TMS vs Spravato (Esketamine): A Side-by-Side Comparison

TMS and Spravato are both used for depression that has not improved with antidepressants, but they are very different treatments. TMS (transcranial magnetic stimulation) is an FDA-cleared device that delivers magnetic pulses to the left prefrontal cortex in brief office sessions, usually every weekday for about six weeks, with no sedation, so most people go straight back to their day. Spravato (esketamine) is an FDA-approved nasal spray drug that is self-administered in a certified clinic under observation, with monitoring for at least two hours after each dose and no driving until the next day.

No large randomized trial has compared the two directly. The choice usually turns on schedule, side effects, medical history (blood pressure, seizure risk, substance use), whether you want to change your medications, and what your insurance plan will authorize.

TMS and Spravato at a glance

How each treatment works

TMS uses a coil held against the scalp to create brief magnetic pulses strong enough to induce electrical activity in prefrontal neurons. Repeated daily sessions are thought to change activity in mood-regulating networks over weeks; the neuroscience of TMS covers this in detail. Nothing enters the bloodstream, which is why TMS has no systemic drug effects.

Esketamine is the S-enantiomer of ketamine and blocks the NMDA glutamate receptor. Its label is candid that "the mechanism by which esketamine exerts its antidepressant effect is unknown." Because it acts on the whole brain and body, its side effects are drug side effects: dissociation, sedation, and transient rises in blood pressure.

FDA status, labels and the 2025 monotherapy change

Spravato was first approved on 5 March 2019 for treatment-resistant depression, at that time only together with an oral antidepressant. A second indication, for depressive symptoms in adults with major depression and acute suicidal thoughts or behavior, followed on 31 July 2020. On 17 January 2025 FDA approved Spravato as monotherapy for TRD, meaning it can now be used without a daily oral antidepressant; the manufacturer reported week-4 remission of 22.5% with Spravato versus 7.6% with placebo in that trial.

TMS devices are not "approved" in the drug sense. NeuroStar was authorized through the De Novo pathway in October 2008, and later devices were cleared through 510(k) as Class II devices. Labels now include adult depression with comorbid anxiety symptoms, adjunctive use in adolescents aged 15–21 on several systems, and accelerated schedules on some. Accelerated TMS and theta burst stimulation shorten either the session or the course.

What a course of each looks like

TMS

The first visit includes motor threshold measurement and coil positioning. Standard 10 Hz sessions take as little as 18.75 minutes on current NeuroStar settings, and FDA-cleared intermittent theta burst sessions take about 3 minutes. A conventional acute course runs 20 to 30 daily treatments over 6 weeks. You stay awake, can return to work, and can drive.

Spravato

You give yourself the spray under the direct observation of a clinician in a REMS-certified setting, then remain under monitoring for at least two hours; blood pressure is checked around 40 minutes after the dose and afterward as needed. Induction is twice weekly for four weeks at 56 or 84 mg, then weekly for four weeks, then weekly or every two weeks for as long as treatment continues. You need someone else to drive you home, because the label says not to drive or operate machinery until the next day after a restful sleep.

The practical difference is large. TMS is front-loaded: many short visits over about six weeks, then usually stops. Spravato is lighter in frequency but each visit takes an afternoon, and maintenance dosing is open-ended.

What the evidence shows

TMS

In sham-controlled trials, the gap between active and sham remission is modest: 14.1% versus 5.1% in the NIMH OPT-TMS trial, for example. In the 2018 THREE-D trial of 414 patients, theta burst stimulation was non-inferior to 10 Hz rTMS, with a 49% response rate and 32% remission in the theta burst arm. CANMAT 2023 rates rTMS for treatment-resistant depression as first line, with Level 1 evidence for acute efficacy. Response and remission figures vary widely depending on study design, so compare like with like.

Spravato

In TRANSFORM-2 (2019; 227 randomized adults who had not responded to at least two antidepressants), esketamine plus a new oral antidepressant reduced MADRS scores by 4.0 points more than a new antidepressant plus placebo spray at day 28. In ESCAPE-TRD (2023; 676 patients, open-label with blinded raters), 27.1% remitted by week 8 with esketamine versus 17.6% with extended-release quetiapine augmentation. CANMAT 2023 places intranasal esketamine at second line, citing side effects and feasibility. The VA/DoD guideline gives a "weak for" recommendation to rTMS after two or more adequate medication trials and to ketamine or esketamine augmentation after several adequate trials.

Head to head

Only indirect comparisons exist. A 2025 individual-patient analysis matched participants from THREE-D and TRANSFORM-2 (94 per arm after matching): both rTMS and esketamine beat starting a new antidepressant, and the rTMS-versus-esketamine difference (2.46 HDRS points favoring rTMS) was not statistically significant. A 2026 analysis of US health records (1,690 matched patients per group) found fewer hospitalizations and injuries after starting rTMS, while suicide-related outcomes were broadly similar, with an esketamine advantage in the 30–90-day window. These are observational or cross-trial analyses; neither can replace a randomized head-to-head trial.

