Spravato Treatment: What It Is, How It Works, and Who It's For

Key takeaways

• Spravato (esketamine) is an FDA-approved nasal spray prescribed for treatment-resistant depression and major depressive disorder with suicidal thoughts.
• It works differently from standard antidepressants, targeting glutamate pathways for faster effects.
• Treatments are given in certified clinics under medical supervision for safety and monitoring.
• Common side effects include dizziness, dissociation, or drowsiness, which usually fade within a few hours.
• While expensive, insurance may cover Spravato for eligible patients, and assistance programs can help reduce costs.

Spravato (the brand name for esketamine nasal spray) is a relatively new way to treat depression. This nasal spray is taken in a clinic, under supervision, and is often prescribed for major depressive disorder (MDD) with suicidal thoughts or treatment-resistant depression (TRD). Spravato can sometimes bring relief quicker than other treatments, which can be life-changing if you’ve spent months or years struggling with depression.

While standard antidepressants and psychotherapy help many recover, about half of those who try these approaches don’t find lasting relief. That can leave people feeling stuck, exhausted, and unsure where to turn next. Spravato treatment may be the next thing to try. It’s designed to work differently in the brain and bring relief when other medicines haven’t. 

This guide will walk you through Spravato for depression so you can feel more confident exploring whether this treatment might be right for you.

What is Spravato?

Spravato is the brand name for esketamine, a FDA-approved depression medication that’s delivered as a nasal spray in a certified clinic. This medication belongs to a different class of antidepressants than SSRIs or SNRIs. It works on glutamate — a brain chemical that plays a key role in learning and memory—instead of serotonin. In practice, this means it can provide faster relief (we’re talking within hours or days instead of weeks). 

The medication’s FDA approval came in three distinct stages:

• 2019: Approved as an adjunctive treatment for TRD. This means the medication had to be used alongside an antidepressant. 
• 2020: Approved as an adjunctive treatment for MDD with suicidal ideations.
• 2025: Approved as a standalone treatment for patients with TRD.

Because of potential side effects, like dissociation and dizziness, Spravato is only available through certified treatment centers in a program called REMS (Risk Evaluation and Mitigation Strategy). This means every dose is given in a safe, supervised environment, with trained staff nearby to support you throughout the process. REMS management is due to the risk for sedation, dissociation, respiratory depression, and the potential for abuse and misuse.

Esketamine vs. Ketamine: What’s the difference?

The words ketamine and esketamine sound similar, but there is a difference between the two. Ketamine is a well-known anesthetic that’s also used off-label to treat depression, usually through IV infusions. Esketamine is its close chemical relative: In fact, it’s one of the two “mirror image” molecules that make up ketamine.

Here are the key differences between esketamine versus ketamine:

• Chemical composition: Ketamine is 50% R-ketamine (AKA arketamine)  and 50% S-ketamine (AKA esketamine), while esketamine is composed only of S-ketamine. S-ketamine has a stronger effect on NMDA-recptors than R-ketamine.. 
• The experience: Because ketamine is delivered to the bloodstream, it causes more intense dissociation and psychedelic effects. Esketamine may result in some dissociative effects, though they are usually less intense.
• FDA-approval: Esketamine is FDA-approved for TRD and MDD with suicidal ideations, while ketamine is not. 
• Dosing: Every dose is carefully measured for esketamine, while IV ketamine doses can vary by clinic. Esketamine dosages are pre-determined while IV ketamine is typically dosed by weight and at varying amounts depending on the desired effect.

Both can be effective for depression, but Spravato’s approval and structured program mean it’s more widely covered by insurance and comes with clearer safety protocols. For many people, that extra layer of oversight can bring peace of mind during a vulnerable time.

Who is Spravato for?

Spravato is designed for two types of depression: treatment-resistant depression, which is when at least two different antidepressants didn’t work, and MDD with suicidal ideation.  

“[It’s] probably more effective than attempting a third or a fourth antidepressant medication,” says Jonathan Downar, MD, PhD, a psychiatrist and founder of Ampa Health. That means if standard treatments haven’t worked, Spravato may help.

Who should not take Spravato

Spravato is not recommended if you have:

• A history of aneurysms or certain blood vessel conditions 
• Uncontrolled high blood pressure
• A history of bleeding in the brain.
• Allergies or hypersensitivity to esketamine or ketamine

It’s also not recommended during pregnancy or breastfeeding, because there isn’t enough research to know if it’s safe for a developing baby. 

We break down who is and isn’t a good fit in more detail in our guide on who is eligible for Spravato treatment. 

How Spravato works in the brain

Spravato targets NMDA receptors in the brain. This  is a different mechanism than traditional antidepressants, which increase brain chemicals like serotonin or norepinephrine. 

NMDA receptors boost the activity of glutamate, a chemical that helps brain cells connect and communicate. Think of glutamate as the brain’s construction team: It helps lay down roads and clean up "traffic patterns" that depression often slows down or shuts off.

