Esketamine (Spravato) for Treatment-Resistant Depression: How It Works, REMS Monitoring, and What Telehealth Can (and Cannot) Do

Last updated: August 15, 2026

Esketamine (brand name Spravato) is a prescription nasal spray for some adults with treatment-resistant depression, and for some adults with major depression plus suicidal thoughts or behavior. It is not a pill you pick up and use at home. Sessions happen in a certified clinic. A clinician watches you for at least two hours after each dose.

Need help with depression that has not responded to the first medicines you tried? Klarity Health connects you with over 2,000 licensed providers who can review your history, discuss oral antidepressants, and talk through next steps. Spravato itself is given only in certified in-person settings. Coverage varies by plan. See if you may qualify → · Browse health conditions · Online prescriptions

TLDR

• Esketamine is the S-enantiomer of ketamine. The FDA-approved nasal product is Spravato, a Schedule III medicine. Mayo Clinic describes use with or without an oral antidepressant for treatment-resistant depression, and with an oral antidepressant for major depressive disorder with suicidal ideation or behavior ([Mayo Clinic](https://www.mayoclinic.org/drugs-supplements/esketamine-nasal-route/description/drg-20458442)).
• Johns Hopkins defines treatment-resistant depression as at least two antidepressant trials of six weeks or more without remission or a 50% mood improvement ([Johns Hopkins Medicine](https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/esketamine-for-treatment-resistant-depression)).
• You self-administer the spray in a certified healthcare setting. Staff monitor you for at least two hours because of sedation, dissociation, blood-pressure rise, and breathing risk ([FDA label](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/211243s016lbl.pdf); [Mayo Clinic](https://www.mayoclinic.org/drugs-supplements/esketamine-nasal-route/description/drg-20458442)).
• Typical TRD dosing starts at 56 or 84 mg twice weekly for weeks 1-4, then weekly, then weekly or every two weeks ([Mayo Clinic](https://www.mayoclinic.org/drugs-supplements/esketamine-nasal-route/description/drg-20458442)).
• You cannot legally take Spravato home for unsupervised use. Telehealth still helps with diagnosis, oral medicines, therapy planning, and referrals. Insurance may or may not pay for the clinic sessions. Verify benefits first.

Table of contents

• What esketamine is
• Who it may fit
• How it works
• What a session looks like
• Dosing schedule
• Side effects and who should avoid it
• Esketamine vs IV ketamine and other options
• Why you cannot do this fully online
• How Klarity can still help
• FAQ

What esketamine is

Esketamine comes from ketamine, a long-used anesthetic that clinicians have also used off-label for depression. Johns Hopkins notes that esketamine is a more potent part of the ketamine molecule, which lets clinicians use a lower dose in a nasal spray with an FDA label ([Johns Hopkins Medicine](https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/esketamine-for-treatment-resistant-depression)).

The brand name in the United States is Spravato. The FDA label classifies it as CIII (Schedule III). Distribution is limited to the Spravato REMS program ([Mayo Clinic](https://www.mayoclinic.org/drugs-supplements/esketamine-nasal-route/description/drg-20458442); [FDA label](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/211243s016lbl.pdf)).

This is not the same as a compounded ketamine lozenge or at-home spray sold on social media. Those products sit outside the Spravato label and REMS rules. A licensed clinician should explain the difference before you pay cash for an unregulated product.

If you are still on first-line oral care, start with our guide to online depression treatment.

Who it may fit

Johns Hopkins says current approval is for people with treatment-resistant depression: at least two other antidepressants, each for at least six weeks, without remission or at least a 50% improvement ([Johns Hopkins Medicine](https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/esketamine-for-treatment-resistant-depression)).

Mayo Clinic also lists a second labeled use: esketamine plus an oral antidepressant for depressive symptoms in adults with major depressive disorder and suicidal ideation or behavior ([Mayo Clinic](https://www.mayoclinic.org/drugs-supplements/esketamine-nasal-route/description/drg-20458442)).

Pediatric use has not been established. Mayo Clinic notes that safety and efficacy in children have not been shown ([Mayo Clinic](https://www.mayoclinic.org/drugs-supplements/esketamine-nasal-route/description/drg-20458442)).

