When two or three antidepressants have come and gone without much changing, the next conversation usually turns to TMS vs Spravato. Both are real options for depression that has not responded to medication. Both carry FDA backing for that situation. Neither is experimental, and neither is a last resort you have to fail your way toward.
The strongest head-to-head evidence does not crown a winner. A 2025 analysis in eClinicalMedicine pooled individual patient data from two randomized trials and compared repetitive TMS directly against intranasal esketamine, the active drug in Spravato. Both outperformed starting another antidepressant. Against each other, the gap was not statistically significant. Patients rarely expect that answer, and it changes what the decision is actually about.
So the choice rarely turns on which treatment works better. It turns on four things that have little to do with efficacy. Whether you qualify for each one. What the schedule takes out of your week. How the side effects land in your particular life. What your insurance will actually pay for.
At WBMA we offer both TMS for treatment-resistant depression and Spravato, which spares this conversation from becoming a case for whichever machine happens to be in the building. The figures below come from FDA labeling and the trial data, not from either manufacturer’s brochure.
In short – the strongest head-to-head trial found no statistically significant difference between TMS and Spravato. What separates them in practice is who qualifies for each one, what the schedule costs you in time, how the side effects land, and what your plan actually covers.
What the Research Says About TMS vs Spravato
The 2025 analysis, led by Tyler Kaster and published in eClinicalMedicine, drew individual participant data from two randomized trials known as THREE-D and TRANSFORM-2. After propensity-score matching, 282 patients were compared across three arms of 94 each. One group received repetitive TMS, another intranasal esketamine, and the third simply started a new antidepressant.
Measured on the Hamilton Depression Rating Scale at four weeks, both interventions beat the new medication. TMS pulled ahead by 5.35 points and esketamine by 2.89, both statistically significant. Compared against each other, TMS led by 2.46 points with a confidence interval running from minus 5.82 to positive 0.89. The interval crosses zero, so the difference did not reach significance.
The authors put it carefully. TMS “may be superior, or at least similarly effective, to intranasal esketamine.” They also flagged real limits, and I should not skate past them. The comparison was not itself a randomized trial, and it measured outcomes at four weeks when a standard TMS course runs six weeks or longer. Read it as a strong signal rather than a verdict.
What it does settle is worth holding onto. Both treatments outperformed the most common next step in psychiatry, which is trying yet another antidepressant. If you have been told your only remaining option is a fourth medication trial, the evidence does not support that framing.
Who Qualifies for TMS and Who Qualifies for Spravato
Candidacy is where the two treatments genuinely part ways. The FDA cleared the NeuroStar TMS system for major depressive disorder in adults who have failed one prior antidepressant. The clearance language specifies that medication must have run “at or above the minimal effective dose and duration in the current episode.” One failed medication opens the door, which surprises people who assume TMS is a last resort.
Spravato sets a higher bar. Its label covers treatment-resistant depression, and the trials behind it enrolled patients who “had not responded adequately to at least two different antidepressants of adequate dose and duration.” Two failed trials, not one. A patient who has failed a single antidepressant may already be a candidate for TMS while not yet meeting the threshold for ketamine and Spravato therapy.
One thing changed recently and it matters. In 2025 the FDA approved an expansion of the Spravato indication to include monotherapy, meaning it no longer has to be paired with an oral antidepressant. The label now reads “as monotherapy or in conjunction with an oral antidepressant.” For patients who cannot tolerate daily antidepressants, a route opened that did not exist before.
Spravato also carries a restriction TMS does not. The drug “is available only through a restricted program under a REMS,” which means it can be given only in a certified healthcare setting with monitoring built in. You cannot take it home. TMS has no equivalent program, though it still happens entirely in a clinical office.
What TMS and Spravato Ask of Your Week
Candidacy gets you in the door. The calendar decides whether you can finish. In practice the TMS vs Spravato decision often turns right here. The two ask very different things of a working week, and patients underestimate this part more than any other. Mapping both against your real schedule before committing tends to prevent an abandoned course later.
| Practical factor | TMS | Spravato |
|---|---|---|
| Visit frequency | Once daily in the THREE-D trial protocol | Twice per week during weeks 1 to 4 |
| Course length | Six weeks in that trial protocol | Four-week induction, then a maintenance phase |
| Time on site | Short sessions, roughly three minutes for theta-burst | At least two hours of monitoring after each dose |
| Driving afterward | No restriction from the treatment itself | Not until the day after a restful sleep |
| Ongoing dosing | Course ends, with retreatment considered if symptoms return | Weekly, then every one to two weeks long term |
Look at the shape of each burden rather than the totals. TMS takes a small piece of many mornings across six weeks. Spravato takes two long afternoons a week for a month, and you will need a ride home from each one. Neither is harder in the abstract. One of them is probably harder for you. It sounds obvious, and patients still work it out only after starting.
The maintenance question separates them further. A TMS course has an ending, and many patients finish it and stop. Spravato dosing continues past the induction phase, with the label directing clinicians toward “the least frequent dosing to maintain remission/response.” Choosing it means choosing an ongoing relationship with a certified treatment center.
TMS and Spravato Side Effects in Daily Life
Both treatments have side-effect profiles that are well characterized, and the difference between them is more about kind than severity. TMS side effects tend to be local and physical. Scalp discomfort during stimulation and headache afterward are the ones patients mention most, and they commonly ease over the first week or two of a course.
Spravato carries a boxed warning covering sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors. Dissociation is the one that surprises people. Patients often describe feeling detached from their body or surroundings for a stretch after dosing. The label therefore requires that patients be “monitored for at least 2 hours at each treatment session.”
