• Journal of Oriental Neuropsychiatry
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• v.30 no.2
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• pp.71-88
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• 2019

Objectives: The present study aims to review the antidepressant effect of herbal medicines reported in Korean local journals. Methods: We searched in electronic databases (Koreantk, KISS, OASIS, NDSL) for studies, published in Korean national journals, that assessed herbal medicine effect of depression model. The search term was 'depression' in the abstract or whole text. Depression model, herbal material, experimental results, mechanisms were extracted. Results: We included 43 articles in which 38 studies were in vitro experiments, and the rest 5 were in vivo experiments. The most common experiment subject model was a rat and the most widely used method to induce depression was Despair behavior test. 21 studies used simple herbal medicines, and 22 studies used complex herbal medication. Glycyrrhizae Radix was the most commonly used herbal material to improve depression model. The most common mechanisms of herbal medicine with antidepressant effect were inhibition of Monoamine activation mechanism and depression related neurohormone secretion. Conclusions: Herbal medicines may be a promising resource for treating depression.

• Journal of Ginseng Research
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• v.45 no.3
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• pp.420-432
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• 2021

Background: Many ginsenosides have been shown to be efficacious for major depressive disorder (MDD), which is a highly recurrent disorder, through several preclinical studies. We aimed to review the literature assessing the antidepressant effects of ginsenosides on MDD animal models, to establish systematic scientific evidence in a rigorous manner. Methods: We performed a systematic review on the antidepressant effects of ginsenoside evaluated in in vivo studies. We searched for preclinical trials from inception to July 2019 in electronic databases such as Pubmed and Embase. In vivo studies examining the effect of a single ginsenoside on animal models of primary depression were included. Items of each study were evaluated by two independent reviewers. A meta-analysis was conducted to assess behavioral changes induced by ginsenoside Rg1, which was the most studied ginsenoside. Data were pooled using the random-effects models. Results: A total of 517 studies were identified, and 23 studies were included in the final analysis. They reported on many ginsenosides with different antidepressant effects and biological mechanisms of action. Of the 12 included articles assessing ginsenoside Rg1, pooled results of forced swimming test from 9 articles (mean difference (MD): 20.50, 95% CI: 16.13-24.87), and sucrose preference test from 11 articles (MD: 28.29, 95% CI: 22.90-33.69) showed significant differences compared with vehicle treatment. The risk of bias of each study was moderate, but there was significant heterogeneity across studies. Conclusion: These estimates suggest that ginsenosides, including ginsenoside Rg1, reduces symptoms of depression, modulates underlying mechanisms, and can be a promising antidepressant.

• Journal of Physiology & Pathology in Korean Medicine
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• v.32 no.4
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• pp.247-254
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• 2018

A This study evaluated the antidepressant effects of the herbal mixture CPAE(Cynanchum wilfordii Hemsley, Phlomis umbrosa Turcz, and Angelica gigas Nakai) using several tests, including a test for serotonin 6($5-HT_6$) receptor activity, the forced swimming test(FST), and tests for corticosterone(CORT) and monoamine levels. CPAE showed antagonistic effects on the $5-HT_6$ receptor in a stable $5-HT_6$ receptor-expressing cell line. We subsequently confirmed the antidepressant effects of CPAE in chronic stress model in mice and explored the underlying mechanisms of its action. Specifically, we observed that CPAE treatment significantly reduced immobility time in the FST and effectively restored abnormal levels of CORT in plasma and of monoamines(serotonin, dopamine, and norepinephrine) in hippocampus and prefrontal cortex. These results suggest that CPAE has significant antidepressant effects.

• Korean Journal of Biological Psychiatry
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• v.13 no.3
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• pp.144-151
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• 2006

Objectives : Cognitive therapy is the most extensively researched psychological treatment for nonpsychotic unipolar outpatient depressive disorders. This review focused on the utility of this approach in severe or chronic depressive disorders, in relapse prevention and also on the potential benefits of combining cognitive therapy with medication. Methods : The author reviewed original studies and quantitative analyses on the effects of cognitive therapy, predictors of response, and neuroimaging studies of cognitive therapy in major depressive disorder. The sources used for the literature search were data bases : PubMed, EMBASE, CDSR on the internet, references in papers or books. Results : This review suggests that cognitive therapy is as effective as antidepressant medication in severe depressive disorders. And cognitive therapy can be an effective alternative to antidepressant medication. Patients benefited significantly more from combined cognitive therapy and antidepressant treatment than from either treatment alone. Most importantly, the addition of cognitive therapy to usual treatment appears to protect against future relapse in individuals known to be at high risk of repeated episodes of depression. In addition, subjects who received cognitive therapy showed significantly greater improvements in chronic depression than receiving antidepressant medication. Pooled data suggests that there is a significant relationship between the therapist's level of training or experience, the type of therapy used and patient outcome. Recent functional imaging studies examining brain changes following cognitive therapy report a variety of regional effects, but there is no consistent pattern across the few published studies. Conclusion : Cognitive therapy has proved beneficial in treating depressive patients. Despite empirical data supporting its efficacy, there are still problems in gaining access to cognitive therapy in clinical practice.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.4
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• pp.321-329
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• 2013

