Objective: We aimed to identify the expectations and preferences for medication and medical decision-making in patients with major psychiatric disorders. Methods: A survey was conducted among patients with major psychiatric disorders who visited psychiatric outpatient clinics at 15 hospitals between 2016 and 2018 in Korea. The survey consisted of 12 questions about demographic variables and opinions on their expectations for medication, important medical decision-makers, and preferred drug type. The most preferred value in each category in the total population was identified, and differences in the preference ratio of each item among the disease groups were compared. Results: A total of 707 participants were surveyed. In the total population, patients reported high efficacy (44.01%±21.44%) as the main wish for medication, themselves (37.39%±22.57%) and a doctor (35.27%±22.88%) as the main decision makers, and tablet/capsule (36.16%±30.69%) as the preferred type of drug. In the depressive disorders group, the preference ratio of high efficacy was significantly lower, and the preference ratio of a small amount was significantly higher than that of the psychotic disorder and bipolar disorder groups. The preference ratio of a doctor as an important decision maker in the bipolar disorder group was higher compared to the other groups. Conclusion This study revealed the preference for medications and showed differences among patients with psychiatric disorders. Providing personalized medicine that considers a patient’s preference for the drug may contribute to the improvement of drug compliance and outcomes.

Objectives: After the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was developed in 2002, its fifth revision was completed in 2022 to reflect the recent rapid developments and research into bipolar disorder and its psychopharmacology. Methods: According to the methodology for previous versions, the depressive episode section of KMAP-BP 2022 was revised based on a survey consisting of 11 questions. Among ninetythree experts, eighty-seven members of the review committee (93.5%) completed the survey.The executive committee analyzed the results and discussed the final production of an algorithm by considering the scientific evidence. Results: Overall, the results from this study showed little change in comparison with previous versions of KMAP-BP. However, there have been significant changes in recommendations over the span of about 20 years. The preferences for lamotrigine and atypical antipsychotics, especially aripiprazole, quetiapine, and olanzapine, have shown a tendency to continuously increase, but the preferences for risperidone and ziprasidone have not increased, but have decreased. Moreover, the preference for typical antipsychotics has significantly decreased. Additionally, concerns over the use of antidepressants in bipolar depression have been raised, and their use is not recommended in KMAP-BP 2022 as a first-line treatment. Conclusion Pharmacotherapy for acute depressive episodes with various clinical progressions and various subtypes still shows diversity, compared to pharmacotherapy for mania. We look forward to the development of bipolar depressive, episode-specific therapeutic drugs in the future, and hope the fifth update of KMAP-BP will be a complementary option for clinicians and their patients with bipolar disorder.

Objective: In the 19 years since the Korean College of Neuropsychopharmacology and the Korean Society for Affective Disorders developed the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) in 2002, four revisions have been conducted. Methods: To increase survey efficiency in this revision, to cover the general clinical practice, and to compare the results with previous KMAP-DD series, the overall structure of the questionnaire was maintained. The six sections of the questionnaire were as follows: 1) pharmacological treatment strategies for major depressive disorder (MDD) with/without psychotic features; 2) pharmacological treatment strategies for persistent depressive disorder and other depressive disorder subtypes; 3) consensus for treatment-resistant depression; 4) the choice of an antidepressant in the context of safety, adverse effects, and comorbid physical illnesses; 5) treatment strategies for special populations (children/adolescents, elderly, and women); and 6) non-pharmacological biological therapies. Recommended first-, second-, and third-line strategies were derived statistically. Results: There has been little change in the four years since KMAP-DD 2017 due to the lack of newly introduced drug or treatment strategies. However, shortened waiting time between the initial and subsequent treatments, increased preference for atypical antipsychotics (AAPs), especially aripiprazole, and combination strategies with AAPs yield an active and somewhat aggressive treatment trend in Korea. Conclusion We expect KMAP-DD to provide clinicians with useful information about the specific strategies and medications appropriate for treating patients with MDD by bridging the gap between clinical real practice and the evidence-based world.

