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Ketamine Use in Psychiatry

What is Ketamine?

Ketamine is an NMDA antagonist meaning it blocks the NMDA (N-METHYL-D-ASPARTATE) brain receptor. It is a schedule III anesthetic agent that was approved by the FDA in 1970. Historically, Ketemine has been used as an anesthetic medication during surgery. In recent years, the use of low dose intravenous ketamine (single dose) has been used in severely depressed patients to quickly decrease/abort depressed mood. Because of the rapid reduction in symptoms, the low dose single infusion has shown efficacy in patients who suffer from PTSD as well (NIH, 2008).

How does Ketamine work?

For depression: Ketamine increases glutamate activity and promotes the formation of new synapses in the brain’s frontal cortex (Serafini, Howland, Rovedi, Girandi, & Amore, 2014).

For PTSD/trauma: Glutamate contributes to the formation of traumatic memories. Katemine blocks the NMDA receptor and thereby impacts the formation traumatic memories (Serafini, Howland, Rovedi, Girandi, & Amore, 2014).

Chronic pain: At low doses Ketamine has demonstrated intense analgesic effects in neuropathic pain sites. It is believed that ketamine acts by inhibiting NMDA receptors and potentially inhibiting descending central anti-inflammatory effects. The effectiveness of Ketamine for long-term pain management is disputable because of the variance in the research study results, (Gao, Rejaei,& Liu, 2016)

Ketamine: New Research

In 2016, researchers at the National Institute of Health discovered a metabolite created by the breakdown of ketamine that potentially may explain the rapid onset of ketamine’s antidepressant effects (NIH, 2016). This newly identified metabolite will be key to research and development of new ketamine products.

New medications on the horizon: Johnson and Johnson (subsidiary Janssen Pharmaceuticals) and Allergan are each developing new ketamine drugs. Johnsons and Johnson is developing esketamine (a nasal spray). Chemically it is the same as ketamine. Currently, Eskatamine is in phase III clinical trials. Allergan’s new drug, rapastinel (injection), chemically is not ketamine; however, it works in the brain in a similar manner. Rapastinel is a NMDA receptor modulator and is glycine- site partial agonist that enhances glutamate activity. In clinical trials, it has demonstrated rapid and sustained antidepressant properties and has enhanced cognition (Moskal, Burgdorf, Stanton, Kroes, Disterhoft, Burch, & Khan, 2017).

References Feder, A., Parides, M.K., Murrough, J. (2014). Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry, 71(6):681-688.

Gao, M., Rejaei, D., & Liu, H. (2016). Ketamine use in current clinical practice. Acta Pharmacologica Sinica, 37(7), 865–872.

Moskal, J. R., Burgdorf, J. S., Stanton, P. K., Kroes, R. A., Disterhoft, J. F., Burch, R. M., & Khan, M. A. (2017). The Development of Rapastinel (Formerly GLYX-13); A Rapid Acting and Long Lasting Antidepressant. Current Neuropharmacology, 15(1), 47–56.

National Institute of Health (2016). Ketamine Lifts Depression via a Byproduct of its Metabolism NIH-funded team finds rapid-acting, non-addicting agent in mouse study Retrieved from: depression-via-a-byproduct-of-its-metabolism.shtml

National Institute of Health (2008). Katamine as a rapid treatment for PTSD (KetPTSD). Clinical Trials. Retrieved from: Serafini, G., Howland, R. H., Rovedi, F., Girardi, P., & Amore, M. (2014). The Role of Ketamine in Treatment-Resistant Depression: A Systematic Review . Current Neuropharmacology, 12(5), 444–461.

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