What’s The Difference Between Ketamine & Esketamine?

What’s The Difference Between Ketamine & Esketamine?

What’s The Difference Between Ketamine & Esketamine?

As researchers continue to advance our understanding of mental health, novel treatments like ketamine and its enantiomer, esketamine, have emerged on the scene. These two compounds, while closely related, have distinct characteristics and uses in the field of psychiatry.

Understanding Ketamine

Originally developed as an anesthetic in the 1960s, ketamine has more recently gained attention for its rapid-acting antidepressant, antianxiety, and chronic pain-relieving effects. Its mechanism of action is unique from most psychiatric medicines; it blocks NMDA receptors in the brain, which modulate glutamatergic neurotransmission and are involved in mood, emotional, and pain regulation.

Despite being a rapid-acting medication that can provide relief in a matter of hours or days for some people, ketamine’s greatest strength probably lies in its ability to provide symptom relief where traditional medications like antidepressants, anxiolytics, and chronic pain medications like opioids have had little to no success.

Ketamine is typically administered intravenously in small controlled doses by a licensed medical team, although oral and intranasal forms exist. This form of treatment, widely known as ketamine infusion therapy, is the most common form of ketamine administration.

Some of the conditions ketamine can help address include depression, anxiety disorders, PTSD, bipolar disorder, OCD, substance use disorders, and a variety of chronic pain disorders. However, it is yet to be approved by the FDA for these uses and is mainly considered an experimental treatment.

What is Esketamine?

Esketamine, sold under the brand name Spravato, is a novel nasal spray medication created by splitting the ketamine molecule into two distinct molecules: (R)-ketamine and (S)-ketamine. Esketamine, the (S)-ketamine form, is thought to be more potent, which potentially means the therapeutic benefits of the medication can be achieved using even lower doses of the medication.

Unlike ketamine, in 2019, the FDA approved esketamine (Spravato) for use as a complementary medication for treatment-resistant depression in conjunction with an oral antidepressant. The development of esketamine provides a regulated and standardized treatment option.

Distinguishing Between Ketamine and Esketamine

Molecular Structure

While esketamine is a part of the ketamine structure, it is not identical. Ketamine is a racemic compound, meaning it contains two enantiomers: “S” (esketamine) and “R” (arketamine). These enantiomers are mirror images of each other and can have slightly different effects on the body.

Administration Methods

Ketamine is administered intravenously, usually in a clinic setting, requiring monitoring by healthcare professionals. On the other hand, the esketamine nasal spray is often self-administered, a method that can be more convenient and less invasive. However, similar to ketamine, its administration should be done in a clinical setting under the guidance and supervision of a qualified professional.

FDA Approval

In the United States, esketamine has explicit FDA approval for use in treatment-resistant depression. Conversely, while ketamine is FDA-approved as an anesthetic, its use for depression and other conditions in the clinical setting is considered “off-label,” and is often a last resort when all other conventional interventions have been exhausted.


Ketamine treatments can be expensive and are often not covered by insurance because they’re considered off-label. In contrast, because esketamine is FDA-approved for depression, it’s more likely to be covered by insurance, potentially making it more accessible to some patients.


Ketamine has shown promise for treating a variety of mental and physical health disorders, including depression, anxiety, PTSD, bipolar disorder, OCD, substance use disorders, and various forms of chronic pain. Esketamine is only approved for the treatment of depression. This makes ketamine a more versatile option.

Final Thoughts

Ketamine and esketamine both represent breakthroughs in the treatment of treatment-resistant depression and potentially other disorders. Although they stem from the same root compound and have similarities, their differences in administration, accessibility, and applications are significant.

At Serenity Health, we specialize in administering ketamine infusion therapy in a controlled and safe environment. Our trained professionals are skilled in monitoring and adjusting treatment to ensure optimal outcomes for every individual.

If you or a loved one have been grappling with treatment-resistant depression, chronic pain, or other conditions and traditional therapies have not provided relief, ketamine infusion therapy may be an option worth exploring. We invite you to reach out to us to discuss whether ketamine treatment could be a suitable pathway for you.

If you are interested in learning more about ketamine treatment contact Serenity Health and request your consultation today.

Share Now :

Related Posts