Spravato is the brand-name for esketamine nasal spray, a groundbreaking medication approved by the FDA in March 2019 for adults with treatment‑resistant depression (TRD)—that is, individuals who haven’t experienced adequate relief after at least two proven antidepressant. Esketamine is the S-enantiomer of ketamine and acts as a NMDA receptor antagonist, modulating glutamate pathways involved in mood regulation.
In January 2025, the FDA expanded approval, allowing Spravato to be used alone, without mandatory concomitant oral antidepressants. This represents a significant shift, providing more flexibility for those who struggle with side effects or lack of efficacy from oral options.
How Does Spravato Work?
Traditional depression medications target serotonin, norepinephrine, and dopamine. Spravato, however, focuses on glutamate, the primary excitatory neurotransmitter. By blocking NMDA receptors, it triggers a cascade that boosts glutamate transmission, promoting synaptogenesis—the growth of new neural connections—through BDNF and mTOR pathways.
This novel mechanism offers rapid antidepressant effects, often within hours—much faster than the weeks or months needed for traditional meds.
Treatment Process: What to Expect
Administration: Administered as a 56 mg or 84 mg dose in a certified clinical setting. Patients self-administer 2–3 sprays (28 mg each) per nostril, under supervision
Monitoring: Require at least 2 hours of observation post-dose due to possible sedation, dizziness, dissociation, or elevated blood pressure
Schedule:
Induction: Twice weekly for the first 4 weeks.
Transition: Once weekly for the next 4 weeks.
Maintenance: Every 1–2 weeks, tailored to patient response.
Supervision Required: Must be administered through the REMS program to ensure safety and proper oversight.
Benefits of Spravato
Rapid relief—some patients experience mood improvements within 24 hours.
Effective for TRD—significantly better outcomes compared to placebo in clinical trials.
Standalone use approved—no need for concurrent oral antidepressants.
Unique mechanism—potential to repair neural pathways underlying chronic depressive symptoms.
Evidence for reducing suicidal thoughts—demonstrated decrease in ideation in some studies
Risks, Cost & Accessibility
Side effects: May include dissociation, sedation, dizziness, nausea, increased blood pressure, potential for bladder issues with long-term use.
Cost: Can be substantial—initial monthly costs estimated between $4,700–$6,800, with ongoing expenses of $2,300–$3,500—though many insurance plans may cover it.
Access: Only prescribed and administered at certified clinics. The standalone approval improves accessibility, but supervised administration is still mandatory.
Real‑World Impact & Outlook
Spravato has ushered in a new era of rapid-acting therapy, with clinical data showing 22.5% remission at 4 weeks versus 7.6% for placebo in monotherapy trials. Its unique mechanism and science-backed benefits have led experts to herald it as “revolutionary” for TRD.
However, challenges remain: high cost, need for supervised care, and long-term data on durability and safety (especially bladder risk and dissociative effects) are still emerging.
FAQs About Spravato
Who is Spravato for?
Adults with major depressive disorder who’ve not responded to at least two antidepressants of adequate dose and duration (i.e., TRD)
How quickly does it work?
Many patients experience symptom relief within 24 hours, with peak effects often at 24–48 hours.
Is it safe?
Administered under medical supervision with monitoring for side effects; known risks include dissociation, sedation, hypertension, and rare bladder issues.
Can I take it at home?
No — requires certified clinic setting and participation in the REMS program .
Do I need other antidepressants?
Stand-alone treatment is now approved, though some providers may still combine it with oral antidepressants depending on individual cases.
What does the treatment schedule look like?
- Weeks 1–4: twice weekly
- Weeks 5–8: once weekly
- Maintenance: every 1–2 weeks, based on response
Will insurance cover it?
Many plans do, especially for documented TRD cases. Out-of-pocket costs may still apply. Verify coverage with your provider or insurer directly.
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Sources:
What to Know About Ketamine https://publichealth.jhu.edu/2024/what-to-know-about-ketamine
Verywell Health review of expanded approval https://www.verywellhealth.com/fda-expands-approval-for-spravato-nasal-spray-8781088
EMA’s clinical efficacy summary https://www.ema.europa.eu/en/medicines/human/EPAR/spravato
NCBI. “Long-Term Safety and Maintenance with Intermittent Esketamine Treatment” https://pmc.ncbi.nlm.nih.gov/articles/PMC10267177/