Nearly a third of adults with major depression don’t get relief from standard oral antidepressants, even after trying more than one. For those patients, Spravato offers a different route into the brain entirely, and for some, relief shows up within a day.
Spravato is the brand name for esketamine, a nasal spray the FDA approved for adults living with treatment-resistant depression. It isn’t just another pill added to a stack of failed prescriptions. Esketamine works on the central nervous system in a way that looks nothing like a typical oral antidepressant.
Most antidepressants chase serotonin. Spravato esketamine goes after the brain’s glutamate system instead, targeting the NMDA receptor specifically. That single difference explains a lot. It’s part of why some patients notice their depression symptoms easing within hours instead of weeks.
Given the risk of misuse and sedation, Spravato treatment only happens through a certified provider, under a risk evaluation and mitigation strategy program. Nobody walks out with a bottle. Every dose gets administered in a clinical setting, with a provider watching over the recovery period afterward.
Esketamine is approved for adults with treatment-resistant depression, defined as trying at least two different traditional antidepressants without real improvement. It’s also cleared for adults with major depressive disorder who are experiencing suicidal thoughts or a mental health crisis that needs urgent attention.
That second approval carries real weight. A standard antidepressant can take a month or longer to kick in, and someone in crisis rarely has that kind of runway. Spravato therapy for depression was built, in part, to close that gap.
This isn’t a first-line option, though. Physicians don’t reach for esketamine before trying other routes first. It shows up once efforts to treat depression through conventional means have already come up short.
How does esketamine work, exactly? Once it’s administered, the drug binds to NMDA receptors on brain cells that help regulate glutamate, the brain’s most abundant excitatory neurotransmitter.
That interaction sets off a chain reaction. Researchers believe it prompts new connections to form between neurons, almost like clearing a blocked pathway and letting the brain build a fresh route. This process, known as synaptic plasticity, may explain why relief can arrive faster than it does with older medications.
Patients stay in the clinic for observation after each dose, typically around two hours, since dizziness or a sense of detachment can follow. Blood pressure gets checked before and after, too. A temporary spike is common enough that providers monitor vitals closely before clearing anyone to head home.
A single dose was never the point. How does Spravato work for depression over months rather than one appointment? It comes down to a structured schedule: two sessions a week for the first month, then a taper to weekly, then eventually every other week or monthly for maintenance.
The clinical trials behind the drug’s approval showed meaningful improvement on standard depression rating scales. Some participants showed measurable change within 24 hours of that very first dose, a timeline that’s rare in major depression treatment.
Providers often pair esketamine with talk therapy or an existing oral medication rather than treating it as a standalone fix. That combination tends to hold up better over time.
Every treatment involves tradeoffs, and esketamine is no exception. Common side effects include sedation, dizziness, nausea, and a floaty, detached feeling during the observation window. Most of it fades within a couple of hours.
Because of these effects, patients can’t drive themselves home after a session. It’s a small logistical detail, but it shapes how people schedule appointments. Plenty choose a day off work rather than squeezing a session into a lunch break.
Serious complications remain rare. Even so, providers watch closely for shifts in suicidal thoughts, particularly early on, when mood can swing before it settles into something steadier.
Depression that hasn’t budged with standard care can feel like you’ve run out of road. You haven’t. At Scottsdale TMS, our team builds a treatment plan around what hasn’t worked before and what might work now, esketamine included, for patients who qualify.
If oral antidepressants haven’t given you the relief you’re looking for, it might be worth a conversation about what else exists. Reach out to Scottsdale TMS and find out whether Spravato has a place in your path forward.
Dr. Vines has practiced psychiatry in Arizona for for over 25 years and has experience working with diverse populations that include children, adolescents, adults, geriatrics, SMI patients, and the chemically dependent.
August 17, 2026
