If you’ve tried two or more antidepressants and still don’t feel like yourself, you’re probably not looking for promises. You’re looking for honest answers about what might actually help.
Spravato (the brand name for esketamine) is a nasal spray approved in 2019 for treatment-resistant depression, which simply means depression that hasn’t responded to at least two different antidepressants. For many people in that situation, it has offered real relief. Below is what the research found, what “working” looks like in practice, and what you can reasonably expect when you look past the marketing and focus on the data.
One thing to know up front. Spravato carries an FDA boxed warning for sedation, dissociation (a feeling of being detached from yourself or your surroundings), abuse and misuse, and suicidal thoughts and behaviors. Because of that, you can only take it in a certified clinic, and a nurse stays with you for at least two hours after each dose.
At our Manhattan location on 515 Madison Avenue, those two hours happen in a warm, nature-inspired space designed to feel restorative, not clinical. If you’d like to see the room before you commit to anything, you’re welcome to visit or ask our care team what a session looks like in person. We want you to feel comfortable with the setting, not just the science.
What does the research say about the Spravato success rate?
Let’s start with the number most clinics don’t put on their homepage: a meaningful share of people don’t get enough benefit from Spravato. In the pivotal TRANSFORM-2 trial, published in the American Journal of Psychiatry in 2019, most people who added esketamine to a new antidepressant did not reach full remission by day 28. Roughly half improved a lot. The other half didn’t improve enough, or didn’t improve at all. We say that plainly because you deserve the full picture before anything else.
Now the encouraging part. In that same trial, people who added esketamine to a newly started antidepressant improved more than people who added a placebo spray. In plain terms, adding Spravato helped roughly one to two more people in every ten reach a real response, compared with the antidepressant alone. If you’ve already tried several medications without relief, that kind of difference matters.
It helps to separate two words that often get mixed up. “Improved” (clinicians call it a response) means your symptoms dropped by about half. You feel noticeably better, but some depression remains. “Fully recovered” (remission) means your symptoms are mostly gone. Many people respond without fully recovering, and that is still a meaningful result.
These numbers came from people in a similar situation to yours. To join the trial, they had to have already tried more than one antidepressant without enough relief. That matters, because the odds shift the longer depression resists treatment. In the large STAR*D study, the chance of reaching remission fell with each new medication tried: about 37 in 100 on the first try, then 31, then 14, then 13. Your own history is exactly why a different kind of treatment is worth exploring.
How long does Spravato take to work?
There’s no single answer, but here’s the general arc. A few people notice something in the first week or two. Many need the full first month of twice-weekly doses. A smaller group takes longer than that. A fast response is a good sign, but it’s not required for a strong outcome. A slow start doesn’t mean it won’t help you.
“Noticing something” rarely feels like a switch flipping. Early on, it tends to show up in small, ordinary ways rather than on a mood score. You sleep through the night. Your appetite comes back. The wall of morning dread is a little lower. People around you sometimes notice before you do.
The dosing schedule shapes the timeline. According to the FDA prescribing information, Spravato comes in 56 mg and 84 mg doses, given twice a week for the first four weeks. If it helps, visits usually spread out to weekly, then to every one or two weeks. So the first month is the real test of whether the medicine is working, not the first session. That twice-weekly schedule is easier to keep when your clinic is accessible. Our Midtown Manhattan location is steps from the E, F, and 6 trains, which matters when you’re committing to eight visits in four weeks.
Does the improvement from Spravato last?
For people who become stable, the evidence points toward staying well longer, though the research does come with a few caveats. In the SUSTAIN-1 relapse-prevention trial, people who had reached stable remission and kept taking esketamine cut their risk of relapse by about half compared with those switched to a placebo spray. For people who got well, continuing treatment helped them stay that way. If you’d like to understand how ongoing or “booster” doses fit in over time, we cover that on our maintenance and boosters page.
Trials are not real life, and that’s worth saying. People in studies are carefully screened and closely monitored, so results in an everyday clinic often look more modest. A real-world French study called ESKALE found that after one month about four in ten people responded and about two in ten reached remission, with those numbers climbing over the following months. Lower than the trial numbers, but still real relief for people who felt they had run out of options. What seems to help in practice is finishing the full course, having therapy and integration support alongside the medicine, and not going through it alone. That’s why every Spravato session at Nushama includes access to preparation guidance and integration coaching, so the two-hour monitoring window becomes part of your healing rather than just a waiting period.
What does “better” actually feel like, and what if it doesn’t come?
When Spravato helps, the improvement tends to arrive in a loose order. Sleep and appetite settle first. Then small things start landing again: food tastes like something, you can follow a whole episode of a show, a song you used to love reaches you. People around you may notice before you do. Many describe it as the volume on depression turning down rather than a light switching on. It varies from person to person, and someone else’s experience is not a guarantee of yours.
If your whole history is treatments that didn’t work, this part matters most: there’s always a plan for when Spravato doesn’t help enough. A fair trial is usually that first month of twice-weekly doses at an adequate dose. If you’ve responded only partly, your clinician may adjust the dose (often from 56 mg to 84 mg) before deciding anything. A partial response is useful information, not a dead end. Spravato is one route among several, and that’s one reason we offer more than one. At Nushama, our clinical team can also recommend IV ketamine infusions, medication management, or deeper integration therapy, all in the same practice with the same care team who already knows your history. Other options outside our center include TMS (transcranial magnetic stimulation, a non-drug treatment that uses magnetic pulses) or different medication combinations with your psychiatrist. If one path doesn’t get you there, we’ll help you find the next one rather than sending you somewhere else to start over.
Questions worth asking any clinic about results
If a clinic quotes you a success rate, a few straightforward questions will tell you how honest the number is:
- Is that a response rate or a full-remission rate, and over how many weeks?
- Do you publish your own outcomes, or are you quoting the published trials?
- What happens if I only partly respond, or don’t respond at all?
- Will I have therapy and integration support, or just the doses?
The figures on this page come from the published research, not from our own outcomes data. We share them because you deserve honest numbers before you walk through any clinic’s door.
If reading this raised more questions than it answered, that’s a good thing. Our care team at 515 Madison Avenue in Midtown Manhattan is happy to sit with you, talk through what the research means for your situation, and help you figure out whether Spravato is the right fit. There’s no pressure and no obligation.
You can see what a Spravato visit actually looks like before you come in, and if cost is on your mind, we accept most major insurance plans, including Oxford, UnitedHealthcare, Cigna, Aetna, and Humana. We also accept Fidelis Care at our Manhattan and Rockland locations; benefits and out-of-pocket costs vary by plan.
Book a consultation when you’re ready, or just call us to ask the questions on this page out loud. We’d rather you feel informed than rushed.
