Therapeutic Advances in Psychopharmacology
January 1, 2020
D. Matveychuk, Rejish K Thomas, Jennifer Swainson et al.
209 citations
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.
CNS Drugs
February 14, 2022
Jennifer Swainson, L. Klassen, Stefan Brennan et al.
42 citations
Intravenous ketamine and intranasal esketamine are used for depression but face cost and access barriers. Non-parenteral racemic ketamine (oral, sublingual, intranasal) might improve access, though evidence is limited. Concerns about ketamine's addictive potential have not been examined against available evidence. The authors argue that ketamine misuse risks are similar to those of stimulants or benzodiazepines, and prescribing should balance patient access with misuse concerns. A consortium of mood disorder specialists considers non-parenteral ketamine a reasonable option for select treatment-resistant depression cases and provides practical prescribing recommendations.
Journal of Military Veteran and Family Health
February 1, 2026
Ian Stefanuk, Kaitlin Chivers-Wilson, Rakesh Jetly et al.
A retrospective chart review of 56 Veterans who completed a program combining sublingual ketamine therapy with a transdiagnostic intensive outpatient program (IOP) found significant reductions in symptoms of depression, anxiety, and posttraumatic stress, along with improved quality of life. Clinically meaningful improvements were most notable among those with moderate to severe baseline symptoms. The intervention is thought to enhance neuroplasticity and emotional learning while increasing treatment engagement and long-term resiliency. The lack of a control group limits the findings, and further research is needed to validate the results and adapt the model for Veterans.