Ketamine May Hold Promise for Treating Depression

Dr. Sharon Orrange
Dr. Orrange is an Associate Professor of Clinical Medicine in the Division of Geriatric, Hospitalist and General Internal Medicine at the Keck School of Medicine of USC.
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There is a huge need for rapidly acting antidepressants. Suicide is a leading cause of death in young adults in the United States and currently available antidepressants often take weeks to kick in. There is great interest in glutamate mechanisms in major depression as a promising new target. One of the drugs that works on glutamate you may know as an illegally obtained illicit drug called ketamine or Special-K. Ketamine is used rarely for anesthesia in people and more commonly in animals.

Try to wrap your mind around the use of ketamine in depression and remember that SSRI antidepressants like citalopram (Celexa) improve depression only about 28% of the time and take 3 – 4 weeks for any effect.

Let’s look at the science. In studies on people with depression, one intravenous dose of ketamine can alleviate depressive symptoms in patients within hours, and its effects last up to 14 days. If someone is suicidal this may present a better solution than taking an antidepressant for 3 weeks before you may feel improvement.

How does ketamine work for depression? The answer lies in the NMDA glutamate receptor, and ketamine is an NMDA receptor antagonist (which means it blocks the effects). While we don’t know the true role of glutamate in major depression, ketamine causes an increase in glutamate release which may be the mechanism of its antidepressant effect.

How is ketamine used? In studies on depression and bipolar disorder, ketamine is given as an infusion over 40 minutes. Many studies are now looking at repeated infusions which have a more sustained effect than a single dose.

Does it work? Yes. The response rate in people with major depression is 20 – 90%. In people given repeat infusions it’s better, and after the 6th ketamine infusion one study showed significant improvement in 85% of folks with depression. In those who have received Ketamine infusions for 5 days, the improvement in their symptoms lasted for 12 months after use.

What’s the downside? Well, the psychotomimetic effects of Ketamine are impressive. Psychotomimetic effects mean Ketamine causes psychosis, delusions, delirium, and hallucinations. It also causes dissociative effects meaning users feel detached from reality.

What other drugs work like ketamine and can be used for depression? GLYX-13 (this will get a new name if it’s FDA approved) is a new NMDA receptor partial agonist that has completed trials and been shown to be effective for major depressive disorder. GLYX-13 does not cause those dissociative effects like Ketamine with less visual and auditory distortions among other things.

Stay tuned because there appears to be a role for ketamine in bipolar disorder as well.

Dr O.

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