What Is Spravato? How This FDA-Approved Treatment Works for Depression

If you’ve been struggling with depression that hasn’t responded to other treatments, you may have heard about Spravato®. But what exactly is it? How is it different from other medications? And most importantly, could it help you?

Let’s break it down.

What Is Spravato?

Spravato is the brand name for esketamine, a medication derived from ketamine. While ketamine itself has been used for decades in medical settings, Spravato was developed specifically to target treatment-resistant depression (TRD) and major depressive disorder with suicidal thoughts or behaviors (MDSI).

In 2019, the U.S. Food and Drug Administration (FDA) approved Spravato for adult patients who haven’t found relief from at least two other antidepressant treatments. This approval made Spravato the first new type of depression medication approved in decades, offering hope for people who hadn’t responded to more traditional options.

Unlike standard antidepressants (such as SSRIs or SNRIs) that target serotonin or norepinephrine, Spravato works on a different system in the brain: glutamate.

How Does Spravato Work?

Spravato works by targeting receptors in your brain’s glutamate system, which plays a major role in mood regulation, memory, and brain plasticity.

This unique mechanism allows it to:

Promote neuroplasticity: Spravato helps your brain form new connections, which may support healthier mood patterns.
Act quickly: Many patients report improvement within hours or days, while traditional antidepressants may take 4-6 weeks to show full effects.
Support treatment-resistant depression: By working on a different pathway, Spravato may help even when multiple other medications haven’t provided relief.

While researchers are still studying the full range of its effects, the emerging science suggests that Spravato’s ability to “reset” certain brain circuits may be one key to its success for many patients.

Whom Is Spravato Approved For?

Spravato is FDA-approved for:

Treatment-Resistant Depression (TRD): Adults who haven’t responded to at least two different antidepressant medications.
Major Depressive Disorder with Suicidal Ideation (MDSI): Adults experiencing suicidal thoughts or behaviors, where rapid symptom relief is critical.

It’s important to note: Spravato is not a first-line treatment. It’s designed for patients who have already tried other antidepressants without lasting results.

How Is Spravato Different From Ketamine Infusions?

Many people ask: isn’t Spravato just ketamine? The answer: yes and no.

Esketamine vs Ketamine: Ketamine is made of two mirror-image molecules: R-ketamine and S-ketamine. Spravato is made only from the S-enantiomer (esketamine).
FDA Approval: Spravato has gone through full FDA clinical trials and regulatory approval for specific diagnoses; ketamine infusions are often prescribed off-label.
Insurance Coverage: Because of its FDA-approved status, Spravato is often covered by insurance for eligible patients.
Delivery: Spravato is administered as a nasal spray in a certified clinic setting, while ketamine infusions are typically delivered intravenously (IV).

Both ketamine and Spravato work on the glutamate system, but their dosing, protocols, and administration differ.

What Is a Spravato Appointment Like?

Spravato must be administered under medical supervision at an approved treatment center like New Pathways Clinic.

Here’s what you can expect:

Before Your Session

You’ll complete a comprehensive evaluation to ensure Spravato is a safe fit for you.

During Your Session

You self-administer the nasal spray under supervision.
You’ll be monitored for about two hours in a comfortable, private setting.
Staff will observe your blood pressure, mental state, and any potential side effects.

After Your Session

You will need a ride home (no driving the day of your treatment).
You may feel tired, dizzy, or mildly dissociated, all of which typically wear off within a few hours.

How Often Is Spravato Given?

Spravato treatment happens in two phases:

1. Induction Phase (First Four Weeks):

2 treatments per week
Designed to help initiate symptom relief

2. Maintenance Phase:

Frequency is gradually reduced based on how you’re responding, first to weekly treatments
Some patients eventually receive treatment every 2-4 weeks

Throughout both phases, your care team closely monitors your progress and adjusts as needed.

Is Spravato Safe?

The FDA approval process involved extensive clinical trials. In these studies, Spravato showed significant effectiveness for many people with treatment-resistant depression, but it’s not for everyone.

Common side effects may include:

Dizziness or lightheadedness
Nausea
Mild dissociation or a dreamlike state
Increased blood pressure during treatment

Your care team will screen for any factors that may make Spravato inappropriate (such as certain medical conditions or substance use history).

Does Insurance Cover Spravato?

In many cases, yes.

Because Spravato is FDA-approved, most major insurance plans offer coverage for eligible patients who meet diagnostic criteria. At New Pathways, we work directly with your insurance provider to confirm your benefits, obtain pre-authorizations, and minimize any out-of-pocket surprises.

Why Spravato Represents a New Era in Depression Care

For decades, most depression treatments worked by adjusting serotonin levels. Spravato introduces a new way of thinking by targeting glutamate, building new neural pathways, and offering relief faster than most traditional medications.

While it’s not a cure or a one-size-fits-all solution, Spravato gives many people new hope when other treatments haven’t worked. And as part of a comprehensive care plan—alongside therapy, lifestyle support, and integration work—it can be a powerful tool in long-term recovery.

Ready to Learn If Spravato Is Right for You?

At New Pathways, we walk with you through every step of your care, from the initial assessment to ongoing support. Our team of experienced providers will take time to fully understand your history, your needs, and your goals—so we can help you decide whether Spravato may be the right next step.