Rodents exposed to a 15-min pretest swim in the forced swimming test (FST) exhibit prolonged immobility in a subsequent 5-min test swim, and antidepressant treatment before the test swim reduces immobility. At present, neuronal circuits recruited by antidepressant before the test swim remain unclear, and also less is known about whether antidepressants with different mechanisms of action could influence neural circuits differentially. To reveal the neural circuits associated with antidepressant effect in the FST, we injected desipramine or citalopram 0.5 h, 19 h, and 23 h after the pretest swim and observed changes in c-Fos expression in rats before the test swim, namely 24 h after the pretest swim. Desipramine treatment alone in the absence of pretest swim was without effect, whereas citalopram treatment alone significantly increased the number of c-Fos-like immunoreactive cells in the central nucleus of the amygdala and bed nucleus of the stria terminalis, where this pattern of increase appears to be maintained after the pretest swim. Both desipramine and citalopram treatment after the pretest swim significantly increased the number of c-Fos-like immunoreactive cells in the ventral lateral septum and ventrolateral periaqueductal gray before the test swim. These results suggest that citalopram may affect c-Fos expression in the central nucleus of the amygdala and bed nucleus of the stria terminalis distinctively and raise the possibility that upregulation of c-Fos in the ventral lateral septum and ventrolateral periaqueductal gray before the test swim may be one of the probable common mechanisms underlying antidepressant effect in the FST.

• YAKHAK HOEJI
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• v.57 no.4
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• pp.289-292
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• 2013

A total of 2,080 forensic autopsies in Seoul, Incheon and Gyeonggi province were performed by the National Forensic Service (NFS) in 2010. After analysing blood samples collected at autopsies by GC-MS and LC-MS/MS, the types and prevalence of drugs and poisons in blood were investigated using our laboratory information management system. Among 2,080 cases, 1,061 cases (51%) were positive for drugs and poisons. Surprisingly, antidepressants were identified in 137 cases which comprised 13% of the positive cases. Twelve different kinds of antidepressants were determined: Amitriptyline, fluoxetine, nortriptyline, trazodone, imipramine, mirtazapine, citalopram, venlafaxin, clomipramine, paroxetine, sertraline and bupropion. Amitriptyline was the most frequently detected antidepressant and was identified in 39 cases. Moreover, amitriptyline, fluoxetine, and nortriptyline were included in the list of the 20 most commonly encountered drugs or poisons in the analysis of blood collected at autopsies from 2007 to 2009, indicating the prevalence of their use. In this study, the 137 antidepressant-related deaths were classified by the mode of death to predict the prevalence of these drugs. As a result, those deaths were divided into four groups based on the cause and mode of death: 56 cases of suicide with fatal concentrations of antidepressant drugs in blood, 6 homicidal cases directly or indirectly related to antidepressants, 59 natural deaths with antidepressants detected in blood and 16 deaths caused by fire or other accidents with antidepressants detected in blood. Because incidents involving antidepressants have been increasing, especially in suicides or homicides, it is necessary for the health authorities and law enforcement administrations to cooperate and share the statistical data for curbing the abuse of antidepressants. This report is expected to provide the reference data related with antidepressants for the investigation of the deaths.

• Animal cells and systems
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• v.14 no.4
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• pp.253-259
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• 2010

Artemisia capillaris Thunb. is widely used in the herbal medicine field. This study describes the antidepressant effect of a flavonoid (chlorogenic acid) isolated from the Artemisia capillaris Thunb. The expression of the pituitary gland and hypothalamic POMC mRNA or plasma ${\beta}$-endorphin levels were increased by extract of Artemisia capillaris Thunb. or its flavoniod administered orally. In addition, antidepressant activity was studied using the tail suspension test (TST), the forced swimming test (FST) and the rotarod test in a chronically restrained immobilization stress group in mice. After restraint stress (2 h/day for 14 days), animals were kept in a cage for 14 days without any further stress, but with drugs. Mice were fed with a diet supplemented for 14 days and during the behavioral test period with chlorogenic acid (30 mg/kg/day). POMC mRNA or the plasma ${\beta}$-endorphin level was increased by the extract of Artemisia capillaris Thunb. and its flavoniod. In addition, the immobility time in TST and FST was significantly reduced by chlorogenic acid. In the rotarod test, the riding time remained similar to that of the control group at 15 rpm. Our results suggest that the flavonoid (chlorogenic acid) isolated from Artemisia capillaris Thunb. shows a potent antidepressant effect.

