Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments
John H. Krystal, Alfred P. Kaye, Sarah J. Jefferson, Matthew J. Girgenti, Samuel T. Wilkinson, Gerard Sanacora, Irina Esterlis
Proceedings of the National Academy of Sciences of the United States of America November 27, 2023 DOI: 10.1073/pnas.2305772120 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression Esketamine Ketamine |
| Citations | 66 |
| Key findings | Ketamine has rapid antidepressant effects, efficacy for treatment-resistant depression, and protection against relapse, distinguishing it from prior antidepressants. |
Abstract
Ketamine has emerged as a transformative and mechanistically novel pharmacotherapy for depression. Its rapid onset of action, efficacy for treatment-resistant symptoms, and protection against relapse distinguish it from prior antidepressants. Its discovery emerged from a reconceptualization of the neurobiology of depression and, in turn, insights from the elaboration of its mechanisms of action inform studies of the pathophysiology of depression and related disorders. It has been 25 y since we first presented our ketamine findings in depression. Thus, it is timely for this review to consider what we have learned from studies of ketamine and to suggest future directions for the optimization of rapid-acting antidepressant treatment.