Spravato vs. TMS for Treatment-Resistant Depression

Spravato and TMS are two different ways to treat depression that hasn't improved enough with antidepressants. SPRAVATO® (esketamine) is a prescription nasal spray that acts on the brain's glutamate system and is given only at certified clinics. TMS (transcranial magnetic stimulation) uses magnetic pulses to stimulate the brain and involves no medicine at all. We found no randomized trial comparing them directly, so this Spravato vs. TMS guide doesn't pick a winner. It shows how they differ on what matters day to day: time, side effects, driving and insurance.

Is Spravato or TMS better for treatment-resistant depression?

There's no evidence-based way to rank them. The research we reviewed contains no head-to-head randomized trial of Spravato versus TMS, so any claim that one "beats" the other is opinion.

Both are legitimate options for adults whose depression hasn't responded to standard medications. The practical differences often decide it: your medical history, your schedule, whether you can arrange rides, how you weigh side effects, and what your insurance will review.

Spravato vs. TMS: what is the difference?

Spravato is a medication. Esketamine is one of the two mirror-image halves of the ketamine molecule, delivered as a nasal spray. It blocks a glutamate receptor called the NMDA receptor. The FDA label says the exact way it relieves depression is unknown; the leading theory, based largely on animal studies, is that it triggers a chain of changes that help brain cells form new connections. It is a Schedule III controlled substance and is available only through a restricted program called the SPRAVATO REMS.

TMS is a device-based treatment. According to the National Institute of Mental Health (NIMH), repetitive TMS "uses an electromagnet to stimulate the brain using repeated low-intensity pulses." NIMH notes it needs no anesthesia and can be done in an office.

Their regulatory status differs too:

• Spravato is FDA-approved for treatment-resistant depression (TRD) in adults, as monotherapy or with an oral antidepressant. It is also approved for depressive symptoms in adults with major depressive disorder who have acute suicidal thoughts or behavior, used with an oral antidepressant.
• TMS devices are FDA-cleared (the term used for medical devices) for depression. NIMH says the first rTMS device was cleared in 2008 for depression in people who hadn't responded to at least one antidepressant in the current episode.

Who is each treatment for?

Spravato is for adults only. Its TRD indication doesn't specify a number of failed medicines, but TRD is commonly defined as an inadequate response to at least two antidepressants, at an adequate dose and for long enough, during the current episode. That two-antidepressant threshold is the one used in a 2021 expert consensus in the American Journal of Psychiatry. Spravato is not for everyone: the label lists contraindications including aneurysmal blood-vessel disease, arteriovenous malformation, and a history of bleeding in the brain, and it is not recommended during pregnancy or breastfeeding.

NIMH says rTMS is used to treat moderate-to-severe depression when medications haven't worked or haven't been tolerated.

If you're not sure whether your history counts as "treatment-resistant," our post on who may qualify for Spravato walks through it, and what to do when an antidepressant stopped working covers the earlier steps.

How much time does each one take?

Spravato:

• Twice a week for weeks 1–4, once a week for weeks 5–8, then weekly or every two weeks after that, per the prescribing information.
• That's about 12 clinic visits in the first two months.
• Each visit includes at least two hours of monitoring after the dose, plus check-in and travel time.
• No food for two hours and no liquids for 30 minutes before a dose.
• Whether it's helping is usually judged at the end of the first four weeks.

TMS:

• NIMH describes the standard course as daily sessions, five days a week, for four to six weeks.
• NIMH also notes accelerated protocols that deliver multiple sessions in a single day.

So Spravato means fewer, longer visits with a ride every time. TMS means more frequent weekday visits over several weeks.

What are the side effects of each?

Spravato carries a boxed warning for sedation, dissociation (feeling disconnected from yourself or your surroundings), respiratory depression, abuse and misuse, and suicidal thoughts and behaviors in people 24 and younger. In the label's short-term TRD trials (adults taking Spravato plus an oral antidepressant), the most common side effects compared with placebo were dissociation (41% vs. 9%), dizziness (29% vs. 8%), and nausea (28% vs. 9%). Spravato can also raise blood pressure; the rise peaks around 40 minutes after a dose and lasts about four hours, which is one reason it's checked before and after treatment.

