What Is Spravato Esketamine? How the FDA-Approved Nasal Spray Works

Chronic depression symptoms that do not respond to standard oral meds require a different clinical approach.

Knowing how this medical breakthrough differs from the meds you may have tried in the past is the first step toward finding relief. Read on to understand what makes Spravato unique and how it could be the treatment option that finally works for you.

What Is Spravato Esketamine: What Is Spravato and How Is It Different from Other Antidepressants?

Spravato is a nasal spray for adults with hard to treat depression. Its active part is esketamine. This medicine works in a new way. Most pills for depression focus on a chemical called serotonin. Spravato targets the glutamate system in the brain. This helps nerve cells talk to each other better.

A new path for hard to treat depression

About 21 million adults in the U.S. have major depressive disorder. For many, common pills do not give enough relief. In fact, about one third of people with depression do not respond to oral drugs. Doctors call this treatment-resistant depression.

You may have this type of depression if you have tried two or more pills but still feel low. Relief Mental Health offers comprehensive depression treatments to help people find a way forward. Our team works to find the right care when other options fail.

Spravato vs standard oral pills

The main difference between Spravato and pills is speed. Standard pills can take weeks to work. Spravato can start to reduce symptoms within 24 to 48 hours. It is an FDA-approved treatment for adults. It can be used alone or with an oral pill.

• Target: Pills often focus on serotonin. Spravato works on NMDA receptors.
• Speed: Pills take time to build up. Spravato can work in just a few days.
• Form: Most drugs are daily pills. Spravato is a nasal spray used in a clinic.
• Care: You take pills at home. You must take Spravato at a certified site with a doctor near you.

Feature	Spravato (Esketamine)	IV Ketamine	Oral Antidepressants
FDA approval for TRD	Yes (2019 adjunctive, 2025 monotherapy)	Off-label only	Yes (first-line)
Administration	Nasal spray in clinic	IV infusion in clinic	Self-administered at home
Onset of action	24-48 hours	Hours to days	Varies
Mechanism	NMDA antagonist (glutamate)	NMDA antagonist (glutamate)	SSRI/SNRI (serotonin)
Clinic monitoring	2 hours post-dose	1-2 hours post-infusion	None required
Frequency	2x week induction, then weekly	2-3x week induction, then monthly	Daily

Why glutamate matters

For years, drugs for depression have focused on serotonin. Spravato is the first of its kind to target glutamate. This is the most common chemical messenger in the brain. By acting as an NMDA receptor antagonist, it helps brain paths that may be weak from stress. You can learn more about SPRAVATO treatment to see if it is right for you.

How Does Esketamine Work in the Brain?

Most oral antidepressants like SSRIs work on serotonin. These drugs aim to raise the levels of chemicals that pass signals between brain cells. This process is slow and often takes several weeks or even months to help a person feel better. When people ask what is spravato esketamine, the answer lies in its unique way of targeting the brain.

The glutamate system

Spravato works on the glutamate system rather than serotonin. Glutamate is a key chemical messenger in the brain. It plays a big role in how the brain learns and adapts. As an NMDA receptor antagonist, esketamine blocks certain paths in the brain. This move starts a chain of events that helps the brain control mood and emotion better.

Traditional pills can take a long time to work. In contrast, esketamine is much faster. Many patients see a real change in their symptoms in just 24 to 48 hours. This quick response is a major help for those who have not found relief from other drugs. It offers a new path for people who need help now rather than weeks from now.

Building new paths

One of the best parts of esketamine is how it helps the brain heal. Long periods of stress or depression can cause links between brain cells to shrink. Esketamine helps start a process that grows new links. You can think of it like a gardener helping a dry plant grow new roots. This helps the brain parts that manage mood start to work well again.

By building these new paths, the brain becomes more flexible. This helps a person break free from negative thoughts. It also makes the brain better at managing stress. At Relief Mental Health, our team uses this science to provide comprehensive depression treatments. This approach helps the brain rebuild itself for long-term health.

