Psychometric Properties of the Hypomania Checklist-32 in Korean Patients with Mood Disorders

OBJECTIVE: The aim of this study was to examine the validity of the Korean version of the Hypomania Checklist-32, second revision (HCL-32-R2) in mood disorder patients. METHODS: A total of 454 patients who diagnosed as mood disorder according to Structured Clinical Interview for DSM-IV Axis I Disorders, clinician version (SCID-CV) (bipolar disorder [BD] I, n=190; BD-II, n=72; and major depressive disorder [MDD], n=192) completed the Korean module of the HCL-32-R2 (KHCL-32-R2). RESULTS: The KHCL-32-R2 showed a three-factorial structure (eigenvalue >2) that accounted for 43.26% of the total variance. Factor 1 was labeled “active/elated” and included 16 items; factor 2, “irritable/distractible” and included 9 items; and factor 3 was labeled “risk-taking/indulging” and included 9 items. A score of 16 or more on the KHCL-32-R2 total scale score distinguished between BD and MDD, which yielded a sensitivity of 70% and a specificity of 70%. MDD and BD-II also could be differentiated at a cut-off of 15 with maximized sensitivity (0.67) and specificity (0.66). Cronbach’s alpha of KHCL-32-R2 and its subsets (factors 1, 2, and 3) were 0.91, 0.89, 0.81 and 0.79, respectively. Correlations between KHCL-32-R2 and Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale and Korean version of Mood Disorder Questionnaire were −0.66 (p=0.41), −0.14 (p=0.9), and 0.61 (p < 0.001), respectively. CONCLUSION: The KHCL-32-R2 may be a useful tool in distinguishing between bipolar and depressive patients in clinical settings.

Korean Medication Algorithm for Bipolar Disorder 2010: Comparisons with Other Treatment Guidelines / 대한정신약물학회지

The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was developed in 2002 and thereafter revised in 2006. It was secondly revised in 2010 (KMAP-BP 2010). The aim of this study was to compare KMAP-BP 2010 with other recently published treatment algorithm and guidelines for bipolar disorder. The authors reviewed the 4 recently published guidelines and treatment algorithms for bipolar disorder [The British Association for Psychopharmacology Guideline for Treatment of Bipolar Disorder, Canadian Network for Mood and Anxiety Treatments Guidelines for the Management of Patients with Bipolar Disorder, The World Federation Society of Biological Psychiatry Guideline for Biological Treatment of Bipolar Disorder and National Institute for Health and Clinical Experience (NICE) Clinical Guideline] to compare the similarities and discrepancies between KMAP-BP 2010 and the others. In aspects of treatment options, most treatment guidelines had some similarities. But there were notable discrepancies between the recommendations of other guidelines and those of KMAP-BP in which combination or adjunctive treatments were favored. Most guidelines advocated new atypical antipsychotics as first-line treatment option in nearly all phases of bipolar disorder and lamotrigine in depressive phase and maintenance phase. Lithium and valproic acid were still commonly used as mood stabilizers in manic phase and strongly recommended valproic acid in mixed or psychotic mania. Mood stabilizers or atypical antipsychotics were selected as first-line treatment option in maintenance treatment. As the more evidences were accumulated, more use of atypical antipsychotics such as quetiapine, aripiprazole and ziprasidone were prominent. This review suggests that the medication strategies of bipolar disorder have been reflected the recent studies and clinical experiences, and the consultation of treatment guidelines may provide clinicians with useful information and a rationale for making sequential treatment decisions. It also has been consistently stressed that treatment algorithm or guidelines are not a substitute for clinical judgment; they may serve as a critical reference to complement of individual clinical judgment.

Screening of Bipolar Disorders in High School Students / 신경정신의학

OBJECTIVES: This study aimed to assess the prevalence of bipolar spectrum disorders among Korean high school students (individuals in late adolescence) using the Korean version of the Mood Disorder Questionnaire (K-MDQ). METHODS: Two thousand male and female participants were proportionately selected from among high school students nationwide. From November 2007 through February 2008, we conducted an epidemiological survey of, and administered the K-MDQ to, these participants, assessed their psychometric properties, and compared characteristics between K-MDQ-positive and K-MDQ-negative participants. RESULTS: The K-MDQ's internal consistency (Cronbach's alpha) was 0.74. The item-total score correlations ranged from 0.35 to 0.57, and all were statistically significant (p<.001). Factor analysis with varimax rotation revealed 3 factors that explained 42.6% of total variance. We found the cutoff endorsement of the K-MDQ score (7 or more in criteria 1) in 1207 students (60.4%) and found 104 (5.2%) subjects were K-MDQ-positive, meeting all 3 K-MDQ criteria. The mean K-MDQ total score was 7.2+/-2.9 and total scores of K-MDQ-positives and K-MDQ-negatives were 9.9+/-1.7 and 7.0+/-2.9, respectively. K-MDQ-positives and K-MDQ-negatives showed no differences in the sociodemographic variables we assessed. Endorsement of items in total subject ranged from 15.7% to 77.7%. All items except item 8 (more energy) differed significantly in endorsement between K-MDQ-positives and K-MDQ-negatives. Items accounting for over 30% of the endorsement differences between K-MDQ-positives and K-MDQ-negatives were"feel so good," "so irritable," and"excessive, foolish, risky behavior." CONCLUSION: The K-MDQ was a relatively valid screening tool for Korean high school students. Per the result of the K-MDQ survey, suspected lifetime prevalence of bipolar spectrum disorders for those in late adolescence (high school students) seems to be 5.2%, suggesting that systemic screening for bipolar spectrum disorder should be required for this age group.

