Ketamine was initially used as an anesthetic. Now this medication is gaining ground as a promising treatment for some cases of major depression, which is the leading cause of disability worldwide. In the US, recent estimates show 16 million adults had an episode of major depression in the course of a year.
Ketamine can rapidly reduce serious symptoms of depression, including suicidal thinking. Other treatments for suicidal thoughts and depression often take weeks or even months to take effect, and some people need to try several medications to gain relief. This is also true for talk therapies and transcranial magnetic stimulation (TMS).
It’s not entirely clear how ketamine works. One likely target for ketamine is NMDA receptors in the brain. By binding to these receptors, ketamine appears to increase the amount of a neurotransmitter called glutamate in the spaces between neurons. Glutamate then activates connections in another receptor, called the AMPA receptor. Together, the initial blockade of NMDA receptors and activation of AMPA receptors lead to the release of other molecules that help neurons communicate with each other along new pathways. Known as synaptogenesis, this process likely affects mood, thought patterns, and cognition.
Ketamine also may influence depression in other ways. For example, it might reduce signals involved in inflammation, which has been linked to mood disorders, or facilitate communication within specific areas in the brain. Most likely, ketamine works in several ways at the same time, many of which are still being studied.
(Meisner, Robert C. (2019, May 22). Ketamine for major depression: New tool, new question. https://www.health.harvard.edu/blog/ketamine-for-major-depression-new-tool-new-questions-2019052216673)