Spravato® vs. Ketamine Infusions: What's the Difference and Which Is Right for You?

If you've been researching treatment options for depression that hasn't responded to standard medications, you've almost certainly encountered both Spravato® and ketamine infusions. New York City has a growing number of clinics offering both, and the marketing around them can be confusing — sometimes deliberately so.

These are related treatments but they are not the same thing, and the differences matter clinically, practically, and financially. This article explains both clearly so you can have an informed conversation with a psychiatrist about which — if either — is appropriate for your situation.

The Relationship Between Ketamine and Esketamine

Ketamine is an anesthetic agent that has been used in medicine since the 1960s. It was observed decades ago to have rapid antidepressant effects — sometimes within hours — which led to significant research interest in its potential as a depression treatment.

Esketamine — the active ingredient in Spravato® — is a specific component of ketamine. Ketamine is a mixture of two mirror-image molecules (called enantiomers): esketamine and arketamine. Janssen Pharmaceuticals isolated the esketamine component, developed it as a nasal spray, and conducted the clinical trials required for FDA approval.

So: esketamine is derived from ketamine. They share a mechanism of action — NMDA receptor antagonism in the glutamate system — but they are not identical compounds, and they are not administered the same way.

Ketamine Infusions: What They Are

Ketamine infusions involve intravenous administration of racemic ketamine — the full mixture of both enantiomers — in a clinical setting. The dose is delivered directly into the bloodstream over approximately 40 minutes, producing rapid and complete absorption.

Key characteristics:

• FDA status: Not FDA-approved for depression. Used entirely off-label.

• Administration: Intravenous, in a clinical setting

• Insurance coverage: Generally not covered by insurance because it is off-label. Typically paid out of pocket.

• Cost: Typically $400 to $800 per infusion, with initial treatment courses involving 6 infusions over 2 to 3 weeks. Total initial cost commonly runs $2,400 to $4,800 or more.

• Providers: Variable — administered at ketamine clinics, anesthesiology practices, and some psychiatric offices. Quality of psychiatric oversight varies significantly.

• Evidence base: Substantial research evidence but no FDA approval for depression specifically.

Spravato®: What It Is

Spravato® is esketamine delivered as a nasal spray, FDA-approved for treatment-resistant depression and major depressive disorder with acute suicidal ideation. It was approved in 2019 based on clinical trials demonstrating efficacy specifically in these populations.

Key characteristics:

• FDA status: Approved for treatment-resistant depression and MDD with acute suicidal ideation

• Administration: Nasal spray, self-administered under clinical supervision in a certified treatment center

• Insurance coverage: Covered by most major insurance plans when eligibility criteria are met — specifically, documentation of at least two adequate prior antidepressant trials

• Cost: With insurance, patient cost varies by plan. Without insurance, list price is substantial — Janssen's patient assistance program exists for qualifying patients.

• Providers: Must be administered at REMS-certified treatment sites. Not available at every psychiatric practice.

• Evidence base: FDA-approved based on randomized controlled trials in the specific indicated populations.

The Clinical Differences That Matter

Mechanism overlap, not identity

Both treatments work through NMDA receptor antagonism in the glutamate system. But racemic ketamine and esketamine have different receptor binding profiles and different ratios of the two enantiomers, which may produce somewhat different clinical effects and side effect profiles. The research on arketamine — the other component present in racemic ketamine but not in Spravato® — suggests it may have independent antidepressant properties, which is one reason some clinicians believe racemic ketamine infusions may have advantages in certain cases.

Regulatory and oversight differences

Spravato® comes with a mandatory REMS program — a formal FDA risk management system requiring certified treatment sites, patient monitoring, and documentation. This creates a floor of clinical oversight that every Spravato® patient receives. Ketamine infusion clinics have no equivalent federal oversight requirement, which means quality of care varies more widely. Some ketamine clinics have excellent psychiatric oversight. Others do not.

Insurance

This is the most practically significant difference for most patients. Spravato® is covered by insurance when criteria are met. Ketamine infusions almost never are. For a patient who qualifies for Spravato® coverage, the out-of-pocket cost difference between the two options can be substantial — potentially thousands of dollars.

Which Is Right for You?

There is no universal answer. The right choice depends on your specific clinical situation, insurance coverage, prior treatment history, and the quality of providers available to you locally.

In general terms: if you meet criteria for treatment-resistant depression and have insurance that covers Spravato®, starting there is financially logical and provides the benefit of FDA-approved treatment with formal oversight. If you don't meet Spravato® criteria, have no insurance coverage, or have a clinical presentation that a knowledgeable psychiatrist believes may respond better to IV ketamine, infusions may be worth discussing.

What matters most is having this conversation with a psychiatrist who knows your full history — not making the decision based on which clinic has better marketing or shorter wait times.

At Aurora Wellness, our psychiatrists are experienced in evaluating patients for advanced depression treatments and can provide an honest assessment of whether Spravato® is appropriate for your specific situation. We offer Spravato® treatment at our Brooklyn and White Plains locations, with telehealth psychiatric care throughout New York State for ongoing medication management. If you've been researching your options and want a clinical perspective rather than a sales pitch, we're happy to have that conversation.