The Efficacy and Safety of Olanzapine Monotherapy in Patients with Acute Bipolar Mania: A Multi-Center, Open-Label Trial / 대한정신약물학회지

OBJECTIVE: Although atypical antipsychotics are increasingly being used as monotherapy in acute mania, few Korean studies have investigated on them. This study evaluated the efficacy and tolerability of olanzapine monotherapy in patients with acute mania. METHODS: This multicenter, open-label study evaluated the efficacy of olanzapine to treat mania over 6 weeks. Patients with a DSM-IV diagnosis of bipolar I disorder (manic or mixed episodes) were treated with olanzapine (flexible dosage to a maximum of 30 mg/day). Clinical improvements were rated using the Young Mania Rating Scale (YMRS), Clinical Global Impression-Bipolar Version (CGI-BP), Brief Psychiatric Rating Scale (BPRS), and the Montgomery-Asberg Depression Rating Scale (MADRS). Adverse events were measured using the Simpson-Angus Rating Scale (SARS) and Barnes Akathisia Rating Scale (BARS). The general functioning of patients was assessed using the Global Assessment Scale (GAS). All assessments were carried out at baseline and at days 7, 14, 21, and 42, with the exception of the GAS. RESULTS: The subjects comprised 76 patients (male=38, female=38), with 55 patients (72.4%) completing the study. The mean initial dose of olanzapine was 11.7+/-5.0 mg/day and mean daily doses at days 7, 14, 21, and 42 were 16.6+/-5.2, 17.2+/-5.0, 18.1+/-5.3, and 17.4+/-4.7 mg/day, respectively. At days 7, 14, 21, and 42, YMRS, CGI-BP, MADRS and BPRS scores had significantly improved from baseline. More improvement in MADRS scores was observed among patients with mixed mania than patients with euphoric mania. Changes in BPRS scores from baseline did not differ between patients with psychotic symptoms and those with euphoric mania. At days 21 and 42, 42 (55.3%) and 57 (75.0%) patients had responded (YMRS scores decreased from baseline by more than 50%). Also 27 (35.5%) and 46 (60.5%) patients had achieved remission (YMRS scores < or =12) at the same assessment points. GAS scores at days 21 and 42 indicated that olanzapine monotherapy improved patients' global functioning compared to baseline. SARS and BARS scores did not differ significantly between pre- and post-drug trial. CONCLUSION: The data indicate that olanzapine monotherapy has favorable effects across a broad range of mood symptoms and yields functional improvement in acute manic patients with minimal adverse events. Therefore, olanzapine monotherapy may be a preferred first-line agent to treat patients with acute mania. These results support the findings from previous studies and guidelines.

Korean Medication Algorithm for Bipolar Disorder 2006(VI): Comparisons with Other Treatment Guidelines / 대한정신약물학회지

The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was developed in 2002 and revised in 2006. The aim of this study was to compare the KMAP-BP 2006 with other recently published treatment guidelines for bipolar disorder. We conducted a systematic review of the six most recently published guidelines and treatment algorithms for bipolar disorder to compare the similarities and differences between these guidelines and the KMAPBP 2006. Most treatment guidelines had similarities in their treatment options. The guidelines generally advocated atypical antipsychotics as first-line treatment in the manic phase and lamotrigine in the depressive phase. While lithium and divalproex were commonly used as mood stabilizers in the manic phase, divalproex was recommended in mixed or dysphoric mania. Mood stabilizers or atypical antipsychotics were selected as first-line treatment in maintenance. Some guidelines were more concerned about special clinical situations such as pregnancy, obesity, metabolic syndrome, and elderly patients, which were not described in the KMAP-BP 2006. Our findings suggest that the medication strategies for bipolar disorder are based on data from recent studies and clinical experiences. Useful information and a rationale for making sequential treatment decisions can be provided by critically reviewing the treatment guidelines. The treatment algorithms and guidelines are not substitutes for clinical judgment, but can serve as critical references to complement individual clinical assessments.