A clinician still has to rule out conditions that need a different plan, such as bipolar disorder, substance-use disorder, or medical causes of low mood. Mayo Clinic’s overview of treatment-resistant depression lists those review steps before you add a procedure-level option ([Mayo Clinic](https://www.mayoclinic.org/diseases-conditions/depression/in-depth/treatment-resistant-depression/art-20044324)).

How it works

Most oral antidepressants raise serotonin, norepinephrine, or dopamine over weeks. Esketamine acts mainly through glutamate, the brain’s most abundant chemical messenger. Johns Hopkins describes a faster effect on more brain cells at once, with some people noticing relief within hours rather than weeks ([Johns Hopkins Medicine](https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/esketamine-for-treatment-resistant-depression)).

That speed is why clinics keep you on site. Dissociation and blood-pressure changes show up in the same window as the early mood effect. The medicine is a tool, not a standalone cure. Oral antidepressants, therapy, and follow-up still matter.

Johns Hopkins reports that up to 33% of people with depression do not respond to multiple conventional antidepressants, and that esketamine reduced symptoms for a majority of those people in clinical trials ([Johns Hopkins Medicine](https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/esketamine-for-treatment-resistant-depression)). Individual results vary.

What a session looks like

You do not leave the building with a bottle. Certified staff supervise each visit. Johns Hopkins describes three self-administered doses, five minutes apart, then observation until side effects settle ([Johns Hopkins Medicine](https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/esketamine-for-treatment-resistant-depression)).

Mayo Clinic’s patient instructions: do not eat for at least two hours and do not drink for at least 30 minutes before the spray. If you use a nasal steroid or decongestant, take it at least one hour earlier. Each device holds two sprays. You wait five minutes between devices. Staff usually keep you in the facility for at least two hours ([Mayo Clinic](https://www.mayoclinic.org/drugs-supplements/esketamine-nasal-route/description/drg-20458442)).

The FDA label requires healthcare-provider monitoring for at least two hours at each session because sedation can be delayed or prolonged ([FDA label](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/211243s016lbl.pdf)).

Arrange a ride home. Mayo Clinic says not to drive or do anything dangerous until the next day after a restful sleep ([Mayo Clinic](https://www.mayoclinic.org/drugs-supplements/esketamine-nasal-route/description/drg-20458442)).

Dosing schedule

Mayo Clinic lists these typical adult nasal doses. Your clinician may change them.

• Treatment-resistant depression: 56 or 84 mg twice weekly in weeks 1-4; then 56 or 84 mg once weekly in weeks 5-8; then 56 or 84 mg every two weeks or once weekly from week 9 onward.
• MDD with suicidal ideation or behavior: 84 mg twice weekly for 4 weeks, adjusted as tolerated ([Mayo Clinic](https://www.mayoclinic.org/drugs-supplements/esketamine-nasal-route/description/drg-20458442)).

Johns Hopkins describes a similar pattern: twice weekly for the first month, then less often if it helps ([Johns Hopkins Medicine](https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/esketamine-for-treatment-resistant-depression)).

Side effects and who should avoid it

Johns Hopkins lists hallucinations and feeling disconnected from yourself or reality as the most dramatic effects. Those usually peak around 40 minutes and fade within two hours. Nausea, drowsiness, higher blood pressure, feeling drunk, and headache also occur. The first two sessions often feel the strongest ([Johns Hopkins Medicine](https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/esketamine-for-treatment-resistant-depression)).

Mayo Clinic’s more-common list includes anxiety, blurred vision, confusion about identity or place, dizziness, dissociation, headache, spinning sensations, and a slow or fast heartbeat. Less common effects include speech changes, vivid dreams, tremor, and urinary symptoms. Rare reports include chest pain and suicidal thoughts. Breathing problems are listed under incidence not known ([Mayo Clinic](https://www.mayoclinic.org/drugs-supplements/esketamine-nasal-route/description/drg-20458442)).

Do not use esketamine if you have a history of ketamine allergy, aneurysmal vascular disease, arteriovenous malformation, or bleeding in the brain. Mayo Clinic also flags caution for heart disease, stroke history, psychosis, drug-abuse history, high blood pressure, and moderate liver disease, and says severe liver disease is a reason to avoid it ([Mayo Clinic](https://www.mayoclinic.org/drugs-supplements/esketamine-nasal-route/description/drg-20458442)).

