Korean Guidelines for the Pharmacological Treatment of Social Anxiety Disorder: Initial Treatment Strategies

OBJECTIVE: The aim of the present study was to provide clinical consensus and evidence regarding initial treatment strategies for the pharmacological treatment of social anxiety disorder (SAD) in Korea. METHODS: We prepared a questionnaire to derive a consensus from clinicians regarding their preference for the pharmacological treatment of SAD in Korea. Data regarding medication regimens and psychotropic drugs used during initial treatment, the doses used, and the pharmacological treatment duration were obtained. Responses were obtained from 66 SAD experts, and their opinions were classified into three categories (first-line, second-line, third-line) using a chi-square analysis. RESULTS: Clinicians agreed upon first-line regimens for SAD involving monotherapy with selective serotonin reuptake inhibitors (SSRIs) or the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine, or combined therapy using antidepressants with betablockers or benzodiazepines on a standing or as-needed basis. First-line psychotropic drug choices for initial treatment included the following: escitalopram, paroxetine, sertraline, venlafaxine, and propranolol. The medication dosage used by domestic clinicians was found to be comparable with foreign guidelines. Domestic clinicians tended to make treatment decisions in a shorter amount of time and preferred a similar duration of maintenance treatment for SAD when compared with foreign clinicians. CONCLUSION: This study may provide significant information for developing SAD pharmacotherapy guidelines in Korea, especially in the early stage of treatment.

The Effect of Anti-reflux Therapy on Patients Diagnosed with Minor Disorders of Peristalsis in High-resolution Manometry / 대한소화기학회지

BACKGROUND/AIMS: Minor disorders of peristalsis are esophageal motility disorders categorized by the Chicago Classification (CC), version 3.0, which was announced in 2014. This study evaluated the efficacy of anti-reflux therapy in patients with minor peristaltic disorders. METHODS: Patients with minor peristaltic disorders in accordance with CC v3.0 were included. We reviewed the medical records of patients with esophageal high-resolution manometry findings, and investigated the demographic and clinical information as well as the medical therapy. Thereafter, the response to treatment was assessed after at least 4 weeks of treatment. RESULTS: A total of 24 patients were identified as having minor disorders of peristalsis from January 2010 to December 2015. The mean follow-up period was 497 days, and there were 17 patients (70.8%) patients with ineffective esophageal motility. In terms of anti-reflux therapy, proton pump inhibitors (PPIs) with prokinetic agents and PPIs alone were prescribed in 19 patients (79.2%) and 5 patients (20.8%), respectively. When the rate of response to the treatment was assessed, the responders rate (complete+satisfactory [≥50%] responses) was 54.2% and the non-responders rate (partial [<50%]+refractory responses) was 45.8%. Patients in the responder group were younger than those in the non-responder group (p=0.020). Among them, 13 patients underwent 24-hour multichannel intraluminal impedance-pH, and 10 patients (76.9%) were pathologic gastroesophageal reflux. CONCLUSIONS: The majority of esophageal minor peristaltic disorders were accompanied by gastroesophageal reflux, and therefore, they might respond to acid inhibitor. Further well-designed, prospective studies are necessary to confirm the effect of anti-reflux therapy in these patients.

The significance of blood pressure variation and metabolic risk factors in patients with different stages of hypertension / 고신대학교의과대학학술지

OBJECTIVES: Blood pressure variation (BPV) and metabolic syndrome is an independent risk factor for cardiovascular events. Ambulatory blood Pressure (ABP) has been shown to be more closely related to cardiovascular events in hypertensive patients than conventional office BP (OBP). Using both OBP and ABP, 4 groups of patients were identified: (1) normotensive patients (NT); (2) white coat hypertensives (WCHT); (3) masked hypertensives (MHT); and (4) sustainedhypertensives (SHT). We investigated the significance of BPV and metabolic risks of these 4 groups. METHODS: This study is a retrospective analysis of patients between January 2008 and May 2013. Echocardiography and 24 hour ABP monitoring were performed. RESULTS: BMI was significantly higher in the MHT compared with the NT. There were progressive increases in fasting glucose level from NT to WCHT, MHT, and SHT.MHT and SHT had higher 24h and nighttime BPV than NT.MHT was significantly related with BMI (r = 0.139, P = 0.010), creatinine (r = 0.144, P = 0.018), fasting glucose (r = 0.128, P = 0.046), daytime systolic BPV (r = 0.130, P = 0.017), and daytime diastolic BPV (r = 0.130, P = 0.017). Dyslipidemia (r = 0.110, P = 0.043), nighttime systolic BPV (r = 0.241, P < 0.001) and nighttime diastolic BPV (r = 0.143, P = 0.009) shown correlation with SHT. In multivariate logistic regression, MHT was independently associated with Body mass index (OR 1.086, 95% CI 1.005–1.174, P = 0.038) and creatinine (OR 1.005, 95% CI 1.001–1.010, P = 0.045). CONCLUSIONS: BPV and metabolic risk factors were found to be greater in MHT and SHT compared with NT and WCHT. This suggests that BPV and metabolic risks may contribute to the elevated cardiovascular risk observed in patients with MHT and SHT.

