title: Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant.
abstract: Major depression is a serious psychiatric disorder and remains a leading cause of disability worldwide. Conventional antidepressants take at least several weeks to achieve a therapeutic response and this lag period has hindered their ability to attain beneficial effects in depressed individuals at high risk of suicide. The non-competitive N-methyl-D-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in both rodents and humans. The emergence of ketamine as a fast-acting antidepressant provides promising new insights into the development of a rapid treatment response in patients with clinical depression. However, its safety and toxicity remain a concern. In this review, we focus on the limitations of ketamine, including neurotoxicity, cognitive dysfunction, adverse events associated with mental status, psychotomimetic effects, cardiovascular events, and uropathic effects. Studies have shown that its safety and tolerability profiles are generally good at low doses and with short-term treatment in depressed patients. The adverse events associated with ketamine usually occur with very high doses that are administered for prolonged periods of time and can be relieved by cessation. The antidepressant actions of its two enantiomers, S-ketamine (esketamine) and R-ketamine, are also discussed. R-ketamine has greater antidepressant actions than S-ketamine, without ketamine-related side-effects. Future treatment strategies should consider using R-ketamine for the treatment of depressed patients to decrease the risk of adverse events associated with long-term ketamine use.
authors.affiliation: National Institute on Drug Dependence, Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, 100191, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Zhu
authors.affiliation: National Institute on Drug Dependence, Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, 100191, China.
authors.forename: Zengbo
authors.initials: Z
authors.lastname: Ding
authors.affiliation: National Institute on Drug Dependence, Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, 100191, China.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Institute on Drug Dependence, Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, 100191, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shi
authors.affiliation: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: National Institute on Drug Dependence, Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, 100191, China. linlu@bjmu.edu.cn.|Institute of Mental Health/Peking University Sixth Hospital, Key Laboratory of Mental Health, Beijing, 100191, China. linlu@bjmu.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects*; D003072:Cognition Disorders / Q000139:chemically induced*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D006801:Humans; D007649:Ketamine / Q000009:adverse effects*; D019966:Substance-Related Disorders / Q000209:etiology
chemical_list: D000928:Antidepressive Agents; D007649:Ketamine
keywords: Antidepressant; Depression; Fast-acting; Ketamine; Safety