I've been reading that ketamine can help with severe depression when other treatments haven't worked. Should I ask my doctor to try it?

The short answer to this very good question is that this treatment is still considered experimental. Ketamine is not approved by the FDA to treat depression, it is not available outside of research studies. At this point, it is more useful to help us understand the biology of depression and to point the way to future treatments.

However, let’s spend some time describing what ketamine is and what it is supposed to do.

Ketamine is an experimental drug currently under study at the National Institute of Mental Health and other research infrastructures around the world. Under the leadership of Carlos Zarate, MD, this compound has been shown to possess rapid and marked short-term efficacy in the treatment of major depressive episodes in both Major Depressive Disorder (unipolar disorder) and bipolar disorder. Not only do the symptoms of depression go away quite quickly, but thoughts of suicide do so as well. The results of Dr. Zarate’s studies are quite remarkable because it normally takes several weeks to make a major depressive episode go away. Unfortunately, Ketamine can have severe side effects, and it is subject to abuse.

Ketamine is a drug which has been used in human and veterinary medicine. When used in human medicine, it is used prior to surgery by anesthesiologists to induce and maintain general anesthesia. Although Ketamine has been used safely and effectively by anesthesiologists, it has gained some notoriety for its use on the streets as a way to induce hallucinations, known as “Special K”.

Let’s finish by talking about how ketamine is important in the regulation of mood. Ketamine is believed to have its effect by changing how nerve endings talk to one another. When one nerve talks to another nerve within the brain, it does so by putting out neurotransmitters. There are three categories of neurotransmitters amines (norepinephrine, serotonin, dopamine, etc.), peptides (enkephalins, neuropeptide Y, substance P, etc), and amino acids (glutamate, glycine). Ketamine is now known to affect the excitatory amino acid, glutamate. Glutamate is one of 20 amino acids (the building blocks of the human body), and one of only two primary excitatory amino acids the other is aspartate.

Stay tuned for more developments on ketamine as it is likely to lead to major breakthroughs in at least the short-term treatment of major depressive episodes.

About the Doc

About the Doc

Joseph Calabrese, MD, holds the Bipolar Disorders Research Chair and is Professor of Psychiatry at Case Western Reserve University. He is also the Director of the Mood Disorders Program within the Department of Psychiatry at the University Hospitals Case Medical Center. Dr. Calabrese co-directs an NIMH-funded ‘Bipolar Disorders Research Centre, whose projects include child and adolescent research conducted by Bob Findling, geriatric research conducted by Martha Sajatovic, dual diagnosis research conducted by Keming Gao, metabolic research conducted by Dave Kemp, and molecular genetics conducted by Jinbo Fan. Dr. Calabrese has received numerous research grants from the NIMH and other Federal agencies and has published over 300 peer-reviewed papers. Dr. Calabrese has received the NARSAD Lifetime Achievement Award in 2005 and the Gerald L. Klerman Lifetime Achievement Award in 2008.

View all Ask a Doc Features

Have a question for our docs?
Submit Your Question