TL;DR
- •Spravato (esketamine) is an FDA-approved intranasal NMDA antagonist for treatment-resistant depression. TMS (transcranial magnetic stimulation) is FDA-approved non-invasive neuromodulation for the same indication.
- •Spravato requires in-clinic administration at a REMS-certified facility with 2-hour post-dose monitoring. TMS requires daily clinic visits for 4-6 weeks (typically 30+ sessions) of 20-30 minute sessions.
- •Liu 2025 (EClinicalMedicine) meta-analysis suggests comparable efficacy between esketamine and rTMS for treatment-resistant depression, with different practical trade-offs.
- •Spravato has faster onset (within sessions to days). TMS produces gradual response over weeks of treatment.
- •Both have insurance coverage available but typically require demonstrated antidepressant failures and prior authorization.
- •Cost: Spravato is $590-980+ per session even with insurance, twice-weekly for 4 weeks induction, then weekly-to-biweekly maintenance. TMS is $300-500 per session for ~30 sessions ($10,000-15,000 total course).
- •For patients who can't commit to either intensive schedule, sublingual at-home ketamine provides a less-intensive alternative with similar mechanism to Spravato.
Side by side
Spravato
Esketamine intranasal spray
NMDA-receptor antagonist (FDA-approved)
What it treats
Treatment-resistant depression (failure of 2+ antidepressants), Major depression with active suicidal ideation/behavior
Mechanism
Pure S-enantiomer of ketamine. NMDA-receptor antagonism producing rapid antidepressant effect via glutamate surge and BDNF-mediated synaptic plasticity. Intranasal route avoids first-pass liver metabolism.
Strengths
- •FDA-approved specifically for treatment-resistant depression
- •Insurance coverage available (with prior authorization)
- •Rapid onset (within sessions to days)
- •Recently approved as monotherapy (Popova 2025) in addition to combination with antidepressants
Limitations
- •In-clinic only — 2-hour observation each session via REMS protocol
- •Twice-weekly induction for 4 weeks, then weekly-to-biweekly maintenance
- •Cost $590-980+ per session even with insurance
- •Insurance prior-auth burden (multiple documented antidepressant failures required)
- •Dissociation during sessions; transient blood pressure elevation
TMS
Transcranial Magnetic Stimulation
Non-invasive neuromodulation (FDA-approved)
What it treats
Treatment-resistant major depression, OCD, Smoking cessation, Migraine
Mechanism
Magnetic pulses through a scalp coil induce electrical currents in cortical brain regions (typically left DLPFC for depression). Repeated sessions produce lasting changes in cortical excitability.
Strengths
- •Non-pharmacological — no drug interactions, no systemic side effects
- •Patient drives home after each session
- •Insurance coverage available
- •Accelerated protocols (SAINT/SNT) compress to 5 days where available
Limitations
- •Daily clinic visits for 4-6 weeks (~30 sessions) for standard protocols
- •Gradual response — weeks of treatment to evaluate
- •Scalp discomfort, transient headaches during sessions
- •Not effective for psychotic depression
- •Rare seizure risk (~1 in 30,000 sessions)
Which one for your situation?
If:
TRD with active suicidal ideation requiring fastest possible response
Verdict:
Spravato — FDA-approved specifically for this indication; faster onset than TMS
If:
TRD with strong preference to avoid all medications
Verdict:
TMS — non-pharmacological with no systemic effects
If:
Cardiovascular contraindications (recent MI, uncontrolled hypertension)
Verdict:
TMS — Spravato transiently raises BP and HR; cardiovascular contraindications matter
If:
Can't commit to daily clinic visits for 4-6 weeks
Verdict:
Spravato (twice-weekly is less burden than daily) or sublingual ketamine (at-home)
If:
Insurance covers one but not the other
Verdict:
Follow the coverage — both are expensive without insurance
If:
Failed one — try the other?
Verdict:
Different mechanisms; failure of one doesn't predict failure of the other. Sequencing is clinically standard
Where ketamine fits
Tovani provides sublingual ketamine via telehealth in Florida and New Jersey — same NMDA mechanism as Spravato without the in-clinic burden, REMS protocol, or per-session cost. For patients who want the ketamine mechanism but can't commit to twice-weekly clinic visits, sublingual at-home ketamine is the practical alternative.
Spravato: response within sessions to days. TMS: gradual response over weeks. Sublingual ketamine: response within hours of first session.
5-minute screening · Reviewed by a board-certified physician · FL & NJ
Frequently asked
Is Spravato or TMS more effective?
Comparable in head-to-head and meta-analytic comparisons for treatment-resistant depression. The practical differences usually drive the choice: Spravato is faster but requires drug administration and longer per-session observation; TMS is slower but drug-free with shorter per-session time. Most patients choose based on insurance coverage, schedule constraints, and personal preference for drug vs device.
Will insurance cover either?
Both are insurance-covered for treatment-resistant depression with prior authorization, though specific coverage varies by plan and state. Spravato typically requires documentation of 2+ failed antidepressants in the current episode. TMS typically requires documentation of 4+ antidepressant failures across episodes. Out-of-pocket costs without coverage are substantial for both.
Can I do both — Spravato and TMS?
In sequence, yes — many TRD patients who don't respond to one try the other. Some clinicians combine them in difficult-to-treat cases, though combination protocols aren't formally established. Discuss with your prescriber if you're considering combined treatment.
Is Spravato safer than ketamine?
"Safer" depends on context. Spravato's REMS protocol (in-clinic observation, vital sign monitoring, no driving after sessions) provides one safety layer. Sublingual ketamine's safety depends on physician screening and protocol — Tovani screens for cardiovascular risk, bipolar disorder, dissociation history, and other factors before starting. For a healthy candidate, both routes are well-tolerated.
What if both don't work?
After Spravato and TMS failures, options include ECT (gold-standard for severe TRD), MAOIs (often underused), augmentation strategies (lithium, atypical antipsychotics), or sub-specialist referral for clinical trial enrollment. Combination strategies and accelerated TMS (SAINT/SNT) are also considered when available.
References
- 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
- Janik A et al. 2025, JAMA Psychiatry. Esketamine monotherapy RCT in adults with treatment-resistant depression — supports monotherapy use, not just adjunct to antidepressants. PMID 40601310
- 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. PMID 34711062