Guide

Ketamine therapy vs esketamine (Spravato): what's the difference?

Reviewed by the editorial team · Written in plain language for St. Charles County readers

If you have been researching newer depression treatments, you have probably run into two names that sound almost the same: ketamine and esketamine. Some clinics advertise "ketamine therapy" or "ketamine infusions." Others talk about esketamine, or its brand name Spravato. Are they the same thing? Not quite. The difference matters for your safety, your insurance, and what to ask a clinic. Here is a clear, no-hype comparison.

The short version

Ketamine is a medicine that has been used safely as an anesthetic in hospitals for decades. Esketamine is one specific half of the ketamine molecule, packaged as a nasal spray. Think of ketamine as the whole molecule and esketamine as one carefully separated part of it. Both can affect the brain in similar ways, but they reach patients through different routes, carry very different regulatory approval, and are usually paid for very differently.

Esketamine (Spravato): the FDA-approved option

Esketamine, sold as Spravato, was approved by the U.S. Food and Drug Administration in 2019 for adults with treatment-resistant depression, and later for adults with major depression who are having suicidal thoughts. Because it is FDA-approved for depression, it comes with a defined, standardized process:

• It is a nasal spray you take yourself, in a certified clinic, with staff present.
• You are monitored for about two hours afterward, and you arrange a ride home.
• Because it is FDA-approved for this use, many insurance plans cover it, including MO HealthNet through providers who accept it.

Our full esketamine (Spravato) guide walks through a typical visit in detail.

IV ketamine infusions: the off-label route

The other thing people mean by "ketamine therapy" is usually racemic ketamine given as an intravenous (IV) infusion. This is the original anesthetic medicine, delivered through a vein over roughly 40 minutes while you are monitored. Research has shown it can rapidly reduce depression symptoms for some people, which is why interest is high. But there is an important distinction: IV ketamine for depression is used off-label. That means the drug itself is FDA-approved as an anesthetic, but not specifically approved by the FDA to treat depression. Off-label prescribing is legal and common across medicine, but it changes a few practical things.

How they compare at a glance

• What it is: Esketamine is a nasal spray (one half of the molecule). IV ketamine is the whole molecule given through a vein.
• FDA status for depression: Esketamine is approved for treatment-resistant depression. IV ketamine is used off-label.
• Setting: Both are given in a supervised clinical setting with monitoring, and both require a ride home.
• Insurance: Esketamine is often covered, including MO HealthNet in some cases. IV ketamine is frequently out of pocket.
• Who decides: A qualified clinician, based on your history, other medications, and health conditions.

What about TMS?

These are not the only options for depression that has not responded to medication. TMS (transcranial magnetic stimulation) is a non-drug, FDA-cleared treatment that uses magnetic pulses instead of any medicine, with no sedation and no ride needed. Many people weighing ketamine or esketamine also consider TMS. Our TMS therapy guide compares that path, and our guide on when antidepressants aren't working puts all of these next-line options in context.

Questions to ask a clinic

• Are you offering FDA-approved esketamine (Spravato), off-label IV ketamine, or something else?
• Is a doctor supervising treatment, and how is monitoring handled?
• Will you verify my insurance, and what would I owe out of pocket?
• How will we know if it is working, and what is the plan if it is not?

The names are confusingly similar, but the takeaway is simple. Both come from the same family of medicine, both are given under supervision, and the biggest practical differences are FDA approval for depression and how the bill gets paid. Knowing which one you are being offered lets you make a genuinely informed choice with your doctor.