The Science behind Spravato: How Ketamine is Changing the Game

Spravato is a breakthrough medication approved by the U.S. Food and Drug Administration (FDA) in 2019 for treating treatment-resistant depression (TRD). Spravato is a nasal spray formulation of esketamine, the S-enantiomer of ketamine, an anesthetic and dissociative hallucinogen. Ketamine has been used for decades as an anesthetic in medical settings, but it has expanded to treat various psychiatric conditions, including depression and bipolar disorder. Here are some insights from Dr. Bryon K Evans on the science behind Spravato and how ketamine is changing the game in mental health treatment.

Mechanism of action

Ketamine works differently from traditional antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). While SSRIs and SNRIs primarily target neurotransmitters like serotonin and norepinephrine, ketamine acts on a different receptor in the brain called the N-methyl-D-aspartate (NMDA) receptor. By blocking the NMDA receptor, ketamine modulates glutamate, an excitatory neurotransmitter involved in learning, memory, and mood regulation.

Rapid and sustained effects

One of the key advantages of Spravato is its rapid onset of action. Traditional antidepressants can take weeks or months to alleviate symptoms, but Spravato can produce noticeable improvements within hours. This fast-acting effect is crucial for individuals with severe depression who are at an increased risk of suicide or have not responded to other treatments. Studies have shown that the benefits of Spravato treatment can be sustained longer than traditional antidepressants.

Neuroplasticity and synaptic connections

Another fascinating aspect of ketamine’s mechanism of action is its ability to promote neuroplasticity—the brain’s capacity to rewire and form new synaptic connections. Chronic stress and depression have been associated with reduced synaptic connections in certain brain regions, including the prefrontal cortex. Ketamine administration can increase the production of brain-derived neurotrophic factor (BDNF), a protein that promotes the growth and survival of neurons. This, in turn, helps to restore and strengthen synaptic connections, which can reverse the negative effects of depression.

Glutamate and the default mode network

The modulation of glutamate by ketamine can affect the default mode network (DMN), a collection of brain regions active during introspection and mind wandering. In depression, the DMN can become overactive, leading to excessive rumination and negative self-referential thinking. Ketamine’s action on the NMDA receptor helps to reduce DMN activity, allowing for a shift in thought patterns and a break from the cycle of negative thinking.

Safety and side effects

While ketamine has shown significant promise in treating depression, it is important to consider safety and potential side effects. Spravato administration requires close monitoring, which can cause dissociation, sedation, and increased blood pressure and heart rate. Therefore, it is only administered in a healthcare setting under the supervision of a healthcare professional. The potential for abuse and addiction is also a concern, which is why Spravato is classified as a controlled substance. As researchers continue to study the science behind Spravato and ketamine, ongoing studies are exploring the use of ketamine for other psychiatric conditions, such as Post-traumatic stress disorder (PTSD), as well as its potential in combination with other therapies.

Speak to your doctor at Psychiatric Consultants of Atlanta to learn more about Spravato treatment.