Because this pathway acts more directly on how brain cells talk to each other, the effects can show up much faster than with SSRIs, which can take longer to kick in.

For some people who take Spravato, that means changes in mood and energy can happen within hours or days instead of weeks. Still, how long Spravato takes to work can vary from person to person.

What is Spravato treatment like?

With Spravato, every session follows a structured plan designed to keep you safe, supported, and cared for from start to finish. Here’s what to expect throughout the process.

Before treatment

Your first step is a consultation with your provider at a REMS-certified clinic. If Spravato is a good fit, they will prescribe the medication and walk you through what treatment may look like. You don’t usually need a separate referral from your primary care doctor unless your insurance requires it. At this point, the clinic will also enroll you in the FDA’s Spravato REMS program, which is required to ensure treatment happens in a safe, supervised setting. 

Spravato isn’t a one-time treatment. Most people begin with two sessions per week for the first month, then shift to once-weekly sessions for another month or two. Between weeks eight and 12, your provider will reassess your progress and adjust the Spravato dosage and treatment schedule if necessary. 

During treatment

When you arrive, the care team will check your blood pressure and walk you through what to expect during the session. Many people bring a friend or family member to wait for them during treatment, because you'll need someone to drive you home.

You administer Spravato nasal spray yourself, but don’t worry — trained staff will guide you through every step. After using the spray, you’ll get comfortable in a recliner in a quiet, calming room. Some clinics even offer meditative music or dim lighting to help you relax during the session. 

To learn more about what this experience may look like, see our Spravato administration guide.

After treatment

When the monitoring period ends, the staff will recheck your blood pressure and discuss how you’re feeling. Because Spravato can cause temporary drowsiness or disorientation, you can’t drive for the rest of the day after treatment.

Many people find it helpful to set aside the rest of the day for restorative activities. Journaling, gentle movement, or simply resting can give you space to process the experience. This time is part of what’s called integration: reflecting on how you feel and making sense of anything that came up during your session. Integration helps  turn the immediate effects of Spravato into longer-term insights and healing.

How effective is Spravato at treating depression?

In the SUSTAIN-3 study, 50.9% of participants with TRD were in remission one year after starting Spravato. For many people with TRD or MDD with suicidal ideation, this medication can bring meaningful relief faster than traditional oral antidepressants.

What research shows

• It can help where other medicines haven’t: In a study published in JAMA Psychiatry, of people with TRD, those who stayed on Spravato with an oral antidepressant were much less likely to relapse than those who stopped. For people in depression remission, Spravato cut the chance of relapse by about half. For those who were improving but not fully recovered, it reduced relapse risk by about 70%.
• It often works faster: Traditional antidepressants like SSRIs can take weeks to work. Because Spravato acts on a different brain pathway, some people experience shifts in their mood and energy within hours or days. In people with major depression and active suicidal thoughts, Spravato plus standard care has been shown to reduce symptoms quickly—sometimes within the first 24 hours. 
• It prevents relapse: Another study published in JAMA Psychiatry  found that people with TRD who stayed on Spravato were far less likely to relapse than those who stopped. For many, continuing treatment lowered the risk of depression relapse by half or more.

What patients say

“Watching someone respond well to Spravato is unforgettable,” says Michelle Bernabe, RN, a nurse educator at Radial. She recalls sitting with a first responder during one of their treatment sessions. When the session ended, they began to cry so intensely that she worried something was wrong. 

“But through tears, they told me it was the first time they had felt joy since the events of twenty years earlier,” she says. “To witness that kind of release, the return of joy after two decades of pain, stays with you.”

Here’s what some Spravato reviews say:

• “I have now been on Spravato for one year. I have had depression and suicidal thoughts nearly every day for the past 25 years. Except for the last year on Spravato. Every month I see a gradual improvement. The biggest improvement my first six months was the cessation of suicidal ideation. The last six months, not only has my general sadness gone away, but I can now bounce back when things are rough. I still have healing to do, but none of it would be possible without Spravato.”
• “I can only speak about my own experience. The medicine does the work it sets out to do. I am a person struggling with CPTSD and depression. Spravato has helped significantly reduce suicidal ideation, reduce depression, and overall increase my well-being. The post-nasal drip is similar to that of any allergy nasal spray. The onset lasts approximately two hours in which I meditate, listen to audiobooks, and practice mindfulness.”
• “My first treatment was February 7, 2020, and my life has been completely changed thanks to this medication. For one thing, it has given me hope that there are new treatments to fight depression. The best thing is it is working! I no longer stay in bed all the time. I have more energy, and I enjoy living life again. As far as the treatments themselves, I get a feeling of euphoria for the first 40 minutes. My face, lips, and nose have a very numb feeling which goes away within about 2 hours. Some days after my treatment I feel fatigued, and some days I have a good amount of energy.”