Obesity and Insulin Resistance According to Age in Newly Diagnosed Type 2 Diabetes Patients in Korea / 고신대학교의과대학학술지

OBJECTIVES: With the rapid increase in the prevalence of diabetes, the age groups of diabetic patients are becoming diversified. This study will examine the degree of obesity, insulin resistance, and insulin secretion ability among patients first diagnosed with diabetes according to age and gender. METHODS: The subjects of this study included 616 patients who were first diagnosed with diabetes during a routine physical examination. This sample was obtained from a total of 28,075 adults aged 19 years and older who received the examination among 33,829 participants in the Korea National Health & Nutrition Examination Survey (KNHANES) from 2007–2010. The subjects were categorized by age into young age (age: 19 – 39 years), middle age (age: 40 – 59 years), and old age (age: 60 years and older). The degree of obesity was categorized according to body mass index (BMI) into normal weight (BMI: 18.5 ~ 22.9), overweight (BMI: 23 ~ 24.9), and obesity (BMI: 25 or above). Insulin resistance was evaluated by homeostatic model assessment of insulin resistance (HOMA-IR). RESULTS: It was found that 14.1% (n = 87) of a total of 616 subjects (324 men, 292 women) were in the young age group, 43.8% (n = 270) were in the middle age group, and 42.1% (n = 259) were in the old age group. In addition, 83.3% of men that were overweight or obesity were in the young age group, while 79.2% and 60.5% were in the middle age and old age groups, respectively. A total of 82.2% of women that were overweight or obesity were in the young age group, while 79.5% and 77% were in the middle age and old age groups, respectively. For men, the more obesity they were in all age groups, the higher their HOMA-IR. For women, the more obesity they were in the young age and middle age groups, the higher their HOMA-IR; however, women in the old age group showed the highest HOMA-IR when they were of normal weight. CONCLUSION: Among diabetic patients first diagnosed with the disease in Korea, the youth population had the highest obesity rate. Insulin resistance increases as an individual's weight increases among those patients who are first diagnosed with diabetes; the only exception noted is for elderly women.

Serotonin Transporter and COMT Polymorphisms as Independent Predictors of Health-related Quality of Life in Patients with Panic Disorder

There is growing evidence of poor health-related quality of life (HRQOL) in patients with panic disorder (PD). However, little is known about the factors affecting HRQOL in patients with PD. The authors examined whether 5-HTTLPR tri-allelic approach and Cathechol-O-methyltransferase (COMT) Val(158)Met polymorphism can predict HRQOL in patients with PD controlling for sociodemographic factors and disorder-related symptom levels. The sample consisted of 179 patients with PD consecutively recruited from an outpatient clinic and age- and gender ratio-matched 110 healthy controls. The SF-36 was used to assess multiple domains of HRQOL. Hierarchical multiple regression analysis was performed to determine the independent effect of the 5-HTTLPR and COMT Val(158)Met on the SF-36 in panic patients. Patients with PD showed lowered HRQOL in all sub-domains of the SF-36 compared to healthy controls. The 5-HTTLPR independently and additively accounted for 2.2% of variation (6.7% of inherited variance) of perceived general health and the COMT Val(158)Met independently and additively accounted for 1.5% of variation (5.0% of inherited variance) of role limitation due to emotional problems in patient group. The present study suggests that specific genetic polymorphisms are associated with certain domains of HRQOL and provides a new insight on exploring the factors that predict HRQOL in patients with PD.