• YAKHAK HOEJI
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• v.57 no.2
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• pp.101-109
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• 2013

Depressive disorders are the most common psychiatric problem in the elderly. Most depression treatment guidelines emphasize treatment with antidepressant medication and recommend that benzodiazepine use be minimized for limited period, particularly to elderly patients. In order to evaluate appropriate use of antidepressants and benzodiazepine, retrospective review of prescriptions was performed. The study population are older than 65 years who had been newly diagnosed with major depressive disorder in specialty mental health at a community general hospital from January $1^{st}$, 2007 to October $31^{th}$, 2012 (N=373). Initial antidepressant accounted for 89.5% with SSRI, and escitalopram accounted for 60.9% of SSRI group. 79% or more of the patients were prescribed the recommended dosage. The maintenance rate for 4 weeks of initial antidepressant was 48% and 6 weeks was 39%. Treatment-discontinuation rate was 68% at 3 month. Alprazolam (short acting benzodiazepine) was prescribed the most, followed by clonazepam (long acting benzodiazepine) and then diazepam. 55% of patients received a duplicated prescription for short acting plus long acting benzodiazepine. 61% of patients used long acting benzodiazepines. Prescribed dosages of benzodiazepines were commonly within a recommended range, while no one was prescribed a appropriate period (up to 2 weeks) except for the early discontinued patients. Appropriate use of zolpidem was only 16.2%. The depressed elderly treated in specialty mental health mostly received long-term treatment with benzodiazepines in combination with antidepressants, guideline recommendations was not followed. Multidisciplinary interventions like audit and feedback of benzodiazepine use are needed and education for the elderly is needed to properly maintain antidepressant treatment.

• Journal of Oriental Neuropsychiatry
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• v.33 no.1
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• pp.79-111
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• 2022

Major depressive disorder (MDD) causes a persistent feeling of sadness and loss of interest. It can lead to emotional and physical problems. Treatments such as antidepressant and cognitive behavioral therapy for MDD have many limitations. Traditional East Asian Herbal Medicine (TEAM) is a representative modality of Complementary and Integrative Medicine (CIM) which can be used for MDD. However, no study has systematically reviewed the efficacy or safety of TEAM for MDD so far. Therefore, we performed a systematic review and meta-analysis to evaluate effectiveness and safety of TEAM as a monotherapy for MDD. We only included TEAM that could be used in context of clinical setting in Korean Medicine. Outcomes were the Hamilton Depression Rating Scale (HAMD) and total effective rate (TER). After comprehensive electronic search of 11 databases, we included 28 randomized controlled trials (RCTs) that compared HM as monotherapy with antidepressant for MDD. Meta-analysis showed that TEAM had significant benefits in reducing HAMD (MD=-0.40, 95% CI: -0.67 to -0.13, p=0.003, I²=85%) and improving TER (RR=1.06, 95% CI: 1.02 to 1.10, p=0.003, I²=0%). It also appeared to be safer than antidepressant in terms of adverse effects. Methods used for RCTs were poor and the quality of evidence was graded 'low' or 'moderate'. These findings indicate that the use of HM as a monotherapy might have potential benefits in MDD treatment as an alternative to antidepressant. However, considering the methodological quality of included RCTs, the clinical evidence is uncertain. Further well-designed RCTs are required to confirm these findings.

• Journal of Ginseng Research
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• v.47 no.4
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• pp.552-560
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• 2023

Background: Ginseng Radix (Panax ginseng Meyer, Araliaceae) has been used medicinally to treat the brain and nervous system problems worldwide. Recent studies have revealed physiological effects that could potentially benefit cognitive performance or mood. The present study aimed to investigate the antidepressant effects of Korean red ginseng water extract (KGE) and its active component in an unpredictable chronic mild stress (UCMS)-induced animal model and elucidate the underlying mechanisms. Methods: The antidepressant potential of the UCMS model was evaluated using the sucrose preference test and open field tests. The behavioral findings were further corroborated by the assessment of neurotransmitters and their metabolites from the prefrontal cortex and hippocampus of rats. Three doses of KGE (50, 100, and 200 mg/kg) were orally administered during the experiment. Furthermore, the mechanism underlying the antidepressant-like action of KGE was examined by measuring the levels of brain-derived neurotrophic factor (BDNF)/CREB, nuclear factor erythroid 2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap1) proteins in the prefrontal cortex of UCMS-exposed rats. Results: KGE treatment normalized UCMS-induced depression-related behaviors. Neurotransmitter studies conducted after completing behavioral experiments demonstrated that KGE caused a reduction in the ratio of serotonin and dopamine, indicating a decrease in serotonin and dopamine turnover. Moreover, the expression of BDNF, Nrf2, Keap1 and AKT were markedly increased by KGE in the prefrontal cortex of depressed rats. Conclusion: Our results provide evidence that KGE and its constituents exert antidepressant effects that mediate the dopaminergic and serotonergic systems and expression of BDNF protein in an animal model.