What Is Spravato? The Complete Guide to Esketamine Treatment

If you have been living with depression for a long time, trying one medication, then another, then another and still not feeling like yourself, you are not alone. And you are not out of options. You may just not have heard about the right one yet.

Spravato is a treatment that a lot of people with depression have never been told about. 

Despite being FDA-approved, clinically proven, and covered by most major insurance plans, it still flies under the radar for many patients who could genuinely benefit from it. That is something we hear from patients at Marpa Minds almost every week. 

They had no idea this existed until their previous doctor mentioned it as a last resort, or they stumbled across it online after years of searching for something different.

This guide is here to change that. Whether you are researching Spravato for the first time, trying to understand whether it might be right for you or someone you love, or just wanting a clear, honest explanation of what esketamine treatment actually involves, this is the guide you have been looking for.

We are going to cover everything: what Spravato is, where it comes from, how it works in the brain, who it is designed for, what a treatment session looks like, what to expect in terms of side effects, how insurance coverage works, and how it compares to other options. 

No jargon. No unnecessary complexity. Just a straightforward, thorough answer to the question most patients start with: what exactly is Spravato?

What Is Spravato, Exactly?

Spravato is the brand name for esketamine, a nasal spray medication approved by the US Food and Drug Administration (FDA) for the treatment of depression. It is made by Janssen Pharmaceuticals, a division of Johnson & Johnson, and it has been available since March 2019.

There are actually two specific conditions that are approved to treat. The first is treatment-resistant depression, which means depression that has not responded adequately to at least two different antidepressant medications. 

The second is major depressive disorder in adults who have active suicidal thoughts with intent or behaviour, where it can be used alongside a standard oral antidepressant for faster relief.

The reason Spravato is such a big deal is not just that it works; it is that it works in a way that nothing before it has. It is the first truly new class of antidepressant to be approved by the FDA in over 35 years. 

Every antidepressant that existed before Spravato, SSRIs like Prozac and Zoloft, SNRIs like Effexor and Cymbalta, TCAs, and MAOIs, all of them work on the serotonin and/or norepinephrine systems. Spravato does something completely different, which is exactly why it helps people who have failed those medications.

It is also worth noting that Spravato is a Schedule III controlled substance, which is why it must be administered in a certified clinic rather than taken at home. We will talk about what that looks like shortly.

Spravato and Esketamine — What Is the Difference?

This is one of the most common points of confusion, so let us clear it up right away.

Ketamine and esketamine are related, but they are not the same thing. Ketamine is a molecule that has been used in medicine since the 1960s, first as a surgical anaesthetic, and more recently as an off-label treatment for depression. 

When you hear about ketamine infusion therapy or IV ketamine, that refers to the original ketamine molecule being administered intravenously.

Esketamine is a specific part of ketamine. 

Ketamine is what chemists call a racemic mixture; it contains two mirror-image molecular forms, known as the S-enantiomer and the R-enantiomer. Janssen isolated and patented the S-enantiomer specifically, called it esketamine, and developed it into the nasal spray formulation we now know as Spravato.

So to be direct about it: esketamine is one-half of ketamine, refined, patented, and turned into an FDA-approved nasal spray. Spravato is the brand name for that nasal spray. They are all referring to the same thing.

The distinction matters practically because it explains why Spravato is covered by insurance while IV ketamine typically is not. IV ketamine is still technically an off-label use of a generic anaesthetic.

Spravato went through the full FDA approval process for depression specifically, which is why it can be prescribed for that indication and billed through your health insurance.

How Does Spravato Work in the Brain?

This is where things get genuinely fascinating — and also where Spravato departs most dramatically from everything that came before it.

The Problem With SSRIs

Most antidepressants work by increasing the availability of serotonin in the brain. The theory called the serotonin deficiency hypothesis is that depression is caused at least in part by low serotonin levels, and that boosting those levels should help. 

And it does, for many people.

