• 생물정신의학
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• 제8권1호
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• pp.37-46
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• 2001

Whenever a clinician manages the patients with depression, he may meet various problems that make it difficult to treat them. Even though he has good skills and knowledge about depression, some barriers will be appear during his practice. In general, the difficulties in treating depression are treatment-resistance, adverse effects of antidepressants, pregnancy in female patients, comorbid medical conditions, poor compliance, drug-drug interactions, and so on, which are related with pharmacological treatments. Here, only the two of them, the treatment-resistant depression and difficult problems concerned with pregnancy, were discussed. Some level of treatment resistance is the norm rather than the exception. As the treatment failure stems from inadequate treatment, it is important that the clinician should prescribe medications with sufficient doseage and adequate duration. And to overcome the treatment resistant depression the polypharmacy is necessary, in that case, the side effects and toxicities should be explored and managed immediately. So the clinician have to learn more about the pharmacokinetic and pharmacodynamic mechanisms of each drugs used in treatment of depression. When the risk of the fetus by the exposure is higher than the risk of untreated maternal psychiatric disorder, psychotropic medications should be used during pregnancy. Women who are maintained on psychotropics and become pregnant, as well as women with the new onset of psychiatric symptoms during pregnancy, should be carefully reassessed. However, data concerning the potential risk of long-term behavioral changes following prenatal exposure to psychotropics is rare, so further longitudinal follow-up studies are needed.

• 생물정신의학
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• 제23권1호
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• pp.1-11
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• 2016

Development of various antidepressants such as monoamine oxidase inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressant has led to a tremendous progression of pharmaceutical treatment for depression, but still there are some limitations of current antidepressants, such as treatment-resistant depression and delayed onset of antidepressants. The pathogenesis of depression is unclear because depression is a heterogeneous disease state, and the mechanisms of antidepressants remain uncertain as well. Nevertheless, in an attempt to develop novel antidepressants, some trials have been conducted based on the potential biological mechanism discovered in the numerous research results. This review will provide information about the potential novel antidepressants and the current states of clinical studies using them. In particular, some potential novel antidepressants anti-inflammatory agents, antioxidants, anticholinergics, modulators of Hypothalamic Pituitary Adrenal Axis, glutamate, and opioid systems, as well as some neuropeptides such as susbstance P, neuropeptide Y, and galanin will be discussed.

• 생물정신의학
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• 제23권2호
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• pp.37-40
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• 2016

Treatment-resistant depression (TRD) is a major public health problem. It is estimated that about 30% of patients with major depressive disorder do not show substantial clinical improvement to somatic or psychosocial treatment. Most of studies for TRD have focused on the subjects already known as TRD. Patients with unipolar depressive episodes that do not respond satisfactorily to numerous sequential treatment regimens were included in the TRD studies. Such post hoc experimental design can be regarded only as consequences of having TRD, rather than as causal risk factors for it. Although informative, data derived from such studies often do not allow a distinction to be made between cause and effect. So, we should shift paradigm toward examining the risk for developing TRD in untreated depressed patients. To deal with this problem, untreated depressed patients should be enrolled in the study to identify biological markers for treatment resistance. The peripheral or central biological markers should be explored before starting treatment. Subsequent systematic administration of treatments with appropriate monitoring in the subjects can determine the risk for developing treatment resistance in untreated individuals. Such information could give a cue to improve the initial diagnosis and provide more effective treatment for TRD.

• Journal of Yeungnam Medical Science
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• 제36권3호
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• pp.249-253
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• 2019

There is considerable overlap in the clinical presentations of apathy and depression. However, differential diagnosis between apathy and other psychiatric conditions, including depression and dementia, is important. In this report, we present the case of a 67-year-old woman with a history of receiving selective serotonin reuptake inhibitor (SSRI) treatment for depression. Differential diagnosis between treatment-resistant depression and SSRI-induced apathy syndrome was required. The symptoms of her apathy syndrome were relieved after the discontinuation of SSRIs and the addition of olanzapine, methylphenidate, and modafinil. Furthermore, we briefly review related literature in this article.

