Spravato is the brand name for esketamine, a prescription nasal spray for adults with certain kinds of depression. You spray it yourself, but only in a certified healthcare setting, and a healthcare provider then monitors you for at least 2 hours and decides when you are ready to leave. It is never taken home.
Part of our guide: A Patient’s Guide to Ketamine and Spravato
According to the current FDA label, it is approved for two uses: treatment-resistant depression in adults, on its own or with an oral antidepressant, and depressive symptoms in adults with major depressive disorder who have acute suicidal thoughts or behavior, together with an oral antidepressant.
If you are thinking about suicide or are in danger, call or text 988 (988 Suicide & Crisis Lifeline), call 911 or go to the nearest ER.
What the two approved uses mean
The first use covers depression that has not improved enough with earlier treatment. In the main short-term studies described in the label, participants had not responded adequately to at least two different antidepressants of adequate dose and duration in their current episode. There is no single agreed definition of the term, which this guide to treatment-resistant depression explains.
The second use is for people with major depression and acute suicidal thoughts or behavior. The label sets clear limits here:
- Spravato has not been shown to prevent suicide or reduce suicidal thoughts or behavior.
- It does not remove the need for hospital care when that is clinically warranted, even if someone feels better after a first dose.
- Use with an oral antidepressant beyond 4 weeks has not been systematically evaluated for this purpose.
Spravato is not approved for children or teens, and it is not approved as an anesthetic. Safety and effectiveness in pediatric patients have not been established.
How esketamine relates to ketamine
Ketamine is made of two mirror-image molecules. The FDA describes it as a mixture of R-ketamine and S-ketamine, and esketamine is the S form. The two drugs are related, but they are separate products with different approvals. Ketamine is FDA-approved as a general anesthetic, and its use for depression is off-label. This side-by-side comparison goes through the differences.
Esketamine blocks the NMDA receptor, which is part of the brain's glutamate system. Even so, the label states plainly that the way esketamine produces its antidepressant effect is unknown.
The boxed warnings
A boxed warning is the strongest warning the FDA requires. Spravato's boxed warning covers:
- Sedation, dissociation and respiratory depression. Patients can become sleepy, feel disconnected, or have slowed or stopped breathing after a dose, so they must be monitored for at least 2 hours at each session and then assessed before they can leave.
- Abuse and misuse. Spravato is a Schedule III controlled substance. Risk should be weighed before prescribing and watched for during treatment.
- Suicidal thoughts and behaviors in young people. Antidepressants increased these risks in pediatric and young adult patients in short-term studies. All antidepressant-treated patients should be watched closely for worsening or new suicidal thoughts. Spravato is not approved for anyone under 18.
Because of the first two risks, Spravato is available only through a restricted safety program called the SPRAVATO REMS (Risk Evaluation and Mitigation Strategy).
What the REMS program requires
The FDA-approved REMS shapes how treatment is delivered. Certified healthcare settings must:
- have a prescriber onsite during administration and monitoring
- have healthcare providers and a pulse oximeter available to monitor patients
- enroll outpatients in the program before the first dose
- not dispense Spravato for use outside the certified setting
Pharmacies must be certified too, and they may dispense it only to certified healthcare settings.
If a website offers to mail you esketamine or ketamine nasal spray, it is not Spravato treatment under this program. This article on the FDA's at-home ketamine concerns explains why that matters.
What the research shows
The label describes randomized, placebo-controlled trials, and the results are real but should be read carefully.
- Short-term use with an antidepressant. In a 4-week study, people using Spravato with a new oral antidepressant improved more on a standard depression scale than people using a placebo spray with a new antidepressant. Both groups improved. Most of the difference between groups appeared at 24 hours and did not appear to grow through Day 28.
- Use on its own. A separate study found Spravato alone was statistically better than placebo spray at Day 28, with an effect seen at about 24 hours.
- Staying well. In a long-term study, people who had improved and continued Spravato with an antidepressant went longer before relapse than those switched to placebo spray.
- Older adults. In a 4-week study of people 65 and older, the main result did not reach statistical significance.
- Acute suicidal thoughts. Two studies found greater improvement in depression scores at 24 hours, but no advantage over placebo on a clinician-rated measure of suicidal severity.
Outside the label, the ESCAPE-TRD trial compared esketamine with extended-release quetiapine, each added to an SSRI or SNRI. At week 8, 27.1% of the esketamine group and 17.6% of the quetiapine group were in remission. The trial was open-label and funded by the manufacturer. These numbers also show that most people in either group were not in remission at that point.
Common side effects
In the label's trials, the most common side effects included dissociation, dizziness, nausea, sedation, a spinning sensation, numbness, anxiety, low energy, higher blood pressure, vomiting and feeling drunk. Headache is also listed. The Medication Guide says these usually happen right after a dose and go away the same day.
Two other figures show why the monitoring period exists. In clinical trials, 48% to 61% of people developed sedation on a standard rating scale, and 61% to 84% developed dissociative or perceptual changes. Blood pressure rises at all recommended doses, peaking at about 40 minutes and lasting about 4 hours.
The label also lists bladder symptoms, short-term effects on thinking and reaction time, and impaired driving. You should not drive until the next day, after a restful sleep, so you will need a ride home. This hour-by-hour guide shows how a visit runs.
Who should not take Spravato
The label says it must not be used by people with:
- aneurysmal vascular disease or an arteriovenous malformation
- a history of bleeding in the brain
- an allergy to esketamine, ketamine or the other ingredients
Other situations call for careful review with a prescriber, including heart or blood vessel conditions, past psychosis, liver problems and any history of substance misuse. The label says Spravato is not recommended during pregnancy because it may cause fetal harm. The Medication Guide says you should not take it if you are pregnant and should not breastfeed during treatment. Tell your prescriber about all your medicines, especially central nervous system depressants, psychostimulants and MAOIs.
How treatment is usually scheduled
For treatment-resistant depression, the label describes twice-weekly sessions for the first 4 weeks. Benefit should be assessed at the end of that phase to decide whether to continue. Sessions then move to weekly, and later to every 2 weeks or weekly, at the least frequent schedule that maintains improvement. For depressive symptoms with acute suicidal thoughts or behavior, the label describes twice-weekly sessions for 4 weeks, then a check of benefit. Your prescriber sets the plan. This article on what comes after the first series covers the longer term.
Where to learn more
You can read how Mind Body Seven describes this treatment on its Spravato page, or see depression and treatment-resistant depression care. A psychiatric evaluation is the place to decide whether it fits your situation.
FAQs
Is Spravato a psychedelic?
The FDA label does not use that word. It describes dissociation and perceptual changes as side effects to monitor at each session, and it treats Spravato as a medicine for specific depression uses.
Can Spravato be mailed to a home?
No. Under the REMS, certified pharmacies dispense it only to certified healthcare settings, those settings may not dispense it for use elsewhere, and it is taken under direct observation on site.
Does it have to be taken with another antidepressant?
For treatment-resistant depression, the label allows use alone or with an oral antidepressant. For depressive symptoms with acute suicidal thoughts or behavior, it is used with an oral antidepressant. Do not start or stop any medicine on your own; your prescriber makes this decision with you.
Does it work right away?
Some people notice changes quickly, and trials measured differences at about 24 hours, but response varies and not everyone improves. The label calls for checking benefit at the end of the first 4 weeks.