 But for roughly a third of all patients with depression, SSRIs and SNRIs simply do not provide enough relief, no matter how many they try or how high the dose goes.

The reason is not fully understood, but the emerging view in psychiatry is that depression is not purely a serotonin problem. It is also a problem of neuroplasticity, the brain’s ability to form new connections and adapt. In people with chronic depression, certain brain regions show reduced synaptic density.

 The neural circuitry involved in mood regulation, reward processing, and resilience becomes impaired. And serotonin-boosting drugs do not directly address that.

The NMDA Receptor – A Different Pathway

Spravato works through an entirely different mechanism. It targets the NMDA receptor, a receptor for the neurotransmitter glutamate, which is the brain’s primary excitatory chemical. 

By blocking the NMDA receptor, esketamine triggers a cascade of downstream effects that ultimately lead to rapid synaptogenesis, the growth of new synaptic connections in key brain regions associated with mood and cognition.

Think of it this way: years of depression can damage the brain’s communication pathways, like years of neglect can damage a road. SSRIs work at the surface level, managing traffic. Spravato essentially repairs the road, stimulating the regrowth of neural pathways that depression has degraded.

The clinical effect of this is remarkable in its speed. While SSRIs take four to eight weeks to build up and begin working, Spravato can produce noticeable antidepressant effects within hours to days of the first session. This is not a small difference in timeline; it is a fundamentally different mechanism of action, and for patients who have been suffering for years or decades, that speed of response can be genuinely life-changing.

“What we see clinically at Marpa Minds is that many patients come to us having genuinely given up hope. They have tried five, six, even eight different medications. When Spravato starts working — sometimes after just one or two sessions — it is not just the lifting of symptoms. It is the restoration of belief that things can actually be different.”
— Amy Della Rocca, MSN, MPH, PMHNP-BC, Clinical Director, Marpa Minds

Who Is Spravato Designed For?

Spravato has two FDA-approved indications, and it is important to understand both of them.

1. Treatment-Resistant Depression (TRD)

The primary indication is treatment-resistant depression. To meet the clinical definition of TRD, a patient must have a diagnosis of major depressive disorder and have not achieved adequate relief from at least two antidepressant medications taken at the right dose for a sufficient duration — typically at least six weeks each.

This is more common than most people realise. Studies suggest that approximately one in three people with depression do not respond adequately to standard antidepressant therapy. That is a significant portion of all people diagnosed with major depression. 

And yet, despite how common it is, treatment-resistant depression is chronically undertreated — partly because the options historically available were limited and often complex to access.

Spravato is specifically designed to serve this population. If you have tried multiple antidepressants and continue to struggle, that does not mean your depression is untreatable. It may simply mean you have not yet tried a treatment that works on the right mechanism.

2. Major Depressive Disorder with Acute Suicidal Ideation

The second FDA indication is for adults with major depressive disorder who are experiencing active suicidal thoughts with intent or behaviour (called MDSI). In this context, Spravato is used alongside a standard oral antidepressant and is specifically valued for its speed — because waiting four to six weeks for an SSRI to work is not appropriate when someone is in acute crisis.

The rapid antidepressant effect of esketamine makes it particularly well-suited to this urgent clinical situation.

Who Is Not a Good Candidate?

Spravato is not appropriate for everyone. There are certain contraindications that your clinical team will assess during your initial consultation. These include a history of psychosis or schizophrenia, active substance use disorder, certain cardiovascular conditions, and pregnancy. 

A thorough clinical assessment is always conducted before anyone begins treatment, which is part of the reason the REMS programme exists (more on that shortly).

What Does a Spravato Treatment Session Look Like?

This is often the question that patients are most curious and most anxious about. What actually happens at a session? What does it feel like? How long does it take?

The practical reality of a Spravato treatment session is straightforward, though the experience itself is quite unlike anything most people have encountered in a medical setting.

