The dissociative anesthetic (R, S) -ketamine produces rapid-acting antidepressant effects and reduces suicidal ideation in treatment-resistant patients with depression. At present,(R, S) -ketamine is one of the most attractive antidepressants. Although (R, S) -ketamine-induced side effects (i. e., psychotomimetic effects, dissociation, and abuse risk) remain unresolved, off-label use of (R, S) -ketamine is common in the United State (US). On March 5th, 2019, the US Food and Drug Administration (FDA) approved Janssen's (S) -ketamine nasal spray for treatment-resistant depression. However, there are several concerns regarding (S) -ketamine nasal spray. We previously reported that (R) -ketamine, another enantiomer of (R, S) -ketamine, has greater potency and longer-lasting antidepressant effects in rodents than (S) -ketamine, and that the side effects of (R) -ketamine were milder than those of (R, S) - or (S) -ketamine. Clinical studies of (R) -ketamine are currently being performed overseas. In this article, we discuss recent reports on the two enantiomers of ketamine as an antidepressant for treatment-resistant depression.
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