Ketamine For Depression

How an anesthesia medication is used to treat depression

Psychiatrists at Yale were the pioneers in the field of Ketamine in the treatment of depression. If you’d like to read their full take on it, you can do so here.

The FDA cleared esketamine (a derivative of ketamine) in the form of a nasal spray for the treatment of depression back in March 2019. This represented the first new treatment for depression to hit the market in decades.

“This is a game changer,” says John Krystal, MD, chief psychiatrist at Yale Medicine and one of the pioneers of ketamine research in the country. The drug works differently than those used previously, he notes, calling ketamine “the anti-medication” medication. “With most medications, like valium, the anti-anxiety effect you get only lasts when it is in your system. When the valium goes away, you can get rebound anxiety. When you take ketamine, it triggers reactions in your cortex that enable brain connections to regrow. It’s the reaction to ketamine, not the presence of ketamine in the body that constitutes its effects,” he says.

Chemically speaking, there are two types of ketamine: the nasal spray noted above and the traditional IV administered version that was originally used for anesthesia. I dug a little deeper to see what was really different other than the mechanism of delivery and found this:

The chemical structure of ketamine is a racemic mixture made up of two molecules, S-ketamine and R-ketamine. One way to think of the two molecules is like hands. They are mirror images of each other but can’t be superimposed on each other, just as your hands mirror each other but aren’t exactly identical. The two molecules bind differently with different receptors in your brain, helping to reduce symptoms of depression, including suicidality.

Apparently, the nasal spray contains ONLY the S-ketamine and the mechanism of action is theorized to be:

[It] appears that the S molecule in the medication binds to N-methyl-D-aspartate (NMDA) receptors in the brain.

NMDA receptors bind to glutamate, a type of neurotransmitter. The bond between glutamate and NMDA receptors restricts the function of glutamate, which can trigger depressive symptoms. S-ketamine can increase glutamate levels, allowing the neurotransmitter to connect to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. AMPA receptors improve communication among neurons in the brain, helping to stabilize mood and enhance cognition and thought patterns.

On the other hand, the IV ketamine contains both the S and the R types but is not yet fully FDA approved (it is being used off-label for this purpose since it IS approved as an anesthetic. In fact, since the announcement that ketamine was producing such clinical results with depression, ketamine clinics and services have been popping up across the country. There is even an online service that ships it to your home (I’m not saying who this is because I recognize some downsides to this which I will talk about below).

The Pros for ketamine have been pretty widely shown, but let’s take a look at the downsides:

Ketamine — the Cautions

All medications are going to have some potential side-effects, and ketamine is no different. Potential problems include: dizziness, high blood pressure, feelings of derealization or detachment. At higher doses, there can even be amnesia, delirium, slowed breathing, impaired motor function, seizures, brain damage, or even death. When administered and properly supervised by a physician, most of these side-effects are likely to be minimal.

However, ketamine has serious abuse potential. Maybe you’ve never heard of ketamine as a drug of abuse, but then again maybe you have — by its street name “Special K.” According to https://www.verywellmind.com/basic-facts-about-ketamine-67495:

As a street drug, ketamine has become popular as a “club drug,” used by teens and young adults at dance clubs and events known as raves. Because it is odorless and tasteless and can be added to beverages without being detected, there are also reports of it being used as a date-rape drug. In addition to rendering victims immobile, it can also induce amnesia making it difficult to recall events that took place while under the influence.

Some people worry that by making ketamine more accessible (remember I said it can be shipped to your home?), we are risking that there will be even more abuse potential.

Ketamine — Only one piece of the solution

Even the researchers at Yale have pointed out that ketamine is only PART of a comprehensive approach to the treatment of depression.

“Patients will call me up and say they don’t want any other medication or psychotherapy, they just want ketamine, and I have to explain to them that it is very unlikely that a single dose, or even several doses of ketamine alone, will cure their depression,” says Dr. Sanacora. Instead, he explains, “I tell them it may provide rapid benefits that can be sustained with comprehensive treatment plans that could include ongoing treatments with ketamine. Additionally, it appears to help facilitate the creation new neural pathways that can help them develop resiliency and protect against the return of the depression.”

Yes, I have to say it again here, There is No Wisdom in Drugs (Alone).

This is why Dr. Sanacora believes that ketamine may be most effective when combined with cognitive behavioral therapy (CBT), a type of psychotherapy that helps patients learn more productive attitudes and behaviors. Ongoing research, including clinical trials, addressing this idea are currently underway at Yale. — https://www.yalemedicine.org/news/ketamine-depression

If you or a loved one are struggling with depression, be sure to seek out CBT-trained therapists to assist you in changing negative thoughts and behavior patterns. Ketamine might be the right thing for you initially, but it’s not the only thing you likely need.