Esketamine: A New Frontier in Depression Treatment

In early 2019, the FDA approved an esketamine nasal spray for adults with treatment-resistant depression. Later, its approved uses expanded to include individuals experiencing acute suicidal ideation. But what exactly is esketamine, and how does it differ from traditional ketamine?

Understanding Ketamine

Ketamine is a chiral compound, existing in two mirror-image isomers. The term "chiral" hails from the Ancient Greek for "hand," which it is named after, seeing that the two isomers are nonsuperimposable, similar to your left and right hands. Ketamine's two isomers include S-ketamine (esketamine) and R-ketamine (arketamine). When ketamine is referred to without qualification, it is generally understood to be a 50/50 mixture of both isomers.

Esketamine vs. Arketamine

Esketamine and arketamine interact differently with the brain. Research indicates that arketamine may offer stronger and longer-lasting antidepressant effects. However, esketamine is more likely to induce dissociative experiences, such as ego dissolution and hallucinations.

While ego dissolution can be therapeutically beneficial, it raises questions about why esketamine, rather than arketamine, has gained FDA approval for treating depression—especially when arketamine appears to have more potent antidepressant properties.

Ketamine in Modern Medicine

Ketamine has been in use for decades and is relatively inexpensive. The development and patenting of esketamine have led to criticism. According to some experts, such as Dr. Wesley Ryan, this is a classic example of pharmaceutical companies making money off of patenting specific isomers of generic drugs. In 2022, a Canadian court even ruled that esketamine was not an "innovative drug.

That being said, esketamine does possess some advantages over traditional ketamine, including less drowsiness, lethargy, and cognitive impairment. Meanwhile, arketamine remains under investigation, with the FDA recently greenlighting clinical trials to explore its potential.

Esketamine may not be a perfect solution, but it marks an important step forward in the management of complex mental health disorders.