BACKGROUND: The ratio of the steady-state 24-hour area under the concentration-time curve (ssAUC24) to the MIC (AUC24/MIC) for vancomycin has been recommended as the preferred pharmacodynamic index. The aim of this study was to assess whether the calculated AUC24 (cAUC24) using the creatinine clearance (CLcr) differs from the ssAUC24 based on the individual pharmacokinetic data estimated by a commercial software. MATERIALS AND METHODS: The cAUC24 was compared with the ssAUC24 with respect to age, body mass index, and trough concentration of vancomycin and the results were expressed as median and interquartile ranges. A correlation between the cAUC24 and ssAUC24 and the trough concentration of vancomycin was evaluated. The probability of reaching an AUC24/MIC of 400 or higher was compared between the cAUC24 and ssAUC24 for different MICs of vancomycin and different daily doses by simulation in a subgroup with a trough concentration of 10 mg/L and higher. RESULTS: The cAUC24 was significantly lower than the ssAUC24 (392.38 vs. 418.32 mg.hr/L, P < 0.0001) and correlated weakly with the trough concentration (r = 0.649 vs. r = 0.964). Assuming a MIC of 1.0 mg/L, the probability of reaching the value of 400 or higher was 77.5% for the cAUC24/MIC and 100% for the ssAUC24/MIC in patients with a trough concentration of 10 mg/L and higher. If the MIC increased to 2.0 mg/L, the probability was 57.7% for the cAUC24/MIC and 71.8% for the ssAUC24/MIC at a daily vancomycin dose of 4,000 mg. CONCLUSIONS: The cAUC24 using the calculated CLcr is usually underestimated compared with the ssAUC24 based on individual pharmacokinetic data. Therefore, to obtain a more accurate AUC24, therapeutic monitoring of vancomycin rather than a simple calculation based on the CLcr should be performed, and a more accurate biomarker for renal function is needed.
Area Under Curve ; Body Mass Index ; Creatinine* ; Drug Monitoring ; Humans ; Vancomycin*

Although peroxisome proliferator receptor (PPAR)-alpha and PPAR-gamma agonist have been developed as chemical tools to uncover biological roles for the PPARs such as lipid and carbohydrate metabolism, PPAR-delta has not been fully investigated. In this study, we examined the effects of the PPAR-delta agonist GW0742 on fatty liver changes and inflammatory markers. We investigated the effects of PPAR-delta agonist GW0742 on fatty liver changes in OLETF rats. Intrahepatic triglyceride contents and expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and monocyte chemo-attractant protein-1 (MCP-1) and also, PPAR-gamma coactivator (PGC)-1alpha gene were evaluated in liver tissues of OLETF rats and HepG2 cells after GW0742 treatment. The level of TNF-alpha and MCP-1 was also examined in supernatant of Raw264. 7 cell culture. To address the effects of GW0742 on insulin signaling, we performed in vitro study with AML12 mouse hepatocytes. Rats treated with GW0742 (10 mg/kg/day) from 26 to 36 weeks showed improvement in fatty infiltration of the liver. In liver tissues, mRNA expressions of TNF-alpha, MCP-1, and PGC-1alpha were significantly decreased in diabetic rats treated with GW0742 compared to diabetic control rats. We also observed that GW0742 had inhibitory effects on palmitic acid-induced fatty accumulation and inflammatory markers in HepG2 and Raw264.7 cells. The expression level of Akt and IRS-1 was significantly increased by treatment with GW0742. The PPAR-delta agonist may attenuate hepatic fat accumulation through anti-inflammatory mechanism, reducing hepatic PGC-1alpha gene expression, and improvement of insulin signaling.
Animals ; Anti-Inflammatory Agents/*pharmacology/therapeutic use ; Blood Glucose ; Cytokines/genetics/metabolism ; Diabetes Mellitus/blood/immunology/metabolism ; Fatty Liver/blood/*drug therapy/immunology ; Glucose Tolerance Test ; Hep G2 Cells ; Humans ; Insulin Resistance ; Liver/metabolism ; Male ; PPAR delta/*agonists/metabolism ; Rats ; Rats, Long-Evans ; Thiazoles/*pharmacology/therapeutic use ; Triglycerides/metabolism