The Setting

Spravato must be administered in a certified clinical setting — not at home. This is a requirement of the FDA’s REMS (Risk Evaluation and Mitigation Strategy) programme, which exists because the medication can cause temporary dissociation and other effects that require monitoring. At Marpa Minds, our treatment rooms are private, quiet, and designed to feel calm and comfortable — more like a relaxation space than a clinical room.

Before the Session

You should avoid eating for at least two hours before your session (and avoid drinking fluids other than water for at least 30 minutes before). You should also avoid blowing your nose or using any nasal decongestants shortly before treatment. Your care team will check in with you, review how you are feeling, and take your blood pressure and other baseline measurements.

The Administration

Each session involves two nasal spray devices, each administered five minutes apart. You hold the device to one nostril, press the plunger, and breathe in gently. The dose is either 56mg or 84mg, depending on your treatment plan — your clinician will determine the right dose for you.

After administering the spray, you sit back in a comfortable reclined position. Within a few minutes, you may begin to notice effects — a mild sense of lightness, altered perception, or detachment from your surroundings. This dissociative state is normal and is actually part of how the treatment works. It typically peaks within the first hour and resolves by the end of your monitoring period.

The Monitoring Period

You remain at the clinic for at least two hours after administration — this is non-negotiable and is part of the FDA REMS requirement. During this time, your blood pressure is monitored at regular intervals, and a member of the clinical team is available to you at all times. Most patients find this period to be surprisingly pleasant — many listen to music, rest, or simply allow their mind to settle.

You cannot drive on the day of your treatment session. You will need to arrange for someone to take you home or use a rideshare service.

The Treatment Schedule

The acute treatment phase involves two sessions per week for four weeks, a total of eight sessions. After the acute phase, sessions are reduced to once weekly for four weeks, and then to a personalised maintenance schedule, typically once every one to two weeks based on how you are responding.

How Quickly Does Spravato Work?

This is one of the most remarkable aspects of esketamine treatment, and it is worth spending a moment on it because it is so different from the experience most patients are used to.

Traditional antidepressants — SSRIs, SNRIs, TCAs — work gradually by building up in the bloodstream over several weeks. Most doctors tell patients to expect four to eight weeks before they notice any significant effect. For someone in acute depression, that wait can feel endless.

Spravato works differently. Because it acts directly on NMDA receptors and promotes rapid neuroplastic changes, some patients begin to notice a shift in their mood, energy, or outlook within hours of their first session. Many report feeling something after the first or second session. A measurable antidepressant effect is typically seen by the end of the first two weeks for most responders.

Clinical trial data report a 91% mood lift rate in patients with treatment-resistant depression treated with Spravato. 

That is not a cure rate; it means 91% of trial participants experienced a clinically meaningful improvement in their symptoms. For context, response rates to additional oral antidepressants after two failures hover around 10 to 20 per cent.

It is important to say clearly that Spravato is not a magic fix. 

Not everyone responds, and for those who do, some will require ongoing maintenance sessions to sustain the benefit. 

But for the right patient, the speed and degree of response can be genuinely transformative.

Spravato Side Effects — What to Expect

Being honest about side effects is important. Spravato does have them, and they are worth understanding — not to scare anyone off, but because knowing what to expect makes the experience significantly less daunting.

Common Side Effects

The most commonly reported side effects during and immediately after a Spravato session include:

• Dissociation — a temporary feeling of detachment from your surroundings, your body, or your sense of self. This is the most characteristic effect and usually peaks within 40 minutes of administration, resolving fully within two hours.
• Dizziness and sedation — feeling lightheaded or sleepy during the session. This is common and usually resolves within the monitoring period.
• Nausea — some patients experience mild to moderate nausea, particularly in early sessions. This typically improves with subsequent treatments.
• Elevated blood pressure — Spravato can temporarily increase blood pressure during and shortly after administration. This is why your blood pressure is monitored throughout the session.
• Headache — some patients report a headache after the session, usually mild and short-lived.

Almost all of these effects are temporary and occur during or immediately after the session. They do not typically persist into the following day.

