Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments
J. Krystal, Alfred P. Kaye, S. Jefferson, M. Girgenti, Samuel T. Wilkinson, Gerard Sanacora, I. Esterlis
Proceedings of the National Academy of Sciences of the United States of America November 27, 2023 DOI: 10.1073/pnas.2305772120 via Semantic Scholar
Summary
Ketamine represents a new type of antidepressant that works quickly, helps people whose depression has not responded to other treatments, and reduces the chance of relapse. Its development came from a new understanding of depression's biology, and studying how ketamine works has deepened knowledge of depression and related conditions. Twenty-five years after the first findings on ketamine for depression were presented, this review examines what has been learned and suggests future ways to improve rapid-acting antidepressant therapy.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Keywords | Medicine |
| Citations | 66 |
| Key finding | 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.