TMS and ketamine are both used when depression has not improved enough with antidepressants, but they are very different treatments. TMS (transcranial magnetic stimulation) is a device treatment: magnetic pulses stimulate a mood-related area at the front of the brain, usually in daily sessions over several weeks, without anesthesia. Ketamine is a medication. Its nasal-spray form, esketamine (Spravato), is an FDA-approved drug for treatment-resistant depression, while IV or intramuscular ketamine for depression is used off-label, because racemic ketamine is FDA-approved only as an anesthetic.
Neither one wins on every count. Ketamine-type treatments can act within days but are given repeatedly under supervision, and each Spravato session requires at least two hours of monitoring. TMS builds more slowly, but it is not a drug and does not require anesthesia. Which fits better depends on how urgent things are, your medical history, your schedule and what your insurance will cover.
TMS vs ketamine at a glance
| TMS | Esketamine (Spravato) | IV or IM ketamine | |
|---|---|---|---|
| What it is | FDA-cleared medical device | FDA-approved nasal spray (a drug) | Anesthetic drug used off-label for depression |
| Typical early schedule | 5 sessions a week for about 6 weeks, then a taper (NeuroStar label) | Twice a week for weeks 1 to 4, then weekly for weeks 5 to 8, then weekly or every 2 weeks | Varies by clinic; in the ELEKT-D trial, twice weekly for 3 weeks |
| Monitoring after each session | No anesthesia; done in an office setting | At least 2 hours on site; no driving until the next day after restful sleep | Supervised infusion or injection; clinic protocols vary |
| Common side effects | Scalp discomfort, headache | Dissociation, dizziness, nausea, sedation, raised blood pressure | Dissociation, raised blood pressure, nausea (similar class effects) |
| Speed | Usually builds over weeks | Can begin within days | Can begin within days |
The schedule figures come from the NeuroStar 510(k) summary, the Spravato prescribing information and the ELEKT-D trial.
How each treatment works
TMS
Standard TMS for depression targets the left dorsolateral prefrontal cortex, a region involved in mood regulation and planning. A coil held against your scalp delivers repeated magnetic pulses that induce small electrical currents in the brain tissue underneath. The dose is set individually, as a percentage of your motor threshold (the strength needed to make your fingers twitch). Over many sessions, the goal is to change activity in mood circuits. For a fuller explanation, see our plain-language guide to TMS therapy.
Ketamine and esketamine
Ketamine and esketamine act on the brain's glutamate system: the Spravato label describes esketamine as the S-enantiomer (one mirror-image form) of ketamine and a blocker of the NMDA receptor, a type of glutamate receptor. The nasal spray is taken in a certified clinic under the direct supervision of a healthcare provider, because it is available only through a restricted program called the SPRAVATO REMS. If you want to understand the ketamine side in more depth, the site has a step-by-step guide to ketamine treatment and KAP sessions.
What the evidence shows
There is no large head-to-head trial of TMS against esketamine, so most comparisons rest on how each did against placebo or sham and on how guidelines rank them.
TMS
In sham-controlled trials, the gap between real and sham TMS remission is typically about 9 to 18 percentage points. In the NIMH-funded OPT-TMS trial, for example, 14.1% of people remitted with active TMS vs 5.1% with sham. The Canadian CANMAT 2023 guideline rates rTMS as a first-line treatment for treatment-resistant depression and notes response rates of 40% to 50% in difficult-to-treat depression. The U.S. VA/DoD guideline suggests offering rTMS after partial or no response to two or more adequate medication trials, a "weak for" recommendation.
Esketamine
Spravato was first approved by the FDA on March 5, 2019, for treatment-resistant depression alongside an oral antidepressant. In January 2025 it was approved for use on its own (monotherapy); the company reported week-4 remission of 22.5% with Spravato vs 7.6% with placebo in that program. CANMAT 2023 rates adjunctive IV ketamine and intranasal esketamine as second line, citing side-effect potential and feasibility issues.
IV ketamine
A large recent trial is ELEKT-D (NEJM, 2023), an open-label study in which 403 people with non-psychotic treatment-resistant depression were randomized to IV ketamine or ECT. Self-rated response was 55.4% with ketamine vs 41.2% with ECT, which showed ketamine was noninferior, not that it is better. A 2025 network meta-analysis of 35 trials found no significant difference in response, remission or tolerability among ECT, rTMS and IV ketamine, but rated confidence in that evidence "very low". A 2017 consensus statement in JAMA Psychiatry noted that ketamine studies were small, with limited long-term efficacy and safety data.
The fair summary: both TMS and ketamine-type treatments have real evidence in treatment-resistant depression, and the data do not crown either one as clearly superior.