Common Gene Expression Pattern in the Rat Brain Induced by Several Mood: Stabilizing Drugs / 대한정신약물학회지

OBJECTIVE: This study sought to identify candidate genes related to the clinical effects of several mood stabilizers through gene expression profiles using microarrays and real time RT-PCR. METHOD: Rats were treated with lithium carbonate, valproate, or clozapine for 10 days. Total RNA was extracted from the rat brains and used for microarray analysis. Of 54 genes showing more than 1.5-fold changes induced by all three mood stabilizers, seven genes were selected, and drug-induced changes in gene expression were confirmed by real time RT-PCR. In addition, genotype distribution of the GRIK2 gene was compared between 181 patients with bipolar disorder and 350 normal controls. RESULTS: Of the seven candidate genes, GRIK2 and PRKAR were confirmed as being downregulated by lithium and valproate. However, none of the genes was affected by all three drugs. The allele and genotype distribution in two SNPs of GRIK2 did not differ between the patient and control groups. CONCLUSIONS: Although this study demonstrated overall negative results, the present findings will be used in future studies for establishing various mechanisms of mood stabilizers.

Korean Medication Algorithm for Bipolar Disorder 2006(V): Maintenance Therapy / 대한정신약물학회지

OBJECTIVE: Since the previous publication of Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) in 2002, there has been a substantial need for the revision of treatment algorithm due to rapid progress in the management for bipolar disorder. We focused on the maintenance treatment of bipolar I and bipolar II disorders of KMAP-BP revised in 2006. METHOD: The questionnaire to survey the expert opinion of medication for bipolar disorder was completed by the review committee consisting of 70 experienced psychiatrists. It was composed of 37 questions, and each question includes various sub-items. We classified the expert opinion to 3 categories (the first-line treatment, the second-line, the third-line) by x2 test. A part of this revision regarding maintenance treatment had 6 items ; 2 on bipolar I and 4 on bipolar II disorder. RESULTS: There was no 'treatment of choice' in maintenance treatment. In case of bipolar I mania without history of depression, mood stabilizer (MS) monotherapy was 1st-line treatment. In maintenance management for bipolar II disorder, two treatment options were recommended. Treatment with MS alone or combinations of MS and atypical antipsychotics were preferred in recently recovered patients from hypomania. Atypical antipsychotics were more favored in the maintenance treatment for bipolar I and II disorders than previous KMAP-BP. CONCLUSIONS: There is no 'treatment of choice' in maintenance strategies for bipolar disorder. Atypical antipsychotics are more preferred than the previous KMAP-BP. Also there is an increasing interest on the maintenance use of lamotrigine in bipolar depression.

The Feasibility Test of Korean Medication Algorithm for the Treatment with Schizophrenic Patients(I): Analysis Focusing on the Effectiveness of Treatment / 대한정신약물학회지

OBJECTIVES: The Korean College of Neuropsychopharmacology and the Korean Academy of Schizophrenia developed the Korean algorithm project for schizophrenia to aid clinical decisions. The purpose of this study was to assess the feasibility of Korean Medication Algorithm for Schizophrenia patients in clinical settings in Korea. METHODS: A total of 108 schizophrenia and schizophreniform disorder patients were enrolled at 19 centers and treated according to the algorithm. PANSS (Positive and Negative Symptom Scale) and CGI (Clinical Global Impression) were used to evaluate symptom severity. Also UKU (UKU side effect rating scale) and LUNSERS (Liverpool University Neuroleptic Side Effect Rating Scale), DAI-10 (Drug Attitude Inventory-10), PPS (Patient Preference Scale), SWN (Subjective Well-Being under Neuroleptic treatment) and WHOQOL (World Health Organization Quality of Life) were used to evaluate tolerability and satisfaction of patient respectively. RESULTS: Overall ratings including symptom severity, compliance of medication, side effect of medication, quality of life were favorable. The treatment response (PANSS improvement > or = 20%) rate was 63%, 75% at the first Clinical decision point (CDP) and 4 month respectively. CONCLUSION: Symptom improvement, tolerability and quality of life were all favorable. These results suggest that this algorithm can be useful in clinical practices.