Most of the previous studies on immune dysregulation in end-stage renal disease (ESRD) have focused on T cell immunity. We investigated B cell subpopulations in ESRD patients and the effect of hemodialysis (HD) on B cell-associated immune profiles in these patients. Forty-four ESRD [maintenance HD patients (n = 27) and pre-dialysis patients (n = 17)] and 27 healthy volunteers were included in this study. We determined the percentage of B cell subtypes, such as mature and immature B cells, memory B cells, and interleukin (IL)-10+ cells, as well as B cell-producing cytokines (IL-10, IL-4 and IL-21) by florescent activated cell sorting (FACS). B cell-associated gene expression was examined using real-time PCR and B cell producing cytokines (IL-10, IL-4 and IL-21) were determined using an enzyme-linked immunosorbent assay (ELISA). The percentage of total B cells and mature B cells did not differ significantly among the three groups. The percentages of memory B cells were significantly higher in the pre-dialysis group than in the HD group (P < 0.01), but the percentage of immature B cells was significantly lower in the pre-dialysis group than in the other groups. The percentages of IL-10-expressing cells that were CD19+ or immature B cells did not differ significantly (P > 0.05) between the two subgroups within the ESRD group, but the serum IL-10 concentration was significantly lower in the pre-dialysis group (P < 0.01). The results of this study demonstrate significantly altered B cell-associated immunity. Specifically, an imbalance of immature and memory B cells in ESRD patients was observed, with this finding predominating in pre-dialysis patients.
Adaptor Proteins, Signal Transducing/genetics ; Adult ; Antigens, CD19/metabolism ; B-Lymphocyte Subsets/immunology/metabolism ; B-Lymphocytes/*immunology/metabolism ; Cytokines/biosynthesis ; Female ; Humans ; Immunophenotyping ; Interleukin-10/metabolism ; Kidney Failure, Chronic/*immunology/metabolism ; Leukocytes, Mononuclear/metabolism ; Male ; Middle Aged ; Proto-Oncogene Proteins/genetics ; T-Lymphocytes, Regulatory/immunology/metabolism

OBJECTIVE: Psychopharmacological treatment of bipolar disorder is quite complex because of its clinical features of different episodes and various course. We published Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) in 2002, that appeared to be helpful in clinical situation by feasibility study in 2005, and revised KMAP-BP in 2006. New papers in which some drugs are effective in treating bipolar disorder have been published, and the demand for revision of KMAP-BP are increased. METHODS: The questionnaire was sent to 94 experts, 65 of whom replied. It was composed of 40 questions about clinical situations, and each question includes various sub-items. Based on KMAP-BP 2006 and new data, some questions sub-items are amended. Safety issues and consideration on special populations were added in this revision. Each option was categorized on three parts (the first-line, the second-line, or the third-line) by its 95% confidence interval. RESULTS: In acute manic episode, even though it is euphoric, mixed, or psychotic, combination of a mood stabilizer (MS) with an atypical antipsychotic (AAP) is recommended as first-line strategy. Mood stabilizer monotherapy is first-line in hypomanic episode. Among the mood stabilizers, valproic acid and lithium are selected as first-line. Monotherapy with mood stabilizer is recommended in mild to moderate bipolar depression. However, triple combination of a mood stabilizer, an atypical antipsychotic and an antidepressant (AD), is the first-line strategy in non-psychotic severe depression. Also combination of MS and AAP (MS+AAP) and combination of MS and AD (MS+AD) are recommended as first-line. In psychotic bipolar depression, combination of MS, AAP, and AD (MS+AAP+AD), combination of MS and AAP (MS+AAP), and combination of AAP and AD (AAP+AD) are first-line strategies. In bipolar depression, lithium, lamotrigine, and valproic acid are selected as first-line mood stabilizer, and quetiapine, olanzapine and aripiprazole are preferred antipsychotics. Bupropion and (es)citalopram are first-line antidepressant in moderated depression, and (es)citalopram, bupropion, and paroxetine are recommended as firstline in severe depression. Preferred strategy for rapid cycling patients is combination of MS with AAP. In maintenance treatment, combination of MS with AAP and monotherapy of MS are recommended as first-line. CONCLUSION: In treating bipolar disorder, even the first step of treatment, consensus of experts are changed from our studies in 2002 and 2006. This medication algorithm, with some limitations, may reflect the clinical practice and recent researches.
Antipsychotic Agents ; Benzodiazepines ; Bipolar Disorder ; Bupropion ; Consensus ; Depression ; Dibenzothiazepines ; Humans ; Lithium ; Oligopeptides ; Paroxetine ; Piperazines ; Surveys and Questionnaires ; Quinolones ; Resin Cements ; Triazines ; Valproic Acid ; Aripiprazole ; Quetiapine Fumarate

