Ketamine Offers Clues About How to Develop a Faster-Acting Antidepressant

Currently existing antidepressants often take weeks to work, which may seem like an eternity when you are depressed. In contrast, the experimental drug ketamine can relieve depression in a matter of hours. Unfortunately, ketamine will probably never come into use as an antidepressant because of its side-effects. Researchers are looking at ketamine, however, to learn how they can develop a faster-acting antidepressant and the results are promising.

Previously, scientists at the National Institute of Mental Health (NIMH) had learned that ketamine works by blocking a brain cell receptor called NMDA and, in a study published July 23 in the online edition of Biological Psychiatry, NIMH researchers Husseini K. Manji, MD, Guang Chen, MD, PhD, Carlos Zarate, MD, and colleagues reported that blocking the NMDA receptor actually was an intermediate step in the process which led to the increased activity of another receptor, AMPA. This increase in activity is what is responsible for the antidepressant effect of ketamine.

Both NMDA and AMPA are receptors for the neurotransmitter glutamate, one of the key messengers that facilitates brain cell communication. The idea of targeting the glutamate system is vastly different from the current way of thinking about depression treatment because it would directly affect key targets rather than waiting for a biochemical trickle down effect, which is what is believed to occur with existing antidepressants. Both methods relieve depression, but directly targeting these receptor sites would have a faster effect.

Although ketamine will probably never be used as an antidepressant, it is a very real possibility that scientists will be able to use this knowledge to create a whole new generation of rapid-action antidepressants.

More information about the study is available from NIMH.