Ketamine as well as its individual enantiomers and related compounds have been at the forefront of drug development for the treatment of depression. The United States Food and Drug Administration (USFDA) approval of esketamine for the indication of treatment-resistant depression in 2019 has rapidly increased use of the treatment in clinical settings. As such, it is important for clinicians and researchers to be familiar with the current knowledge surrounding efficacy, safety, and proposed mechanisms of action of this treatment modality. It is equally important to be aware of the remaining unanswered questions related to the treatment to provide the optimal care to patients and promote meaningful translational research. This chapter briefly reviews the history of ketamine, explores proposed mechanisms of action, outlines data pertaining to efficacy and safety, and considers “real-world” usage and the challenges to implementation.
Managing Treatment-Resistant Depression Road to Novel Therapeutics 2022, Pages 205-219,