TMS side effects listed by NIMH include discomfort where the magnet sits on the head, mild headaches or brief lightheadedness, and dizziness.

What about driving?

After Spravato, the label says not to drive or operate machinery until the next day, after a restful sleep. Plan for someone to drive you home from every session. TMS doesn't use anesthesia, per NIMH; ask the TMS clinic what it advises about driving after sessions.

How does insurance handle Spravato and TMS?

Spravato usually requires prior authorization, meaning your plan reviews your records before approving treatment. Plans commonly ask for documentation of the antidepressants you've tried, and criteria vary from plan to plan. TMS coverage rules are also plan-specific, so ask your insurer whether TMS requires prior authorization and what records they need. Our insurance page explains how coverage questions work at MindVibe.

Where do medication changes and ECT fit?

Spravato and TMS aren't the only next steps. Changing or adding an oral medication remains a core part of depression treatment, and so does ECT for severe depression. Any medication change should come from your prescriber; don't stop or switch a medication on your own.

Medication changes. One large trial, ESCAPE-TRD (New England Journal of Medicine, 2023), compared Spravato with quetiapine XR, an add-on medicine, in adults with TRD who stayed on an SSRI or SNRI. At week 8, 27.1% of the Spravato group and 17.6% of the quetiapine group were in remission. The study was open-label with blinded raters, was funded by the manufacturer, took place in Europe, and used a strict remission cutoff. It also shows that most people in both groups had not reached remission by week 8.

ECT. Electroconvulsive therapy uses an electric current to induce seizure activity under short-acting general anesthesia. NIMH says a typical course is three times a week until symptoms improve, usually within 6–12 treatments, and that some people have memory loss, "especially of memories around the time of treatment."

A large randomized trial, ELEKT-D (New England Journal of Medicine, 2023), compared ECT with IV ketamine, which is a different drug from Spravato, in adults with non-psychotic TRD. It found IV ketamine non-inferior to ECT, and ECT was associated with more memory decline. These results can't be carried over to Spravato. If you're weighing ketamine-based options, see Spravato vs. ketamine infusions.

Can you do Spravato and TMS together?

The research we reviewed includes no trials of combining Spravato with TMS. Whether to combine them, use them in sequence, or choose one is a decision for your psychiatric clinician, based on your history and medications.

What if Spravato or TMS doesn't work?

If Spravato doesn't bring enough relief by the end of the first four weeks, your clinician may talk about medication strategies, TMS, or ECT. The reverse is also true: if medications, and even TMS or ECT, haven't helped enough, Spravato may be another option to discuss. It isn't guaranteed to work when other treatments haven't.

A clear record of what you've tried, at what dose and for how long, helps. Our guide to reviewing your depression medication history shows how to build one.

If you're having thoughts of suicide, don't wait for any treatment decision. Call or text 988 (the Suicide & Crisis Lifeline), or call 911 if you're in immediate danger. Spravato has not been shown to prevent suicide or reduce suicidal thoughts.

How do I decide between Spravato and TMS?

Bring these questions to your next appointment:

• Based on what I've tried, which options make sense for me now?
• Does anything in my medical history, like blood pressure or a blood-vessel condition, rule out Spravato?
• Can I realistically manage twice-weekly Spravato visits with a driver, or daily weekday TMS sessions?
• What would we try next if this doesn't help?

MindVibe has REMS-certified Spravato treatment centers and offers psychiatric evaluation and medication management. An evaluation is a reasonable place to talk through every option on this page — when you're ready, you can start the booking process.

Important safety information

Spravato is a prescription medicine for adults with treatment-resistant depression, used alone or with an oral antidepressant, and for depressive symptoms in adults with major depressive disorder with suicidal thoughts or actions, used with an oral antidepressant. It has not been shown to prevent suicide and is not approved as an anesthetic.

