If you are weighing IV ketamine against Spravato for depression that has not responded to antidepressants, the honest answer is that neither has been shown to be the stronger treatment. No completed head-to-head trial exists. What separates them in practice is what your insurance will pay for, how long approval takes, and how you want to receive care.
Our position should be clear from the start. We offer Spravato at our Cleveland west-side clinic on Rocky River Drive, and we do not offer IV ketamine.
Read our reasoning with that in mind. Below, we set out what each option involves, where each one holds the genuine advantage, and how to work out which fits your situation.
IV ketamine vs Spravato at a glance
| IV ketamine | Spravato (esketamine) | |
| Molecule | Racemic ketamine, the full original molecule | Esketamine, one half of that molecule |
| How it is given | Intravenous infusion, typically 0.5 mg/kg over about 40 minutes | Nasal spray you administer yourself |
FDA status | No FDA approval for any psychiatric condition; used off-label | Approved for treatment-resistant depression since 2019, and as a standalone treatment since January 2025 |
Where | Infusion clinics and some psychiatric practices | REMS-certified clinics only |
Time on site | Around one to two hours | At least two hours of monitoring, required by the FDA |
Typical course | Around six infusions over two to three weeks, then maintenance | Twice weekly for four weeks, then weekly for four, then every one to two weeks |
Cost to you | Usually paid in cash: $400 to $800 per session nationally | Typically covered by insurance after prior authorization |
Driving after | Not the same day | Not the same day |
Used for | Depression, and off-label for PTSD, OCD, and chronic pain | Treatment-resistant depression, and major depressive disorder with suicidal ideation |
The clinical differences between the two are real but narrow. The differences in cost, coverage, and access are wide.
Is Spravato the same thing as ketamine?
Not quite. Spravato contains esketamine, which is one half of the ketamine molecule. IV ketamine uses the full molecule, both halves. They act on the same receptor system and produce similar effects, but they are separate products with different legal status, different delivery, and very different treatment by insurers.
This matters because “ketamine therapy” gets used as an umbrella term for at least four different things: clinic IV infusions, intramuscular injections, Spravato nasal spray, and compounded oral or sublingual ketamine mailed to your home. They are not equivalent, and the last one carries risks the others do not.
If you want the fuller background on how one anesthetic became four different treatments, we have written about ketamine’s path from operating room to psychiatry separately. We have also covered how esketamine acts on the brain in more depth than we can here.
Is IV ketamine more effective than Spravato?
No study has answered this properly yet. There is no completed head-to-head trial comparing the two. Comparisons drawn across separate studies have favored IV ketamine on response and remission rates, but those are not direct comparisons and should not be read as though they were. A head-to-head trial is now running.
What the indirect comparisons show
Pooling results from separate trials, racemic ketamine has come out ahead of esketamine on response, remission, and dropout rates. Those figures circulate widely and they are real.
They are also not a comparison. The patients were different, the trials were designed differently, and the placebo arms were not the same. Two treatments that were never tested against each other cannot be ranked by lining up their separate scorecards.
Why the evidence is harder to read than it looks
Both drugs produce noticeable effects within minutes, which means most participants can tell whether they received the active treatment. That undermines blinding, and unblinded trials tend to overstate benefit.
In 2023, a Stanford team tested this directly. Forty depressed patients received either IV ketamine or saline while under general anesthesia for an unrelated surgery, which achieved genuine masking. At one to three days, ketamine showed no greater antidepressant effect than placebo, and participants’ guesses about what they had received tracked how much better they felt rather than what they had actually been given.
That finding cuts against the treatment we do not offer, and it complicates the one we do. We think you should have it anyway.
It is not the whole picture. Spravato’s monotherapy trial found 22.5% of patients in remission at four weeks against 7.6% on placebo, and real-world IV ketamine clinics report response rates of roughly 55%. Both treatments help a substantial number of people who had run out of options.
The trial that will settle it, and why it won’t help you this year
Yale began recruiting for the EQUIVALENCE trial in January 2025. It is the first adequately powered head-to-head comparison of IV ketamine and Spravato, funded by the Patient-Centered Outcomes Research Institute rather than by either drug’s manufacturer, and its central question is whether IV ketamine is no worse than the approved nasal spray.
