🧪 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.
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 (varies by state), and most major commercial insurers. However, prior authorization is almost always required, and you must typically demonstrate failure of at least 2 adequate antidepressant trials. Copays can be significant — Janssen offers a Spravato Savings Program that reduces copays to $0 for eligible patients with commercial insurance. Patients without insurance can expect to pay $590–$885 per session.
What is the difference between Spravato and ketamine?
Spravato (esketamine) is the S-enantiomer of ketamine, administered as a nasal spray. Regular ketamine (racemic ketamine) is a mixture of both S- and R-enantiomers, typically given via IV or IM injection. Key differences: Spravato is FDA-approved and may be covered by insurance, while IV/IM ketamine is off-label. Spravato requires administration at certified REMS centers, while IV/IM ketamine can be given at any licensed clinic. Some clinicians believe racemic IV ketamine may be more effective for certain patients, but head-to-head trials are limited.
How long does Spravato take to work?
Some patients notice improvement within hours to days of the first Spravato treatment. However, the full clinical effect typically develops over the first 4 weeks of treatment (the induction phase with twice-weekly dosing). Clinical trials measured primary outcomes at 4 weeks. Your provider will assess your response during the induction phase and adjust the treatment plan accordingly. Not all patients respond — clinical trial response rates were approximately 50–70%.
Is Spravato nasal spray safe?
Spravato has been evaluated in clinical trials involving over 1,700 patients. Common side effects include dissociation, dizziness, nausea, sedation, and transient blood pressure increase. The REMS program requires 2-hour post-dose monitoring to manage these effects. Spravato carries a boxed warning for sedation, dissociation, and abuse/misuse potential. It should not be used by patients with aneurysmal vascular disease or arteriovenous malformation. Long-term safety data from the SUSTAIN-2 open-label study showed a consistent safety profile over 1 year of treatment.