Ketamine Therapy vs. TMS: Evidence-Based Depression Guide

Ketamine Therapy vs. TMS for Depression at a Glance

Ketamine therapy and TMS are two of the main options for depression that has not responded to antidepressants, and on the measures that matter most, response and remission, they perform about the same. Where they diverge is speed, effort, and access.

• Speed: Ketamine eases symptoms within hours to days. In one landmark trial, most patients responded within a day of a single IV dose.⁷ TMS works gradually, building over several weeks.
• Regulatory status: TMS is an FDA-cleared depression device and is more consistently covered by insurance.⁵ Ketamine is used off-label, though esketamine nasal spray (Spravato) is separately FDA-approved for treatment-resistant depression.⁶
• Treatment burden: A standard TMS course runs about 20 to 36 in-clinic visits over four to eight weeks, and roughly 1 in 4 patients do not complete it.³ Ketamine therapy asks for fewer sessions and, in head-to-head research, patients found it more acceptable.²

_{Reported outcomes from separate real-world studies (not head-to-head), all on PHQ-9. Remission = under 5; response = 50%+ reduction, except esketamine (shown as the share reaching under 10, its only reported figure). TMS cohorts started more severe (baseline ~18 to 20 vs ~15 to 16). Individual results vary. Sources: Sackeim 2020, Carpenter 2012 (TMS); Mathai 2024, Parks 2026 (Mindbloom at-home); McInnes 2022 (IV); Marci 2025 (esketamine); Senova 2019 (durability).}

How Ketamine Therapy and TMS Work for Depression

Ketamine and TMS both target the brain circuits that regulate mood, but from opposite directions. Ketamine works from the inside out, using a medicine to shift brain chemistry and reopen the brain's capacity to change. TMS works from the outside in, using magnetic pulses to stimulate a mood-regulating region directly. One also adds a guided psychological experience; the other does not.

How Ketamine Changes the Brain

Ketamine works on two levels: what it does in the brain, and what happens during the session itself.

• In the brain: Ketamine blocks a receptor called NMDA, which triggers a brief rise in glutamate, the brain's main excitatory messenger. That surge is thought to promote neuroplasticity, the growth of new connections between neurons, which researchers believe underlies ketamine's rapid and sometimes lasting effects on mood (Zanos and Gould 2018).¹³
• In the session: Ketamine also produces a temporary shift in consciousness that can loosen rigid, self-critical thinking and create distance from painful material. In a structured ketamine therapy program, that window is paired with preparation and integration, so the relief and insight are more likely to last rather than fade when the medicine wears off.

That second layer is a real difference from TMS: the guided experience is part of how ketamine helps, not just the biology.

How TMS Stimulates the Brain

TMS works through the skull, not through brain chemistry. A magnetic coil rests against the scalp and delivers repeated pulses to the left dorsolateral prefrontal cortex, a region that tends to be underactive in depression. Over a course of sessions, that stimulation is thought to strengthen activity across the wider network that regulates mood.¹⁴

Standard treatment is high-frequency (10 Hz) repetitive TMS, done in a clinic. Unlike ketamine, it involves no medicine and no altered state, so you stay alert and can drive yourself home afterward. The effect comes from the stimulation itself, with no psychological component.

Which Is More Effective, Ketamine Therapy or TMS?

The honest answer is that they are about equally effective. Across large real-world studies, response (a 50% or greater drop in symptoms) and remission (scores low enough to no longer signal depression) land in a strikingly similar range, and head-to-head comparisons show differences that are small and not statistically significant. The studies below all use the same measure, the PHQ-9, which makes the comparison unusually clean.

_{Within-group results from separate real-world studies, same measure (PHQ-9): response = 50%+ reduction; remission = under 5. †Carpenter defined response as a final PHQ-9 under 10. TMS cohorts started more severe (baseline ~18 to 20 vs ~15 to 16 for ketamine), so similar remission from a higher baseline is a strong TMS result. Individual results vary}.

When researchers compare the two more directly, the same picture holds:

• No randomized trial has compared ketamine and TMS head-to-head; the direct evidence is non-randomized comparisons and pooled analyses.
• A 2025 network meta-analysis of 35 randomized trials found no significant difference in response, remission, or tolerability between IV ketamine, rTMS, and ECT (Terao et al. 2025).²
• Non-randomized esketamine comparisons found effectiveness broadly similar, with rTMS numerically ahead in one and esketamine faster in another, neither difference significant (Kaster et al. 2025; Benster et al. 2026).¹⁵⁻¹⁶
• A larger network meta-analysis ranked ketamine slightly behind rTMS on some outcomes, but that gap was also not significant and has been debated (Saelens et al. 2024).¹⁷
• Both rest on solid evidence: TMS is proven over placebo in blinded trials (George et al. 2010; O'Reardon et al. 2007), and ketamine's rapid effect is established in controlled trials.¹⁸⁻¹⁹

The fair conclusion is parity: neither is meaningfully more effective for depression. The real differences show up in speed, effort, and access, which the next sections cover.

