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Ketamine의 속효성 항우울효과와 임상 적용

Rapid-Acting Antidepressant Effect of Ketamine and Its Clinical Application

김용구|신철민
대한신경정신의학회 (Korean Neuropsychiatric Association)|2018.05|신경정신의학 (JOURNAL OF THE KOREAN NEUROPSYCHIATRIC ASSOCIATION)|제57권 제2호|pp. 108-118|DOI https://doi.org/10.4306/jknpa.2018.57.2.108

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참고문헌

키워드

Depression.KetamineGlutamateN-methyl-D-aspartate receptorRapid-acting antidepressant
주제분류정신과학

초록

Although the biological causes of depression have been well established, the current use of antidepressants are still mostly based on the monoamine hypothesis of depression. However, monoamine antidepressants delay treatment of depression, and there is the problem of depressed patients who are resistant. Ketamine, a N-methyl-D-aspartate receptor (NMDAR) antagonist, is firstly introduced as an anesthetic. The hypothesis on the mechanism of ketamine as an antidepressant has been proposed through direct NMDAR inhibition, inhibition of γ-aminobutyric acid-ergic interneuron NMDARs and the role of ketamine metabolite (2R,6R)-hydroxynorcetamine (HNK). The ketamine also reverses the lack of synaptic connectivity and neurotrophic factors in depressed states by downstream mechanism of action. Through preclinical trials, there is a growing body of evidence indicating that ketamine has the potential for treatment of depression. In recent clinical studies, ketamine exhibits rapid-acting antidepressants effects and improvement of depression and even suicidality. This review examines current researches on molecular and cellular mechanisms of ketamine as an antidepressant, and reviews the current status of clinical studies, problems, and clinical applicability of ketamine.

Abstract

Although the biological causes of depression have been well established, the current use of antidepressants are still mostly based on the monoamine hypothesis of depression. However, monoamine antidepressants delay treatment of depression, and there is the problem of depressed patients who are resistant. Ketamine, a N-methyl-D-aspartate receptor (NMDAR) antagonist, is firstly introduced as an anesthetic. The hypothesis on the mechanism of ketamine as an antidepressant has been proposed through direct NMDAR inhibition, inhibition of γ-aminobutyric acid-ergic interneuron NMDARs and the role of ketamine metabolite (2R,6R)-hydroxynorcetamine (HNK). The ketamine also reverses the lack of synaptic connectivity and neurotrophic factors in depressed states by downstream mechanism of action. Through preclinical trials, there is a growing body of evidence indicating that ketamine has the potential for treatment of depression. In recent clinical studies, ketamine exhibits rapid-acting antidepressants effects and improvement of depression and even suicidality. This review examines current researches on molecular and cellular mechanisms of ketamine as an antidepressant, and reviews the current status of clinical studies, problems, and clinical applicability of ketamine.

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