Blood pressure is monitored during that window as well, and the label lists specific contraindications including aneurysmal vascular disease and a history of intracerebral hemorrhage. These are not minor screening items. They rule some patients out entirely, which is one more reason candidacy gets settled before scheduling rather than after.
Insurance and Cost for TMS vs Spravato
Coverage is where most patients get stuck, and it is also where general figures mislead. What you pay depends on your plan, your documented treatment history, and whether your treating practice holds the right certifications. Asking about a national average price is less useful than asking your own plan four specific questions.
- How many documented trials does the plan require before approving each treatment, and does its threshold match the FDA labeling or exceed it?
- Prior authorization is common for both, so ask what clinical documentation the prescribing psychiatrist has to submit alongside it.
- If the treating site sits out of network for this specific service, the quoted benefit will not apply, and Spravato can only be given at a REMS-certified location.
- Ask for the per-session cost share, then multiply it across a full course rather than reading it as a single visit.
Cost share is where the arithmetic turns. A modest copay looks very different when a course involves roughly thirty visits instead of eight. Run the numbers across the whole course for both options before you decide, since the cheaper per-session treatment is not always the cheaper course. I have seen that comparison flip.
Documentation matters more than most patients expect. Records showing which antidepressants you took, at what dose, and for how long are frequently what a prior authorization turns on. Our team handles that paperwork as part of evaluating whether Spravato fits, and gathering it early tends to shorten the wait considerably.
Can You Have TMS and Spravato Together?
Patients ask this constantly, and it is a reasonable question rather than a greedy one. The two treatments work through entirely different mechanisms. TMS applies magnetic pulses to stimulate cortical activity, while esketamine acts pharmacologically through a different pathway, so there is no obvious reason they would interfere with each other.
What we can say honestly is that the head-to-head research compared them as alternatives rather than as a combination. The 2025 analysis studied three separate arms, and none of them received both. Sequencing is a different matter and comes up often in practice, particularly when a patient completes a TMS course with partial improvement.
Those decisions belong in a clinical conversation rather than an article, because they depend on your history, your response so far, and what your insurance will authorize. What matters here is that choosing one now does not permanently close the other.
How the Choice Gets Made in Practice
Set the efficacy question aside, since the trial data will not settle it for you. What actually decides this is a proper workup for treatment-resistant depression, starting with your medication history, because one failed antidepressant and three failed antidepressants lead to different doors. Then it covers your calendar, your transportation, your blood pressure and vascular history, and your coverage.
Patients who have failed a single medication and can protect a daily slot for six weeks often land on TMS. Patients with a longer history of failed trials, or who cannot commit to daily visits, frequently land on Spravato. Plenty of people sit between those descriptions, which is exactly when a real evaluation earns its keep.
If antidepressants have stopped working for you, the next step is a conversation with a psychiatrist who can offer both options. Someone with no reason to steer you toward one of them. Individual results vary, and effectiveness depends on each patient’s circumstances. Working through TMS vs Spravato with your full history on the table is what turns a coin flip into a decision.
Frequently Asked Questions
Is TMS better than Spravato?
Current head-to-head evidence does not show a statistically significant difference between them. The 2025 eClinicalMedicine analysis found TMS ahead by 2.46 points on the Hamilton scale, with a confidence interval that crossed zero. Both performed better than starting a new antidepressant, so the practical decision usually rests on candidacy, schedule, and coverage.
Do I need to have failed more antidepressants for Spravato than for TMS?
Generally yes, and the gap is meaningful. TMS clearance covers adults who failed one prior antidepressant at an adequate dose and duration. The trials supporting Spravato enrolled patients who had not responded adequately to at least two different antidepressants. Individual insurance plans may apply their own requirements on top of the FDA labeling.
Why do I have to stay two hours after a Spravato dose?
The FDA label requires that patients be monitored for at least two hours at each treatment session, followed by an assessment before leaving. The monitoring exists because of the risks of sedation, dissociation, and blood pressure changes after dosing. It is a labeling requirement rather than a clinic preference.
Can I drive myself home after treatment?
After TMS, the treatment itself places no driving restriction on you. After Spravato, you cannot drive or operate machinery until the next day following restful sleep, so you will need transportation arranged for every session. Patients often underestimate how much this shapes which treatment is workable for them.
How long does each course take?
In the trial protocol behind the recent comparison, TMS ran once daily for six weeks. Spravato uses a four-week induction phase at twice-weekly dosing, followed by a maintenance phase of once weekly and later every one to two weeks. TMS courses have a defined end, while Spravato dosing typically continues.
Is Spravato the same thing as ketamine therapy?
They are related but not identical. Spravato is esketamine, FDA-approved for treatment-resistant depression and given as a nasal spray under a restricted program. Intravenous ketamine is used off-label for depression, which is a different regulatory status. Our comparison of ketamine and TMS covers that distinction in more detail.
What if I try one and it does not help?
Choosing one treatment does not rule out the other later. Because they work through different mechanisms, a limited response to one does not predict a limited response to the other. Sequencing decisions depend on your specific response and history, and they are worth revisiting with your psychiatrist rather than assuming options are exhausted.
Talk it through with a psychiatrist who offers both
A full evaluation can tell you which of these two your history, your schedule and your coverage actually support.
This article is for educational purposes only and does not constitute medical advice or a treatment recommendation. Individual results may vary, and treatment effectiveness depends on each patient’s unique circumstances. Whether TMS or Spravato may be appropriate for you is a decision to make with a qualified psychiatrist who knows your full history.