Ketamine Therapy vs. TMS: Speed and Durability

Speed is where the two most clearly diverge: ketamine works within hours to days, while TMS builds gradually over weeks. Durability is closer to a tie, since a single course of either fades over the following year without maintenance. What differs there is not how long results last, but what it takes to keep them.

How Fast Each One Works

Ketamine is the faster of the two, by a wide margin at the start. Given by IV, it has reduced depression symptoms within about two hours, and in one landmark trial most patients (71%) responded within a single day (Zarate et al. 2006).⁷

At-home ketamine is not measured that early, but the pattern is similar: in Mindbloom's subcutaneous study, about 70% of patients reported meaningful relief by their second session, roughly two weeks in (Parks et al. 2026).⁹ That is the earliest point measured, not the first moment relief appears.

TMS works the other way, building over the weeks of a course rather than the first days; timing analyses show ketamine's effect present by day 7 while TMS keeps building through day 14 (Chen et al. 2022).²⁰ For someone who needs relief soon, that gap can be decisive.

How Long the Results Last

Here the two are much closer, and a single course of either is rarely a permanent fix. In pooled TMS data, only about half of initial responders still held their gains at 12 months (Senova et al. 2019),¹² and a one-year follow-up found most relapses in the first six months (Janicak et al. 2014).²¹ Ketamine follows a similar, maintenance-dependent pattern: its benefits also fade without repeat sessions.

What differs is the upkeep. Maintaining TMS means another in-clinic course; in that cohort about a third of patients needed retreatment, averaging roughly 16 more sessions (Janicak et al. 2014).²¹ Maintaining at-home ketamine means repeating an at-home course on a maintenance schedule set with your clinician. The results last about as long; the effort to sustain them does not.

Ketamine Therapy vs. TMS: Sessions, Effort, and Cost

This is the biggest practical difference between them. TMS means 20 to 36 clinic visits over four to eight weeks; at-home ketamine therapy is a short course you do from home. For many people that gap weighs as heavily as the clinical results, and it shows up in how many people finish.

The Time and Effort Each Requires

TMS puts the highest burden on your calendar. In-clinic ketamine (IV and esketamine) requires fewer sessions but still involves the logistics of clinic visits, while at-home ketamine therapy is the lowest-effort option by comparison.

• TMS: the heaviest schedule. About 20 to 36 sessions, usually every weekday for four to eight weeks, roughly 20 to 40 minutes each in a clinic chair, plus travel both ways.
• IV ketamine: fewer visits (about six infusions over two to three weeks), but each is an in-clinic appointment of an hour or more with monitoring, plus travel.
• Esketamine (Spravato): in-clinic and required to be, with two hours of on-site monitoring after every dose, typically twice a week during the first month.
• At-home ketamine therapy: a short course of guided sessions done at home (Mindbloom's is six), with no commute and no clinic schedule to arrange your life around.

That heavier TMS schedule shows up in who finishes:

• About 1 in 4 TMS patients do not complete a full course (Sackeim et al. 2020).³
• Roughly 18% stop before reaching 30 sessions (Hutton et al. 2023).²²
• The reasons are consistent: travel, the time and scheduling demands of daily visits, cost and insurance, and discouragement when relief is slow (Caola et al. 2026; Constantin et al. 2025).²³⁻²⁴
• Even inpatient, where travel is removed, 25 to 35% still quit before 20 sessions, so the frequency itself is part of the burden (Barnes et al. 2023).²⁵

By contrast, ketamine was rated more acceptable than TMS in head-to-head research, with fewer patients discontinuing treatment (Terao et al. 2025).²

Cost and Insurance Coverage

Cost is the one area where TMS often has the edge, because it is FDA-cleared and more consistently covered by insurance:

• TMS: usually covered by insurance, so out-of-pocket cost can be modest, though it still means a copay for each of the 20-plus visits.
• At-home ketamine (Mindbloom): usually out of pocket, $165 to $215 per session, the most affordable ketamine option.
• IV ketamine: usually out of pocket, about $400 to $800 or more per infusion.
• Esketamine (Spravato): often partially covered, but a high list price plus an in-clinic, monitored visit for every dose.

Bottom line: it depends on your coverage. Fully covered TMS may cost less out of pocket; otherwise the two are comparable, and at-home ketamine saves weeks of daily travel either way.

Side Effects and Safety: Ketamine Therapy vs. TMS

Both treatments are considered safe, and serious problems are rare with either. What differs is the kind of side effect: ketamine's are short-lived and tied to the dosing session, while TMS's are mostly local, at the treatment site.

Ketamine Therapy Side Effects

Ketamine's side effects are mostly mild and fade as the medicine wears off.

• Most common: a temporary sense of dissociation (feeling detached or floaty), mild nausea, dizziness, and a short-lived rise in blood pressure and heart rate, generally resolving within about two hours. Dissociation tends to lessen over the first couple of weeks of treatment.
• Serious events are rare: with medically supervised ketamine therapy, serious adverse events are uncommon.

