Ketamine vs. Spravato: What's the Difference?

If you've started researching ketamine therapy, you've probably noticed that some clinics offer "ketamine infusions" while others advertise "Spravato." They're closely related — but legally, financially, and practically they are quite different treatments. Understanding the difference will save you a lot of confusion when you compare clinics.

The short version

• Ketamine is a decades-old anesthetic that contains two mirror-image molecules (R-ketamine and S-ketamine). When used for depression or chronic pain, it's prescribed off-label — legal and common, but not FDA-approved for those conditions. It's usually given as an IV infusion or intramuscular (IM) injection at a clinic, and is rarely covered by insurance.
• Spravato (esketamine) is a nasal spray containing only the S-ketamine molecule. It is FDA-approved — for treatment-resistant depression and for depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior — and is often covered by insurance.

What "off-label" actually means

Off-label prescribing is when a licensed clinician prescribes an approved drug for a condition it wasn't specifically approved to treat. It's a normal, legal part of medicine — a large share of all prescriptions in the U.S. are off-label. Ketamine is FDA-approved as an anesthetic, and clinicians have used it off-label for depression since the 2000s, supported by a substantial body of clinical research.

The practical consequence isn't about legality — it's about insurance. Insurers generally won't pay for off-label ketamine infusions, which is why generic ketamine treatment is usually cash-pay while Spravato usually runs through your insurance.

How each is administered

Generic ketamine at clinics is most often given as:

• IV infusion — typically around 40 minutes, dosed by body weight, adjustable in real time
• IM injection — a single injection, slightly less controllable but simpler and often cheaper

Some prescribers also use oral or sublingual lozenges, mostly for at-home maintenance protocols. (See our guide on IV vs. IM ketamine for a deeper comparison of routes.)

Spravato is a nasal spray you administer yourself — but only at a certified clinic, under supervision. Because of its FDA risk-management program (REMS), you can't take it home. After each dose you're monitored at the clinic, typically for about two hours, before someone drives you home.

Effectiveness

Both treatments target the same underlying mechanism (NMDA-receptor modulation and downstream effects on synaptic plasticity), and both have meaningful evidence behind them:

• Racemic (generic) ketamine has been studied for treatment-resistant depression since the early 2000s, with rapid antidepressant effects — often within hours to days — in many patients.
• Esketamine's approval was based on large randomized trials in treatment-resistant depression.

Head-to-head data is more limited, and individual response varies a lot. Some patients respond to one and not the other. A reasonable clinic will talk you through both options rather than only selling what they happen to offer.

Cost comparison

• Ketamine infusions: usually cash-pay. Expect several hundred dollars per infusion, with an initial series of about six infusions over 2–3 weeks. See our cost guide for detailed numbers.
• Spravato: the drug itself is expensive at list price, but insurance (including Medicare) frequently covers it for eligible patients, leaving you with copays plus any clinic administration fees. Manufacturer savings programs can reduce out-of-pocket costs further for commercially insured patients.

If you have insurance and qualify for Spravato, it's often the cheaper path. If you're paying cash either way, generic ketamine is usually less expensive per treatment.

Which one is right for you?

That's genuinely a conversation for a licensed clinician, but the practical decision often comes down to:

1. Diagnosis — Spravato's approval covers treatment-resistant depression and MDD with acute suicidal ideation; if you're seeking ketamine for chronic pain, PTSD, or anxiety, that's off-label territory where generic ketamine is the usual route.
2. Insurance — if you're covered for Spravato, the financial math changes dramatically.
3. Logistics — both require clinic visits and a ride home; Spravato's monitoring window is longer per visit.
4. Prior response — some patients simply do better on one than the other.

Many clinics in our directory offer both, which makes it easier to switch if your first option doesn't work well.

Bottom line

"Ketamine vs. Spravato" isn't really a rivalry — Spravato is a form of ketamine, packaged and approved differently. The FDA approval is what unlocks insurance coverage and standardized safety monitoring; generic ketamine offers more flexibility in route, dosing, and conditions treated. Ask any clinic you're considering which they offer, why, and what your total cost will look like either way.