Is Spravato FDA-Approved? What the Approval Covers

Yes, Spravato (esketamine) is an FDA-approved nasal spray used to treat complex mood disorders. The FDA approved Spravato first in 2019 for adults with treatment-resistant depression (TRD). Since then, its uses have grown to help more people who do not find relief from standard oral drugs. At Relief Mental Health, you can learn more about SPRAVATO treatment and how it fits into a full care plan.

The timeline for TRD and suicidal ideation

When Spravato first came out, doctors had to give it along with an oral antidepressant. It was the first new type of drug for depression in over 30 years. Later, the FDA also cleared it to treat depressive symptoms in adults with major depressive disorder (MDD) who have acute suicidal thoughts or actions. This was a big shift in how clinics treat urgent mental health crises.

A major milestone for monotherapy

In January 2025, the FDA reached a key milestone. It approved Spravato as the first and only monotherapy for adults with TRD. This means patients can now use the nasal spray on its own. They do not need to take a daily oral pill at the same time. The FDA monotherapy approval followed a priority review. It offers a new path for those who want to limit the number of drugs they take.

Clinical results and rapid response

The approval for use on its own came from strong test data. Researchers used the Montgomery-Asberg Depression Rating Scale (MADRS) to track how well patients did. The results showed that Spravato worked much better than a placebo. Many people saw their symptoms start to drop as early as 24 hours after their first dose. These gains stayed strong through the four-week check. This fast action makes it a vital tool for those who need help right away.

What Happens During a Spravato Treatment Session?

A Spravato session is a set process kept to a strict plan to keep you safe. Because of how the drug works in the brain, you must take it in a clinic. You cannot take Spravato at home. Knowing the steps can help you feel ready for your visit and learn what the SPRAVATO experience is like for new patients at a clinic.

The dosing process

When you arrive, a nurse will check your blood pressure. You will then use the spray tool yourself while they watch. Each tool has 28 mg of drug. You will use two or three tools to get a full dose of 56 mg or 84 mg. You will rest for five minutes between each spray to help your body take in the drug. The FDA label for Spravato sets this timing to make sure the drug works well.

Safety and rest

After you take the dose, you must stay in the clinic for two hours. During this time, the team will watch you for side effects like sleepiness. Some people feel like they are in a dream, but this usually ends before you leave. The Spravato REMS program needs this rest time to check your blood pressure. You should bring a book or music to stay calm during this time.

The treatment plan

The care follows a clear path to help your brain. In the first part, you will have regular visits each week for an initial period. After this initial phase, you may move to a second part. This stage often means one visit a week or every two weeks. Your team will check your progress to find the best plan for your needs.

• Safe travel: You must find a ride home after every visit. You cannot drive or use big tools until the next day after a full night of sleep.
• Food and drink: Do not eat for two hours before your visit and do not drink for 30 minutes before your dose. This helps to stop nausea.
• Stay calm: Many people bring headphones or a light wrap to help them rest during the two-hour stay.

1. Pre-visit prep. Do not eat for two hours before your visit or drink for 30 minutes before your dose. Arrange a ride home.
2. Arrival and check-in. A nurse checks your blood pressure. You review any changes in your health with your provider.
3. Spravato administration. You use 2-3 nasal spray devices (28 mg each) with a five-minute rest between each spray. The total dose is 56 mg or 84 mg.
4. Two-hour monitoring. After dosing, you rest in a recliner for two hours. Staff monitor your blood pressure and watch for side effects like sedation or dissociation.
5. Discharge. A staff member confirms your vital signs are stable. Your ride takes you home. Do not drive or operate machinery for the rest of the day.

Why Is Spravato Administered Only in a Certified Clinical Setting?

The safety of patients is the main reason why this drug is given only in a clinic. If you want to know what is spravato esketamine, it is an FDA-approved nasal spray. It helps adults with depression that has not responded to other pills.

Because it is a strong drug, the government has set up a strict safety plan called a Risk Evaluation and Mitigation Strategy (REMS). This program ensures that patients get the drug under the direct care of a doctor or nurse. These visits happen in an approved clinical setting. The spray is never sold at a local drug store or sent to your home for self-use.

