Yes, Spravato (esketamine) is FDA approved. It received its first approval in March 2019 for treatment-resistant depression in adults, and gained a second approval in August 2020 for depressive symptoms in adults with major depressive disorder who have acute suicidal ideation or behavior. It is delivered as a nasal spray and is classified as a Schedule III controlled substance.
What Spravato Is Approved to Treat
Spravato currently carries two distinct FDA-approved indications. The first is treatment-resistant depression (TRD) in adults, either on its own or alongside an oral antidepressant. Treatment-resistant depression generally means a person has tried at least two different antidepressants at adequate doses and durations without sufficient improvement.
The second indication covers depressive symptoms in adults with major depressive disorder (MDD) who are experiencing acute suicidal ideation or behavior. For this use, Spravato must be taken alongside an oral antidepressant. One important caveat: the FDA label notes that Spravato has not been shown to prevent suicide or directly reduce suicidal thoughts. It targets the broader depressive symptoms in people who happen to be in that acute crisis.
How It Works Differently Than Other Antidepressants
Most antidepressants developed over the past 50 years work by adjusting serotonin, norepinephrine, or dopamine levels in the brain. Spravato takes a fundamentally different approach. It blocks a receptor called NMDA, which is involved in a separate signaling system built around glutamate, the brain’s most abundant excitatory chemical messenger.
By blocking NMDA receptors, esketamine triggers a cascade that increases glutamate activity in certain brain circuits. This appears to help the brain form new neural connections more rapidly than traditional antidepressants allow. The practical result is speed: where conventional antidepressants typically take weeks to produce noticeable effects, Spravato can begin improving symptoms within hours to days. In clinical trials for the suicidal ideation indication, patients showed statistically significant improvement within 24 hours of the first dose compared to placebo.
What the Clinical Trials Showed
In the pivotal trial for treatment-resistant depression, 52.5% of patients taking Spravato plus an oral antidepressant achieved remission at four weeks, compared to 31% of those receiving a placebo nasal spray plus an oral antidepressant. Remission here meant their depression scores dropped to a level considered near-normal. About 7.9% of Spravato patients achieved a meaningful response (at least 50% improvement) by day two and maintained it through day 28, versus 4.6% on placebo.
For the suicidal ideation indication, two identical Phase 3 trials enrolled adults with moderate-to-severe depression and active suicidal ideation with intent. Both studies showed Spravato plus standard-of-care treatment was superior to placebo at reducing overall depression scores within 24 hours. However, neither trial showed a statistically significant difference in a direct measure of suicidal severity, which is why the FDA label carries that limitation about not being proven to reduce suicidal thoughts specifically.
How Treatment Sessions Work
Spravato is not something you pick up at a pharmacy and take at home. Because of its safety profile, the FDA requires it to be administered only in certified healthcare settings through a program called REMS (Risk Evaluation and Mitigation Strategy). You self-administer the nasal spray under direct supervision of a healthcare provider, then remain at the clinic for monitoring.
The treatment schedule follows a phased approach. During weeks one through four (the induction phase), sessions happen twice per week. In weeks five through eight, frequency drops to once per week. From week nine onward, sessions taper to once every one or two weeks depending on how you respond. Each session for the suicidal ideation indication uses an 84 mg dose twice weekly for four weeks, with the option to reduce to 56 mg if side effects are difficult to tolerate.
Before each dose, your blood pressure is checked. After the spray, you’re monitored for at least two hours. Staff track your blood pressure again around the 40-minute mark (when the drug reaches peak levels in your system) and watch for sedation, dissociation, and changes in vital signs before clearing you to leave. You cannot drive for the rest of the day after a session.
Side Effects and Safety Warnings
Spravato carries an FDA boxed warning, the most serious type of safety alert, covering five risks: sedation, dissociation, respiratory depression, potential for abuse and misuse, and suicidal thoughts and behaviors (a warning that applies broadly to all antidepressants in younger adults).
The most common side effects during treatment for TRD include dissociation (a feeling of being detached from yourself or your surroundings), dizziness, nausea, sedation, vertigo, numbness or tingling, anxiety, lethargy, increased blood pressure, vomiting, and feeling drunk. For the suicidal ideation indication, the profile is similar, with euphoric mood also appearing more frequently than in the placebo group. These effects typically peak within the two-hour monitoring window and resolve before you leave the clinic.
Blood pressure increases are common enough that they receive specific attention in the prescribing information. If your resting blood pressure is already above 140/90 before a session, your provider needs to weigh whether the temporary spike from Spravato is safe for you. After dosing, blood pressure is tracked for at least two hours, and if it stays elevated, staff will involve someone experienced in managing blood pressure.
Why It Requires a Restricted Program
Esketamine is closely related to ketamine, a well-known anesthetic that also has a history of recreational misuse. The REMS program exists to minimize the risk of diversion and abuse while still making the drug available to people who need it. Every healthcare setting that offers Spravato must complete a certification process, train all relevant staff, and verify that each patient is enrolled in the program before every single session. Pharmacies can only dispense Spravato to certified clinics, never directly to patients. After each administration, the clinic submits a monitoring form within seven days.
This restricted access means Spravato is not as convenient as a daily pill. But for people whose depression has not responded to multiple other treatments, the clinical benefit can justify the logistical demands of regular clinic visits and post-dose monitoring.