What About Addiction or Dependency?

This is a concern that comes up frequently, and it is a legitimate one. Ketamine has a known potential for misuse in recreational settings. However, it is important to understand the clinical context. Spravato is administered at a fixed medical dose in a certified clinical setting, under supervision, on a scheduled basis. It is not something you take home. 

The REMS programme was specifically designed to mitigate misuse risk, and to date, there have been no significant signals of dependency from patients treated under clinical protocols.

Your clinical team will discuss this with you thoroughly during your intake assessment.

Is Spravato Covered by Insurance?

Yes — and this is one of the most important practical differences between Spravato and IV ketamine infusions.

Because Spravato went through the full FDA approval process for treatment-resistant depression, it is covered by most major commercial insurance plans as a standard benefit. This includes Blue Cross Blue Shield, Aetna, UnitedHealthcare, Cigna, Humana, and most other large commercial insurers. Medicare also covers Spravato in many cases.

IV ketamine, by contrast, is still technically an off-label use of a generic anaesthetic, meaning it was never approved by the FDA for depression specifically. 

As a result, most insurance plans do not cover it, and patients typically pay $400 to $800 per infusion session out of pocket.

The insurance coverage question matters enormously in practice. A full acute course of Spravato involves eight sessions. If each session required a $600 out-of-pocket payment, the barrier to access would be significant. With insurance coverage, most patients pay only their standard co-pay or co-insurance amount for each session.

How Does the Insurance Process Work?

The most common hurdle is the prior authorisation process; your insurer needs to approve Spravato before treatment begins. This typically involves providing documentation of your depression diagnosis and confirming that you have tried at least two antidepressant medications without adequate response.

At Marpa Minds, we manage the entire prior authorisation process for our patients. We handle all the paperwork, communicate with your insurer directly, and ensure that approval is in place before your first session. 

This is something we have built into our intake process because we know it is often the single biggest obstacle between a patient and the treatment they need.

Spravato vs IV Ketamine — What Is the Difference?

Patients often ask how Spravato compares to IV ketamine infusions, since both involve ketamine-derived compounds and both are used for depression. They are related but meaningfully different, and the distinction matters.

The Molecule

IV ketamine uses the full racemic ketamine molecule. Spravato uses only the S-enantiomer (esketamine). Research suggests esketamine may have a slightly stronger affinity for NMDA receptors, though both are clinically effective.

The Administration Method

IV ketamine is administered intravenously over 40 to 60 minutes. Spravato is self-administered as a nasal spray under clinical supervision. Most patients find the nasal spray significantly more comfortable than an IV infusion.

FDA Status

Spravato is FDA-approved for treatment-resistant depression and MDD with suicidal ideation. IV ketamine is used off-label — effective, but not approved for depression specifically.

Insurance Coverage

Spravato is covered by most major insurance plans. IV ketamine is almost always self-pay.

Setting and Monitoring

Both require clinical supervision. The monitoring protocols and setting requirements are similar — private room, blood pressure monitoring, and no driving after the session.

Neither is inherently better for every patient. For some, IV ketamine may be appropriate. For most patients with treatment-resistant depression who want insurance-covered treatment in a structured clinical setting, Spravato is the more accessible and practical option.

Is Spravato a Psychedelic?

This is a question we hear more and more frequently, particularly following the Trump Administration’s April 2026 Executive Order to accelerate psychedelic medicine research and access in the United States.

The short answer: yes. Esketamine is classified as a dissociative psychedelic. It produces altered states of consciousness, temporary changes in perception, and dissociative experiences — all of which are characteristic of the broader psychedelic category.

Here is why that matters: Spravato is currently the only FDA-approved psychedelic medicine in the United States. While psilocybin (from magic mushrooms), MDMA, and other classic psychedelics remain in clinical trials and are not yet legally available outside of research settings, Spravato is available right now — covered by insurance, administered in a certified clinic, and backed by full FDA approval.

