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SPRAVATO® vs. Ketamine Therapy: The Differences That Actually Decide It
Quick Answer
SPRAVATO® is esketamine, a nasal spray FDA-approved for adults with treatment-resistant depression and for depressive symptoms in adults with major depressive disorder who have acute suicidal thoughts or actions; it is given only in certified clinics and many insurance plans cover it. Ketamine therapy uses ketamine itself, is not FDA-approved for any psychiatric condition, is prescribed off-label, and is usually self-pay. Both are supervised, monitored treatments at Denver Ketamine Clinic; which one fits usually comes down to eligibility, coverage, and your psychiatrist's judgment.
The chemistry, in one paragraph
Ketamine is a mixture of two mirror-image molecules. Esketamine is one of them, isolated and formulated as a nasal spray and sold under the brand name SPRAVATO®. Both act on the brain's glutamate system rather than the serotonin pathways most antidepressants target, which is why both are considered for people who have not improved on conventional medication. They are related compounds with different regulatory histories, delivery methods, and price tags — not interchangeable products.
Approval: the difference that drives everything else
SPRAVATO® was approved in 2019 for treatment-resistant depression alongside an oral antidepressant, received a further approval for depressive symptoms in adults with major depressive disorder and acute suicidal thoughts or actions, and in January 2025 was approved as a standalone treatment for treatment-resistant depression. It is dispensed only through a restricted program (REMS) at certified centers. Ketamine, by contrast, is approved as an anesthetic. Using it for depression is off-label: legal and common, but outside any FDA-approved indication, which means no manufacturer labeling, no REMS, and in most cases no insurance coverage.
Cost and coverage
Because SPRAVATO® is FDA-approved for depression, many commercial plans and TRICARE cover it when their criteria are met — typically a treatment-resistant depression diagnosis documented by prior antidepressant trials. Our team verifies benefits and submits prior authorization before the first dose. Ketamine therapy is almost always self-pay; we give you the per-session and full-course cost in writing before you decide.
Visits
Both require you to stay in the clinic for monitoring and to have someone drive you home. A SPRAVATO® visit is the spray followed by roughly two hours of observation, usually twice weekly during the first month and less often after. A ketamine therapy session runs roughly one to two hours including recovery; the number and spacing of sessions is individualized.
Who qualifies
SPRAVATO® has defined criteria tied to its approvals. Ketamine therapy has no labeled criteria, which places more weight on the psychiatrist's evaluation: uncontrolled blood pressure, certain heart conditions, active substance use disorder, and a history of psychosis require careful review for either treatment and may rule them out.
How we decide at Denver Ketamine Clinic
If you meet the criteria for SPRAVATO® and your plan covers it, that is usually the first ketamine-based option we discuss, because it is approved, monitored under a formal program, and affordable. Ketamine therapy is the alternative for patients who do not qualify, whose coverage does not apply, or who choose it after an informed conversation. And if neither is the fit, FDA-cleared TMS is available in the same clinic — one evaluation covers all three.
Frequently asked questions
Is SPRAVATO® just ketamine in a nasal spray?
No. SPRAVATO® contains esketamine, one of the two molecules that make up ketamine, in an FDA-approved formulation given under a restricted program at certified clinics. Ketamine therapy uses ketamine itself and is off-label.
Does insurance cover ketamine therapy?
Rarely. Ketamine therapy for depression is off-label and is generally self-pay. SPRAVATO® is FDA-approved and is covered by many plans when their criteria are met.
Can I drive after either treatment?
No. Both require that someone drive you home, and you should not drive until the next day.
Which one works better?
There is no head-to-head answer that applies to everyone. Your psychiatrist weighs your history, eligibility, coverage, and medical conditions and recommends the pathway that fits — and revisits it if your response changes.
Not sure which pathway you qualify for? One evaluation answers it.
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