According to the ADAA, depression affects 40 million adults in the United States, yet it remains a mystery as to what really causes depression and how it can be effectively treated. Traditionally, doctors will prescribe antidepressants known as SSRIs. But unfortunately, this medication isn’t always effective. So in the 1990s, Dr. John Krystal, MD, chief psychiatrist at Yale Medicine, was pioneering research into ketamine as an antidepressant. To understand why ketamine is such a game-changer when treating depression, we must first understand how traditional SSRIs work.

The Discovery of SSRIs

It is believed that people with depression have low serotonin levels. This theory came about by observing patients given certain drugs to treat other diseases like high blood pressure and tuberculosis. These drugs seemed to affect people’s moods drastically. Those that lowered serotonin levels caused depression-like symptoms; others that raised serotonin levels created euphoric-like feelings in depressed patients. As a result, a new class of drugs meant to treat depression, known as selective serotonin reuptake inhibitors (SSRIs), were introduced. The first of these drugs to come to market was Prozac. But eventually, it was revealed that serotonin levels alone didn’t fully explain depression. 

GABA and Glutamate

Based on data collected, SSRIs were of little help to more than one-third of people given them for depression. Still, growing research showed that the neurotransmitters these drugs target (like serotonin) account for less than 20 percent of the neurotransmitters in a person’s brain. The other 80 percent are neurotransmitters called GABA and glutamate.    

The two neurotransmitters form a complex push-and-pull response, controlling electrical activity in the brain. Researchers believe they may be responsible for regulating most brain activity, particularly mood. In addition, intense stress can alter glutamate signaling in the brain and affect the neurons, making them less adaptable and less able to communicate with other neurons. This indicates stress and depression make it harder to deal with challenging events, a cycle that can make matters even worse for people struggling with complex life events.  

How Ketamine Differs

Research suggests that one of ketamine’s significant actions is as an N-methyl-D-aspartate (NMDA) receptor antagonist; that is, it blocks activation of the NMDA receptor. This action leads to increased release of glutamate, which is involved in neuronal plasticity and synaptic growth and repair. Through complex pathways, these effects lead to the release of Brain-derived neurotrophic factor (BDNF), a substance responsible for the maintenance of healthy neurons and their connections, known as synapses.

Increased BDNF has been shown to repair and regrowth of damaged synapses and their neuronal connections caused by chronic stress in animal models. Likewise, in humans, ketamine is thought to create new neuronal circuits and/or repair of the healthy neuronal connections that existed in the brain before the patient suffered from depression, PTSD, OCD, and/or chronic anxiety.

“I think the interesting and exciting part of this discovery is that it came largely out of basic neuroscience research, instead of by chance,” says Gerard Sanacora, MD, PhD, a psychiatrist at Yale Medicine who was also involved in many of the ketamine studies. “It wasn’t just, ‘let’s try this drug and see what happens.’ There was increasing evidence suggesting that there was some abnormality within the glutamatergic system in the brains of people suffering from depression, and this prompted the idea of using a drug that targets this system.”

Research and studies continue to be conducted on Ketamine Infusion Therapy and its effectiveness in treating depression, anxiety, and PTSD. If you or someone you know is suffering from any of these disorders, find out how Ketamine Infusion therapy could help by clicking here or calling our clinic at (505) 639-4973.