Stories like these show the potential for deep, meaningful change. At the same time, it’s important to remember that not everyone responds in the same way. 

For a better idea of the variety of Spravato experiences, read these Spravato reviews. 

How Spravato compares to other treatments

While Spravato can be effective, it’s not the only option out there. If you’re weighing next steps, it helps to see how Spravato compares to other common treatments:

• SSRIs/SNRIs (standard antidepressants): These are often the first-line medicines for depression. They work well for many people, but they can take weeks to show effects. Spravato may be considered if at least two of these medicines haven’t worked.
• Psychotherapy (talk therapy): Approaches like cognitive behavioral therapy, interpersonal therapy, and group therapy can be highly effective for managing depression and building long-term coping skills. The challenge is that access can be limited—quality therapy isn’t always easy to find, and insurance coverage can be inconsistent.
• TMS (transcranial magnetic stimulation): This is a non-invasive brain stimulation therapy that can help reduce depression symptoms. It is generally well-tolerated and doesn’t require medication. 
• ECT (electroconvulsive therapy): This is one of the most effective options for severe depression. However, it requires repeated exposure to general anesthesia—usually about 12 sessions in a month—and can cause short-term memory issues, says Downar. Spravato offers another option for people who want something less invasive.

While Spravato works for some, other treatments may be more appropriate for others. Plus, this medication can take some time to work. 

Explore our guide on how to know if Spravato is working if you’re starting this medication and curious if it will be effective for you.

Is Spravato safe?

For many people, Spravato is a safe, effective treatment. That said, like any medicine for depression, it does come with possible side effects. During or shortly after a session, people may notice:

• Feeling lightheaded or dizzy
• Nausea
• A dream-like sense of disconnection (dissociation)
• Unusual or metallic tastes
• Drowsiness or fatigue

Spravato side effects usually peak around  40-45 minutes into the treatment,  and then fade by the end of the two hour treatment period, which is why patients stay in the clinic for monitoring. Some people also experience a temporary dip where it feels like depression gets worse. 

Less commonly, people may experience temporary spikes in blood pressure, headaches, or anxiety. Rare but more serious side effects include sustained increases in blood pressure or severe dissociation. 

What is the REMS program?

Spravato is only available through certified clinics under the FDA’s REMS (Risk Evaluation and Mitigation) program because of these side effects. This ensures every dose is given in a safe environment, with blood pressure checks and staff nearby to support you until the short-term side effects of the medicine wear off.

Spravato cost, insurance coverage, and access

Without insurance, Spravato can be expensive—one session can cost up to $1,600, depending on your dose and clinic. The good news is that many insurance plans may cover Spravato for people who meet set criteria.

The manufacturer of Spravato also offers patient assistance programs for those who qualify, which can make treatment more affordable. Your provider’s office can often help you apply for these resources.

The bottom line

For people who haven’t found relief with traditional medications, Spravato can open new doors. Backed by FDA approval, strict safety protocols, and years of research, it offers hope where other options have fallen short. While Spravato is not right for everyone, the structured clinic setting, close medical oversight, and advanced monitoring make it a safe and carefully managed treatment for many people. 

Frequently asked questions (FAQs)

Is Spravato covered by insurance?

Most major insurance plans may cover Spravato if you meet criteria for treatment-resistant depression. Coverage usually requires proof that you’ve tried at least two other antidepressants without lasting relief. 

How long does a Spravato treatment last?

Each Spravato session takes about two hours at the clinic. Esketamine nasal spray itself enters the system quickly — and the peak of the intoxication side effects happens at roughly 40-45 minutes into the treatment. Those sensations are mostly gone at the end of the two hours. 

Can Spravato be taken at home?

Because of safety concerns like temporary drowsiness, dissociation, and changes in blood pressure, Spravato cannot be taken at home. It is administered in certified clinics under the FDA’s REMS program. 

Does Spravato get you high?

Some people experience temporary dissociation or a dreamlike state after taking Spravato. These effects can feel unusual or even pleasant, but they’re short-lived and happen under medical supervision.

Deep dive recommendations:

Interested in learning more? These expert-recommended resources are a great place to start.

• NEI Podcast. Treatment Resistant Depression and Suicide Prevention: Hot Off the PRess Ketamine Guidelines. 
• Psycround. Ketamine/Esketamine (Spravato) with Dr. Joshua Rosenblat. 
• Psychiatry and Psychotherapy Podcast. Ketamine and Psychedelics with Dr Michael Cummings.
• Psychiatry and Psychotherapy Podcast. Ketamine Update with Brandon Kitay, MD.
• Huberman Lab Podcast. Ketamine: Benefits and Risks for Depression, PTSD & Neuroplasticity. 
• The Frontier Psychiatrist Podcast. Ketamine in the Land of Taylor Swift. 
• The KevinMD Podcast. Ketamine, What PCPs Need to Know with Carlene MacMillan, M.D., FCTMSS, DFAACAP.

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