Won Myong Bahk

Revised Korean medication algorithm for bipolar disorder

The rapid progress in treatments for bipolar disorder makes it necessary to revise the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) published in 2002. This study was performed to timely revise KMAP-BP 2002. A questionnaire comprising 37 questions and 645 treatment options was developed for surveying the opinions of Korean experts. We classified the opinions into three categories: first-, second-, and third-line treatments. Fifty-three (75.7%) of the 70 selected experts answered the questionnaire. For an acute manic episode, the combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP) was the preferred first-line treatment. Most experts recommended divalproex and lithium as MSs, and olanzapine, quetiapine, and risperidone as AAPs. For moderately to severely depressed bipolar patients, MS monotherapy and a combination of an MS and an antidepressant (AD) were considered to be preferred treatments respectively. A combination of an MS and an AD was the preferred strategy in severe nonpsychotic depression. Most ADs were rated as second-line drugs. Overall, the preference for lamotrigine and AAPs was higher than in KMAP-BP 2002. The algorithm was developed mainly using consensus among experts supplemented with findings of recent clinical trials to ensure that our algorithm was both up to date and balanced. These results suggest that the medication strategies of KMAP-BP are changing rapidly, reflecting recent studies and clinical experiences.

THE VALIDITY OF THE MOOD DISORDER QUESTIONNAIRE FOR SCREENING BIPOLAR DISORDER: A META-ANALYSIS

We conducted a meta‐analysis to review the diagnostic accuracy of the Mood Disorder Questionnaire (MDQ) among patients with mood disorders. We used a bivariate random effects model to calculate summary sensitivity and specificity. Twenty‐one studies were included. At the standard or modified cutoff value of 7, summary sensitivity was .62 and summary specificity was .85. When we pooled 11 studies including both patients with bipolar disorder (BD) and those with unipolar depression, the summary sensitivity was .76 and summary specificity was .81. However, among the six studies that excluded patients with known BD, the summary sensitivity was significantly reduced to .37 and summary specificity was .88. There were no significant differences on the diagnostic accuracy of the MDQ between studies from Eastern and Western countries after adjusting for various clinical correlates. The overall diagnostic accuracy of the MDQ was relatively good. However, when the MDQ is applied among patients with depression without previous diagnoses of BD, its sensitivity was significantly reduced. This suggests that when the MDQ is applied among this population, its optimal cutoff value should be adjusted to enhance its sensitivity.

Prevalence of Dementia and Its Correlates among Participants in the National Early Dementia Detection Program during 2006-2009

Objective To investigate the prevalence of dementia and its correlates among people with poor socioeconomic status, poor social support systems, and poor performance on the Korean version of the Mini-Mental Status Exam (MMSE-KC). Methods We used 2006-2009 data of the National Early Dementia Detection Program (NEDDP) conducted on Jeju Island. This program included all residents >65 years old who were receiving financial assistance. We examined those who performed poorly (standard deviation from the norm of <-1.5) on the MMSE-KC administered as part of the NEDDP, using age-, gender-, and education-adjusted norms for Korean elders. A total of 1708 people were included in this category. Results The prevalence of dementia in this group was 20.5%. Multivariate logistic regression analysis revealed that the following factors were statistically significantly associated with dementia: age of 80 or older, no education, nursing home residence, and depression. Conclusion The prevalence of dementia is very high among those with lower MMSE-KC scores, and significant correlates include older age, no education, living in a nursing home, and depression. Enhancing lifetime education to improve individuals cognitive reserves by providing intellectually challenging activities, encouraging living at home rather than in a nursing home, and preventing and treating depression in its early phase could reduce the prevalence of dementia in this population.

The Relationship between Depressive Symptoms in Outpatients with Chronic Illness and Health Care Costs

Purpose To evaluate the relationship between depressive symptoms and health care costs in outpatients with chronic medical illnesses in Korea, we screened for depressive symptoms in 1,118 patients with a chronic medical illness and compared the severity of somatic symptoms and health care costs. Patients and Methods Data were compared between outpatients with depressive symptoms and those without depressive symptoms. Depression and somatic symptoms were measured by Zungs Self-rating Depression Scale (SDS) and Patient Health Questionnaire (PHQ)-15, respectively. We also investigated additional data related to patients health care costs (number of visited clinical departments, number of visits made per patients, and health care costs). A total of 468 patients (41.9%) met the criteria for depressive disorder. Results A high rate of severe depressive symptoms was found in elderly, female and less-educated patients. A positive association between the severity of somatic symptoms and depressive symptoms was also identified. The effects of depressive symptoms in patients with chronic illnesses on three measures of health services were assessed by controlling for the effects of demographic variables and the severity of somatic symptoms. We found that the effects of depressive symptoms on the number of visited departments and number of visits made per patients were mediated by the severity of somatic symptoms. However, for health care costs, depressive symptoms had a significant main effect. Furthermore, the effect of gender on health care costs is moderated by the degree of a patients depressive symptoms. Conclusion In summary, there is clearly a need for increased recognition and treatment of depressive symptoms in outpatients with chronic medical illnesses.

