The executive committee analyzed results, and discussed the results to produce the final algorithm. Results : In elderly patients with bipolar disorder, first-line treatment option for acute manic episode is monotherapy, with atypical antipsychotics or mood stabilizer, and a combination of mood stabilizer and atypical antipsychotics. First-line treatment option for acute depressive episode, was a combination of mood stabilizer and atypical antipsychotics, monotherapy with atypical antipsychotic or mood stabilizer, and atypical antipsychotics with lamotrigine. Conclusion : In KMAP-BP 2018, the recommendation for treatment option in elderly patients with bipolar disorder, was newly introduced. We expect this algorithm may provide valuable information, and facilitate treatment of elderly patients with bipolar disorder.

• Korean Journal of Biological Psychiatry
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• v.2 no.2
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• pp.281-286
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• 1995

Objects : Manic phase of bipolar disorder is treated with a combination of mood stabilizer and antipsychotic drug, especially in the acute phase. Such combined treatment is often required for the clinical management of manic symptoms until therapeutic effects of mood stabilizer become evident. The present study was the first open trial to evaluate the efficacy of risperidone, and safety of the combination of mood stabilizer and risperidone in the treatment of acute manic patients. Method : This study was performed as an open clinical study. The subjects of this study were 42 patients who had been admitted with first manifestations or acute exacerbations of illness were selected, using DSM-III-R criteria for bipolar disorder, manic episode. Patients were rated using the the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), Extrapyramidal Symptom Rating Scale(ESRS). Other adverse events were assessed by a symptom checklist and by observation by medical personnel. Vital signs were monitored in a standard way and electrocardiography, routine laboratory analysis were performed. Results : Thirty patients(67%) completed the 12-week trial period. The CGI showed a good therapeutic effect with a minimal incidence or severity of side effects. The majority of patients showed a continuos reduction in their BPRS scores. The extrapyramidal symptoms assessed on ESRS generally showed mild to moderate degree. laboratory porameters showed no significant changes during the course of treatment. Conclusion : The results of the study showed a good efficacy of the risperidone in manic patients and further controlled studies are warranted.

• 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.

• 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.151-158
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• 2013

Objectives To investigate the pattern of subclinical hypothyroidism (SCH) in patients with bipolar disorders managed by lithium or valproic acid. Methods The study participants were 106 patients with DSM-IV bipolar disorders receiving planned maintenance treatment at the Mood Disorders Clinic of Seoul National University Bundang Hospital (aged between 17 and 64, mean duration of follow-up = 875.65 days). Using the bipolar disorder registry, thyroid function data were analyzed to assess the frequency of and the risk factors for SCH in patients managed by lithium (n = 64) or valproic acid (n = 42) for more than 5 months. Results Overall frequencies of SCH were 20.3% (13/64) in the lithium group, 14.3% (6/42) in the valproic acid group, and between the two groups there is no difference (p = 0.43). No differences were observed in the potential risk factors for SCH between the two groups including age, sex, subtype of bipolar disorder, baseline TSH, and concomitant antipsychotic use. In cases with SCH, thyroid-stimulating hormone (TSH) showed a tendency to increase at 3 month after the initiation of lithium or valproic acid. A gradual increase in the number of patients showing SCH was found within the first 3 years of medication. Conclusions With regular monitoring and careful assessment, there was no difference in the risk of SCH between lithium and valproic acid maintenance. The risk of mood stabilizer-associated SCH may gradually increase within 3 years following the commencement of medication, thereby mandating close monitoring for the first 3 years of treatment. Further studies with large sample size would be needed to confirm these findings.

• Clinical Psychopharmacology and Neuroscience
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• v.16 no.4
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• pp.376-382
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• 2018

We reviewed clinical studies investigating the pharmacological treatment of major depressive episodes (MDEs) with mixed features diagnosed according to the dimensional criteria (more than two or three [hypo]manic symptoms+principle depressive symptoms). We systematically reviewed published randomized controlled trials on the pharmacological treatment of MDEs with mixed features associated with mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD). We searched the PubMed, Cochrane Library, and ClinicalTrials.gov databases through December 2017 with the following key word combinations linked with the word OR: (a) mixed or mixed state, mixed features, DMX, mixed depression; (b) depressive, major depressive, MDE, MDD, bipolar, bipolar depression; and (c) antidepressant, antipsychotic, mood stabilizer, anticonvulsant, treatment, medication, algorithm, guideline, pharmacological. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We found few randomized trials on pharmacological treatments for MDEs with mixed features. Of the 36 articles assessed for eligibility, 11 investigated MDEs with mixed features in mood disorders: six assessed the efficacy of antipsychotic drugs (lurasidone and ziprasidone) in the acute phase of MDD with mixed features, although four of these were post hoc analyses based on large randomized controlled trials. Four studies compared antipsychotic drugs (olanzapine, lurasidone, and ziprasidone) with placebo, and one study assessed the efficacy of combination therapy (olanzapine+fluoxetine) in the acute phase of BD with mixed features. Pharmacological treatments for MDEs with mixed features have focused on antipsychotics, although evidence of their efficacy is lacking. Additional well-designed clinical trials are needed.

• 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.

• 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.