Association Study between Two Single Nucleotide Polymorphisms in the NOTCH4 Gene and Schizophrenia in Koreans / 신경정신의학

OBJECTIVES: Previous studies on NOTCH4 gene and schizophrenia have not produced consistent results, and more studies with various ethnicities and populations were warranted. This study was performed with Korean population to find the role of the NOTCH4 gene in the development of schizophrenia. METHODS: 235 schizophrenics and 236 normal controls participated in the study. Two SNPs (-1725 A/G and -25 T/C) on the NOTCH4 gene were investigated. Genotyping was done by Taqman assay, and statistical analysis was done by contingency chi-square test for the allele and genotype frequencies and PowerMarker V3.0 for the haplotype. RESULTS: The two SNPs did not deviate from Hardy-Weinberg equilibrium in neither schizophrenics or normal controls. Two groups were not different in terms of allele and genotype distribution for both SNPs. Two SNPs were found to be in linkage disequilibrium. Haplotype analysis could not find an association between schizophrenia and these two SNPs. There was no association between the age at onset and the genotypes for both SNPs. CONCLUSION: We could not find any significant association between schizophrenia and the NOTCH4 gene in this Korean population. Although there are limitations in this study, this result supports the conclusion that the NOTCH4 gene is less likely to play a major role on the development of schizophrenia in the Asian population.

Validity and Reliability of the Korean Version of the Hamilton Depression Rating Scale(K-HDRS) / 신경정신의학

OBJECTIVES: The reliability and validity of the Korean version of Hamilton Depression Rating Scale (K-HDRS) were examined in Korean patients depressive symptoms. METHODS: 33 inpatients and 70 outpatients diagnosed as major depressive disorder or depressive episode of bipolar I disorder according to the DSM-IV criteria were assessed with K-HDRS, Clinical Global Impression score(CGI), Beck Depression Inventory (BDI) and Montgomery-Aberg Depression Rating Scale (MADRS). RESULTS: Internal consistency (Cronhach's alpha coefficeint=0.76) and interrater reliability (r=0.94, p<0.001) were statistically significant. Principal axis factoring analysis revealed 4 factors that accounted for 50.4% of the total variance. The correlations of K-HDRS with CGI, BDI and MADRS were 0.84, 0.54, 0.58 respectively. CONCLUSION: These results showed that the K-HDRS could be a reliable and valid tool for the assessment of depressive Korean patients. The K-HDRS will be a useful tool for assessing depressive symptoms in Korea.

Efficacy of Combination of Mood Stabilizer with Quetiapine for Treatment of Acute Episode of Bipolar Disorder: an Open Label Study / 대한정신약물학회지

OBJECTIVE: The atypical antipsychotics are being increasingly used to control acute episode of bipolar disorder, and data are emerging to support their mood-stabilizing and antidepressant properties. This study investigated the short-term efficacy of quetiapine as a combination therapy in the treatment of acute bipolar I disorder. METHODS: This study was a 4-week, open-label, combination, prospective investigation using quetiapine in addition to mood stabilizers. Data of 18 patients fulfilling DSM-IV diagnostic criteria for bipolar I disorder were analyzed. The Young Mania Rating Scale (YMRS), the Hamilton Scale for Depression (HDRS), the Brief Psychiatric Rating Scale (BPRS) and the Extrapyramidal Symptom Rating Scale (ESRS) were applied at baseline and at week 1, 2 and 4. The Clinical Global Impression Scale (CGI) was evaluated at baseline and week 4. RESULTS: The addition of quetiapine produced a statistically significant improvement on the YMRS, HDRS, BPRS and CGI score at week 4 from baseline (p<0.01). Significant improvement on the ESRS-Parkinsonism subscore was observed at week 1, 2 and 4 from baseline (p<0.05). Quetiapine was well tolerated, with no subjects discontinuing because of side effects. CONCLUSION: This study suggests that combination of quetiapine was an effective and safe treatment in patients with acute episode of bipolar disorder. Randomized placebo-controlled prospective studies with increased sample size are needed.

Combination of Topiramate in Acute Mania / 대한정신약물학회지

OBJECTIVE: The rapid therapeutic action of mood stabilizers is critical to the initial management of acute mania, because it enables to minimize the psychological sequelae of the patients commonly occurred in post manic episodes and to increase the compliance to the medications. The aim of this study was to evaluate the efficacy and safety of topiramate as the combination regimen in the treatment of acute mania. METHODS: Twenty manic patients were selected through various screening tests. Ten patients were randomly assigned to valproate alone and the other ten patients to the combination of topiramate and valproate. Antipsychotics were not allowed and benzodiazepines were available as needed. Young Mania Rating Scale (YMRS) and Clinical Global Impression severity of illness scores (CGI-S) were used to evaluate the improvement of manic symptoms at pre-drug baseline and at 1st, 2nd, 4th and 8th week of post-drug. UKU side effect rating scales were done for assessment of drug-induced side effects. Additionally, body weights were checked at weekly basis to monitor the weight change. Repeated measures ANOVA was done to compare the effects between two groups. RESULTS: YMRS of topiramate combination groups were significantly decreased at 1st, 2nd weeks. There were no marked differences in side effects. There was significant weight decrease in topiramate combination group whereas the increase of weight in valproate alone group. CONCLUSION: The results suggest that the combination of topiramte may be used effectively and safely in treatment of acute mania and can be the good choice in manic patients with weight problem.