Bioequivalence of Generic and Brand Name Clozapine in Korean Schizophrenic Patients: A Randomized, Two-Period, Crossover Study

Objective Clozapine is the treatment of choice for refractory schizophrenia. The aim of this study was to compare the pharmacokinetics of the brand name (Clozaril) formulation and a generic formulation (Clzapine) of clozapine in Korean schizophrenic patients. Methods A prospective, randomized, crossover study was conducted to evaluate the steady-state pharmacokinetic profiles of Clozaril and Clzapine. Schizophrenic patients were randomized to receive either the brand name or generic formulation (100 mg twice daily) for 10 days, followed by the other formulation for 10 days. Plasma samples were collected on the last day of each treatment period. Results Twenty-two of 28 patients (78.6%) completed the study. The mean Cmax,ss values for Clzapine and Clozaril were 524.62 and 551.18 ng/mL, and the mean AUC0-12 values were 4479.90 hr·ng/mL and 4724.56 hr·ng/mL, respectively. The 90% CI values for the natural logarithmically transformed Cmax,ss and AUC0-12 ratios (Clzapine to Clozaril) after a single oral dose (100 mg) were 0.934 (0.849-1.028) and 0.936 (0.869-1.008), respectively. Five patients (20.8%) among 24 patients who took Clzapine reported 11 adverse events and six adverse events were reported by four patients (15.4%) among 26 who took Clozaril; there were no significant differences on physical examination or in vital signs, ECG, and laboratory tests between groups. Conclusion Generic clozapine (Clzapine) appears to be bioequivalent to brand name clozapine (Clozaril).

Is it useful to use the Korean version of the mood disorder questionnaire for assessing bipolar spectrum disorder among Korean college students

The purpose of this study was to assess the usefulness of the Korean version of the Mood Disorder Questionnaire (K‐MDQ) as a screening tool for the identification of bipolar spectrum disorder (BSD) among Korean college students.

Comparison between long-acting injectable aripiprazole versus paliperidone palmitate in the treatment of schizophrenia: systematic review and indirect treatment comparison

We investigated the relative efficacy and tolerability of aripiprazole once monthly (AOM) versus paliperidone palmitate (PP) for treating schizophrenia. Extensive databases searches on short-term, placebo-controlled, randomized studies of AOM and PP were performed. Indirect treatment comparisons were performed between the two long-acting injectable antipsychotics (LAIAs). The primary efficacy endpoint was the mean change in the Positive and Negative Syndrome Scale total score from baseline between each LAIA and placebo. The effect sizes were mean differences and odds ratio (ORs) with 95% confidence intervals (CIs) for the primary efficacy endpoint and safety/tolerability between two LAIAs, respectively. Mean difference in the primary efficacy endpoint was significantly different, favouring AOM over PP (OR: −6.4; 95% CI: −11.402 to −1.358); sensitivity analyses and noninferiority test (AOM vs. PP) confirmed the primary results. The overall early dropout rate was not significantly different between AOM and PP (OR: 1.223; 95% CI: 0.737–2.03). However, there was a significant difference in the early dropout rate in terms of lack of efficacy favouring AOM over PP (OR: 0.394; 95% CI: 0.185–0.841). Within the context of the inherent limitations of the current analysis, our results may suggest that there may be relative advantages for AOM over PP in the short-term treatment of schizophrenia.

Neuroscience-based Nomenclature (NbN) for Clinical Psychopharmacology and Neuroscience.

