What Spravato is
Spravato is the brand name for esketamine, given as a nasal spray you spray into your own nose in the clinic while staff watch. Esketamine is a close chemical cousin of ketamine, the anesthetic used in operating rooms for decades. It is a controlled medicine (Schedule III) and, by law, can only be given in a certified clinic under a safety program called a REMS (Risk Evaluation and Mitigation Strategy). It is never sent home from a pharmacy for depression treatment. There is no take-home bottle. Ever.
Nearly every standard antidepressant works on the serotonin, norepinephrine, or dopamine messenger systems and takes four to eight weeks to show its full effect. Esketamine works mainly on the glutamate system — the brain's most common excitatory messenger — by blocking a docking site called the NMDA receptor. The leading explanation for its speed is that this triggers a rapid burst of new connection-building between brain cells in circuits depression has thinned out. In plain terms: most antidepressants slowly turn up the supply of a messenger; esketamine appears to help the wiring itself reconnect, within hours to days rather than weeks.
What Spravato is FDA-approved for — exactly
- Treatment-resistant depression (TRD) in adults — major depression that has not responded adequately to at least two oral antidepressants. Since January 2025 it is also approved as a standalone treatment (monotherapy) for TRD — the first and only medicine approved that way — as well as together with an oral antidepressant. In the monotherapy trial, about 22.5% of Spravato patients reached remission at week four versus about 7.6% on placebo nasal spray, with improvement measurable as early as 24 hours.
- Depressive symptoms in adults with major depressive disorder with acute suicidal thoughts or behavior — given together with an oral antidepressant, for rapid reduction of depressive symptoms.
A treatment day, step by step
- Before leaving home: no food for at least 2 hours and no liquids for at least 30 minutes before dosing, to lower the chance of vomiting. Bring a driver or arrange the ride both ways in advance. If you use a nasal medicine or decongestant, the clinic will give timing instructions.
- Check-in: blood pressure is measured. Staff ask about sleep, substances, medicine changes, how you feel that day, and any effects left from a prior session. If blood pressure is too high that day, dosing can be delayed or skipped.
- Dosing: 56 mg or 84 mg for TRD. Each spray device delivers 28 mg, so a dose is two or three devices. Coached and observed, you spray one spray into each nostril per device, rest about five minutes between devices, and do not sniff hard afterwards — the medicine is meant to coat the inside of the nose and absorb there.
- The two-hour watch: you settle into a recliner in a monitored room for at least two hours after the last device. This is the heart of the REMS rule and is not negotiable. Staff re-measure blood pressure (typically around 40 minutes, when it tends to peak) and watch sedation, dissociation, breathing, and blood pressure until you are clinically stable and ready to leave.
- Leaving: only when staff clear discharge, and only into the hands of your arranged ride. No driving, no operating machinery, and no major decisions until after a full night's sleep — not until the next day.
What the two hours can feel like
The most discussed effect is dissociation — a floaty, spaced-out, dreamlike, or briefly unreal feeling, as if watching yourself from a slight distance, or as if sounds and colors are turned up or oddly far away. It usually peaks in the first 40 minutes and clears by about an hour and a half to two hours. Other common effects: dizziness, nausea or vomiting, feeling sleepy or slowed, anxiety during the experience, a spinning feeling, and numbness or tingling. Most people describe it as strange rather than frightening when they have been prepared for it — and you should hear this description at the consult, not discover it in the chair.
The schedule
| Phase | How often | Notes |
|---|---|---|
| Induction (weeks 1–4) | Twice a week | 56 mg or 84 mg per session for TRD. Benefit is judged at the end of this phase; if there is no meaningful movement, the doctor should say so plainly and re-plan. |
| Maintenance (weeks 5–8) | Once a week | Same dose range, adjusted to response and tolerability. |
| Maintenance (week 9 onward) | Once a week or every two weeks | The least frequent schedule that holds the response. Indefinite treatment at a set rhythm without review is not good care. |
| MDD with acute suicidal thoughts / behavior | Twice a week for 4 weeks, with an oral antidepressant | Then reassess. Hospital-level safety decisions stay separate from the spray schedule. |
Pros and cons
Pros
- Speed: improvement can begin within 24 hours to a few days for some — a different clock from the four-to-eight-week wait for a standard antidepressant.
- A different system: when serotonin medicines have failed again and again, a glutamate medicine is not “more of the same.”
- Works where others did not, for a meaningful minority: roughly one in five TRD patients reached remission at four weeks on monotherapy in the approval trial; more reached partial improvement.
- No daily pill burden for the Spravato part itself, and no daily sexual, weight, stomach, or sweating effects of the kind that make people quietly stop antidepressants.
- Every dose is supervised; blood pressure and mental state are measured at every visit.
Cons, risks, and burdens
- The visit is long and the ride rule is absolute. Budget half a day door to door during induction, twice a week, with a reliable driver every time. For many families, logistics — not the medicine — decide whether Spravato is workable.
- Dissociation, sedation, and dizziness are common on treatment days; nausea and vomiting happen often enough that the fasting rule exists.
- Blood pressure rises for a few hours after dosing in many patients. People with certain blood-vessel conditions — an aneurysm, a prior brain bleed, fragile vessels — or uncontrolled high blood pressure may not be candidates. Tell the clinic your full cardiac and stroke history.
- Abuse and dependence potential are real; the medicine is controlled for that reason. A history of substance use disorder is not an automatic bar, but it changes screening and monitoring.
- Other threads to cover with the doctor: the boxed warning about suicidal thoughts in young adults, pregnancy risk (it can harm a fetus — contraception belongs in the consult), bladder irritation reported with long-term frequent ketamine-class exposure, and every sedating medicine, sleep apnea, and liver problems.
- Cost and authorization are heavy. The drug is expensive, billed as a medical (not pharmacy) benefit in most plans, with documented TRD and prior authorization the norm. Ask for your actual out-of-pocket exposure, in writing, before the first dose.
Safety screening checklist
- Blood pressure and cardiovascular history, aneurysm or prior brain bleed, stroke history.
- Pregnancy possibility and contraception; breastfeeding.
- Substance use history, sedating medicines, sleep apnea, liver problems.
- History of mania or bipolar disorder, psychosis, and suicidal thinking — and a safety plan.
- All medicines, over-the-counter products, and supplements, on one complete list.
Spravato is not the same thing as IV ketamine
Intravenous ketamine for depression is off-label: ketamine the drug is FDA-approved as an anesthetic, not as a depression treatment, and IV clinics vary widely in protocols, doses, screening, and monitoring. Spravato is the on-label, FDA-approved, REMS-controlled, insurance-billable esketamine product with a set dose range, a set two-hour watch, and a trial record behind its label. You are entitled to know which one is actually being offered, and to ask: “Why IV ketamine instead of the on-label Spravato, in my case, in writing?”
On medicines you already take, read Meds & Weaning.