Ketamine in psychiatry: a systematic review of clinical applications, safety considerations, and emerging challenges
- 1College of Human Medicine, Michigan State University , , ,
- 2Department of Psychology, Alma College , , ,
Abstract
Ketamine has progressed from solely being an anesthetic agent to a drug of rising clinical and research interest due to its distinctive pharmacological properties. Its dissociative properties and rapid-acting antidepressant effects have made it a prominent area of investigation across many medical and psychiatric applications. This systematic review examines ketamine’s history, mechanisms of action, clinical uses, and significant challenges. A systematic search of PubMed, SCOPUS, PsycINFO, and other sources, generated peer-reviewed publications that addressed the history of ketamine, its pharmacology, clinical applications, recreational use, safety considerations, and societal consequences. Overall, 106 articles were identified for inclusion in this study. At the receptor level, ketamine is an antagonist of NMDA receptors that triggers a number of downstream effects ranging from heightened glutamate transmission, AMPA receptor activation, increased BDNF expression, synaptogenesis, and mTOR pathway signaling. At the network level, it alters activity within large-scale brain circuits including the default mode network, affecting cognition, mood, and perception. Clinically, ketamine is used for anesthesia, treatment-resistant depression, and pain, with off-label uses for PTSD, anxiety disorders, and bipolar disorder. The review also examines current challenges related to ketamine’s recreational use, associated risks, sociocultural factors, and key clinical and ethical considerations, including safety, monitoring, and telehealth prescribing of oral and sublingual formulations. It integrates previously fragmented research from anesthesiology, neuroscience, pharmacology, psychiatry, and public health, consolidates clinical and ethical guidance, identifies critical gaps in current knowledge, and proposes directions for future research.
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BibTeX
@article{kinney2026ketamine,
title = {{Ketamine in psychiatry: a systematic review of clinical applications, safety considerations, and emerging challenges}},
author = {Matthew M. Kinney and Zackary L. Bowers},
journal = {Frontiers in psychiatry},
year = {2026},
month = oct,
doi = {10.3389/fpsyt.2026.1949261},
url = {https://europepmc.org/article/PMC/PMC13668871},
note = {CC BY},
}
RIS
TY - JOUR
TI - Ketamine in psychiatry: a systematic review of clinical applications, safety considerations, and emerging challenges
AU - Matthew M. Kinney
AU - Zackary L. Bowers
PY - 2026
DA - 2026/10/01
JO - Frontiers in psychiatry
DO - 10.3389/fpsyt.2026.1949261
UR - https://europepmc.org/article/PMC/PMC13668871
AB - Ketamine has progressed from solely being an anesthetic agent to a drug of rising clinical and research interest due to its distinctive pharmacological properties. Its dissociative properties and rapid-acting antidepressant effects have made it a prominent area of investigation across many medical and psychiatric applications. This systematic review examines ketamine’s history, mechanisms of action, clinical uses, and significant challenges. A systematic search of PubMed, SCOPUS, PsycINFO, and other sources, generated peer-reviewed publications that addressed the history of ketamine, its pharmacology, clinical applications, recreational use, safety considerations, and societal consequences. Overall, 106 articles were identified for inclusion in this study. At the receptor level, ketamine is an antagonist of NMDA receptors that triggers a number of downstream effects ranging from heightened glutamate transmission, AMPA receptor activation, increased BDNF expression, synaptogenesis, and mTOR pathway signaling. At the network level, it alters activity within large-scale brain circuits including the default mode network, affecting cognition, mood, and perception. Clinically, ketamine is used for anesthesia, treatment-resistant depression, and pain, with off-label uses for PTSD, anxiety disorders, and bipolar disorder. The review also examines current challenges related to ketamine’s recreational use, associated risks, sociocultural factors, and key clinical and ethical considerations, including safety, monitoring, and telehealth prescribing of oral and sublingual formulations. It integrates previously fragmented research from anesthesiology, neuroscience, pharmacology, psychiatry, and public health, consolidates clinical and ethical guidance, identifies critical gaps in current knowledge, and proposes directions for future research.
SN - 1664-0640
ER -