Ketamine vs Spravato for depression: what is the difference?

By the STL Depression Clinics Editorial TeamIndependent, medically reviewed for accuracy

A lot of people in the St. Louis area have heard the word "ketamine" for depression and are not sure how it relates to Spravato, or which one insurance actually covers. They are related but not the same. Here is a plain-language comparison so you can ask a clinician the right questions.

Why this is confusing

The two names get used interchangeably in casual conversation, and that causes real mix-ups about cost and coverage. In short: Spravato is a specific, FDA-approved prescription form of the medicine, delivered as a nasal spray in a certified clinic. "Ketamine infusions" usually means generic ketamine given through an IV, used off-label for depression. They come from the same family, but they are regulated, delivered, and paid for very differently. Most people do not search for either term by name at first. They search for how they feel, then run into these two words and have to sort them out.

Spravato (esketamine) in plain terms

Spravato is the brand name for esketamine, a nasal spray the U.S. Food and Drug Administration approved in 2019 for treatment-resistant depression, and later for depressive symptoms in adults with major depression who have suicidal thoughts. Because it is FDA-approved for depression, it is covered by many insurance plans, including Medicare and MO HealthNet (Missouri Medicaid), when a person meets the criteria. It is only given in a certified clinic, where you are monitored for at least two hours and arrange a ride home afterward. Our Spravato guide walks through a visit in detail.

Ketamine infusions in plain terms

IV ketamine is the original medication. It has been used for decades as an anesthetic and is given off-label for depression, meaning the FDA has not approved that specific use even though many clinicians use it based on research and experience. Because it is off-label, it is frequently not covered by insurance, so ketamine infusion clinics often charge out of pocket, and a series of infusions can add up. It is usually delivered as an IV drip over roughly forty minutes with monitoring. Some people respond well to it, but the cash cost is the practical catch that surprises people.

The side-by-side that actually matters

• Form. Spravato is a nasal spray you self-administer under supervision. Ketamine infusions are given through an IV.
• FDA status. Spravato is FDA-approved for treatment-resistant depression. IV ketamine is used off-label for depression.
• Coverage. Spravato is covered by many plans, including MO HealthNet, when criteria are met. IV ketamine is often not covered and paid out of pocket.
• Setting. Both require in-clinic monitoring, and after either one you do not drive yourself home that day.
• What they share. Both are options considered when standard antidepressants have not worked, and neither is a cure. Results vary from person to person.

For a lot of people, the coverage difference is the deciding factor. If cost is a barrier, the FDA-approved, insurance-covered option is worth asking about first. Our insurance and cost guide covers how that works in Missouri.

How to bring this up with a clinician

You do not need to arrive knowing which one you want. A useful way to start is simply: "My antidepressants have not worked and I have read about ketamine and Spravato. Which of these might make sense for me, and what would my insurance cover?" A responsible clinician will walk you through the trade-offs rather than pushing a single answer. If you are weighing non-drug options too, our TMS guide covers a treatment that involves no medication and no driving restriction, and our page on when antidepressants stop working lays out the full range of next steps.

A word of caution

Be wary of any clinic, for either treatment, that promises a guaranteed cure or calls the medicine a miracle fix. Responsible providers talk about likelihood, monitoring, and follow-up, not guarantees. Both options have helped people who felt out of choices, but they work best as part of ongoing, supervised care. If things ever feel unsafe, call or text 988 at any time.