Almost everything else described as ketamine therapy for depression is an off-label use of an anesthetic. This one is not.
That regulatory difference drives almost everything else about it, including what insurance will do.
Spravato is esketamine, delivered as a nasal spray, FDA-approved for treatment-resistant depression. It must be given in a certified healthcare setting under a monitoring program, and in January 2025 it became approved for use on its own rather than only alongside an antidepressant.
What Spravato Is
Spravato is the brand name for esketamine, a nasal spray form of one of the two mirror-image molecules that make up ketamine. It holds FDA approval for treatment-resistant depression in adults, and for depressive symptoms in adults with major depressive disorder who have acute suicidal ideation or behavior. It is a Schedule III controlled substance. You self-administer the spray under supervision in a certified healthcare setting, then remain for a monitored observation period of at least two hours before going home.
Racemic ketamine, the anesthetic used in most clinics, contains both mirror-image forms.
Esketamine is one of them, isolated and developed in particular as a psychiatric medication.
The 2025 Monotherapy Approval
This is the part most sites are out of date on.
Until January 2025, Spravato was approved only as an add-on. You had to take an oral antidepressant alongside it. If you could not tolerate antidepressants, you were effectively excluded.
On 21 January 2025, the FDA approved Spravato as a monotherapy for adults with treatment-resistant depression. It became the first and only treatment of its kind approved to be used on its own for that indication.
Why it matters practically:
People who cannot tolerate oral antidepressants now have a route that was previously closed
People whose side effects come mainly from their oral antidepressant have an option to discuss
It changes the conversation about what a treatment plan has to include
It does not mean stopping your antidepressant. Approval for use as monotherapy is not advice to discontinue anything. Never stop or change a psychiatric medication without your prescriber, since several classes carry discontinuation effects.
The FDA publishes the approved labeling.
How It Differs From Ketamine
Spravato (esketamine)
Ketamine, other routes
FDA status
Approved for TRD
Off-label
Molecule
Esketamine only
Both mirror-image forms
Route
Nasal spray, self-administered
Injection, infusion, sublingual
Setting
Certified site only
Clinic, or at home for compounded
Observation
At least 2 hours, required
Varies by clinic
Insurance
Often covered
Usually not
Schedule
Fixed by the label
Set by the clinic
Driving
Not until the next day after rest
Not for the rest of the day
The dosing schedule difference is worth understanding. Spravato follows a schedule defined by its approved labeling, typically twice weekly initially and reducing over time. Off-label routes have no single authoritative schedule, which is why session counts differ between clinics.
Neither is universally better. Approval brings coverage and structure. Off-label routes bring flexibility in dose, route and scheduling.
What REMS Means for You
REMS stands for Risk Evaluation and Mitigation Strategy, an FDA safety program for medications with particular risks.
For Spravato it means specific requirements you will experience directly.
Certified sites only. The clinic must be enrolled. Not every psychiatry practice is, and this is worth asking before you plan around it.
Administered on site. You spray it yourself, supervised. It is never dispensed to take home.
Observation for at least two hours, with monitoring of blood pressure and sedation.
Blood pressure checked before dosing and during observation.
No driving until the next day, after a full night of sleep. Arrange transport for every appointment.
Enrollment in a registry for safety monitoring.
The two-hour observation is the practical cost. Each appointment consumes half a day, and the schedule is twice weekly at first. Factor that into work and childcare before committing.
Insurance and Access
The strongest argument for Spravato over off-label routes.
It is frequently covered, by commercial insurance and by Medicare, since it is FDA-approved for the indication.
Prior authorization is normally required, and typically means documenting that you have tried and not adequately responded to at least two antidepressants at adequate dose and duration.
Documentation matters. Vague notes about past medications are a common reason authorizations fail. Bring a written list with names, doses, dates and outcomes.
Coverage varies by plan and can require step therapy through other treatments first.
The manufacturer runs patient support programs that may help with cost. Ask the certified site.
Even with coverage, expect copays across a course, and the two-hour observation has a time cost that no insurance offsets. Our post on ketamine cost and insurance covers the comparison.
Who It Suits and Who It Does Not
Tends to suit someone with a documented history of at least two failed antidepressant trials, someone who needs insurance coverage to afford treatment, someone who cannot tolerate oral antidepressants now that monotherapy is approved, and someone able to attend twice weekly and stay two hours.
Tends not to suit someone who cannot commit to the observation schedule, someone without transport for every appointment, someone whose insurance denies it and cannot self-fund, and someone for whom a different route is clinically preferable.
Not suitable where there is a history of aneurysmal vascular disease, arteriovenous malformation, or intracerebral hemorrhage, and it requires careful assessment with uncontrolled high blood pressure. Screening covers this properly, as described in our post on ketamine candidacy.
The choice between Spravato and an off-label route is usually decided by insurance and schedule rather than by clinical preference.
FAQs About Spravato
Is Spravato the same as ketamine? Not quite. Ketamine contains two mirror-image molecules and Spravato is esketamine, one of them, formulated as a nasal spray. Spravato is FDA-approved for treatment-resistant depression, must be given in a certified setting with at least two hours of observation, and is frequently covered by insurance.
Does insurance cover Spravato? Often, unlike off-label ketamine. Prior authorization is normally required and typically means documenting inadequate response to at least two antidepressants at adequate dose and duration. Bring a written medication history with names, doses and dates, since poor documentation is a common reason authorizations are denied.
Can I take Spravato without an antidepressant? Since January 2025, yes. The FDA approved it as a monotherapy for adults with treatment-resistant depression, having previously required an oral antidepressant alongside it. That is not advice to stop anything you are taking. Only your prescriber should change a psychiatric medication.
Why do I have to stay for two hours? It is a REMS requirement, an FDA safety program. Blood pressure and sedation are monitored during that period, since esketamine reliably raises blood pressure and produces sedation and dissociation. You cannot drive until the next day after a full night of sleep.
How often would I need appointments? The schedule is set by the approved labeling rather than by the clinic, typically twice weekly at first and reducing over time. With a two-hour observation each visit, expect it to take half a day. Plan around that before starting.
Ask Which Route Fits
Whether Spravato or another route suits you depends on your insurance, your schedule and your history.
Call (770) 817-9200 or see our ketamine therapy page.
Atlanta Ketamine Clinic, 5755 North Point Parkway Suite 256, Alpharetta, GA 30022.
Reviewed by Angelo Sambunaris, M.D., Atlanta Ketamine Clinic.This article is general information, not medical advice. If you are having thoughts of suicide or self-harm, call or text 988 to reach the Suicide and Crisis Lifeline, available 24 hours a day.