Side effects, safety and abuse potential

The most common TMS side effects are scalp discomfort and headache, usually mild; the manufacturer describes them as transient and, for most patients, gone after the first week of treatment. In the NeuroStar development program 4.5% of patients stopped because of adverse events. Seizure is the serious risk, and it is rare: fewer than 1 per 60,000 sessions when given within guidelines to people without risk factors. Details are in TMS safety and seizure risk.

Spravato carries a boxed warning for sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors. Common reactions in TRD trials included dissociation, dizziness, nausea, sedation, vertigo, anxiety, increased blood pressure, vomiting and feeling drunk. It is a Schedule III controlled substance, and it is dispensed only through the SPRAVATO REMS program in certified healthcare settings. The label lists aneurysmal vascular disease, arteriovenous malformation and a history of intracerebral hemorrhage as contraindications, which matters for people with vascular disease.

The second Spravato indication concerns acute suicidal thoughts, and neither treatment replaces emergency care. If you are thinking about suicide or are in crisis, call or text 988 (the 988 Suicide & Crisis Lifeline) or go to the nearest emergency room.

Coverage and access

Insurers handle the two very differently. TMS is billed as a procedure with written medical-necessity criteria: New York Medicare, for example, requires no clinically significant response to one medication trial using agents from at least two different classes (or one of a few listed alternatives), plus a trial of evidence-based psychotherapy without significant improvement, and commercial plans each set their own medication-failure rules. See the plan-specific pages such as Aetna TMS coverage and Medicare TMS coverage in New York. Spravato is a drug, so coverage runs through medical or pharmacy benefits with their own prior authorization rules; ask your plan directly rather than assuming the TMS criteria apply.

Access is also a matter of logistics: TMS requires a clinic with a device and trained staff; Spravato requires a REMS-certified site with space to monitor patients for two hours. General information about how this practice handles payment for psychiatric care, not specific to either treatment, is on the insurance and payment page.

Can TMS and Spravato be combined?

Some clinics combine them, but the combination has not been established in the trials cited here. At least one major insurer, Aetna, classifies adjunctive ketamine given with TMS as experimental and investigational. Sequencing (finishing one, then trying the other if needed) is the alternative. How TMS interacts with other medications is covered in combining TMS with medication.

Which one might suit you

• TMS may fit better if you cannot tolerate medication side effects, have high blood pressure or vascular disease, have a history of substance misuse, need to drive yourself, or prefer a time-limited course. CANMAT notes rTMS can be a first choice when medication tolerability is a concern.
• Spravato may fit better if you cannot attend daily visits, have conductive or magnetic metal implanted in or near the head (a contraindication to TMS), have a seizure history that calls for extra caution with TMS, or need a medication-based option your plan covers.
• TMS is not the right first step for psychotic depression or acute suicidal ideation; expert consensus points those patients toward treatments with established efficacy such as ECT. Spravato does carry an indication for depressive symptoms with acute suicidal thoughts or behavior, given with an oral antidepressant, but its label states that effectiveness in preventing suicide or reducing suicidal ideation has not been demonstrated and that it does not remove the need for hospitalization when warranted. See TMS vs ECT.

For the full menu of next steps after two or more failed medications, see every treatment-resistant depression option compared; for a patient-friendly comparison with IV ketamine, see TMS vs ketamine therapy, and this site's ketamine-assisted psychotherapy page. The TMS guide collects the rest of the series, and the practice's current TMS information is on the TMS service page. The current Spravato prescribing information is on DailyMed.

Frequently asked questions

Is Spravato the same as ketamine?

Spravato is esketamine, one of the two mirror-image forms of ketamine, given as a nasal spray in a certified clinic. IV ketamine for depression is a different, off-label use of an anesthetic.

Which works faster, TMS or Spravato?

Esketamine trials measured their main outcome at four weeks, with some improvement seen earlier, while a standard TMS course runs about six weeks and benefit usually builds gradually across it. Accelerated TMS schedules compress the course, but speed alone should not decide the choice.

Can I drive after a Spravato session?

No. The label says not to drive or operate machinery until the next day after a restful sleep, so you need a ride home. After a TMS session you can usually drive yourself.

Do I have to stop my antidepressant for either treatment?

No. Since January 2025 Spravato can be used alone or with an oral antidepressant, and TMS is commonly given while patients continue their medication. Any change should be planned with your psychiatrist.

If one does not work, can I try the other?

Yes. They work through different mechanisms, and trying one after the other is a recognized approach. Your psychiatrist will review what happened during the first treatment before recommending the next.

Sources

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Educational information, not medical advice. Whether TMS or any treatment fits you is a decision to make with a psychiatrist who knows your history.