Ketamine, an anesthetic from the 1960s, has gained attention as a treatment for major depressive disorder, especially treatment-resistant depression, with potential anti-suicidal effects. Unlike traditional antidepressants that take weeks, ketamine can produce rapid antidepressant effects within hours. Its mechanism involves glutamate modulation through NMDA and AMPA receptors, plus activation of BDNF and mTOR pathways to enhance synaptic plasticity. This paper reviews ketamine's pharmacology, toxicology, clinical trial status, and proposed antidepressant mechanisms, along with potential biomarkers—biochemical, inflammatory, metabolic, neuroimaging, sleep-related, and cognitive—for predicting or monitoring therapeutic response.
Intravenous ketamine and intranasal esketamine are effective for treatment-resistant depression but are limited by cost, availability, and monitoring requirements. A literature review up to June 2023 and a community case study from two public hospital sites in Edmonton, Canada, describe how evidence on ketamine for treatment-resistant depression can be applied in real-world settings. The paper synthesizes knowledge on off-label racemic ketamine versus FDA-approved esketamine, dosing, safety, and long-term maintenance. To overcome cost barriers, public programs may incorporate sublingual or intranasal ketamine. Three such sustainable treatment models are described, though large-scale randomized trials and long-term outcome data remain lacking.