If your depression has hung on through a couple of medications, you have probably run into the word ketamine and felt more confused, not less. Some clinics advertise ketamine infusions. Others talk about a nasal spray called Spravato. They sound like the same thing, and they are related, but for a patient in the St. Louis metro the practical differences, especially around cost and coverage, are large. This is the map.
Start with the chemistry, briefly, because it explains everything that follows. Ketamine is a decades-old anesthetic. The ketamine molecule is actually a mix of two mirror-image forms. One of those forms, esketamine, was developed on its own into a nasal spray and given the brand name Spravato. So Spravato is not a knockoff of ketamine. It is a purified piece of it, packaged and studied specifically for depression.
Spravato (esketamine) is FDA-approved for treatment-resistant depression. Plain IV ketamine is FDA-approved as an anesthetic and is used off-label for depression. That single fact drives most of the cost and coverage difference.
IV ketamine infusions: powerful, but off-label
When a clinic offers ketamine "infusions," they usually mean the full ketamine molecule delivered slowly through an IV, sometimes as an injection, in a series of sessions. There is real research behind it, and many people report fast relief. But the FDA has never approved ketamine itself for depression, so this use is off-label. That is legal and common in medicine, but it has one big downside for patients: because it is off-label, most insurance plans, including MO HealthNet, generally will not pay for it. People typically cover a course of infusions out of pocket, and it is not cheap.
Spravato (esketamine): the FDA-approved path
Spravato took the esketamine piece through formal FDA trials and, in 2019, earned approval for treatment-resistant depression, meaning depression that has not responded to at least two antidepressants. It is also approved for adults with major depression who are having suicidal thoughts. Because it carries an FDA approval, it behaves very differently in the insurance world: many plans cover it for people who meet the criteria, usually after a prior authorization documenting the medications you have already tried. For a lot of Missouri patients, that makes Spravato the version they can actually access without draining savings. Our full Spravato in St. Louis guide walks through visits, schedule, and coverage in detail.
Two treatments can be similar in the body and worlds apart at the front desk. Because Spravato is FDA-approved for depression, it is often a covered benefit. Because IV ketamine is off-label, it usually is not. If money is tight, that difference alone often points people toward asking about Spravato first.
What they have in common
Both work on the brain's glutamate system rather than the serotonin pathway that standard antidepressants target, which is why either can lift mood faster than a typical pill, sometimes within days. Both can cause temporary dissociation, a floaty or detached feeling, along with dizziness and a short rise in blood pressure. For that reason, both are given under medical supervision, and you are monitored afterward and cannot drive for the rest of that day. Neither is something you take home. And neither is a magic switch: they help a meaningful share of people who had run out of options, and they do nothing for others.
So which should you ask about?
That is a conversation for a qualified clinician, not a search result, and the honest answer depends on your history, your other health conditions, and your coverage. But two practical truths hold for most people in the metro. First, because Spravato is FDA-approved and often covered by insurance including MO HealthNet, it is usually the more accessible starting point. Second, whichever you consider, it belongs in a supervised clinic that will evaluate whether you are a candidate rather than sell you a package sight unseen.
The question is rarely ketamine or nothing. It is which supervised, evidence-based option fits you, and which one you can actually afford to finish.
If you have not yet worked through the earlier next-line steps, our guide on what to do when antidepressants are not working covers switching, augmentation, therapy, and TMS, a drug-free option that many people reach for before or alongside any form of ketamine. And your own doctor is the key that unlocks a referral: a clear conversation with them is still the single most reliable way into treatment.