Discovering new treatments for mental health (and other) diseases is a complicated endeavor with plenty of dead ends. Sometimes, however, an impractical finding opens the door to new possibilities. This is the case with ketamine for the treatment of depression.


The Food and Drug Administration has approved ketamine as an anesthetic for children and animals. It's also an abused substance. Users call it Special K, or K. Ketamine produces feelings of disconnection from oneself and reality, but users do not experience the post-high crash associated with some psychotic substances. Ketamine can be toxic and causes damage with repeated use.

In initial lab studies with animals and clinical studies with small groups of patients, ketamine-or, more precisely, the mechanism by which it works-shows promise as a treatment for depression.

Ketamine and Depression Treatment

Most antidepressants target the neurotransmitter serotonin and work by triggering the birth of new neurons in the hippocampus, an area of the brain involved in forming memories. Ketamine, in contrast, affects glutamate, an excitatory neurotransmitter. When we're under stress, the brain releases an excess of glutamate, which can damage or kill cells, especially in the hippocampus, and may lead to depression.

Ketamine appears to shut down one class of cell receptors for glutamate. Rather than stimulate development of new neurons, as serotonin-based drugs do, ketamine seems to stimulate the connection of existing neurons in the prefrontal cortex, the area of the brain responsible for cognitive thinking and judgment. In other words, it restores connections between brain cells damaged by stress. Some scientists call ketamine a "reset button" for brains stuck in dysfunctional ruts.

In preliminary studies, many patients with hard-to-treat depression improved following an infusion of ketamine. Unlike most antidepressants, which can take weeks to take effect, ketamine takes affect within hours. This can be critical for patients having suicidal thoughts.

Ketamine is not a practical solution for routine depression treatment. It may produce significant side effects, such as short-term psychotic symptoms, and physicians must administer ketamine intravenously. Furthermore, although it produces a rapid response, it is short lasting and patients eventually relapse.

However, by understanding how ketamine works and what makes it effective, scientists may find a drug or drug component that works in similar ways without the dangerous side effects. This knowledge may also help researchers develop effective new depression treatments that target the glutamate system and take effect quickly. Furthermore, ketamine may have a role as an add-on medication when conventional antidepressants alone fail to relieve depressive symptoms.


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National Institute of Mental Health. "NIMH Radio: Dr. Ron Duman of Yale University Talks About Ketamine Research and Treatment for Major Depression." Web. 9 September 2010.

Medical News Today. "New Form Of Ketamine Treats Depression 'Like Magic'." Web. 20 August 2010.

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