What Is Spravato? Esketamine Benefits, Side Effects & Cost

If you’ve tried multiple antidepressants without relief, you’re not alone—and you’re not out of options. Many people live with treatment-resistant depression, and it can feel frustrating when one medicine after another doesn’t work. Spravato treatment offers a new approach: One designed to work differently in the brain and bring relief when other medicines haven’t. Here’s everything you need to know about Spravato treatment for depression.

For millions of people, depression isn’t a short chapter—it’s a long story marked by trial and error. Standard antidepressants and psychotherapy help many recover. But about half of those who try these approaches still don’t find lasting relief. That can leave people feeling stuck, exhausted, and unsure where to turn next.

Spravato (the brand name for esketamine nasal spray) offers a different path. FDA-approved in 2019, Spravato treatment is approved for people with treatment-resistant depression (TRD) and for adults with major depressive disorder (MDD) who are experiencing suicidal thoughts. Unlike traditional options, Spravato works in the brain through a novel mechanism compared to standard anti-depressants and can sometimes bring relief much more quickly.

This guide will walk you through what Spravato is, how it works, what treatment feels like, and how it compares to other depression options 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 new depression medication that’s delivered as a nasal spray. Unlike most antidepressants, which usually come in pill form, Spravato is taken in a clinic under medical supervision.

Spravato 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). That rapid effect is part of what makes it such an important option for people who have felt like nothing else has helped.

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.

Esketamine vs. Ketamine: What’s the difference?

If you’ve heard of ketamine therapy, you may be wondering how Spravato fits in. 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:

• Spravato is FDA-approved: While ketamine infusions are sometimes used, they’re considered an off-label treatment for depression. Spravato has been studied, tested, and approved for treatment-resistant depression by the FDA.
• Spravato is a nasal spray, not an infusion: Instead of sitting through an IV drip, you self-administer the spray in a clinic with a care team nearby.
• Spravato offers standardized dosing: Every dose is carefully measured, while IV ketamine doses can vary by clinic.

‍

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.

How Spravato works in the brain

Most antidepressants focus on brain chemicals like serotonin or norepinephrine, which play a role in mood. For about 50% of patients, those medicines work well. But they can take weeks to kick in, and sometimes they don’t work at all. That long wait can feel discouraging when you’re already struggling.

Spravato takes a different path. It targets something called NMDA receptors in the brain, which boosts 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 slowly build up serotonin levels over time. 

For some people, that means changes in mood, energy, and even suicidal thoughts can happen within hours or days instead of weeks. That speed can make a world of difference, especially if you’ve been waiting a long time for relief.

Who is Spravato for?

Spravato is designed for a specific type of depression: treatment-resistant depression, a diagnosis used when at least two different antidepressants haven’t brought lasting relief, according to Jonathan Downar, MD, PhD, a psychiatrist and founder of Ampa Health. 

If you’ve tried medication after medication without feeling better, you may fall into this group. A thorough clinical evaluation is a good place to start if you’re curious about Spravato.. “[It’s] probably more effective than attempting a third or a fourth antidepressant medication,” he says—a reminder that if standard treatments haven’t worked, it’s not your fault and other options exist.

Spravato is also FDA-approved for adults with major depressive disorder who are experiencing suicidal thoughts or behaviors, when faster relief can be especially important.

That said, Spravato isn’t the right fit for everyone. Because of how it works in the brain and body, it’s 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, since there isn’t enough research to know if it’s safe for a developing baby.

What is Spravato treatment like?

Starting a new treatment can feel overwhelming, especially if you’ve already been through a long journey with depression care. Knowing what to expect can help you know if Spravato may be the right treatment for you.

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. Together, you’ll talk through your treatment history, current symptoms, and overall health to confirm Spravato is a good fit. 

In most cases, this consultation happens right at the certified clinic where Spravato is offered—you don’t usually need a separate referral from your primary care doctor unless your insurance requires it. If the clinic team determines you’re eligible, they’ll guide you through the next steps and schedule your first session.

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. Depending on your insurance, you may also need a prior authorization before treatment can begin. Because of these steps, it’s common for there to be a short waiting period—often one to two weeks—between your initial consultation and your first session.

When you arrive, the care team will check your blood pressure, answer any last-minute questions, and walk you through what to expect during the session. Many people bring a friend or family member for extra support (and also because you won’t be able to drive yourself home afterward).

During treatment

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.

As the medicine takes effect, your care team will stay nearby, checking in often to make sure you feel safe and supported. The effects usually peak within the first 40 minutes and begin to fade about an hour later, though you’ll stay for a little over two hours in total for monitoring.

It’s common to notice temporary side effects such as a sense of lightness, dream-like thoughts, or mild disconnection from your body. These sensations can feel unusual, but they typically pass. What matters most is that you’ll never go through it alone—your provider will be there to reassure you, answer questions, and keep you comfortable throughout the process.

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’ll need a ride home. 

