In early 2019, an esketamine nasal spray was approved by the FDA for adults with treatment-resistant depression. Its FDA-approved uses were later expanded to include patients suffering from acute suicidal ideation. But what is esketamine, and how is it different from regular ketamine?
Breaking Down Ketamine
Ketamine is a chiral compound consisting of two isomers. “Isomers” are molecules with the same chemical formula and the term “chiral” comes from the Ancient Greek word for hand.
Like your hands, the isomers are mirror images of each other. There is a right-handed version of ketamine and a left-handed version of ketamine. These are S-ketamine and R-ketamine, also known as esketamine and arketamine, respectively. When we hear of ketamine without qualifiers, this usually refers to an equal mixture of both isomers.
What’s the Difference?
Esketamine and arketamine affect the brain in different ways. Arketamine has shown more marked and longer-lasting antidepressant-like effects. Someone taking esketamine is more likely to experience dissociative effects. This could include ego-disintegration and hallucinatory phenomena.
Ego dissolution can be a very good thing, but it is natural to wonder why esketamine has received FDA approval for treating depression while its mirror image, a more powerful antidepressant has not.
Ketamine has been around for a long time. In 2022, it is relatively inexpensive.
Some have cynically attributed the development of esketamine to the greed of Big Pharma. As Dr. Wesley Ryan says, “This is one of the oldest tricks in the book. We see this all the time with pharmaceutical companies patenting isomers of generic drugs.”
Last year, a Canadian court even ruled that esketamine was not an “innovative drug”. Nonetheless, esketamine does appear to have some benefits over ketamine, including less drowsiness, lethargy and cognitive impairment.
As for arketamine, the FDA just gave a pharmaceutical company permission to perform clinical trials.