BACKGROUND: While there is an evidence that the anti-inflammatory properties of spironolactone can attenuate proteinuria in type 2 diabetes, its effects on vascular endothelial growth factor (VEGF) expression in diabetic nephropathy have not been clearly defined. In this study, we examined the effects of spironolactone, losartan, and a combination of these two drugs on albuminuria, renal VEGF expression, and inflammatory and oxidative stress markers in a type 2 diabetic rat model. METHODS: Thirty-three Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats were divided into four groups and treated with different medication regimens from weeks 25 to 50; OLETF diabetic controls (n=5), spironolactone-treated (n=10), losartan-treated (n=9), and combination of spironolactone- and losartan-treated (n=9). RESULTS: At week 50, the albumin-to-creatinine ratio was significantly decreased in the losartan and combination groups compared to the control OLETF group. No decrease was detected in the spironolactone group. There was a significant reduction in renal VEGF, transforming growth factor (TGF)-beta, and type IV collagen mRNA levels in the spironolactone- and combination regimen-treated groups. Twenty-four hour urine monocyte chemotactic protein-1 levels were comparable in all four groups but did show a decreasing trend in the losartan and combination regimen groups. Twenty-four hour urine malondialdehyde levels were significantly decreased in the spironolactone- and combination regimen-treated groups. CONCLUSION: These results suggest that losartan alone and a combined regimen of spironolactone and losartan could ameliorate albuninuria by reducing renal VEGF expression. Also, simultaneous treatment with spironolactone and losartan may have protective effects against diabetic nephropathy by decreasing TGF-beta and type IV collagen expression and by reducing oxidative stress in a type 2 diabetic rat model.
Albuminuria ; Animals ; Chemokine CCL2 ; Collagen Type IV ; Diabetic Nephropathies ; Losartan ; Malondialdehyde ; Oxidative Stress ; Proteinuria ; Rats ; RNA, Messenger ; Spironolactone ; Transforming Growth Factor beta ; Transforming Growth Factors ; Vascular Endothelial Growth Factor A

BACKGROUND: Both aspirin and simvastatin are prescribed as treatments or prevention of cardiovascular diseases. The aim of this study was to investigate the influence of simvastatin on pharmacokinetics and pharmacodynamics of aspirin after oral co-administration in healthy subjects. METHODS: Subjects were orally administered aspirin 100 mg for 7 days followed by co-administration of aspirin 100 mg and simvastatin 40 mg for 7 days once daily. A series of blood samples were collected before and till 24hours after drug administration on Day 1 (single-dose of aspirin), Day 7 (multiple-dose of aspirin) and Day 14 (multiple-dose of aspirin and simvastatin). The effects of simvastatin on pharmacokinetics of acetylsalicylic acid and salicylic acid were assessed with the 90 % confidence intervals (CIs) of thegeometric mean ratios (GMRs) of Day 14 over Day 7 for maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC0-24). Pharmacodynamics was assessed with maximal changes of platelet aggregation from baseline. RESULTS: Twenty-fourhealthy men aged 20 to 36 years were enrolled and 23 of them completed the study. GMRs (90 % CIs) of Cmax and AUC0-24 for acetylsalicylic acid were 1.21 (1.04 - 1.42) and 1.28 (1.19 - 1.38), respectively. For salicylic acid, GMRs of Cmax and AUC0-24 were 0.96 (0.91 - 1.00) and 1.00 (0.97 - 1.04), respectively. Maximal changes of platelet aggregation on Day 7 and Day 14 from baseline were not significantly different (p=0.41); 87.5 +/- 8.8 % and 87.3 +/- 9.2 %, respectively. CONCLUSION: Coadministration of simvastatin slightly increased the systemic exposure of acetylsalicylic acid with no changes of systemic exposure of salicylic acid or inhibition of platelet aggregation.
Aged ; Aspirin ; Cardiovascular Diseases ; Drug Interactions ; Humans ; Male ; Plasma ; Platelet Aggregation ; Salicylic Acid ; Simvastatin

The Korean Society for the Study of Obesity (KSSO) has defined the waist circumference cutoff value of central obesity as 90 cm for men and 85 cm for women. The purpose of this investigation was to determine the corresponding waist circumference values. A total of 3,508 persons in the Korean Rural Genomic Cohort Study were enrolled in this survey. Receiver operating characteristic (ROC) curve analysis was used to find appropriate waist circumference cutoff values in relation to insulin resistance determined by homeostasis model assessment for insulin resistance (HOMA-IR), body mass index (BMI), and components of metabolic syndrome. The optimal waist circumference cutoff values were 87 cm for men and 83 cm for women by ROC analysis to HOMA-IR and 86 cm for men and 83 cm for women by ROC analysis to value with more than two components of metaobolic syndrome. By using a BMI > or =25 kg/m2, 86 cm for men and 82 cm for women were optimal waist circumference cutoff values. In this study, we suggest that the most reasonable waist circumference cutoff values are 86-87 cm for men and 82-83 cm for women.
Cohort Studies ; Diagnosis, Computer-Assisted/*methods ; Female ; *Health Status Indicators ; Humans ; Korea/epidemiology ; Male ; Metabolic Syndrome X/*diagnosis/*epidemiology ; Middle Aged ; Physical Examination/methods/statistics & numerical data ; Prevalence ; Reproducibility of Results ; Risk Assessment/methods ; Risk Factors ; Rural Population/*statistics & numerical data ; Sensitivity and Specificity ; *Waist Circumference