For a long time, treating depression meant trying antidepressants until something worked. Or didn’t. For people who cycled through multiple medications without improvement, options got limited fast. That’s part of the clinical reality that led to the approval of Spravato.
Spravato (esketamine) is an FDA-approved nasal spray for adults with treatment-resistant depression. It works through a different brain pathway than standard antidepressants, gets administered in a clinic, and tends to act faster.
This piece gets into what that means for psychiatric treatment, how clinicians use it, where it fits in a care plan, and what the experience involves.
Quick Answer Summary
Spravato (esketamine) is an FDA-approved nasal spray used to treat treatment-resistant depression and major depressive disorder with suicidal ideation. Unlike traditional antidepressants, it works through the brain’s glutamate system and may provide rapid symptom relief. Administered in a certified clinical setting under supervision, Spravato is integrated into broader psychiatric treatment plans that include therapy, medication management, and ongoing monitoring to ensure safety and effectiveness.
What Is Spravato?
Spravato is the brand name for esketamine, a nasal spray that received FDA approval in 2019. It was the first antidepressant in decades to work through a genuinely new mechanism, which is actually kind of a big deal given how long the field had been working within the same basic framework.
Standard antidepressants mostly target serotonin, norepinephrine, or dopamine. Esketamine does something different. It blocks NMDA receptors, which sets off a surge in glutamate, the brain’s most abundant neurotransmitter. That surge seems to help rebuild synaptic connections that depression erodes.
One practical effect of this is speed: Where most antidepressants take weeks, patients on esketamine for depression treatment sometimes notice shifts within hours. Not everyone, but enough that clinicians pay attention to it.
Where Spravato Fits
Spravato isn’t something a doctor typically reaches for early on. It sits further down the treatment pathway, specifically for patients who’ve already tried at least two oral antidepressants without enough improvement. That’s what psychiatric treatment guidelines call treatment-resistant depression.
The FDA prescribing information outlines two main approved uses: adults with treatment-resistant depression (either standalone or paired with an oral antidepressant), and adults with major depressive disorder experiencing acute suicidal ideation, where it’s used alongside an oral antidepressant. The National Institute of Mental Health defines treatment-resistant depression as depression that doesn’t improve after two or more antidepressant trials, which is generally where esketamine enters the picture.
Worth noting is that this isn’t a prescription you fill at a pharmacy. Every dose happens at a certified clinic, in person, with clinical staff present. That setup is built into how the treatment works.
How Spravato Is Integrated Into Psychiatric Treatment Plans
One thing worth emphasizing is that Spravato never operates in isolation. It sits inside a psychiatric treatment plan: the intake evaluation, the follow-ups, and coordinating with whoever else is involved in the patient’s care. That structure comes with the territory.
With Oral Antidepressants
Historically, Spravato was always used alongside an oral antidepressant. The 2025 FDA label update changed that. It now permits monotherapy for treatment-resistant depression, opening the treatment up for people who’ve had serious tolerability issues with oral medications. Esketamine monotherapy may expand options, especially for those who’ve struggled with side effects rather than just a lack of response.
With Therapy
With Monitoring
Tracking how a patient responds over time is genuinely built into Spravato care. Clinicians watch symptom changes across sessions, note any tolerability concerns, and adjust the schedule accordingly. That ongoing reassessment is what keeps the plan from just running on autopilot regardless of whether things are improving.
What Patients Should Expect
Per the FDA prescribing information, Spravato starts at twice-weekly sessions for four weeks, then shifts to once weekly through week eight, then every two weeks or once weekly from week nine on, adjusted based on response.
Each session involves self-administering the nasal spray at the clinic under supervision, then staying for at least two hours of monitoring. The observation window exists because esketamine can cause dissociation, sedation, and temporary respiratory effects. Providers track vitals and mental state throughout. Patients can’t drive home afterward.