Its investigators have written openly that if the answer is yes, insurance coverage for infusions could expand.
Results are not expected until the end of 2030.
So the comparison you are trying to make will be answered, but not in time to help you decide this month. That is the argument for choosing on the grounds you can actually assess: what your plan covers, how soon you can start, and how you want to be looked after.
What each option costs you in Northeast Ohio
Most comparison articles tell you Spravato is cheaper because insurance covers it. That is true if you are insured, and it answers the wrong question if you are not.
Two different numbers get called “cost.” What a treatment is billed at, and what you actually pay. Insurance decides which one applies to you, and the two can point in opposite directions.
Spravato carries the higher billed price. It is also the one your plan is likely to pay for, which is why insured patients usually pay far less for it than for infusions.
IV ketamine is billed at less and covered at almost nothing. Ohio clinics that publish their pricing generally sit in the range of several hundred dollars per session, with an initial course of six to eight sessions before maintenance. Prices vary widely and clinics do not always list them, so ask for the full course cost in writing before you commit to the first infusion.
So if you are uninsured or carrying a high deductible, the arithmetic can favor the treatment we do not offer. We would rather say that plainly than have you work it out afterwards.
What Spravato will cost you depends on your plan, your deductible, and whether we are in network. That is worth knowing before you commit to a schedule.
Does insurance cover ketamine infusions or Spravato in Ohio?
Spravato is typically covered, including by Ohio Medicaid plans. IV ketamine generally is not, because it has no FDA approval for any psychiatric condition, which means most patients pay out of pocket. Coverage for Spravato almost always requires prior authorization, and the requirements vary by plan.
Ohio Medicaid managed care plans currently treat Spravato as a non-preferred product, with prior authorization required and a monthly quantity limit. Medical Mutual maintains its own authorization policy. Same state, same diagnosis, different answer depending on the card in your wallet.
The FDA approved Spravato as a standalone treatment in January 2025, but plan policies have updated on their own timelines. Some still carry criteria written when the drug could only be prescribed alongside an oral antidepressant. What your plan requires and what the label allows are not always the same thing.
We verify your benefits before treatment starts, so you know what you are facing before you commit to a schedule.
How long you will wait, and what the schedule asks of you
Prior authorization takes days to weeks. IV ketamine, paid in cash, can usually start almost immediately.
For someone in acute crisis, that difference is clinically meaningful, and it is an honest point in IV ketamine’s favor. At our clinic, a typical first Spravato session lands 7 to 10 days after your initial call, once intake and evaluation are complete. If you cannot wait that long, say so on the first phone call.
Then there is the schedule, which is worth planning properly rather than worrying about.
The first four weeks mean eight visits, two hours each, and you cannot drive yourself afterwards. Weeks five to eight step down to one visit a week.
We deliver Spravato at one location, 3951 Rocky River Drive in Cleveland, so if you are coming from Summit or Lorain County there is a drive on either side of each session.
Plenty of people make that drive, and in our experience the mileage is rarely what decides how treatment goes. So it helps to sort the practical side before your first session rather than during your second week. Who is collecting you on each of those eight days. Whether one person can cover them all.
Our intake team plans this with you.
Safety, and where the FDA’s ketamine warnings apply
You may have seen FDA warnings about ketamine. They are frequently misapplied.
The FDA issued alerts in February 2022 and October 2023 about compounded ketamine used at home without supervision, including a case of respiratory depression in a patient whose blood levels reached roughly twice the typical range.
They do not apply to monitored IV ketamine given in a clinic, which is off-label but legitimate medical practice.
On longer-term risk, the bladder and memory problems associated with ketamine come overwhelmingly from near-daily recreational use at doses far above therapeutic levels. In one series of 6,630 patients receiving six or more infusions for depression, 0.7% stopped because of a side effect.
Spravato’s label reports no adverse cognitive effects over a one-year study, and effects beyond one year have not been evaluated. We include that second half because it is part of the answer.
Our detailed guide to Spravato’s side effects covers what each session actually feels like.
