Ketamine in clinical practice: transitioning from anesthetic agent to psychiatric therapeutic

Jun 30, 2025CNS spectrums

Ketamine moving from anesthesia use to psychiatric treatment

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Abstract

Ketamine has rapid and sustained antidepressant effects in treatment-resistant depression (TRD).

Ketamine acts on multiple neurotransmitter systems, including blocking NMDA receptors and enhancing AMPA receptor activity.
It serves as a valuable anesthetic and pain management agent for both acute and chronic conditions.
Research indicates ketamine may possess anti-inflammatory, neuroprotective, and potential antitumor properties.
Chronic misuse of ketamine is linked to adverse health outcomes, such as bladder dysfunction and liver complications.
Regulatory scrutiny is increasing due to ketamine's potential for abuse alongside its medical utility.
Ongoing studies are investigating ketamine's long-term effects and optimal dosing to enhance benefits and reduce risks.

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Ketamine, originally synthesized in 1962, has gained increasing attention due to its rapid and sustained antidepressant effects in treatment-resistant depression (TRD). Unlike traditional antidepressants, ketamine acts on multiple neurotransmitter systems, including NMDA receptor antagonism and AMPA receptor potentiation, offering a novel mechanism for mood regulation. Beyond psychiatry, ketamine remains a valuable anesthetic and analgesic agent with applications in acute and chronic pain management. Its anti-inflammatory, neuroprotective, and potential antitumor properties further underscore its versatility in clinical medicine. Despite its therapeutic promise, ketamine poses challenges due to its dissociative and hallucinogenic effects, contributing to widespread recreational use. Chronic misuse is associated with adverse health outcomes, including bladder dysfunction and hepatobiliary complications. As a result, ketamine has been subject to increasing regulatory scrutiny, balancing its medical utility with concerns about abuse potential. The rediscovery of ketamine's antidepressant effects in the early 2000s has revolutionized psychiatric treatment, particularly in TRD and suicidality. Recent studies have also explored its efficacy in bipolar depression, posttraumatic stress disorder, obsessive-compulsive disorder, and substance use disorders, expanding its therapeutic applications. Additionally, ongoing research aims to elucidate its long-term effects and optimize dosing regimens to maximize clinical benefits while minimizing risks. This review highlights ketamine's multifaceted pharmacological properties, its evolution from an anesthetic to a novel psychiatric treatment, and its broader medical applications. As research advances, a comprehensive understanding of ketamine's mechanisms and clinical implications will be crucial for optimizing its therapeutic potential while mitigating its risks.

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Ketamine in clinical practice: transitioning from anesthetic agent to psychiatric therapeutic

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