Neuroscientific Basis of Ketamine as an Analgesic and Emerging Role in the Management of Depression.
Level 5 - mechanism / opinion, no new human data
Narrative review without systematic search or meta-analytic methodology
PubMed 42012726 · doi:10.1007/s11916-026-01475-7
What was done
This narrative review synthesized preclinical and clinical literature evaluating the neuroscientific mechanisms and clinical utility of ketamine and its S-enantiomer, esketamine. It evaluated its noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonism and modulation of central sensitization across anesthesia, perioperative multimodal analgesia, chronic refractory neuropathic pain conditions, and major depressive disorder.
What was found
The abstract reports no numerical data, sample sizes, or effect sizes. It qualitatively reports that intravenous ketamine confers short-term analgesic benefits in resistant neuropathic pain, phantom limb pain, and complex regional pain syndrome, and provides opioid-sparing effects in low-dose perioperative settings. It also notes rapid antidepressant effects in major depressive disorder and treatment-resistant depression, while highlighting adverse dissociative effects, cardiovascular changes, and potential for misuse.
Why it matters
This review outlines the shared neurobiological basis linking centralized refractory pain states and mood disorders through NMDA receptor modulation. It highlights ketamine's expanding therapeutic role across perioperative, chronic pain, and psychiatric settings.
Limits
As a narrative review, it lacks a systematic literature search, formal risk-of-bias evaluation, and meta-analytic pooling. The underlying evidence base is limited by high heterogeneity across dosing protocols, variable response duration, scarce long-term safety data, and adverse side-effect profiles.
Cited by
- supports Ketamine is classified pharmacologically as a dissociative anesthetic.