What treatment looks like week to week
A standard NeuroStar course is 5 sessions a week for 6 weeks, followed by a 3-week taper, for 36 sessions in total. A session can take as little as about 19 minutes with the current label, and theta-burst sessions take about 3 minutes. Accelerated protocols compress treatment into fewer days with several sessions a day; see a typical TMS course, week by week for what each stage feels like.
Spravato for treatment-resistant depression is given twice a week in weeks 1 to 4, once a week in weeks 5 to 8, and then every 2 weeks or weekly, aiming for the least frequent dosing that keeps you well. You need to avoid food for at least 2 hours before a dose, stay for at least 2 hours of monitoring, and not drive until the next day after a restful sleep. That usually means arranging a ride home every time.
IV ketamine schedules vary by clinic because there is no FDA label for depression. ELEKT-D used 0.5 mg/kg over 40 minutes, twice weekly for 3 weeks.
Side effects and safety monitoring
With TMS, the most common side effects are scalp discomfort at the coil site and headache, which tend to fade after the first week; in the NeuroStar program, 4.5% stopped treatment because of side effects. Seizure is the serious risk, and it is rare: when TMS is given within published guidelines to people without risk factors, one survey of labs and clinics estimated fewer than 1 seizure per 60,000 sessions. More detail is in our guide to TMS side effects.
Spravato's label lists dissociation, dizziness, nausea, sedation, vertigo, numbness, anxiety, lethargy, increased blood pressure, vomiting, feeling drunk and headache as the most common adverse reactions in treatment-resistant depression. In clinical trials, 61% to 84% of people had dissociative or perceptual changes and 48% to 61% had sedation. The label also carries warnings about respiratory depression, abuse and misuse, and blood pressure, and it is contraindicated for people with aneurysmal vascular disease, arteriovenous malformation or a history of bleeding in the brain. IV ketamine shares the class effects, and the FDA has warned about the risks of compounded ketamine products, including oral forms used at home.
Where ketamine-assisted psychotherapy (KAP) fits
KAP pairs ketamine sessions with structured psychotherapy before, during and after dosing. A 2026 systematic review of 11 studies found KAP was associated with lower depressive symptoms, but in the three studies with control groups there was no significant difference between KAP and the control condition, and the authors call for randomized trials. If you are drawn to the therapy side of ketamine, this article on the role of therapy during ketamine treatment explains the approach. TMS can also be combined with talk therapy, which we cover in TMS and talk therapy together.
Coverage and cost, in general terms
Coverage differs for each option and changes often. TMS is commonly covered for major depression after medication trials have not worked, but plans set their own criteria and usually require prior authorization. Spravato is a branded drug given in certified settings, so coverage runs through the plan's drug or medical benefit with its own rules. IV ketamine for depression is off-label, so ask any plan directly, in writing, whether and how it is covered. For TMS specifically, start with our guide to insurance coverage for TMS in New York.
Who might lean toward which
These are starting points for a conversation with your psychiatrist, not rules.
- TMS may suit you if you want to avoid another drug, you have had side effects from medications, you can commit to frequent visits for several weeks, or a ride home after every session is hard to arrange (the Spravato label rules out driving until the next day; ask a TMS team about driving after sessions). CANMAT notes rTMS can be a first-choice treatment when medication tolerability is a concern.
- Esketamine or ketamine may suit you if speed matters, daily visits are not realistic but twice-weekly supervised sessions are, and you have no uncontrolled high blood pressure or vascular conditions that rule it out.
- Either may be off the table if you have certain metal implants in or near the head (TMS) or specific vascular conditions (esketamine). Both questions belong in your medical screening.
Some people use both over time, for example TMS for one episode and esketamine for a later one. If you want a broader view of all the next-step options, read TMS or another antidepressant? and the physician-level TMS vs Spravato comparison on drlewis.com.
When neither is the right first step
If depression comes with psychotic symptoms or acute suicidal thinking, expert consensus recommends treatments with established efficacy in those situations, such as ECT, rather than starting with TMS. The VA/DoD guideline gives ECT a "strong for" recommendation for severe depression with features such as psychosis, catatonia or severe suicidality. Spravato does have a separate approved use for depressive symptoms in adults with acute suicidal ideation or behavior, given with an oral antidepressant, but it is part of a wider safety plan, not a substitute for 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.
If you are still deciding whether your depression counts as "treatment-resistant", start with what treatment-resistant depression means. You can also return to the TMS guide or read about TMS treatment for depression.