TMS Side Effects

TMS involves no medicine and no altered state, so its side effects are physical and centered on the treatment site.

• Most common: scalp discomfort or a tapping sensation at the coil site, and headache, usually mild and easing after the first few sessions.
• No systemic exposure: because nothing enters the bloodstream, there is no dissociation and no post-session monitoring, and you can drive yourself home.
• Serious events are rare: the main serious risk is a seizure, which is very uncommon, historically well under 1 in 30,000 sessions (Rossi et al. 2021).²⁶

Who Is Not a Candidate?

Neither treatment is right for everyone, and a clinician screens for specific reasons someone should not have each one.

• TMS may not be suitable for people who have metal or electronic implants in or near the head (such as aneurysm clips, cochlear implants, or certain neurostimulators), or a history of seizures or epilepsy (Rossi et al. 2021).²⁶
• Ketamine therapy may not be suitable for people who have uncontrolled high blood pressure or serious heart conditions, a history of psychosis, or active substance use concerns, or who are pregnant. Certain forms of active suicidal ideation are also screened, and a clinician assesses this case by case (covered below).

Ketamine Therapy vs. TMS: FDA Approval and Treatment Guidelines

The two have different regulatory histories, but the leading guidelines land in the same place: both are recommended once antidepressants have not worked. The divergence is mostly on paper, not in how strongly experts endorse them.

What Is FDA-Approved

This is where the two differ most on paper:

• TMS: FDA-cleared as a medical device for depression since 2008, for people who have not responded to at least one antidepressant.⁵
• Esketamine (Spravato): FDA-approved for treatment-resistant depression in 2019, delivered in-clinic under a required monitoring program.⁶
• IV and at-home (racemic) ketamine: used off-label. Ketamine is FDA-approved as an anesthetic, and prescribing it for depression is legal and widespread but has not been formally reviewed by the FDA for that use (Sanacora et al. 2017).²⁷

Off-label does not mean unproven or unsafe. It means the FDA has not formally evaluated that specific use, which is true of a large share of everyday prescriptions, including many compounded medications. The stronger signal for any depression treatment is its published outcomes, covered above.

What the Guidelines Recommend

The major clinical guidelines put ketamine and TMS on similar footing:

• The VA/DoD 2022 depression guideline gives the same strength of recommendation, a "suggested" (weak for), to both rTMS and ketamine or esketamine for people who have not responded to two or more medication trials.²⁸
• Two honest caveats come with that: the guideline's ketamine evidence rests on IV racemic ketamine and esketamine (not at-home sublingual or subcutaneous), and it frames both as later-line options used with monitoring, not first treatments.
• The CANMAT 2023 update likewise recognizes rTMS, IV ketamine, and esketamine as options for difficult-to-treat depression.²⁹
• NIMH describes rTMS as FDA-cleared for treatment-resistant depression.¹⁴

Bottom line: no major guideline ranks one above the other. Both are endorsed options once first-line treatments have not worked.

Who Should Consider Ketamine Therapy, TMS, or Both

There is no universally right choice, and for many people either treatment is reasonable once antidepressants have not worked. The best fit depends on how quickly you need relief, what you can access and afford, and your medical history. A clinician helps match the treatment to your situation.

• Ketamine therapy may fit better if you need faster relief, want to avoid a daily in-clinic schedule (the at-home option), prefer fewer sessions, or value the guided psychological side of treatment.
• TMS may fit better if you would rather avoid any medication or altered state, want a treatment more reliably covered by insurance, or have a condition that makes ketamine unsuitable.

Ketamine, TMS, and Suicidal Ideation

Depression often comes with suicidal thoughts, and two things matter at once here: whether a treatment can help quickly, and whether it is appropriate for that person.

• Ketamine acts fast, which can matter when symptoms are severe, though on its own it is not a crisis or emergency treatment.
• Suicidal ideation is not automatically a reason to choose or rule out ketamine. Certain forms of active suicidal ideation are screening exclusions in supervised programs, and this is best assessed by a clinician case by case. Many people who arrive with suicidal thoughts are appropriate for treatment, and they tend to do well: in a peer-reviewed study of Mindbloom's sublingual program, 77% of clients who reported suicidal ideation at the start no longer reported it after treatment (Hull et al. 2022).³⁰
• TMS is also used for people whose depression includes suicidal thoughts, though it works gradually rather than rapidly.

Suicidal ideation here means a score of 1 or higher on PHQ-9 item 9. Of 295 clients reporting it at baseline, clients who did not complete the final assessment are counted as no longer reporting it. If you are in crisis, call or text 988 (US).

Combining or Sequencing Ketamine Therapy and TMS

Some clinicians use both, but the evidence is very limited: no controlled trial has tested combining or sequencing ketamine and TMS, only a handful of small studies (Arubuolawe et al. 2024).³¹ The rationale is that ketamine briefly increases neuroplasticity, which could make the brain more receptive to TMS, though this is unproven. For most people it is one treatment or the other, and a clinician can advise on a combined approach.

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