Effectiveness of Duloxetine Monotherapy Compared to Combination Therapy with Other Antidepressants in Patients with Major Depressive Disorder: A Short-Term, Retrospective Study

OBJECTIVE: The purpose of this study was to compare duloxetine monotherapy to combination therapy with other antidepressants in patients with major depressive disorder in a clinical, real world setting. METHODS: An eight-week, retrospective, multi-center study of outpatients with major depressive disorder was undertaken. After screening 415 patients, enrolled in this study from July 2009 to June 2014 were 82 patients from among three centers who had been taking duloxetine with or without other antidepressant and not administered with atypical antipsychotics. We compared the mean changes of the Clinical Global Impression-Severity Scale (CGI-S) as a primary measure and the discontinuation rate as a secondary measure between the duloxetine monotherapy group (n=36, 43.9%) and the combination therapy with other antidepressants group (n=46, 56.1%) at baseline, one, two, four and eight weeks. RESULTS: There were no significant differences across the demographic characteristics between two groups. There was, however, a statistically greater improvement on the CGI-S at weeks 2, 4 and 8 in the combination group compared with the monotherapy group. There were no significant differences in discontinuation rate and adverse events between two groups. No serious adverse events were reported in both groups during the study period. CONCLUSION: This result suggests that the duloxetine combination therapy with other antidepressants could improve effectiveness and have comparable tolerability with the monotherapy in the treatment of outpatients with major depressive disorders in a naturalistic setting. Adequately powered, well-controlled clinical trials are strongly warranted to confirm our findings due to methodological shortcomings.

A Case of Improved Leukocytoclastic Vasculitis after Successful Treatment of Hepatocellular Carcinoma and Membranous Obstruction of Inferior Vena Cava

Vasculitis is a heterogeneous group of diseases that destroy blood vessel walls by inflammation. Approximately half of vasculitis cases are idiopathic, but sometimes associated with genetic factors, medicines, chronic infection, autoimmune diseases, and malignancies. Although the mechanism remains unclear, vasculitis secondary to malignancy, also known as paraneoplastic vasculitis, has been reported. It is generally associated with hematologic malignancies rather than solid malignancies and commonly presents as leukocytoclastic vasculitis or polyarteritis nodosa. We experienced a case of leukocytoclastic vasculitis in a patient with hepatocellular carcinoma and membranous obstruction of the inferior vena cava. Here, we report this case with a brief review of literature.

Two Cases of Hypersexuality Probably Associated with Aripiprazole

Sexual dysfunction is a common side effect in patients treated with antipsychotics but significant differences exist across different compounds. We report hypersexuality symptoms in two female patients with schizophrenia who were receiving treatment with aripiprazole. The patients experienced more frequent sexual desire and greater sexual preoccupation after taking aripiprazole. We discuss the potential neuro-chemical mechanisms for this and argue that aripiprazole's unique pharmacological profile, partial agonism with high affinity at dopamine D2-receptor, may have contributed to the development of these symptoms.

Clinical Significance of National Patients Sample Analysis: Factors Affecting Mortality and Length of Stay of Organophosphate and Carbamate Poisoned Patients / 대한의료정보학회지

OBJECTIVES: This study considered whether there could be a change of mortality and length of stay as a result of inter-hospital transfer, clinical department, and size of hospital for patients with organophosphates and carbamates poisoning via National Patients Sample data of the year 2009, which was obtained from Health Insurance Review and Assessment Services (HIRA). The utility and representativeness of the HIRA data as the source of prognosis analysis in poisoned patients were also evaluated. METHODS: Organophosphate and carbamate poisoned patients' mortality and length of stay were analyzed in relation to the initial and final treating hospitals and departments, as well as the presence of inter-hospital transfers. RESULTS: Among a total of 146 cases, there were 17 mortality cases, and the mean age was 56.8 +/- 19.2 years. The median length of stay was 6 days. There was no inter-hospital or inter-departmental difference in length of stay. However, it significantly increased when inter-hospital transfer occurred (transferred 11 days vs. non-transferred 6 days; p = 0.037). Overall mortality rate was 11.6%. The mortality rate significantly increased when inter-hospital transfer occurred (transferred 23.5% vs. non-transferred 7.0%; p = 0.047), but there was no statistical difference in mortality on inter-hospital and inter-department comparison at the initial treating facility. However, at the final treating facility, there was a significant difference between tertiary and general hospitals (5.1% for tertiary hospitals and 17.3% for general hospitals; p = 0.024), although there was no significant inter-departmental difference. CONCLUSIONS: We demonstrated that hospital, clinical department, length of stay, and mortality could be analyzed using insurance claim data of a specific disease group. Our results also indicated that length of stay and mortality according to inter-hospital transfer could be analyzed, which was previously unknown.