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. This can help turn the immediate effects of Spravato into longer-term insights and healing.

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 to fit your needs moving forward. Think of it as a gradual process; not an instant cure, but a structured path designed to help you feel better, step by step.

‍

How effective is Spravato at treating depression?

Just like any treatment, Spravato doesn’t work for everyone. But for many people with treatment-resistant depression, it can bring meaningful relief faster than traditional antidepressants.

Here’s what the research shows:

• It can help where other medicines haven’t: In a study of people with treatment-resistant depression, 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%. In short, staying on Spravato made it more likely that progress lasted.
• 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: One study found that people with treatment-resistant depression 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.

Beyond the research, real-life stories can offer a window into what Spravato treatment feels like and the kinds of changes it can bring. 

“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.”

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. Some people describe life-changing improvements, while others say it didn’t help them at all. Both experiences are valid. What matters most is working closely with your care team to track progress and decide whether Spravato is the right path for 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.”

While Spravato can be effective for treatment-resistant depression, 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. According to Downar, the most modern TMS treatments may be more effective than Spravato.
• 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. Because of the anesthesia, patients are advised not to drive while receiving ECT, and access to treatment centers can be limited. Spravato offers another option for people who want something less invasive.

Is Spravato safe?

Safety is one of the first questions most people have when considering Spravato. The good news is that Spravato has gone through extensive clinical trials and is FDA-approved for treatment-resistant depression. 

That said, like any medicine for depression, it does come with possible side effects and important safety considerations. 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 within the first 40 minutes and fade within a couple of hours, which is why patients stay in the clinic for monitoring. 

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

‍

Because of these effects, Spravato is only available through certified clinics under the FDA’s REMS (Risk Evaluation and Mitigation) program. 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.

Some people also worry about dependency. While Spravato is related to ketamine and does carry some potential for misuse, safeguards like the clinic-only dosing and strict monitoring significantly reduce that risk. Research shows that, when used as prescribed under medical supervision, Spravato does not appear to cause physical dependence.

Overall, Spravato is considered safe in the right setting with the right safeguards. Your care team will help weigh the benefits and risks and make sure you feel supported throughout the process.

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 the criteria for treatment-resistant depression. Just note that coverage usually requires documentation that other treatments have been tried first.

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.

If you’re interested in exploring Spravato, the first step is to talk to a psychiatrist or mental health provider about whether it’s a fit for you. They can help confirm if you meet the criteria and refer you to a certified clinic in your area. Radial can also connect you with providers who offer Spravato and other advanced options for depression care.

The bottom line

Spravato isn’t a first step in treating depression. But for people who haven’t found relief with traditional medications, it 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 that could help you feel better, faster. 

Key takeaways

• Spravato is FDA-approved 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 only 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 often covers Spravato for eligible patients, and assistance programs can help reduce costs.

Frequently asked questions (FAQs)

Is Spravato covered by insurance?

In many cases, yes. 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 works quickly—most people feel its peak effects within 40 minutes, and those sensations fade within a couple of hours. Treatment usually starts with twice-weekly sessions for four weeks, then tapers to once a week or less as you improve.

Can Spravato be taken at home?

No. Because of safety concerns like temporary drowsiness, dissociation, and changes in blood pressure, Spravato can only be given in certified clinics under the FDA’s REMS program. You’ll self-administer the spray at the clinic under the direct supervision of a trained professional, then stay for monitoring before a friend or family member drives you home.

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. Unlike recreational ketamine use, Spravato is tightly controlled, given at specific doses, and monitored in a clinic to reduce the risk of misuse.

Deep dive recommendations:

E104 - The PsychopharmaStahlogy Show: Treatment Resistant Depression and Suicide Prevention: Hot Off the PRess Ketamine Guidelines. Released April 21, 2021. https://podcasts.apple.com/us/podcast/nei-podcast/id288425495?i=1000518096737

Ketamine/Esketamine (Spravato) with Dr. Joshua Rosenblat. PsychRounds: The Psychiatry Podcast. Released April 1, 2025. https://creators.spotify.com/pod/profile/psychrounds/episodes/KetamineEsketamine-Spravato-with-Dr--Joshua-Rosenblat-e31005p

Psychiatry and Psychotherapy Podcast. Episode 030: Ketamine and Psychedelics with Dr Michael Cummings. Released Sep 24, 2018 

Psychiatry and Psychotherapy Podcast. Episode 137: Ketamine Update with Brandon Kitay, MD. Released Jan 27, 2022

Huberman Lab Podcast. Ketamine: Benefits and Risks for Depression, PTSD & Neuroplasticity. Released Aug 7, 2023.

The Frontier Psychiatrist Podcast, Ketamine in the Land of Taylor Swift. Released June 20th, 2025

The KevinMD Podcast. Ketamine, What PCPs Need to Know with Carlene MacMillan, M.D., FCTMSS, DFAACAP. Released November 30th, 2023.

‍