What Is Spravato?
Spravato (esketamine) is an FDA-cleared nasal spray developed by Janssen Pharmaceuticals for treatment-resistant depression (TRD) and major depressive disorder with suicidal ideation. It was approved in March 2019 for TRD and in August 2020 for MDD with acute suicidality.
Unlike traditional antidepressants that work on serotonin and norepinephrine systems, Spravato targets the NMDA glutamate receptor. This triggers a rapid cascade of neurochemical changes — increasing brain-derived neurotrophic factor (BDNF) and promoting the formation of new synaptic connections (synaptogenesis). In plain terms: it helps the brain rebuild connections that depression has weakened.
Why Spravato is different
Traditional antidepressants take 4-6 weeks to work because they gradually shift neurotransmitter levels. Spravato works through a completely different pathway — glutamate signaling — and can produce changes within hours to days.
This makes it particularly valuable for patients in crisis or those who haven't responded to standard medications.
How Treatment Works
Spravato is administered through a REMS (Risk Evaluation and Mitigation Strategy) program. This means it can only be given at certified healthcare facilities — you cannot take it home.
Only REMS-certified clinics can administer Spravato. You cannot get it at a pharmacy or use it at home.
You spray the medication yourself under clinical supervision. Dosing: 56mg or 84mg per session.
You're monitored for dissociation, sedation, and blood pressure changes. Cannot drive until the next day.
Twice weekly for weeks 1-4, then weekly for weeks 5-8, then weekly or biweekly ongoing. Must be used alongside an oral antidepressant.
Spravato vs. TMS: Head-to-Head
| Factor | Spravato | TMS |
|---|---|---|
| Speed of Onset | Hours-Days | 2-3 Weeks |
| Duration of Benefits | Requires ongoing sessions | 6-12 months after course |
| Abuse Potential | Yes (Schedule III) | None |
| Dissociation Risk | Common (~40%) | None |
| In-Office Monitoring | 2 hours required | None needed |
| Drive After? | Not until next day | Yes, immediately |
| Treatment Duration | Indefinite maintenance | 6-9 weeks, then done |
| Cognitive Effects | Temporary impairment | None |
| Insurance Coverage | Most major carriers | Most major carriers |
Who Is Spravato Best For?
Acute Crisis
Patients with suicidal ideation who need rapid relief. Spravato's fast onset makes it uniquely suited for urgent situations.
TMS Non-Responders
If TMS didn't produce adequate response, Spravato works through a completely different mechanism and may succeed where TMS didn't.
Multiple Med Failures
Patients who've failed 2+ antidepressants. Spravato must be used alongside an oral antidepressant, but works through a novel pathway.
Side Effects
The most common side effects occur during or shortly after the session and typically resolve within 1-2 hours:
- Dissociation — about 40% of patients. Feeling disconnected from self or surroundings. Usually mild-moderate and temporary.
- Dizziness and vertigo — about 30%
- Nausea — about 25%
- Sedation — about 20%
- Blood pressure increase — transient, monitored during the 2-hour observation
- Anxiety — about 15%
- Nasal discomfort — from the spray delivery
Important Safety Notes
- Spravato is a Schedule III controlled substance with abuse potential
- Cannot be taken home — must be administered in certified facilities only
- Do not drive or operate machinery until the day after treatment
- Not recommended during pregnancy or breastfeeding
- Must be taken alongside an oral antidepressant — not a standalone treatment
Cost and Insurance
| Item | Cost |
|---|---|
| Per session (56mg) | $590-$700 |
| Per session (84mg) | $700-$900 |
| First year (maintenance) | $15,000-$35,000+ |
| With insurance copay | $10-$150 per session (varies widely) |
Most major insurance carriers cover Spravato with prior authorization. Janssen also offers the Spravato Savings Program for commercially insured patients, potentially reducing copays to as low as $10 per session.
Key difference from TMS: Spravato requires indefinite maintenance sessions, so the lifetime cost is significantly higher than a 6-9 week TMS course. TMS may cost $6,000-$12,000 total vs. $15,000-$35,000+ per year for ongoing Spravato.
When to Choose TMS Instead
TMS may be the better choice if:
- You want a time-limited treatment (6-9 weeks) rather than indefinite maintenance
- Driving immediately after treatment matters (work, childcare)
- You want to avoid dissociation and cognitive effects
- Abuse potential is a concern (personal or family history of substance use)
- You prefer a non-pharmacological approach
- Long-term cost is a factor
Both Spravato and TMS are legitimate, evidence-based options for treatment-resistant depression. The best choice depends on your specific situation — urgency, treatment history, insurance coverage, schedule, and personal preferences. Many patients who don’t respond to one may respond to the other.
Use our clinic finder to find providers offering both TMS and Spravato in your area, or read our detailed TMS vs. Esketamine comparison.