Ketamine Vs. Esketamine For Depression Treatment: What You Need To Know

Antidepressants were first invented in the 50s and have since been redesigned, and their impact is proven. They often work by increasing the abundance of brain communication chemicals, resulting in better moods. But, recent studies have shown that ketamine increases brain communication and mood. Ketamine has been around for longer, but esketamine treatment is a new option showing significant promise in managing depression.

How Do Ketamine and Esketamine Work?

  • Conventional Antidepressants

Antidepressants increase levels of chemicals in the brain, like serotonin, dopamine, and norepinephrine. The chemicals are key in communication in the brain between different cells and sectors. Increased brain communication leads to better moods and the subsiding of depressive symptoms.

  • Ketamine and Esketamine

These medications use a different mechanism for treating depression and do not impact the natural chemicals mentioned above. They increase the levels of an abundant neurotransmitter, glutamate, by blocking NMDA receptors. Additionally, blocking these receptors results in the release of other molecules. These improve communication between brain cells by creating new pathways. The activation of AMPA receptors is key due to the molecules starting this process called synaptogenesis.

What is Ketamine?

Many people have heard about ketamine as an anesthetic commonly used as a veterinary drug or on battlefields. The ketamine used for depression is administered in much lower doses and is a racemic ketamine. While it was FDA-approved as an anesthetic, this mixture of R and S ketamine is not yet approved for treating depression. This is because it is an old drug, and pharma is unwilling to fund trials. So, the American Psychiatric Association has insufficient information on its effectiveness for depression.

What is Esketamine?

Esketamine is better known by its brand name, Spravato. It is a different and newer version of ketamine that delivers the same rapid results as ketamine. It is the S version of ketamine and a new entrant into the pharmaceutical scene, meaning pharma is motivated to run trials. The FDA approved using the nasally administered drug for treating MDD and TRD in 2019. Esketamine is efficient in many aspects of depression treatment. These include lowering suicidal thoughts at the beginning of treatment.

Differences Between Ketamine and Esketamine

  • Potency

The first key difference between the two drugs is the potency levels and the side effects. Esketamine is much more potent and thus requires lower doses. It leads to fewer side effects than the parent drug, ketamine. Yet, both can become addictive and are categorized as DEA Schedule III controlled substances.

  • Administering

The two also differ in the method of administering, with ketamine being an intravenous drug and esketamine being a nasal drug. IV Ketamine administration can be inconvenient and painful. Esketamine, on the other hand, is also doctor administered but does not require any needle pricks and thus not painful and extremely convenient. For more information about Esketamine treatment, visit or call  Wonder Years Psychiatric Services at one of our offices.