The Effects of 5-HTR1A Polymorphism on Cingulum Connectivity in Patients with Panic Disorder

OBJECTIVE: Serotonin-1A receptors (5-HTR1A) is suggested to be involved in the etiology of several psychiatric disorders including panic disorder (PD). A few imaging studies have suggested the alterations of the cingulum bundle in PD. The objective of this study is to examine the structural changes of cingulum related to the 5-HTR1A polymorphism rs6295 in the patients with PD. METHODS: Thirty-two right-handed patients with PD [11 men, 21 women; 40.34+/-13.17 (mean+/-SD) age] who met the diagnostic criteria in Structured Clinical Interview for DSM-IV were examined by means of MRI at 3 Tesla. We divided the patients with PD into CC genotype group and non CC genotype group (GG/CG genotype group) of the 5-HTR1A rs6295 polymorphism to compare the cingulum white matter connectivity. RESULTS: Tract-based spatial statistics showed significantly increased fractional anisotropy (FA) values in cingulate gyrus process of left cingulum in 5-HTR1A CC genotype compared to GG/CG genotype in PD. Significant positive correlations were shown between the Albany Panic and Phobia Questionnaire (APPQ) interoceptive fear subscale scores, the Anxiety Sensitivity Inventory-Revised fear of publicly observable anxiety reaction subscale scores and FA values of cingulate gyrus process of left cingulum in 5-HTR1A rs6295 GG/CG genotype group. In CC genotype group, APPQ total, APPQ agoraphobia subscale and APPQ social phobia subscale scores also showed significant positive correlations with FA values of hippocampal process of right cingulum. CONCLUSION: This preliminary study suggests that 5-HTR1A polymorphism may be associated with the cingulum white matter connectivity in PD.

Factors Associated with Treatment Outcomes in Mindfulness-Based Cognitive Therapy for Panic Disorder

PURPOSE: Although the effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) for panic disorder (PD) has been studied previously, data on the predictors of treatment outcomes in MBCT for PD are scarce. MATERIALS AND METHODS: Eighty patients with PD were screened to analyze treatment outcomes such as MBCT completion, treatment response, and remission after undergoing MBCT for PD. Sociodemographic characteristics, comorbid personality disorders, and baseline medication doses were examined. The study administered the Panic Disorder Severity Scale, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale and Anxiety Sensitivity Inventory-Revised to patients at baseline and at eight weeks. RESULTS: Sixty-five participants were enrolled in the present study. Comorbid personality disorder was significantly associated with MBCT non-completion. We found that anxiety sensitivity (AS) improvement after an eight week MBCT program was a statistically significant factor associated with treatment response. Using logistic regression analysis, AS improvement after MBCT showed significant association with PD remission after MBCT. CONCLUSION: Comorbid personality disorders of participants could be a potential predictor of MBCT non-completion. Furthermore, AS improvement after MBCT may predict treatment response and remission after MBCT for PD. However, better designed studies with a larger number of patients are needed to confirm our findings.

Korean Medication Algorithm Project for Generalized Anxiety Disorder 2009 (II) : Medication Algorithm & Long-Term Medication Treatment Strategy / 신경정신의학

OBJECTIVES: This study was performed to investigate the consensus about medication algorithms, including long-term medication treatment strategies, in the treatment of generalized anxiety disorder (GAD). METHODS: The executive committee of the Korean Medication Algorithm Project for GAD developed questionnaires about the psychopharmacologic treatment strategies for patients with GAD. Fifty-five (65%) of 84 experts of a reviewing committee answered the questionnaires. The consensus of expert opinion was classified into three categories, and the treatments of choice were selected by use of 95% confidence intervals and chi-square-tests. RESULTS: The consensus on the first-line treatment strategy for GAD was as follows. Step 1 is the use of the one of a selective serotonin reuptake inhibitor (SSRI), a serotonin and noradrenaline reuptake inhibitor (SNRI) and buspirone for at least four to six weeks. Step 2 is to switch from a SSRI to a SNRI or buspirone or vice versa. Step 3 is to augment medication with an atypical antipsychotic or add a benzodiazepine or antihistamine. Step 4 is to switch to another combination, which includes a SSRI, a SNRI, mirtazapine or a tricyclic antidepressant Step 6 is to review the diagnosis, and 'benzodiazepines including clonazepam and alprazolam can be combined with another drug even from the initial period'. In terms of long-term medication treatment, the consensus first-line tr-eatment strategy involved the use of venlafaxine XR, escitalopram, fluoxetine, paroxetine CR, sertraline and buspirone. CONCLUSION: This study provided information about the consensus among Korean experts regarding medication algorithms, including long-term medication treatment strategies, in the treatment of GAD.