Esketamine vs Ketamine: 5 Most Common Questions

What are the Main Differences between Ketamine and Esketamine?

About the Author Dr. Steven P. Levine is a board-certified psychiatrist internationally recognized for his contributions to advancements in mental health care. Though he is a psychiatrist who places great emphasis on the importance of psychotherapy, medication is often a necessary component of treatment, and he was dissatisfied with the relatively ineffective available options with burdensome side effects. Dr. Levine pioneered a protocol for the clinical use of ketamine infusions, has directly supervised many thousands of infusions and has helped establish similar programs across the country and around the world.

Esketamine vs ketamine; both drugs are gaining traction as rapid-acting antidepressants. Esketamine is currently under development by Johnson & Johnson and is in the process of seeking FDA approval in a nasal spray formulation for similar indications as ketamine, to treat major depressive disorder and treatment-resistant depression.¹  The news is exciting because esketamine may be the first ketamine-derived medicine approved for clinical use to treat depression. The clinical team at Actify is starting to field questions about this potential breakthrough and what it could mean for the thousands of patients we currently treat and hope to treat. In this post, I’d like like to address 5 of the most frequently asked questions about esketamine.

1. Esketamine vs Ketamine: Molecular Differences

Esketamine is part of ketamine. In nature, many molecules exist as mirror images of each other, the only difference being the direction they spin, making them non-superimposable. A mixture of these two mirror-image molecules is called a racemic mixture. It is possible to separate racemic mixtures into what are called enantiomers. Esketamine is the s-enantiomer of ketamine.

2. Which Treatment is More Effective, Esketamine vs Ketamine?

Many of our patients are curious as to how esketamine compares to ketamine in alleviating treatment-resistant depression and other mental health conditions, but it’s hard to say at this point. The two medicines have not been compared and may never be. That said, esketamine has reported good outcomes in recent clinical trials for treating both depression and suicidal thinking.

3. Why develop esketamine when ketamine works so well?

In order for the FDA to approve ketamine for psychiatric indications and have insurance companies pay for treatment, it would require large-scale clinical trials that cost hundreds of millions of dollars. Ketamine is an older, generic drug that has limited profit potential for a pharmaceutical company to recoup the costs of developing a new indication. Esketamine, however, is patented and therefore has the commercial potential to cover the clinical trial costs. To learn more about Big Pharma and how it operates, read Big Pharma is Watching.

4. Will esketamine be available through infusion?

The primary development of esketamine is for intranasal delivery within a controlled medical setting (e.g. an outpatient medical facility).  An intranasal delivery system has better absorption than other delivery routes, such as oral, but is not as well absorbed as an IV infusion.  With intranasal, less of the medicine reaches the brain and accurate dosing is tricky in comparison to infusion. That aside, clinical study results on intranasal esketamine look promising and we remain hopeful!

5. Will Actify be offering esketamine?

Actify strongly believes in increasing access to care and making the best treatments available. If there is insurance coverage for esketamine, we would certainly want to make it available, adding it to our offerings of advanced mental health treatments.


1. Janssen Press Release.Janssen Submits Esketamine Nasal Spray New Drug Application to U.S. FDA for Treatment-Resistant Depression. Sep 2018.

Steven Levine, MD, is the CEO and founder of Actify Neurotherapies. He has been treating patients with ketamine therapy since 2011.