esketamine or ketamine

Ketamine for Depression | Esketamine vs Ketamine

People who suffer from depression, a mental health disorder and serious illness, can struggle to find relief for their symptoms. Seeking treatment from a professional is a good first step. Mental health treatment can involve the use of evidence-based pharmacology, including the use of esketamine or ketamine for depression.

Treatment-Resistant Depression

In the US, more than 17 million adults are dealing with depression. Most of those individuals receive help in the form of therapy and medication, but as much as 35% of the affected population does not receive treatment, even after they have suffered a major depressive episode.

People who have been diagnosed with a major depressive disorder and who have tried at least two antidepressant treatments but have not responded, are considered to have treatment-resistant depression. These are the individuals who might benefit from the use of esketamine or ketamine for depression.


Major depression is the leading cause of disability throughout the world. Ketamine is a medication that was originally used as an anesthetic, in operating rooms and on the battlefield, but is now showing promise in treating major depression, particularly if it has been shown to be resistant to other treatment approaches.

There are two main types of ketamine. Racemic ketamine is usually given as an infusion into the bloodstream, intravenously. Esketamine, recently approved by the FDA, is administered as a nasal spray. Ketamine is thought to help people successfully manage their depression when other attempts at treatment have not worked and they are diagnosed with treatment-resistant depression.

It is thought that ketamine works by targeting the NMDA receptors in the brain, increasing the amount of a neurotransmitter called glutamate. The process involves activation of another receptor called AMPA and blocking the NMDA receptors, which affects thought patterns, cognition, and mood.

Ketamine may also reduce the signals involved in inflammation which have been linked to mood disorders and may facilitate communication within particular areas of the brain. All of these are being studied to determine whether ketamine actually works in several ways at the same time, making it effective for the treatment of treatment-resistant depression.


In March 2019, the Food and Drug Administration (FDA) approved the medication esketamine, which was the first new medication developed and approved for the treatment of depression in decades. Esketamine, derived from ketamine, is administered by a nasal spray.

Tiffany Farchione, M.D., acting director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research, said, “There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition. Controlled clinical trials that studied the safety and efficacy of this drug, along with careful review through the FDA’s drug approval process including a robust discussion with our external advisory committees, were important to our decision to approve this treatment. Because of safety concerns, the drug will only be available through a restricted distribution system and it must be administered in a certified medical office where the health care provider can monitor the patient.”

Esketamine is a version of the ketamine molecule, making up half of what is found in the anesthetic form of the drug. The two work in similar ways but the chemical makeup of esketamine allows it to bind more tightly to those NMDA receptors, which makes it two to five times more potent than ketamine. Patients will need a lower dose of esketamine and the nasal spray enables the patient to take it more easily, although still under professional supervision, than the intravenous treatment required for the delivery of ketamine.

As part of the FDA approval process, a study was conducted in which 70% of the patients with treatment-resistant depression who were started on the nasal spray esketamine showed improvement. However, it is advised that ketamine and esketamine are most effective when combined with cognitive behavioral therapy (CBT), a type of psychotherapy that helps patients learn more productive attitudes and behaviors for managing their depression.

Contact Recovery Without Walls for Ketamine-Assisted Psychotherapy

At Recovery Without Walls, we provide a unique experience to help you heal. Our approach involves exceptional psychotherapy, evidence-informed research, and integrative healing methods, to help you with the treatment of depression, anxiety, phobias, chronic pain, and addiction. We also offer help with anti-anxiety and antidepressant medications.

During the COVID-19 pandemic, we encourage you to email or call us for care and answers to your questions. Our providers continue to work to help you through treatment and recovery. Contact us today to learn more about the link between mental illness and substance use disorder and to get help.