Understanding Ketamine's Antidepressant Effect

August 24, 2020
Jonathan Alicea

J. John Mann, MD, discusses findings in a new study that uncovers the mechanisms behind Ketamine's antidepressant effect.

A new study on ketamine found that increasing dosage was associated with greater antidepressant effects and lower levels of glutamate. The degree of clinical improvement was unrelated to any experienced side effects.

In an interview with HCPLive®, study investigator J. John Mann, MD, Professor of Translational Neuroscience, Columbia University, offered further insight into these exciting findings and discussed its implications on treatment for major depressive disorder.

Mann explained they were primarily interested in understanding glutamate’s role as mediator between ketamine and its effect. Using a PET scan to capture patient glutamate and GABA levels during and after drug infusion, they discovered ketamine attenuated glutamate levels in exact proportion to the dose received.

“Statistically, we were able to show that dose-dependent antidepressant effect of ketamine was largely explained by the effect of the Glx peak in the part of the brain related to depression circuitry.”

He then said that one could theoretically discover other compounds that have a similar effect on glutamate levels. Furthermore, it would be essential to find compounds that lack the side effects typically associated with ketamine.

By having a better understanding of these mechanisms behind ketamine’s antidepressant effect, researchers might be able to predict the antidepressant potential and impact of future drugs relative to ketamine, Mann added.


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