A Patient’s Guide to Ketamine and Spravato

How are ketamine and esketamine related?

Ketamine is a mixture of two mirror-image molecules. Esketamine, sold as Spravato, is one of those two molecules. The two drugs are related, but they are separate products with different approvals.

Ketamine is FDA-approved as a general anesthetic. It is not FDA-approved for any psychiatric disorder, so using it for depression is off-label. Healthcare providers generally may prescribe an approved drug for an unapproved use when they judge it medically appropriate. Off-label use also means the FDA has not determined the drug is safe and effective for that use. See the two side by side.

What is Spravato approved for?

The FDA label lists two uses, both in adults:

• Treatment-resistant depression, on its own or with an oral antidepressant.
• Depressive symptoms in major depressive disorder with acute suicidal thoughts or behavior, together with an oral antidepressant.

The label sets clear limits on the second use. Spravato has not been shown to prevent suicide or reduce suicidal thoughts or behavior. It does not remove the need for hospital care when that is clinically warranted. Spravato is not approved for children or teens. Read the Spravato overview.

If you are thinking about suicide or are in danger, call or text 988 (988 Suicide & Crisis Lifeline), call 911 or go to the nearest ER.

What does treatment-resistant depression mean?

It usually means major depression that has not improved enough after at least two antidepressants, each taken at an adequate dose for long enough and as prescribed. Experts have not settled on one standard, so clinicians, studies and insurers can apply the term differently. The term describes how past treatment went. It does not mean nothing can help.

A 2023 international review says a significant share of people labeled this way have depression that looks treatment-resistant for other reasons, such as an inaccurate diagnosis or past treatment trials that were not adequate. This is one reason a full look at your history comes before any change in treatment. Learn how the term is used.

How do they work?

Esketamine blocks the NMDA receptor, which is part of the brain's glutamate system. Even so, the label says the way it produces its antidepressant effect is unknown. Claims that either drug "resets" the brain go beyond what the label can support.

How well do they work?

For Spravato, the results are real but should be read carefully. In a 4-week study described in the label, people using it with a new oral antidepressant improved more on a depression scale than people using a placebo spray with a new antidepressant. Both groups improved. In a 4-week study of people 65 and older, the main result did not reach statistical significance.

For ketamine, most studies used IV administration. A 2021 Cochrane review found ketamine may be more effective than placebo at 24 hours, though the evidence for that comparison was rated very low certainty. Research shows rapid effects that are often temporary. No option works for everyone.

Is Spravato or ketamine stronger?

This question has no settled answer. A 2023 meta-analysis of 49 randomized trials found effect sizes numerically greater for ketamine than esketamine, but it compared across separate trials with different doses, routes and study designs. Direct long-term comparisons are still needed. The clearer difference is how much of the safety framework comes from a regulator and how much depends on the clinician and setting.

	Spravato	Ketamine
Status for depression	FDA-approved for specific adult uses	Off-label
Monitoring	At least 2 hours at every session, then an assessment before leaving	Set by the clinician and the setting; practices vary
Safety program	Required REMS with certified settings	The Spravato REMS does not cover it
Insurance	Tends to have a clearer path, often with prior approval and specific criteria	Harder to get covered; at least some insurers consider it experimental

Your own plan's written policy decides coverage. How coverage works.

Does the ketamine route matter?

Routes differ in how much medicine reaches the bloodstream, how predictable that amount is and how much research supports them. IV has the largest body of depression research. Injections into muscle or under the skin are less studied. For oral forms, a 2023 systematic review found only four randomized trials and called the evidence preliminary. None of these routes is FDA-approved for depression, and research does not name one best route for everyone. Compare the routes, or see how Mind Body Seven approaches this treatment on its ketamine therapy page.

Is at-home ketamine safe?

There is no solid answer for all products and all people, because the safety research is limited. The FDA has warned that compounded products are not FDA-approved, and that using them without a clinician monitoring for sedation, dissociation and vital-sign changes may put patients at risk for serious adverse events. If you already use ketamine at home, do not stop or change it on your own. Talk with your prescriber. If you have trouble breathing, cannot stay awake or feel unsafe, call 911. What the FDA warned about.

How do TMS and ECT fit in?

TMS uses magnetic pulses without anesthesia, typically in daily sessions 5 days a week for 4 to 6 weeks. ECT uses an electric current under general anesthesia and has the longest history of use for depression. Its main concerns are repeated anesthesia and memory effects. NIMH still calls it the gold standard for treatment-resistant depression. How ketamine compares with ECT is unsettled. One large 3-week trial, in people without psychosis, found IV ketamine was not meaningfully worse. Another, in hospitalized patients, favored ECT. Reviews pooling the trials disagree, and a 2024 review favored ECT for inpatients.

What can rule an option out?

The Spravato label rules it out for aneurysmal vascular disease, an arteriovenous malformation, a history of bleeding in the brain, or an allergy to esketamine, ketamine or the other ingredients. It is not recommended during pregnancy because it may cause fetal harm, and the Medication Guide says not to breastfeed during treatment. Heart or blood vessel conditions, past psychosis, liver problems and any history of substance misuse call for careful review with a prescriber.

Life-threatening symptoms need emergency evaluation first. If you are thinking about suicide or are in danger, call or text 988 (988 Suicide & Crisis Lifeline), call 911 or go to the nearest ER.

What to do before a consultation

1. Write down your treatment history. List each antidepressant or mood medicine with rough dates, the highest dose you recall, how long you stayed on it and why you stopped. Add any therapy you tried. Please do not change or stop your medicine while you gather this.
2. Share your health picture. Tell your prescriber about all your medicines. If you have ever had periods of unusually high energy, little need for sleep or risky behavior, say so even if they seemed like good times.
3. Call your insurer. Ask whether Spravato is covered and under which benefit, whether prior authorization is needed, whether ketamine for depression is covered by any route, and what out-of-network benefits you have. Criteria vary by plan and change over time. Do not change any treatment to meet a plan's criteria.
4. Check how payment works here. Mind Body Seven is an out-of-network practice and does not accept Medicare or Medicaid, including managed Medicaid. For many clients with Cigna, Aetna or BCBS plans, the practice files out-of-network claims for them. For other carriers, such as UnitedHealthcare, superbills are available in the patient portal. A Good Faith Estimate is available on request. How Spravato specifically is billed is a question for the intake team. See fees and insurance.
5. Request a consultation. The intake team will confirm fit, scheduling and costs.

Questions to bring

• What is the exact product and route, and is it FDA-approved or compounded?
• Who is present during and after dosing, and what is monitored?
• How will progress be judged, and what would lead to stopping?

If Spravato is recommended

The label advises no food for at least 2 hours before the dose and no liquids for at least 30 minutes before. You should not drive until the next day, after a restful sleep, so arrange a ride and leave the rest of the day open. A session can be postponed if your blood pressure is elevated. Each certified setting has its own way of running a visit, so ask for details. What a session is like.

After the first series

You and your clinician review how much it helped, then decide together whether to continue less often, change course or stop. For Spravato's use with acute suicidal thoughts or behavior, the label says use beyond 4 weeks has not been systematically evaluated. Ketamine has no FDA-approved maintenance schedule, so plans vary. Integration therapy is often paired with ketamine treatment, though the evidence is still early, and no one can honestly promise that it will extend the effect of a series. Maintenance and integration.

Between sessions, tell your provider right away about new or worse depression or thoughts of suicide. Do not stop antidepressants or other medicines on your own. If you are thinking about suicide or are in danger, call or text 988 (988 Suicide & Crisis Lifeline), call 911 or go to the nearest ER.