Esketamine is used on top of antidepressants to treat treatment-resistant depression. The reason the esketamine works when antidepressants alone do not is because it does not work like an antidepressant.
Typical antidepressants raise the levels of certain chemicals like dopamine, norepinephrine, and serotonin that naturally occur in the brain as neurotransmitters. Many experts believe that depression and other mental health conditions are linked to an imbalance of these neurotransmitters. Ideally, antidepressants work to restore the balance of these neurotransmitters, resulting in fewer depression symptoms and improved mental health.
Esketamine works similarly to antidepressants, but it increases the brain's most prevalent chemical messenger: glutamate levels. Increased glutamate levels result in a greater reach and more substantial impact on brain cells with a single dose compared to antidepressants alone. While most antidepressants take weeks to work, esketamine can work as quickly as the first few hours or days after starting treatment.
This is not to say that antidepressants don't have a viable place in the treatment of depression. Millions of people each year do get relief from symptoms of depression thanks to these medications. However, they don't work for everyone. Esketamine can be an additional treatment that helps people suffering from TRD find relief, and it could result in having the patient take fewer antidepressants in the future.