TL;DR
- •Ketamine is a pharmacological NMDA-receptor antagonist producing antidepressant effect within hours. TMS (transcranial magnetic stimulation) is a non-invasive neuromodulation requiring 4-6 weeks of daily clinic sessions.
- •Murrough 2013 ketamine RCT showed 64% response vs 28% placebo in treatment-resistant depression. Standard TMS protocols show ~40-50% response rates over a 4-6 week course; accelerated TMS (SAINT/SNT, Cole 2022) shows higher rates with intensive 5-day protocols.
- •Esketamine (Spravato) vs rTMS meta-analyses suggest comparable efficacy in treatment-resistant depression with different practical trade-offs (Liu 2025, EClinicalMedicine).
- •Onset speed favors ketamine — hours to first response vs weeks for standard TMS, 1-5 days for accelerated SAINT protocols.
- •TMS is non-pharmacological, has no systemic side effects, no anesthesia, and patients drive home after each session. Ketamine produces dissociation during sessions and requires medical supervision.
- •Cost: standard TMS course is typically $10,000-15,000 ($300-500 per session for 30+ sessions). Tovani sublingual ketamine is $349/month including maintenance. Insurance coverage varies for both.
- •Both are non-mutually-exclusive — patients with refractory depression sometimes combine or sequence them.
Side by side
Ketamine
Racemic ketamine (NMDA antagonist)
NMDA-receptor antagonist (off-label for depression)
What it treats
Off-label: treatment-resistant depression, anxiety, PTSD, chronic pain
Mechanism
NMDA-receptor antagonism producing acute glutamate surge and BDNF-mediated synaptic plasticity. The brief dissociative experience accompanies the antidepressant effect but isn't required for response in most published models.
Strengths
- •Rapid onset — response often within hours of first session
- •At-home administration option (sublingual) via telehealth
- •Lower total cost than TMS course ($349/month at Tovani vs $10,000-15,000 for TMS course)
- •Flexible maintenance dosing based on response
Limitations
- •Off-label use for depression (esketamine/Spravato is FDA-approved variant)
- •Dissociation during sessions can be uncomfortable for some patients
- •Bladder toxicity with very frequent high-dose chronic use (rare in therapeutic protocols)
- •Requires physician screening for cardiovascular and psychiatric contraindications
TMS
Transcranial Magnetic Stimulation
Non-invasive neuromodulation
What it treats
FDA-approved: treatment-resistant depression, OCD, smoking cessation, migraine
Mechanism
Magnetic pulses through a scalp coil induce electrical currents in cortical brain regions (typically left dorsolateral prefrontal cortex for depression). Repeated sessions produce lasting changes in cortical excitability and network connectivity.
Strengths
- •No systemic side effects, no anesthesia, patient drives home after each session
- •FDA-approved with insurance coverage available
- •Accelerated protocols (SAINT/SNT) compress the course to days rather than weeks
- •No interaction with concurrent medications
Limitations
- •Daily clinic visits for 4-6 weeks (~30 sessions) for standard protocols
- •Lower response rates than ECT or ketamine in some head-to-head comparisons
- •Scalp discomfort, jaw twitches, mild headaches during sessions
- •Cost without insurance is high ($10,000-15,000 typical course)
- •Not effective for psychotic depression or catatonia
Which one for your situation?
If:
Treatment-resistant depression, fastest possible onset is priority
Verdict:
Ketamine — hours to first response vs weeks for standard TMS
If:
Treatment-resistant depression, prefer non-pharmacological option
Verdict:
TMS — no drug, no dissociation, no systemic side effects
If:
Can't commit to daily clinic visits for 4-6 weeks
Verdict:
Ketamine (at-home sublingual) or accelerated TMS (SAINT/SNT) where available
If:
Insurance covers TMS but not ketamine
Verdict:
TMS — coverage is a meaningful practical advantage when available
If:
Failed TMS — what's next?
Verdict:
Ketamine is the typical next-tier option; different mechanism, often responds where TMS didn't
If:
Failed ketamine — what's next?
Verdict:
TMS, ECT, or further augmentation (lithium, atypical antipsychotic) — multiple distinct pathways remain
Where ketamine fits
Tovani provides sublingual ketamine via telehealth in Florida and New Jersey — a faster-onset, lower-cost, at-home alternative to a 4-6 week TMS course. For patients who can't commit to daily clinic visits or who want to respond within hours instead of weeks, ketamine fits the same TRD escalation question that TMS addresses.
Ketamine: response within hours of first session. Standard TMS: response measured at week 4-6 of daily sessions. Accelerated TMS (SAINT): 1-5 days of intensive treatment, slightly slower than ketamine but no medication.
5-minute screening · Reviewed by a board-certified physician · FL & NJ
Frequently asked
Is ketamine or TMS more effective?
Comparable in head-to-head and meta-analytic comparisons for treatment-resistant depression. The practical differences are larger than the efficacy differences: onset speed (ketamine wins), avoidance of any medication (TMS wins), at-home option (ketamine wins), insurance coverage (TMS wins where covered), cost without insurance (ketamine wins). Most patients choose based on these practical factors rather than expected efficacy.
Can I do TMS while on ketamine?
Yes — they're not mutually exclusive. Some refractory patients combine them or sequence them. Combining isn't formally protocolized but isn't contraindicated; clinicians coordinate scheduling to avoid same-day overlap. Sequencing (failed TMS → ketamine, or vice versa) is more common in clinical practice.
Will TMS hurt?
TMS produces a tapping or knocking sensation on the scalp and mild contraction of facial/jaw muscles during pulses. Most patients describe mild discomfort rather than pain. Some patients develop transient headaches that respond to OTC analgesics. The discomfort generally decreases over the first week of sessions.
How is accelerated TMS different from standard TMS?
Standard TMS is one session per weekday for 4-6 weeks. Accelerated TMS (SAINT/SNT) compresses multiple sessions per day for 5 consecutive days. The Cole 2022 SNT trial showed higher response rates with the accelerated approach than standard protocols. SAINT/SNT isn't widely available — only a small number of US clinics offer it, often at higher cost.
Which has more side effects?
Different profiles. Ketamine: dissociation during sessions (the intended therapeutic effect), occasional nausea, rare bladder issues with chronic high-dose use. TMS: scalp discomfort, transient headaches, jaw twitches during sessions, rare seizures (~1 in 30,000 sessions). Most patients tolerate both well; the right side-effect profile depends on individual sensitivity.
References
- Murrough JW et al. 2013, American Journal of Psychiatry. Ketamine RCT in treatment-resistant depression — 64% response vs 28% placebo, establishing rapid-onset antidepressant effect. PMID 23982301
- Cole EJ et al. 2022, American Journal of Psychiatry (SAINT/SNT). Stanford Neuromodulation Therapy (accelerated TMS) double-blind RCT — substantially higher response rates than standard TMS protocols in treatment-resistant depression. PMID 34711062
- Kaster TS et al. 2025, EClinicalMedicine. Meta-analysis of esketamine vs rTMS for treatment-resistant depression — comparable efficacy with different practical trade-offs. PMID 41245530
- Chen JP et al. 2026, Journal of Affective Disorders. Target trial emulation comparing rTMS and esketamine in treatment-resistant depression. PMID 41506390