Pregnancy can harm an unborn baby. Use effective contraception during treatment and tell your clinician if you become pregnant ([Mayo Clinic](https://www.mayoclinic.org/drugs-supplements/esketamine-nasal-route/description/drg-20458442)).

If you are in crisis now, call or text 988, or call 911. This article is education, not emergency care.

Esketamine vs IV ketamine and other options

Mayo Clinic groups IV ketamine and nasal esketamine together as options that work differently from standard antidepressants. IV ketamine is typically given in decreasing frequency over several weeks. Esketamine is the FDA-approved nasal form given in a physician’s office or clinic because of serious side effects and misuse risk ([Mayo Clinic](https://www.mayoclinic.org/diseases-conditions/depression/in-depth/treatment-resistant-depression/art-20044324)).

Other paths for stubborn depression include a longer trial of the current medicine, a higher dose, a switch, a second antidepressant, or an add-on such as an antipsychotic or thyroid hormone. Procedures include rTMS, ECT, and, later, vagus nerve stimulation ([Mayo Clinic](https://www.mayoclinic.org/diseases-conditions/depression/in-depth/treatment-resistant-depression/art-20044324)).

Anxiety often sits next to depression. If that is part of your picture, see online anxiety treatment.

Why you cannot do this fully online

Spravato REMS exists so the spray is not mailed for unsupervised home use. FDA materials and the product label require a certified healthcare setting and at least two hours of monitoring ([FDA label](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/211243s016lbl.pdf); [Spravato REMS](https://www.spravatorems.com/)).

A video visit cannot replace that observation. Anyone who offers “Spravato shipped to your door” is not describing the FDA-approved pathway.

Telehealth still has a job. A licensed clinician can confirm the diagnosis, document failed antidepressant trials, manage oral medicines, screen for bipolar disorder, and refer you to a certified Spravato site if that is the next step.

How Klarity can still help

Klarity Health is a technology platform that connects you with independent licensed providers. Those clinicians can discuss online depression treatment, adjust oral prescriptions when appropriate, and talk through whether a REMS clinic referral makes sense. They do not ship Spravato for home use.

Coverage for visits and for clinic-based esketamine varies by plan. Some plans require prior authorization and proof of two failed antidepressants. Medicaid and Medicare rules differ from commercial formularies. Ask your insurer about both the medical-benefit clinic fee and the pharmacy claim. Do not assume a $0 bill.

Related care: anxiety, ADHD, OCD, and online prescriptions. If you pay cash for talk therapy, see our guide to no insurance therapy.

Disclaimer: This article is for education. It is not a diagnosis or a promise of coverage. A licensed clinician decides whether any medicine is appropriate. Insurance benefits vary. Verify your plan before you book a clinic series. If you have thoughts of suicide, call or text 988 or go to the nearest emergency department.

FAQ

Is esketamine the same as ketamine?

Esketamine is one half of the ketamine molecule. Johns Hopkins describes it as more potent, which is why a lower nasal dose is possible ([Johns Hopkins Medicine](https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/esketamine-for-treatment-resistant-depression)). IV racemic ketamine is a different product and is often used off-label.

How fast does it work?

Some people feel a change within hours. Conventional pills often take weeks ([Johns Hopkins Medicine](https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/esketamine-for-treatment-resistant-depression)). Not everyone responds.

Can I get a Spravato prescription through telehealth only?

A telehealth clinician may evaluate you and refer you. The spray itself is given only in a certified setting with two-hour monitoring ([FDA label](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/211243s016lbl.pdf)).

Will insurance pay?

Sometimes. Plans often ask for documentation of two failed antidepressants and a REMS clinic. Coverage is not guaranteed. Confirm both the visit and the drug benefit.

Do I still need an oral antidepressant?

Mayo Clinic now describes TRD use with or without an oral antidepressant. The suicidal-ideation indication still pairs the spray with an oral antidepressant ([Mayo Clinic](https://www.mayoclinic.org/drugs-supplements/esketamine-nasal-route/description/drg-20458442)). Follow your clinician’s plan.

Ready to talk about next steps for depression? A licensed Klarity-network provider can review your history and discuss oral options or a clinic referral. Coverage varies. See if you may qualify → · Browse conditions