• 생물정신의학
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• 제26권2호
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• pp.39-46
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• 2019

Antidepressants are widely used to treat depression in Korea, however, only a few studies have focused on the provider of the treatment. The aim of the study is to compare the differences between patients who were prescribed antidepressants by psychiatrists and those who were prescribed antidepressants by non-psychiatrists in South Korea. Patients with a diagnosis of depressive disorder who had been newly prescribed antidepressants in 2012 were selected from the Health Insurance Review and Assessment Service database. They were classified into two groups depending on whether they received the antidepressant prescription from a psychiatrist or non-psychiatrist. Sociodemographic, clinical, and depression related cost has been investigated. Treatment resistant depression, which is defined as a failure of two antidepressant regimens to alleviate symptoms, was also investigated. Prescription adequacy was assessed based on whether a regimen was maintained for at least 4 weeks. Among the 834694 patients with pharmaceutically treated depression (PTD) examined in this study, 326122 (39.1%) were treated by psychiatrists. Patients who were treated by psychiatrists were younger and had more psychiatric comorbidities than those treated by non-psychiatrists. They had longer PTD duration (229.3 days vs. 103.0 days, p < 0.05) and a larger proportion of treatment resistant depression (9.3% of PTD) when compared to those patients treated by non-psychiatrists. The patients treated by psychiatrists had a smaller proportion of inadequate antidepressant use compared to those patients in the non-psychiatrist group (44.5% vs. 65.1%, p < 0.05). The costs related to depression corrected with PTD duration were higher in the non-psychiatrist group (32214 won vs. 56001 won, p < 0.05). Patients who receive antidepressants from psychiatrists are patients with more severe, treatment-resistant depression. Psychiatrists prescribe antidepressants more adequately and cost- effectively than non-psychiatrists.

• 생물정신의학
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• 제16권3호
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• pp.170-180
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• 2009

Objectives : To assess clinical improvement and change in plasma brain-derived neurotrophic factor(BDNF) level after repetitive transcranial magnetic stimulation(rTMS) in patients with treatment-resistant schizophrenia. Methods : Seven patients with DSM-IV schizophrenia, who were proven to be treatment-resistant, were treated with 15 sessions of rTMS for three weeks as an adjuvant therapy to antipsychotic treatment. Clinical improvement and change in plasma BDNF level were measured after the treatment period. The symptom severity was assessed with the Positive and Negative Syndrome Scale(PANSS) and the Korean Version of Calgary Depression Scale for Schizophrenia(K-CDSS) at baseline and 7 days after the treatment. Plasma BDNF level was measured by enzyme-linked immunosorbent assay(ELISA) at baseline and 7 days after the treatment. Results : After the rTMS treatment, there was no significant improvement in PANSS total score(Z=-1.693, p=0.090) and no significant change in plasma BDNF was found(Z=-1.183, p=0.237). Negative correlations were found between percentage change in PANSS positive subscale score and duration of illness(rho=-0.991, N=7, p<0.0005, two-tailed), and PANSS negative subscale score at baseline and percentage change in plasma BDNF level(rho=-0.821, N=7, p=0.023, two-tailed). Conclusion : This preliminary study suggests that rTMS didn't make a significant change in clinical symptoms nor in plasma BDNF level in treatment-resistant schizophrenia. Percentage change in plasma BDNF, however, might be correlated with treatment resistance in schizophrenic patients. This is a pilot study with a small sample size, therefore, a further study with a larger sample size is needed.

• Biomolecules & Therapeutics
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• 제31권2호
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• pp.161-167
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• 2023

