🧪 Spravato (Esketamine)
Spravato (esketamine) is an FDA-approved nasal spray for treatment-resistant depression and major depressive disorder with suicidal ideation. It must be administered at certified REMS healthcare facilities.
Reviewed for clinical accuracy against peer-reviewed literature and FDA guidelines · Last reviewed March 2026
About Spravato (Esketamine)
Spravato is the brand name for esketamine nasal spray, manufactured by Janssen Pharmaceuticals (a subsidiary of Johnson & Johnson). It received FDA approval in March 2019 for treatment-resistant depression (TRD) and was subsequently approved in August 2020 for major depressive disorder (MDD) with acute suicidal ideation or behavior. Spravato contains esketamine, the S-enantiomer of ketamine, which has a higher affinity for the NMDA receptor than racemic ketamine.
Spravato must be administered at certified treatment centers under the Spravato REMS (Risk Evaluation and Mitigation Strategy) program. This requirement exists because of risks of sedation, dissociation, and potential misuse. The REMS program mandates that patients self-administer the nasal spray under direct healthcare provider supervision and are monitored for at least 2 hours after each dose. Patients cannot take the drug home. As of 2024, there are over 3,000 certified Spravato treatment centers across the United States.
Clinical trials (TRANSFORM-1, TRANSFORM-2, and SUSTAIN-1) demonstrated that Spravato, combined with a newly initiated oral antidepressant, significantly improved depression symptoms compared to a newly initiated oral antidepressant plus placebo nasal spray. Unlike off-label IV ketamine, Spravato's FDA-approved status means it can be covered by insurance, though prior authorization is typically required and patients must have documented failure of at least two adequate antidepressant trials.
Typical protocol: Twice weekly (weeks 1–4), then weekly or biweekly • Commonly treats: treatment-resistant depression (TRD) and major depressive disorder with acute suicidal ideation
What to Expect During Spravato Treatment
You visit a certified Spravato REMS healthcare facility. You self-administer the nasal spray (56mg or 84mg) under supervision. Treatment takes about 2 hours total: administration, then a 2-hour observation period (required by REMS). During observation, staff monitor blood pressure and sedation. You cannot drive for the rest of the day. Schedule: twice weekly for weeks 1-4, weekly for weeks 5-8, then weekly or every 2 weeks for maintenance.
Side Effects
Dissociation (41%), dizziness (29%), nausea (28%), sedation (23%), vertigo (15%), increased blood pressure (transient), anxiety, headache. Most resolve within 1.5 hours. REMS monitoring required due to sedation and dissociation risk.
Insurance & Cost
Spravato is FDA-approved and often covered by insurance including Medicare and many commercial plans. However, high copays are common. Janssen offers the Spravato Savings Program with $0 copay for eligible commercial insurance patients. Prior authorization typically required — must document failure of 2+ antidepressants.
Frequently Asked Questions
Does insurance cover Spravato?
Yes, Spravato is FDA-approved and covered by many insurance plans including Medicare Part D, Medicaid in most states, and major commercial insurers such as Blue Cross, Aetna, and UnitedHealthcare. However, prior authorization is almost always required, and you must typically demonstrate documented failure of at least 2 adequate antidepressant trials before coverage is granted. Even with approval, copays can be significant depending on your specific plan tier and deductible status. Janssen offers the Spravato Savings Program that reduces copays to $0 for eligible patients with commercial insurance, which has helped thousands of patients afford this treatment since its launch. Patients without insurance can expect to pay $590–$885 per session out of pocket. Ask your treatment center to handle the prior authorization process on your behalf, as experienced centers are familiar with each insurer's specific requirements and documentation standards, which can significantly improve your chances of obtaining coverage approval.
What is the difference between Spravato and ketamine?
Spravato (esketamine) is the S-enantiomer of ketamine, administered as an FDA-approved nasal spray, while regular ketamine is a racemic mixture of both S- and R-enantiomers typically given via IV or IM injection off-label. The most important practical difference is that Spravato may be covered by insurance since it received FDA approval in 2019, whereas IV and IM ketamine are rarely covered. Spravato must be administered at one of the over 3,000 certified REMS treatment centers, while IV or IM ketamine can be given at any licensed clinic. Some clinicians believe racemic IV ketamine may be more effective for certain patients because the R-enantiomer has distinct neurobiological effects, but head-to-head clinical trials comparing the two remain limited. Discuss both options with your psychiatrist to determine which route best fits your clinical needs, insurance situation, and access to local providers.
How long does Spravato take to work?
Some patients notice improvement in depressive symptoms within hours to days of their first Spravato treatment, though the full clinical effect typically develops over the first 4 weeks during the induction phase with twice-weekly dosing at either 56mg or 84mg. The TRANSFORM-2 Phase 3 clinical trial measured primary outcomes at the 4-week mark and found statistically significant improvement compared to placebo nasal spray combined with a new oral antidepressant. Clinical trial response rates were approximately 50–70%, meaning not all patients will respond to Spravato. Your provider will assess your progress throughout the induction period using standardized depression rating scales and adjust the treatment plan if needed. After induction, dosing frequency decreases to weekly or biweekly during the maintenance phase. If you do not see meaningful improvement after 4 weeks of consistent treatment, discuss alternative ketamine treatment options such as IV infusion with your clinician to explore other approaches.
Is Spravato nasal spray safe?
Spravato has been evaluated in clinical trials involving over 1,700 patients and has a well-characterized safety profile. Common side effects include dissociation (41% of patients), dizziness (29%), nausea (28%), sedation (23%), and transient blood pressure increase. The FDA-mandated REMS program requires 2-hour post-dose monitoring at a certified healthcare facility to manage these effects, and patients cannot drive for the rest of the day. Spravato carries a boxed warning for sedation, dissociation, and abuse or misuse potential. It should not be used by patients with aneurysmal vascular disease or arteriovenous malformation due to the risk of blood pressure elevation. Long-term safety data from the SUSTAIN-2 open-label study showed a consistent safety profile over 1 year of treatment with no new safety signals. Talk to your prescriber about your complete medical history to confirm you are an appropriate candidate for Spravato therapy.
Conditions Treated with Spravato
Learn how spravato (esketamine) is used for these conditions.
Depression
Treatment-resistant depression (TRD). 60-70% response rate with ketamine therapy.
Anxiety
Anxiety disorders including GAD and social anxiety. Rapid relief via glutamate modulation.
PTSD
Post-traumatic stress disorder. Facilitates trauma reprocessing and extinction learning.
Chronic Pain
Fibromyalgia, CRPS, and neuropathic pain. NMDA receptor antagonism reduces central sensitization.
OCD
Obsessive-compulsive disorder. Emerging evidence shows rapid reduction in obsessive thoughts.
Bipolar Depression
Depressive phase of bipolar disorder. Rapid mood improvement without triggering mania.
Suicidal Ideation
Acute suicidal ideation. Fastest-acting intervention, effects within hours.