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Ketamine: An Update on Research

Ketamine for Depression and Chronic Pain

Ketamine is a compound that has a very complex mechanism of action and has effects on various receptors. The main being N-methyl-D-aspartate ( NMDA) receptor antagonist with additional effects on α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, opioid receptors, and monoaminergic receptors. 


Ketamine was first developed in 1963 and was approved by the FDA in 1970 as an anesthetic drug.  Since that time, there has been increasing interest for ketamine to be used as a mental health treatment and chronic pain.  In 2019, FDA approved esketamine for treatment-resistant depression trademarked as Spravato. This has led to interestingly more research and studies on ketamine to be used as an antidepressant as well as a chronic pain treatment.


In a 2021 comprehensive systematic review published in the Cambridge Journal BJPsych, 83 published reports were reviewed including 33 systematic reviews, 29 randomized controlled trials and others. The summation of the review suggested that there may indeed be support for the rapid and transient antidepressant and anti-suicidal effect of ketamine.


Chronic pain affects approximately 20% of the global population. Being a multifactorial problem, not all treatments work on everyone. There is consent by the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists for the use of ketamine as an effective treatment option for chronic pain. In another 2021 review of ketamine use in relation to pain management, ketamine was concluded to be a treatment option in those with chronic pain who are highly opioid-tolerant. Ketamine has been studied to be an analgesic tool with low side effects when appropriately administered at the correct dosages. Higher dosages were associated with a dissociation, and emergence phenomenon where patients can have nightmares, hallucinations, fear or excitement. Ketamine can also cause respiratory depression.  

See our other blog on Ketamine here:



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We serve the Bellevue, Seattle, Redmond, Issaquah,Sammamish, and surrounding pacific northwest areas.

Cohen, S. P., Bhatia, A., Buvanendran, A., Schwenk, E. S., Wasan, A. D., Hurley, R. W., Viscusi, E. R., Narouze, S., Davis, F. N., Ritchie, E. C., Lubenow, T. R., & Hooten, W. M. (2018). Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Regional Anesthesia and Pain Medicine, 43(5), 521–546. https://doi.org/10.1097/ aap.0000000000000808 


Israel, J. E., St Pierre, S., Ellis, E., Hanukaai, J. S., Noor, N., Varrassi, G., Wells, M., & Kaye, A. D. (2021). Ketamine for the Treatment of Chronic Pain: A Comprehensive Review. Health psychology research, 9(1), 25535. https://doi.org/10.52965/001c.25535


Walsh, Z., Mollaahmetoglu, O. M., Rootman, J., Golsof, S., Keeler, J., Marsh, B., Nutt, D. J., & Morgan, C. (2021). Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review. BJPsych open, 8(1), e19. https://doi.org/10.1192/bjo.2021.1061


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