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

Ketamine, first made in 1962, has become important for its fast-acting and lasting antidepressant effects in people with treatment-resistant depression. Unlike older antidepressants, it works through multiple brain chemical systems, including blocking NMDA receptors and boosting AMPA receptors. It also remains a useful anesthetic and painkiller for acute and chronic pain, and shows anti-inflammatory, neuroprotective, and possible antitumor properties. However, its dissociative and hallucinogenic effects lead to recreational misuse, which can cause bladder and liver problems. Its rediscovery as an antidepressant in the early 2000s transformed psychiatric care, and research now explores its use in bipolar depression, PTSD, OCD, and substance use disorders. The review covers ketamine's many uses and the need to balance benefits with risks.

Study at a glance

Abstract

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.