If you have been reading about newer depression treatments, you have probably run into two names that seem to point at the same thing: ketamine and Spravato. Clinics advertise both, articles use them almost interchangeably, and it is genuinely confusing. They are related, they even work on the same part of the brain, but the differences are real and they affect what you can get, how it is paid for, and how it is delivered. Let us untangle it.
They come from the same molecule
Ketamine is a medicine that has been used as an anesthetic in hospitals and ambulances for decades, with a long, well-understood safety record. Chemically, the ketamine molecule exists as two mirror-image versions, a bit like a left hand and a right hand. Esketamine is just one of those two halves - the "S" version - isolated on its own. Spravato is the brand name for that esketamine, formulated as a nasal spray. So Spravato is not a different drug family. It is a purified piece of ketamine, packaged and studied as its own product.
Both of them work differently from ordinary antidepressants. Instead of nudging serotonin, they act on the brain's glutamate system, which is involved in how brain cells form and rebuild connections. That different mechanism is why either one can help people whose depression did not budge for the usual pills.
The difference that matters most: FDA approval
This is the crux of it. Spravato (esketamine) is FDA-approved specifically for treatment-resistant depression, and also for depressive symptoms in adults who have suicidal thoughts or actions. That formal approval came after large, controlled studies aimed at exactly those uses.
Ketamine itself is FDA-approved as an anesthetic, not as a depression treatment. When a clinic offers IV ketamine infusions for depression, that is an off-label use. Off-label does not mean shady or illegal - doctors legally prescribe many established medicines off-label based on research and clinical judgment. It simply means the FDA has not put its formal stamp on that particular use, which has real downstream effects on cost and coverage.
How each one is actually given
Spravato is a nasal spray you self-administer inside a certified clinic, then rest and are monitored for about two hours before a planned ride home. It is used alongside an oral antidepressant, and its distribution is tightly controlled through a federal safety program, so you cannot pick it up at a regular pharmacy.
IV ketamine for depression is delivered through a slow infusion into a vein over roughly forty minutes to an hour, also with monitoring, in a clinic that offers it. Dosing and schedules vary more from place to place because there is no single FDA-approved protocol for depression the way there is for Spravato.
What it means for your wallet
FDA approval is the reason coverage tends to split the way it does. Because Spravato is approved for treatment-resistant depression, many insurance plans cover it, and in Missouri that can include MO HealthNet, usually after other treatments have been tried. Off-label IV ketamine, on the other hand, is frequently not covered and is often paid out of pocket. None of this is guaranteed for your specific plan, which is exactly why a good clinic checks your benefits before you commit to anything.
So which one is right?
Honestly, that is not a question a web page can answer for you, and anyone who claims otherwise is overselling. The right choice depends on your history, what you have already tried, your insurance, and a provider's judgment. For a lot of people the practical answer starts with Spravato simply because it is FDA-approved for depression and therefore more likely to be covered. But the useful move is the same either way: bring it to your own doctor. You might say, "I have tried a couple of antidepressants without enough relief. Would esketamine or ketamine be worth looking into for me?" That one sentence turns a confusing search into a real plan.
The bottom line
Ketamine and Spravato are cousins, not twins. They share a mechanism and a heritage, but Spravato is the FDA-approved, insurance-friendlier, nasal-spray version built specifically for stubborn depression, while medical ketamine is the older, off-label infusion. If you live near O'Fallon, both conversations are ones you can have close to home - and your own doctor is the person best placed to help you choose.