Spravato carries a boxed warning. It can cause sedation, dissociation, and respiratory depression (slowed breathing), so a healthcare provider monitors you for at least two hours after every dose. Abuse and misuse are possible with this drug. And since antidepressants may increase suicidal thoughts and behaviors in people 24 and younger, call your provider right away if depression or suicidal thoughts show up or get worse. You can only get Spravato through the SPRAVATO REMS, and only at certified healthcare settings — you administer the spray yourself, but staff supervise you while you do. No driving or operating machinery until the next day, and only after a restful sleep. The full Prescribing Information, including the Boxed Warning, along with the Medication Guide, is worth reading in full.

Frequently asked questions

TMS or Spravato: which one is better for me?

Current evidence can't rank them. The research we reviewed found no randomized trial comparing Spravato and TMS directly. Both are options for adults whose depression hasn't improved enough with antidepressants. The right fit depends on your medical history, your schedule, your ability to arrange rides, how you weigh side effects, and what your insurance requires. A psychiatric clinician can help you compare them.

Can I drive after Spravato or TMS?

Not after Spravato. Per the label, you can't drive or operate machinery until the next day — after a restful sleep — so line up a ride home from every session. TMS is done without anesthesia, according to the National Institute of Mental Health. Ask the TMS clinic directly what it advises about driving after a session.

Can I do Spravato and TMS at the same time?

People sometimes ask about this, but the research we reviewed includes no trials of combining Spravato with TMS. Whether to combine them, try them one after another, or choose one is a decision for your psychiatric clinician. That decision depends on your history, your current medications, and how you've responded to past treatments.

What if Spravato doesn't work for me?

Benefit is usually judged at the end of the first four weeks of treatment. If Spravato hasn't helped enough, your clinician may discuss medication changes, TMS, or ECT. Not responding to one treatment doesn't rule out other options. Keep a record of what you've tried and how you responded, because it makes the next decision clearer.

Do I have to try TMS before Spravato?

No. Treatment-resistant depression is usually defined by antidepressant medication trials, commonly at least two in the current episode, not by device treatments. You don't need to have tried TMS first. Your insurance plan may have its own prior authorization criteria for Spravato, though, so ask your plan what documentation it requires before you start.

Is TMS the same as ECT?

No. According to the National Institute of Mental Health, TMS uses an electromagnet to deliver repeated low-intensity pulses, needs no anesthesia, and can be done in an office. ECT induces seizure activity with an electric current while you're under short-acting general anesthesia. Some people experience memory loss afterward — especially of memories from around the time of treatment.

If you are in crisis

If you are in crisis: call or text 988 to reach the Suicide & Crisis Lifeline, available 24/7, or call 911 or go to the nearest emergency room if you or someone else is in immediate danger.

Sources

• SPRAVATO (esketamine) Prescribing Information, Janssen Pharmaceuticals / Johnson & Johnson: https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/SPRAVATO-pi.pdf
• SPRAVATO Medication Guide: https://www.jnjlabels.com/package-insert/product-patient-information/SPRAVATO-medication-guide.pdf
• National Institute of Mental Health, "Brain Stimulation Therapies": https://www.nimh.nih.gov/health/topics/brain-stimulation-therapies/brain-stimulation-therapies
• McIntyre RS et al. Synthesizing the evidence for ketamine and esketamine in treatment-resistant depression. Am J Psychiatry 2021: https://adaa.org/sites/default/files/Banners/APA%20American%20Journal%20International%20Guidelines%20Ketamine%20Esketamine%20Final%202021.pdf
• Reif A et al. Esketamine nasal spray versus quetiapine for treatment-resistant depression (ESCAPE-TRD). N Engl J Med 2023;389:1298–1309: https://www.nejm.org/doi/full/10.1056/NEJMoa2304145
• Anand A et al. Ketamine versus ECT for nonpsychotic treatment-resistant major depression (ELEKT-D). N Engl J Med 2023: https://www.nejm.org/doi/full/10.1056/NEJMoa2302399

This article is educational only — not medical advice, a diagnosis, or a treatment recommendation. Before changing anything about your care, talk it through with your own clinicians.