Where each option holds the advantage
What is already decided for you
Some of this is not a choice at all.
- Your diagnosis. Spravato is indicated for treatment-resistant depression and for major depressive disorder with suicidal ideation. It is not indicated for PTSD, OCD, or chronic pain. If those are what you need treated, IV ketamine is where that conversation happens, and we will point you there.
- Your treatment history. Spravato eligibility requires that at least two antidepressants have failed you. One is not enough.
- Your coverage. Insured and in-network with us, not in crisis, the economics favor Spravato clearly. Uninsured or on a high deductible with cash available, a course of infusions may cost you less.
- Your urgency. If waiting days to weeks for authorization is not acceptable, the honest answer favors a path that does not depend on a payer.
- Whether you can take oral antidepressants. Until January 2025, Spravato could only be prescribed alongside a daily antidepressant pill. If you cannot tolerate those at all, that ruled you out. The FDA has since approved Spravato as a standalone treatment, which reopened this option for people it had excluded. Worth raising directly if that describes you.
What is genuinely your choice
The rest is preference, and preferences are legitimate.
Some people want a nasal spray they administer themselves. Others would rather have a line in and be still for forty minutes. Some want the person prescribing to be a psychiatrist who will also manage their medication and see them after the course ends. Others are content with an infusion center that coordinates with an outside prescriber. Both are real models of care.
What we can tell you about ours: Spravato at REACH is prescribed by Dr. Neal Swartz, a psychiatrist trained in both medication management and psychotherapy, with a nurse practitioner present throughout your two hours. Your therapy, psychiatry, and follow-up stay inside the same practice. We think the medication is the smaller part of what makes treatment work, which is why we offer the FDA-approved option and not infusions.
Taking the next step
The question worth asking is not which treatment is stronger. It is which one your plan will authorize, how fast you need to start, and whether you want your depression care to sit inside one relationship or several.
Bring that question to a consultation and we will verify your benefits, check eligibility, and tell you if Spravato is not the right fit.
If you are in crisis right now, call or text 988 to reach the Suicide and Crisis Lifeline, available 24 hours a day.
Check your coverage and eligibility with our intake team
Frequently asked questions
Can I have IV ketamine and Spravato at the same time?
That is a decision for your prescriber, not something to arrange yourself. Both act on the same receptor system, so combining them raises dosing and safety questions, and it also creates coverage complications since insurers authorize one and not the other. Raise it with the psychiatrist managing your care.
Why isn’t IV ketamine FDA-approved for depression
FDA approval requires a sponsor to fund the trials and take them through the process, and ketamine has been generic for decades, so there is rarely a company with reason to take that on. IV ketamine still has around twenty-five years of research behind it, and prescribing off-label is ordinary medical practice. What approval adds is standardized dosing, a required safety framework, and insurance coverage. Those are the reasons the two treatments get handled so differently in a clinic.
How much does Spravato cost out of pocket in Ohio?
It depends entirely on your plan, your deductible, and whether your provider is in network. Because Spravato is billed as a medical benefit rather than a pharmacy one, the calculation differs from a standard prescription copay. We verify your specific benefits before treatment begins.
Which has worse side effects?
They are broadly similar, since both produce dissociation, dizziness, and drowsiness in the hours after dosing. Spravato has a required two-hour monitoring period built into every session. Neither treatment lets you drive afterward.
Can I drive home after Spravato?
No. You need someone to collect you after every session, for the whole course. Worth arranging before you start, since getting home is one of the practical details that most often causes trouble later on.
How do I know if I qualify for Spravato?
You must be over 18, diagnosed with treatment-resistant depression or major depressive disorder with suicidal ideation, and have tried at least two antidepressants without remission. Contraindications include uncontrolled hypertension, pregnancy, acute cardiac or respiratory conditions, and a history of psychosis or substance use disorder.
What if Spravato doesn’t work?
Response is assessed over the first four weeks, and if it is not helping, the plan changes. That may mean adjusting dose, revisiting the diagnosis, or considering other options including TMS, ECT, or infusions elsewhere. Nobody should sit in a treatment that is not working.