Despite the various medications used in clinics, the efforts to develop more effective treatments for depression continue to increase in the past decades mainly because of the treatment-resistant population, and the testing of several hypotheses- and target-based treatments. Undesirable side effects and unresponsiveness to current medications fuel the drive to solve this top global health problem. In this study, we focused on neuroinflammatory response-mediated depression which represents a cluster of depression etiology both in animal models and humans. Several meta-analyses reported that proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were increased in major depressive disorder patients. Inflammatory mediators implicated in depression include type-I interferon and inflammasome pathways. To elucidate the molecular mechanisms of neuroinflammatory cascades underlying the pathophysiology of depression, we introduced hycanthone, an antischistosomal drug, to check whether it can counteract depressive-like behaviors in vivo and normalize the inflammation-induced changes in vitro. Lipopolysaccharide (LPS) treatment increased proinflammatory cytokine expression in the murine microglial cells as well as the stimulation of type I interferon-related pathways that are directly or indirectly regulated by Janus kinase-signal transducer and activator of transcription (JAK-STAT) activation. Hycanthone treatment attenuated those changes possibly by inhibiting the JAK-STAT pathway and inflammasome activation. Hycanthone also ameliorated depressive-like behaviors by LPS. Taken together, we suggest that the inhibitory action of hycanthone against the interferon pathway leading to attenuation of depressive-like behaviors can be a novel therapeutic mechanism for treating depression.

• 생물정신의학
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• 제22권4호
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• pp.149-154
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• 2015

Mood disorder is a common psychiatric illness with a high lifetime prevalence in the general population. Many prescribed antidepressants modulate monoamine neurotransmitters including serotonin, norepinephrine and dopamine. There has been greater focus on the major excitatory neurotransmitter in the human brain, glutamate, in the pathophysiology and treatment of major depressive disorder (MDD). Recently, ketamine, an N-methyl-D-aspartate receptor antagonist, has received attention and has been investigated for clinical trials and neurobiological studies. In this article, we will review the clinical evidence for glutamatergic dysfunction in MDD, the progress with ketamine as a rapidly acting antidepressant, and other N-methyl-D-aspartate receptor antagonist for treatment-resistant depression.

• 신경정신의학
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• 제57권2호
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• pp.119-132
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• 2018

Despite the fact that pharmacotherapy depressive disorders have proven efficacy, a substantial number of patients are resistant to conventional management. As neuroscientific research about pathophysiology of depression have accumulated, repeated transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have emerged as an important mechanism-based treatment modality. This overview provides a review of therapeutic application of rTMS and tDCS in patients with depression. The clinical and basic studies of rTMS and tDCS in depression were reviewed and integrated using a literature review and interview with experts. rTMS is a noninvasive procedure of a localized pulsed magnetic field to the surface of the head to cause a depolarization of neurons in the brain cortex. tDCS has a mechanism of modulating cortical excitability in a polarity-specific manner without eliciting action potentials. rTMS and tDCS seem promising for treating depression. Although therapeutic parameters and further technical improvement remain to be systematically investigated, rTMS and tDCS would be a safe and effective intervention to treat depression.

• Tuberculosis and Respiratory Diseases
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• 제82권3호
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• pp.217-226
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• 2019

Background: Depression is a recognized complication of lung cancer underreported in developing countries such as Malaysia. Treating and identifying depression in cancer patients increases survival and quality of life. Our objectives are to study prevalence of depressive symptoms in newly diagnosed lung carcinoma, and examine the relationship of depressive symptoms with other influencing risk factors. Methods: A 2-year, cross sectional study February 2015-February 2017, was conducted at Hospital Tengku Ampuan Afzan, and Penang General Hospital. One hundred and three patients with newly diagnosed, biopsy confirmed primary lung carcinoma were recruited. Self-rated patient's identification sheet, validated Center for Epidemiologic Studies Depression (CES-D), and Dukes University Religion Index score from three different main languages were used. Results: Prevalence of current depressive symptoms (CES-D total score ${\geq}16$) is 37.9%. The result suggests prevalence of those at high risk of moderate to major depression, may need treatment. Multivariate analysis reveals those with good Eastern Cooperation Oncology Group factor (${\eta}2=0.24$, p<0.001) married (${\eta}2=0.14$, p<0.001) with intrinsic religiosity (IR) (${\eta}2=0.07$, p<0.02) are more resistant to depression. Conclusion: One in three of lung carcinoma patients, are at increased risk for depression. Clinicians should be aware that risk is highest in those with poor performance status, single, and with poor IR. We suggest routine screening of depression symptoms as it is feasible, to be performed during a regular clinic visit with immediate referral to psychiatrist when indicated.