What is Esketamine and who may benefit from using it?

Welcome to Mind Matters! Mind Matters is a forum where curious community members can send their questions about anything mental health and our local expert, Sue Wolff, PMHNP, will answer them in our monthly newsletter.

This month, we will answer a question about esketamine.

Dear Mind Matters,

I have been seeing information on the internet about a medication called esketamine and wanted to hear your perspective on what esketamine is and who may benefit from esketamine treatment.

What is Esketamine

Esketamine is a nasal spray derived from ketamine. Unlike traditional antidepressants, which target serotonin or dopamine, esketamine and ketamine work through a non‑traditional pathway, targeting glutamate. This different mechanism helps the brain cells form new connections, repair themselves, and break out of rigid, negative thought patterns associated with depression. This is why esketamine may help people who feel “stuck” despite multiple medication trials especially when treating depression.

Who May Benefit from Esketamine

Esketamine is best known for helping adults with treatment‑resistant depression, typically defined as depression that has not improved after two or more adequate antidepressant trials. For instance, esketamine may be consider when someone has been diagnosed with depression and has tried two different medications, such as escitalopram (Lexapro) and sertraline (Zoloft) but has not seen their depressive symptoms resolved on either medication. These are the cases where esketamine could be a consideration as the next step to treat their depression.

Although esketamine is not formally approved for primary anxiety disorders, research suggests it may help reduce anxiety symptoms that occur alongside depression, particularly in treatment‑resistant cases. Often anxiety and depression walk hand in hand, therefore, improvements in anxiety often parallel improvements in mood.

Unlike standard antidepressants that may take weeks to work, esketamine often shows improvement within 24 hours of the first dose. This rapid onset can be especially meaningful for patients experiencing profound functional impairment or emotional distress. In fact, esketamine may help those with active suicidal thoughts.

While it is not a cure, many patients describe the effects of esketamine as a “lifting” of depressive weight that allows other treatments—therapy, lifestyle changes, and medications—to work more effectively. In some cases, esketamine may also help relapse of depressive symptoms especially if used as “maintenance therapy”. This means that someone may be treated with esketamine for several months, take a break from the treatment and then use esketamine occasionally to prevent the return of their depression.

What Esketamine Does Not Do

Esketamine is not a first‑line treatment, and it is not intended to replace psychotherapy, lifestyle interventions, or comprehensive psychiatric care. Its benefits are most pronounced when used thoughtfully, in structured settings, and as part of an individualized treatment plan.

In Summary:

Esketamine helps by offering a rapid‑acting, evidence‑based option for people with treatment‑resistant depression, with added benefits that may include reduced anxiety symptoms and protection against relapse. For patients who have lost hope after multiple medication trials, esketamine represents a meaningful and science‑backed step forward in care.

Send us a message if you have a question that you would like to ask a mental health provider. Questions may be sent to: lupinemh@gmail.com