Recent Advances in Noncardiac Chest Pain in Korea

Gastroesophageal reflux disease (GERD) is the most common cause of noncardiac chest pain (NCCP) and is present in up to 60% of patients with NCCP in Western countries. In Korea, after a reasonable cardiac evaluation, GERD is reported to underlie 41% of NCCP cases. Typical reflux symptoms are frequent in Korean patients suffering from NCCP. Therefore, a careful history of the predominant symptoms, including heartburn and acid regurgitation, is relatively indicative of the GERD diagnosis in Korea. In Korea, in contrast to Western countries, patients aged 40 years and over who have been diagnosed with NCCP but who are without alarming features should undergo endoscopy to exclude gastric cancer or peptic ulcers because of the higher prevalence of peptic ulcer disease and gastric cancers in the region. In a primary care setting, in the absence of any alarming symptoms, a symptomatic response to a trial of a proton pump inhibitor (PPI) is sufficient for the presumptive diagnosis of GERD. In addition, the optimal duration of a PPI test may be at least 2 weeks, as GERD symptoms tend to be less frequent or atypical in Korean patients than in patients from Western countries. In patients diagnosed with GERD-related NCCP, long-term therapy (more than 2 months) with double the standard dose of a PPI is required to alleviate symptoms. Esophageal dysmotility is relatively uncommon, and pain modulators seem to offer significant improvement of chest pain control in non-GERD-related NCCP. Most traditionally available tricyclics or heterocyclics have many undesirable effects. Therefore, newer drugs with fewer side effects (for example, the serotonin - norepinephrine reuptake inhibitors) may be needed.

No Association between the Response to the Addition of an Atypical Antipsychotic Drug to an Selective Serotonin Reuptake Inhibitor or Serotonin Norepinephrine Reuptake Inhibitor and the Brain-Derived Neurotrophic Factor (Val66Met) Polymorphism in Refracto

OBJECTIVE: This study examined the association between the brain-derived neurotrophic factor (BDNF) (Val66Met) polymorphism and the response to the addition of an atypical antipsychotic drug to a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) in treatment-refractory depression. METHODS: The study enrolled 64 patients meeting the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for major depressive disorder who were treated with at least two courses of a single antidepressant, but who had Hamilton Depression Rating Scale (HAMD-17) scores > or =15 points that were reduced less than 50% over at least a 4-week treatment period. There were 24 males and 40 females (age range 27-68 years; mean+/-SD, 48+/-13 years). The patients' clinical improvement was evaluated using the HAMD-17. Patients with at least a 50% decrease in the HAMD-17 score were defined as responders. Serum BDNF levels were assayed using enzyme-linked immunosorbent assays and the presence of the BDNF (Val66Met) polymorphism was determined using the TaqMan genotyping assay. RESULTS: No correlation was found between the BDNF (Val66Met) polymorphism and a positive response to adding an atypical antipsychotic drug. No differences were observed in the changes in the serum BDNF levels and HAMD-17 scores between Val66Val and Met-carriers. In addition, in patients who experienced remission, the atypical antipsychotic drug was discontinued after at least 3 months of treatment and the patients were then followed for 1 year; 14 of 27 patients (52%) relapsed within 1 year. CONCLUSION: These results suggest that the BDNF (Val66Met) polymorphism is not associated with the response to the augmentation of a SSRI or SNRI with an atypical antipsychotic drug, and that the combination of an atypical antipsychotic drug and a SSRI or SNRI should be continued for 3 months or more in refractory depressed patients in the Japanese population.

The Effect of Initial Duloxetine Dosing Strategy on Nausea in Korean Patients with Major Depressive Disorder

OBJECTIVE: To assess the relative severity of nausea in patients from Korea with major depressive disorder (MDD) who were treated with duloxetine at low (30 mg) or high (60 mg) doses, with or without food, for the first week of an 8 week treatment. METHODS: Adult patients (n=249), with MDD and a 17-item Hamilton Rating Scale for Depression (HAMD17) score of > or =15, received open-label once daily duloxetine. At Week 0, patients were randomized to 4 groups: 30 mg with food (n=63), 60 mg with food (n=59), 30 mg without food (n=64), and 60 mg without food (n=63). At Week 1, all patients switched to duloxetine 60 mg for 7 weeks. The primary outcome measure was item 112 (nausea) of the Association for Methodology and Documentation in Psychiatry adverse event scale. Effectiveness was assessed by change in HAMD17 total score. RESULTS: Overall, 94.4% (235/249) of patients completed Week 1 and 55.0% (137/249) of patients completed the study. For Week 1, nausea was significantly less severe for patients who received 30 mg compared with 60 mg duloxetine (p=0.003), regardless of food intake. In all groups, nausea severity was highest at Week 1 and declined throughout the study. HAMD17 score was reduced in all groups and the most common adverse event reported was nausea (145/249; 58.2%). CONCLUSION: To minimize nausea, Korean patients with MDD who require duloxetine treatment could be given 30 mg once daily, regardless of food, for the first week followed by 60 mg once daily for the course of therapy.

SSRIs and SNRIs for Management of Hot Flushing / 대한폐경학회지

For postmenopausal women who fear hormone therapy, women 60 years of age with continuous, severe hot flushing or women with a history of breast cancer, we should consider selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs) as therapeutic agents. Base on the results from a meta-analysis and clinical trials regarding hot flushing, paroxetine and the conetrolled-release formultation of paroxetine have been shown to effectively reduce hot flushing by 30~40% and 60~70%, respectively, and 13~41% more reductions as compared to placebo. Venlafaxine reduced hot flushes by 30~60% (133% reductions compared to placebo), and desvenlafaxine reduced hot flushes by 30~70%. Fluoxetine and citalopram were shown to be less effective than paroxetine and venlafaxine, by 20% (113% reductions compared to placebo) and 40~50%, respectively. Sertraline reduced hot flushes 3~18% compared to the placebo group, but was considered ineffective. Citalopram (20 mg), paroxetine (10 mg), venlafaxine (37.5~150 mg), and desvenlafaxine (100~200 mg) not only reduced vasomotor symptoms, but demonstrated additional beneficial outcomes with respect to sleep disturbances, mood, the vigor index, and improved quality of life. Citalopram (20 mg), fluoxetine (20 mg), paroxetine (10 mg), venlafaxine (75~150 mg), and desvenlafaxine (150 mg) are recommended at the corresponding doses after weighing the risks and benefits of these medications. SSRIs and SNRIs were shown to interrupt the conversion of tamoxifen into the active metabolite, endoxifen, and thus SSRIs and SNRIs must not be used in breast cancer patients who are taking tamoxifen. Paroxetine suppressed vasomotor symptoms most potently, followed by fluoxetine, sertraline, citalopram, and venlafaxine.