Sources
- SPRAVATO (esketamine) nasal spray, CIII – Prescribing Information. Janssen / DailyMed (U.S. National Library of Medicine), 2026. dailymed.nlm.nih.gov
- FDA warns patients and health care providers about potential risks associated with compounded ketamine products, including oral formulations, for the treatment of psychiatric disorders. U.S. FDA, 2023. web.archive.org
- Drugs@FDA: NDA 211243 SPRAVATO. U.S. FDA, 2019. accessdata.fda.gov
- NDA 211243/S-016 Supplement Approval. U.S. FDA, 2025. accessdata.fda.gov
- SPRAVATO (esketamine) approved in the U.S. as the first and only monotherapy for adults with treatment-resistant depression. Johnson & Johnson, 2025. jnj.com
- Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression. New England Journal of Medicine, 2023. pubmed.ncbi.nlm.nih.gov
- Comparative efficacy and safety of intravenous racemic ketamine, repetitive transcranial magnetic stimulation and electroconvulsive therapy for Stage 2 or higher treatment-resistant depression: A systematic review and network meta-analysis. PCN Reports, 2025. europepmc.org
- Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults. Canadian Journal of Psychiatry, 2024. pmc.ncbi.nlm.nih.gov
- VA/DoD Clinical Practice Guideline for the Management of Major Depressive Disorder. U.S. Department of Veterans Affairs / Department of Defense, 2022. healthquality.va.gov
- Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Archives of General Psychiatry, 2010. pubmed.ncbi.nlm.nih.gov
- K231926 510(k) Summary – NeuroStar Advanced Therapy System. U.S. FDA, 2024. accessdata.fda.gov
- K220177 510(k) Summary – Magnus Neuromodulation System with SAINT Technology. U.S. FDA, 2022. accessdata.fda.gov
- K173620 510(k) Summary – MagVita TMS Therapy System w/Theta Burst Stimulation. U.S. FDA, 2018. accessdata.fda.gov
- Transcranial magnetic stimulation in the treatment of major depressive disorder: a comprehensive summary of safety experience from acute exposure, extended exposure, and during reintroduction treatment. Journal of Clinical Psychiatry, 2008. europepmc.org
- Safety Information. NeuroStar (Neuronetics), 2026. neurostar.com
- Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. Clinical Neurophysiology, 2019. europepmc.org
- Consensus Recommendations for the Clinical Application of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Depression. Journal of Clinical Psychiatry, 2018. pmc.ncbi.nlm.nih.gov
- Class II Special Controls Guidance Document: Repetitive Transcranial Magnetic Stimulation (rTMS) Systems. U.S. FDA, 2011. fda.gov
- Efficacy and safety of deep transcranial magnetic stimulation for major depression: a prospective multicenter randomized controlled trial. World Psychiatry, 2015. pmc.ncbi.nlm.nih.gov
- Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions. World Psychiatry, 2023. pmc.ncbi.nlm.nih.gov
- SPRAVATO (esketamine) nasal spray, CIII – Prescribing Information (dosage, contraindications, warnings and adverse reactions sections). Janssen / DailyMed (U.S. National Library of Medicine), 2026. dailymed.nlm.nih.gov
- A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. JAMA Psychiatry, 2017. pubmed.ncbi.nlm.nih.gov
- Effectiveness of ketamine-assisted psychotherapy as a treatment for treatment-resistant depression: a systematic review. Psychopharmacology, 2026. pubmed.ncbi.nlm.nih.gov
- Transcranial Magnetic Stimulation and Cranial Electrical Stimulation (Clinical Policy Bulletin 0469). Aetna, 2026. aetna.com
- Brain Stimulation Therapies. National Institute of Mental Health (NIMH), 2024. nimh.nih.gov
FAQs
Is ketamine faster than TMS?
Often, yes. Ketamine-type treatments can begin to help within days, while standard TMS usually builds over several weeks. Speed is only one factor, though; the monitoring, side effects and schedule differ a lot.
Can I drive myself home after TMS or Spravato?
The Spravato label says not to drive until the next day after a restful sleep, so you need a ride after each dose. TMS does not require anesthesia; for driving and work during a course, see working and driving during TMS.
Can I have TMS if ketamine did not work for me?
Possibly. Not responding to ketamine does not by itself rule out TMS, which works in a different way. Your psychiatrist will review what you tried, for how long and at what dose.
Is IV ketamine FDA-approved for depression?
No. The FDA states that ketamine is not approved for any psychiatric disorder; IV ketamine for depression is off-label. Esketamine nasal spray (Spravato) is the FDA-approved ketamine-related drug for treatment-resistant depression.
Can TMS and ketamine be combined?
Some clinicians sequence or combine them, but there is little trial data on doing both at once, and insurers may not pay for the combination: Aetna's TMS policy, for example, lists adjunctive ketamine with TMS as experimental. If you are considering it, ask your psychiatrist how the two would be coordinated and monitored.
