Candidate Strategies for Development of a Rapid-Acting Antidepressant Class That Does Not Result in Neuropsychiatric Adverse Effects: Prevention of Ketamine-Induced Neuropsychiatric Adverse Reactions
International Journal of Molecular Sciences October 26, 2020 Motohiro Okada, Yasuhiro Kawano, Kouji Fukuyama et al. 31 citations
Ketamine, an NMDAR antagonist, has been approved for treatment-resistant depression despite its schizophrenia-like side effects. It improves anhedonia, suicidal ideation, and bipolar depression where conventional antidepressants fail. The antidepressant dose is comparable to that producing psychotic symptoms, and psychotropic effects precede antidepressant effects. Repeated administration is often needed but carries risks of abuse and memory deficits. The article reviews clinical evidence for NMDAR antagonists and the temporal mechanisms underlying ketamine's schizophrenia-like and antidepressant-like effects, also discussing rodent pharmacological studies.