This falls under the SPRAVATO REMS program, an FDA-required safety framework that mandates certified clinics, supervised administration, and on-site pulse oximetry monitoring. It’s more involved than a typical prescription, but that structure is what makes outpatient delivery safe.
Why Clinicians Consider Spravato
No single patient profile defines who ends up on Spravato, but a few situations come up repeatedly: failed trials with multiple antidepressants, severe symptoms that haven’t moved, or cases where a weeks-long wait for a medication to work isn’t viable.
Speed is often the point. Esketamine can start relieving symptoms within a couple of hours, versus several weeks for traditional antidepressants. For someone with active suicidal ideation, that difference matters. Esketamine is also a reasonable option for patients who cannot tolerate other medications, not just those who didn’t respond to them.
Spravato Alongside Other Psychiatric Treatments
Modern psychiatric treatment rarely comes down to one thing. Spravato is one layer in a plan that may include other interventions.
With TMS or ECT
Some patients with hard-to-treat depression use Spravato alongside TMS or ECT. These aren’t redundant; each acts through a different mechanism, and combining them is sometimes what it takes for cases that haven’t moved on to anything simpler.
With Psychotherapy
The neuroplasticity effects that come with esketamine treatment make psychotherapy a natural companion. Whether it’s CBT, EMDR, or another evidence-based modality, the idea is that therapy can go deeper when the brain is in a more receptive state. Plenty of providers time their sessions around Spravato appointments specifically for this reason.
With Lifestyle Interventions
Sleep, exercise, and nutrition have real effects on depression treatment outcomes, and they don’t stop mattering once Spravato is in the picture. A solid care plan looks at the full context, not just the dosing schedule.
Expanding the Possibilities for Treatment-Resistant Depression
What Spravato brings to modern psychiatric treatment is something the field genuinely needed: a different mechanism, faster onset, and a care model for patients who haven’t gotten enough from standard depression treatment.
It works best as one coordinated part of a plan; esketamine alongside therapy, monitoring, and regular reassessment. No single component carries everything.
At Zeam, we offer Spravato as part of individualized care that includes therapy, medication management, and ongoing psychiatric support. If you’ve been through multiple depression treatment options and still aren’t where you want to be, it may be worth having a real conversation about whether Spravato fits your situation. Reach out to schedule a consultation. We’re happy to walk through it with you.
Key Takeaways
- Spravato is an FDA-approved treatment for resistant depression – Spravato (esketamine) is approved for adults with treatment-resistant depression and for those with major depressive disorder and acute suicidal ideation.¹
- It works through a different brain mechanism – Unlike traditional antidepressants, esketamine targets the glutamate system, helping promote neuroplasticity and new neural connections.
- It is typically used after other treatments fail – Spravato is introduced after at least two antidepressant trials have not produced sufficient improvement, aligning with treatment-resistant depression criteria.²
- Treatment is administered in a clinical setting – Patients receive Spravato in certified clinics under supervision, with monitoring for at least two hours after each session due to potential side effects.⁴
- It may provide rapid symptom relief – Some patients experience improvements within hours, making it an important option in cases where faster intervention is needed.
- Spravato is integrated into a broader care plan – It is used alongside therapy, medication management, and lifestyle interventions, rather than as a standalone solution.
- Monitoring and adjustment are ongoing – Clinicians track patient response over time and adjust dosing schedules and treatment strategies based on progress.
- Safety is supported through a structured program – The SPRAVATO REMS program ensures safe administration through certified clinics, supervision, and required monitoring protocols.⁴
Citations
- FDA Prescribing Information for Spravato (Esketamine).
https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/211243s016lbl.pdf - National Institute of Mental Health. Mental Health Medications.
https://www.nimh.nih.gov/health/topics/mental-health-medications - PubMed study on esketamine outcomes and treatment-resistant depression.
https://pubmed.ncbi.nlm.nih.gov/40601310/ - SPRAVATO REMS Program Overview.
https://www.spravatorems.com/pdfs/REMSProgramOverview