For patients who are interested in psychedelic-assisted therapy for depression but want a legal, evidence-based, and insurance-covered option rather than waiting for broader legalisation, Spravato is the only currently available pathway.

What Conditions Does Spravato Treat Beyond Depression?

While Spravato is FDA-approved specifically for treatment-resistant depression and MDD with suicidal ideation, there is growing clinical evidence and off-label use for other conditions. At certified ketamine and Spravato clinics, it is also used to treat:

• Anxiety disorders — particularly when anxiety co-occurs with depression
• PTSD — post-traumatic stress disorder, where clinical evidence for ketamine-type treatments is emerging strongly
• Bipolar depression — the depressive phase of bipolar disorder, which is notoriously difficult to treat with standard antidepressants
• Obsessive-compulsive disorder (OCD) — early research is promising

These applications are not the same as the FDA-approved indications, and your clinical team will discuss what is appropriate in your individual case. The point is simply that the therapeutic potential of esketamine extends beyond the narrow FDA labelling.

Frequently Asked Questions About Spravato

How long does a Spravato session take from start to finish?

You should plan for approximately two and a half to three hours for a full session, including check-in, the administration itself (around 10 to 15 minutes), and the mandatory two-hour monitoring period. Most patients schedule their sessions in the morning or early afternoon.

Can I go back to work after a Spravato session?

Most patients feel well enough to return to non-demanding activities by the afternoon following a morning session. However, you cannot drive on the day of your treatment. Whether you feel up to working depends on the person; some patients find they want a quiet afternoon to integrate the experience, while others feel fine relatively quickly after the monitoring period ends.

Is Spravato addictive?

Under the clinical protocols of the REMS programme, dependency has not been a significant clinical concern. You do not take Spravato home, and the administration is controlled and monitored. That said, all ketamine-derived compounds carry some theoretical dependency risk in misuse settings, which is why the strict in-clinic protocol exists.

Do I need to stop my current antidepressants to take Spravato?

Not necessarily. Spravato is often used alongside an existing oral antidepressant. Your clinician will review your current medications and determine the safest and most effective approach for your specific situation.

How many Spravato sessions will I need?

The standard acute course is twice weekly for four weeks. After that, sessions typically reduce to once weekly and then once every one to two weeks. The total number of sessions depends on how you respond and what your maintenance needs are. Some patients achieve sustained remission and are able to taper to infrequent or no maintenance sessions. Others benefit from ongoing periodic treatment.

Does Spravato work for everyone?

No treatment works for everyone, and Spravato is no exception. The clinical trial data is genuinely encouraging — especially the 91% mood lift rate — but around 10% of patients do not respond. Your clinical team will monitor your progress carefully and discuss next steps if Spravato does not achieve the desired effect.

Can I eat before a Spravato session?

You should avoid eating for at least two hours before your session. Eating too close to the session can increase the risk of nausea. Drinking water is fine up to 30 minutes before.

Is Spravato Right for You?

If you have been living with depression that has not responded to antidepressants, or if you have been told you have treatment-resistant depression and feel like you have run out of options, Spravato may genuinely be the next step worth exploring.

It is FDA-approved. It is covered by most major insurance plans. It works through a completely different mechanism than anything you may have tried before. And for the majority of patients who respond to it, it works faster than anything else available today.

At Marpa Minds, our Spravato clinic in White Plains, NY, serves patients across Westchester County, Rockland County, and the New Jersey communities of Mahwah, Ramsey, Saddle River, and Bergen County. Our clinical team — led by Amy Della Rocca, MSN, MPH, PMHNP-BC — provides fully supervised Spravato treatment in a private, spa-like clinical environment, with comprehensive insurance support from the first conversation to your final session.

The first step is simple: contact us to verify your insurance coverage and schedule a free clinical consultation. There is no obligation, and the conversation itself can help you understand whether Spravato is likely to be appropriate in your situation.

If antidepressants have not worked, that is not the end of the story. Spravato may be the chapter that changes everything.