The Risk Evaluation and Mitigation Strategy (REMS)

The REMS program is a safety check required by the Food and Drug Administration (FDA). It exists because this drug can cause sudden changes in how you feel and breathe. When you take the spray, you must stay in the clinic so staff can watch you.

This helps prevent the drug from being used in the wrong way or causing harm. Before starting, patients must enroll in the REMS program. To learn more about SPRAVATO treatment, you can speak with a provider at Relief Mental Health. Our team will help you understand how this plan keeps you safe during each visit.

Safety Monitoring and the Two Hour Rule

After you take your dose, you must stay at the clinic for at least two hours. During this time, a health worker will check on you often. They watch for side effects like sedation, which means feeling very sleepy. They also watch for dissociation, which is a detached feeling.

Doctors track your blood pressure as well. This is vital because the drug can cause a quick rise in blood pressure that peaks about 40 minutes after use. According to the FDA label, this watch period is needed to make sure you are stable before you leave. Experts are there to help if your vital signs change.

Common Side Effects and Safe Transport

Many people feel side effects soon after using the spray. Most of these go away within two hours. You might feel dizzy, sick to your stomach, or like the room is spinning. Some patients feel like they are in a dream or drunk.

Because these feelings can be strong, you cannot drive for the rest of the day. You must also not use heavy tools or machines. You must find a safe ride home after your visit. Having a friend or family member pick you up is a key part of the process. Your doctor will also review your health history to ensure what the SPRAVATO experience is like is safe for you.

• Sedation: Feeling very tired or sleepy after your dose.
• Dissociation: Feeling detached from your body or the world.
• Vertigo: A feeling that you or the room is moving or spinning.
• Blood Pressure: Short-term rises that need clinical checks.

Frequently Asked Questions

How is Spravato different from ketamine?

Spravato is a nasal spray that uses esketamine. This is the S-enantiomer of the ketamine molecule. Standard IV ketamine is a mix of two parts, called arketamine and esketamine. While Spravato has FDA approval to treat depression, using IV ketamine for this is usually off-label. According to Johns Hopkins Medicine, Spravato is a nasal spray, while IV ketamine enters the body through a vein. Both drugs help with mood but have different legal status and methods of use.

Who is not a candidate for Spravato?

Spravato is for adults with depression that has not improved with other drugs. It is not for children or teens. People with a history of certain blood vessel problems, like an aneurysm, should not use it. It is also not for those who are allergic to esketamine or ketamine. Since it is a controlled substance, doctors will check for a history of drug abuse. According to the FDA, your doctor will review your full health history to see if the drug is right for you.

How many Spravato sessions will I need?

The treatment plan has two main parts. First is the induction phase, which usually lasts for an initial period. During this time, you will visit the clinic for regular sessions each week. After the first month, you move to the maintenance phase. Sessions then happen once a week or every two weeks. Your doctor will track your mood to decide how long you should continue. According to Johnson & Johnson, many patients see rapid improvement within the first few weeks of this schedule.

Is Spravato taken with other antidepressants?

Yes, Spravato can be used in two ways. It was first approved for use along with an oral antidepressant pill. However, newer rules allow doctors to use it as a monotherapy. This means it can be the only drug you use for treatment-resistant depression. Your doctor will decide if you should keep taking your current pills or use Spravato alone. According to the FDA label, both options are valid for adults who have not found relief from other depression treatments.

Ready to explore Spravato treatment for depression?

Living with depression that does not get better can feel like a heavy weight. Waiting for weeks to see if a new pill works can also be hard. If you act now, you may start to feel relief in just a few days.

You do not have to wait months to find out if this care is right for you. Our team is here to help you get the fast and expert care you need to move forward. By starting today, you can get a clear plan and stop the cycle of trying things that do not work for your mood.

Ready to find a path that works for you? Call (844) 731-7543 to schedule a consultation at Relief Mental Health.