Sat. Oct 12, 2019 2:50 PM - 4:30 PM Room 13 (501)

Organizer / Chair: Kenji HASHIMOTO (Chiba University Center for Forensic Mental Health, Chiba, Japan), Co-chair: Edward DOMINO (Department of Pharmacology, University of Michigan, USA), Discussants: ‌Tung-Ping T SU (Department of Psychiatry, Cheng-Hsin General Hospital, National Yang-Ming University, Taiwan), Shigeyuki CHAKI (Research Headquarters, Taisho Pharmaceutical Co., Ltd., Japan)

The N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine is a popular abused drug in the world including Asia. In contrast, ketamine is one of the most attractive antidepressants since ketamine can produce rapid-onset and sustained antidepressant effects in treatment-resistant patients with major depression and bipolar disorder. A number of clinical studies make ketamine an attractive rapid-onset therapeutic drug for treatment-resistant depression, although its clinical application may be limited owing to its propensity of causing psychotomimetic effects and abuse liability. The four speakers of this symposium are ketamine research experts in Asia.
Substance addiction has long been associated with dysregulation in stress response systems. Dr. Ming-Chyl Huang (Taiwan) presents the alterations of orexin-A, oxytocin, ACTH, and cortisol levels in treatment-seeking ketamine-dependent patients before and after early abstinence. Chronic ketamine abuse is associated with an abnormal expression of stress-related neuropeptides, which do not normalize after ketamine discontinuation. Those with an anxious phenotype might have a more disrupted stress regulation. These results could provide insight into the development of potential therapeutic strategies to treat ketamine dependence.
Low-dose ketamine has rapid antidepressant effects and brings new hope for patients with treatment-resistant depression. However, while it looks promising, there are still some potential issues unsolved which need to be clarified. Dr. Cheng-Ta Li (Taiwan) would focus not only the positive findings on it but also some potential problems to see while using this compound clinically.
Ketamine (Ki = 500 nM for NMDAR) is a racemic mixture containing equal parts of (S)-ketamine (Ki = 300 nM) and (R)-ketamine (Ki = 1400 nM). Interestingly, (R)-ketamine showed greater potency and longer lasting antidepressant effects than (S)-ketamine in several animal models of depression. Accumulating evidence suggest that gut microbiota may play a role in depression and in the antidepressant effects of certain compounds. Dr. Chun Yang (China) will talk about the role of gut-microbiota in the antidepressant effects of ketamine and its two enantiomers (R)-ketamine and (S)-ketamine. (R)-ketamine is metabolized to (2R,6R)-hydroxynorketamine (HNK) in the liver. Finally, Dr. Kenji Hashimoto (Japan) will talk the recent findings of (R)-ketamine and its metabolite (2R,6R)-HNK in animal models of depression. In this symposium, we discuss the benefits and risks of ketamine and its enantiomers in the treatment of depression.