Rapid-Acting Antidepressant Effect of Ketamine and Its Clinical Application.
10.4306/jknpa.2018.57.2.108
- Author:
Yong Ku KIM
1
;
Cheolmin SHIN
Author Information
1. Department of Psychiatry, College of Medicine, Korea University, Ansan Hospital, Ansan, Korea. yongku@korea.edu
- Publication Type:Original Article
- Keywords:
Ketamine;
Glutamate;
N-methyl-D-aspartate receptor;
Rapid-acting antidepressant;
Depression
- MeSH:
Antidepressive Agents;
Depression;
Glutamic Acid;
Humans;
Interneurons;
Ketamine*;
N-Methylaspartate;
Nerve Growth Factors
- From:Journal of Korean Neuropsychiatric Association
2018;57(2):108-118
- CountryRepublic of Korea
- Language:Korean
-
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.