As of May 2016, Clinical Psychopharmacology and Neuroscience will encourage the use of Neuroscience-based Nomenclature (NbN) for all publications and correspondence. NbN has been developed to replace the current indication-based nomenclature and to provide a contemporary and useful framework for more scientific and better informed pharmacological decisions. Several other leading journals in the field, including Biological Psychiatry, CNS Spectrums, European Psychiatry, International Journal of Neuropsychopharmacology, Neuropsychopharmacology, and others have endorsed this nomenclature for its use in submissions. n nThe current nomenclature is based on clinical indications; for example, drugs used for mania and psychosis they are classified as “mood stabilizers” and “antipsychotic drugs”, respectively. While this conventional nomenclature has been widely used in clinical as well as research settings, there are a number of limitations to this system. First, boundaries among various categories of psychotropic drugs, using the current nomenclature have become unclear. “Antipsychotic drugs” and “mood stabilizers” are good examples; antipsychotic drugs are used for not only schizophrenia, but also mood disorders, including bipolar disorder and treatment resistant depression. On the other hand, mood stabilizers are often prescribed for a mood component in any psychiatric disorder. This discrepancy between their names and indications often confuses patients and their caregivers and sometimes leads to a misunderstanding of the effects of prescribed medications. Second, up-to-date scientific knowledge on these drugs has not been reflected in the current nomenclature. This is a serious issue since the current system was created nearly half a century ago. For example, dopamine receptor antagonists and a partial dopamine receptor agonist are currently included in the same category of “antipsychotic drugs” despite the difference in their drug profiles. Moreover, the involvement of the serotonergic system also has to be considered for some drugs. However, such differences are not reflected in the current system. n nTo overcome these limitations of the current nomenclature, following an initiative of the European Congress of Neuropsychopharmacology (ECNP), a taskforce for psychotropic nomenclature was established with representatives from 5 international organizations: the ECNP, Asian College of Neuropsychopharmacology (AsCNP), American College of Neuropsychopharmacology (ACNP), International College of Neuropsychopharmacology (CINP), and International Union of Basic and Clinical Pharmacology (IUPHAR). The mission of this taskforce is to provide a pharmacologically-driven (rather than indication-based) nomenclature that embeds contemporary neuroscience understanding of how medicines act, to help clinicians to make informed choices when they are trying to figure out what would be the next “pharmacological step”, and to decrease stigma and enhance adherence by a naming system that lays out the rationale for selecting a specific psychotropic.1,2) n nIn the first edition of the NbN, 108 psychotropics are included. The NbN provides a pharmacological driven nomenclature focusing on pharmacology and mode of action, which reflects current knowledge and understanding about the targeted neurotransmitter, molecule, system being modified, and mode/mechanism of action. It also includes 4 additional dimensions: (1) approved indications, (2) efficacy and side effects, (3) “practical note” which summarizes the clinical knowledge that has been prioritized by “filtering” though the taskforce’s “opinion sieve”, and (4) neurobiology.3) The easiest and recommended way to access the newest version of the NbN is to use the approved app, which is freely available on the project’s website (http://nbnomenclature.org/). In this website, there is a special tag - For Authors, too.3) n nThe NbN project has just started. Taking into account new findings and new insights, including feedback from users, the NbN will be updated on a yearly basis. Since it always needs time to change the culture, we understand the transition will likely involve some expected and unexpected responses from the field. However, we rather believe that such responses and feedback will surely improve the quality of the NbN, which in turn will be beneficial for clinicians, researchers, patients as well as their caregivers.

Efficacy and Tolerability of Generic Mirtazapine (Mirtax) for Major Depressive Disorder: Multicenter, Open-label, Uncontrolled, Prospective Study.

Objective Mirtax is a generic mirtazapine widely used since 2003. We conducted an open-label, uncontrolled 6-week study to evaluate the efficacy and safety of Mirtax for major depressive disorder (MDD). Methods Ninety three MDD patients with the diagnosis of MDD and 17-item Hamilton Depression Rating Scale (HDRS) score ≥14 were recruited. The HDRS, Montgomery-Åsberg Depression Rating Scale (MADRS), and the Clinical Global Impressions-Severity Scale (CGI-S) were administered at baseline, 1, 2, 4 and 6 weeks. Response (≥50% decrease in the HDRS or MADRS score), remission (absolute HDRS score ≤7 or MADRS score ≤10) and CGI-I score ≤2 were also calculated. Adverse event (AE) frequency and severity, weight, blood pressure, and pulse rate were checked to assess safety. Results The starting dosage was 11.5±6.4 mg/day, and the maintenance dosage was 23.1±9.4 mg/day. During 6 weeks, HDRS, MADRS and CGI-S scores decreased from 25.1±5.6 to 11.9±8.6 (mean change −13.1±8.3, p<0.001), from 30.2±6.3 to 13.73±10.40 (mean change −16.5±9.8, p<0.001), and from 5.0±0.8 to 2.5±1.3 (mean change −2.5±1.3, p<0.001), respectively. The percentages of responders, remitters by HDRS and patients with a CGI-I score ≤2 were 64.6%, 35.4% and 52.7%, respectively. Significant decreases in HDRS, MADRS and CGI-S scores were confirmed at week 1. The total rate of AEs was 32.3%; the most frequently reported AEs were sedation (4.3%) and constipation (4.3%). Weight was increased from 58.8±10.6 to 60.3±9.3 kg (mean change 0.7±1.7 kg, p=0.004). Conclusion This study, as the first clinical trial of generic mirtazapine, demonstrated the efficacy and tolerability of Mirtax for MDD using a single treatment design.

Blonanserin Augmentation of Atypical Antipsychotics in Patients with Schizophrenia-Who Benefits from Blonanserin Augmentation?: An Open-Label, Prospective, Multicenter Study

Objective The purpose of this study was to investigate the efficacy and tolerability of atypical antipsychotics (AAPs) with augmentation by blonanserin in schizophrenic patients. Methods aA total of 100 patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP were recruited in this 12-week, open-label, non-comparative, multicenter study. Blonanserin was added to their existing AAP regimen, which was maintained during the study period. Efficacy was primarily evaluated using the Positive and Negative Syndrome Scale (PANSS) at baseline and at weeks 2, 4, 8, and 12. Predictors for PANSS response (≥20% reduction) were investigated. Results The PANSS total score was significantly decreased at 12 weeks of blonanserin augmentation (-21.0±18.1, F=105.849, p<0.001). Moreover, 51.0% of participants experienced a response at week 12. Premature discontinuation of blonanserin occurred in 17 patients (17.0%); 4 of these patients dropped out due to adverse events. The patients who benefited the most from blonanserin were those with severe symptoms despite a treatment with a higher dose of AAP. Conclusion Blonanserin augmentation could be an effective strategy for patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP.