SPRAVATO® (Esketamine) for Treatment-Resistant Depression
SPRAVATO® (esketamine) is a prescription nasal spray used in adults with treatment-resistant depression. It is also approved, with an oral antidepressant, for depressive symptoms in adults with major depressive disorder and acute suicidal ideation or behavior.
*Based on the ASPIRE I and ASPIRE II studies in adults with MDD and acute suicidal ideation or behavior, which measured depressive symptoms 24 hours after the first dose. See Clinical Sources below.
Manufacturer Brand
- FDA-approved for adult TRD
- Adult MDD with acute suicidal ideation or behavior
- SPRAVATO® REMS required
- At least 2 hours of monitoring
What Is SPRAVATO®?
SPRAVATO® contains esketamine, an NMDA receptor antagonist, and is administered as a nasal spray under the direct supervision of a healthcare professional. It is used in adults with treatment-resistant depression and, with an oral antidepressant, for depressive symptoms in adults with major depressive disorder and acute suicidal ideation or behavior.
How it differs from ketamine: SPRAVATO® is an FDA-approved prescription product with specific indications, dosing, monitoring, and safety requirements. It is different from ketamine products that may be used in other clinical settings.
- Form
- Prescription nasal spray
- Age group
- Adults 18+
- Administration
- Direct healthcare-provider supervision
- Program
- SPRAVATO® REMS required
- Monitoring
- At least 2 hours of post-dose monitoring
What the Research Shows About SPRAVATO®
SPRAVATO® has been evaluated in randomized clinical trials. Findings describe study populations and do not predict how any one person will respond.
Reduction in Depressive Symptoms
Clinical trials have found reductions in depressive symptom severity in adults with treatment-resistant depression.
Popova et al., 2019Early Symptom Improvement
Some clinical studies found differences in depressive symptoms within the first day of treatment. Response varies between individuals.
Fu et al., 2020Maintenance of Improvement
In a maintenance study, patients who had achieved stable response or remission and continued SPRAVATO® were less likely to relapse than those who discontinued treatment.
Daly et al., 2019Supervised Treatment
SPRAVATO® is administered under direct healthcare-provider supervision with monitoring after each dose.
Prescribing InformationHow Esketamine May Affect Brain Signaling
Esketamine is an NMDA receptor antagonist that affects glutamate signaling in the brain. Researchers believe changes in glutamate activity and downstream signaling may contribute to its antidepressant effects.
NMDA Receptor Activity
Esketamine blocks NMDA receptors and influences glutamate signaling, a pathway involved in communication between nerve cells.
Glutamate Signaling
Changes in glutamate activity may affect downstream signaling pathways involved in communication between brain cells.
Synaptic Plasticity
Researchers are studying how downstream effects of glutamate signaling may influence synaptic plasticity and communication between brain cells.
Note: The exact way esketamine produces antidepressant effects is not fully understood.
What Happens During a SPRAVATO® Treatment Visit?
Step 1 — Supervised Self-Administration
You administer SPRAVATO® nasal spray under the direct supervision of a healthcare provider.
Step 2 — Monitoring After Treatment
You’ll remain at the treatment center while your blood pressure, alertness, breathing, and other potential effects are monitored.
Step 3 — Recovery & Departure
Because SPRAVATO® can affect alertness and coordination, patients should not drive or operate machinery until the next day after a restful sleep.
Monitoring: Blood pressure is assessed before treatment and again at approximately 40 minutes after dosing, with additional assessment when clinically appropriate. Respiratory status is monitored for at least two hours after each dose.
Safety, Boxed Warning & REMS Requirements
SPRAVATO® has a Boxed Warning for sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors in pediatric and young adult patients. The overview below covers key considerations.
Sedation
SPRAVATO® can cause sedation and may affect alertness.
Dissociation
Some people experience changes in perception, awareness, or sense of time after treatment.
Blood Pressure Changes
Blood pressure can temporarily increase after dosing and is monitored during treatment.
Respiratory Depression
Respiratory depression can occur after administration, which is why respiratory status is monitored during the observation period.
Abuse & Misuse
Esketamine is a Schedule III controlled substance and has potential for abuse and misuse.
SPRAVATO® REMS: SPRAVATO® is available only through the SPRAVATO® REMS program and must be administered in a healthcare setting under direct supervision, with post-dose monitoring.
SPRAVATO® Important Safety Information
Watch the official Important Safety Information for key risks and safety requirements associated with SPRAVATO®. Discuss risks and benefits with a qualified healthcare professional.
Read the Prescribing InformationSafety note: This information is a general overview and does not replace the SPRAVATO® prescribing information or evaluation by a qualified healthcare professional.
FDA-Approved Uses of SPRAVATO®
Treatment-Resistant Depression
For adults with treatment-resistant depression, SPRAVATO® may be used alone or together with an oral antidepressant.
MDD With Acute Suicidal Ideation or Behavior
For adults with major depressive disorder and acute suicidal ideation or behavior, SPRAVATO® is used together with an oral antidepressant.
Important clarification: SPRAVATO® has not been established to prevent suicide or reduce suicidal ideation or behavior. Its use does not replace hospitalization when hospitalization is clinically warranted.
Who May Be Considered for SPRAVATO®?
SPRAVATO® may be considered for adults with treatment-resistant depression or, in certain circumstances, adults with major depressive disorder and acute suicidal ideation or behavior. A qualified healthcare professional determines whether the treatment is appropriate based on medical history, previous treatments, current symptoms, and other clinical factors.
Treatment History
A clinician may review previous antidepressant treatments and response when considering treatment options.
Current Symptoms
Current depressive symptoms and the specific clinical situation are part of treatment planning.
Medical History
A healthcare professional considers medical history, medications, and relevant safety factors before treatment.
This information is educational and is not a substitute for an evaluation by a qualified healthcare professional.
Understanding Insurance Coverage for SPRAVATO®
Coverage for SPRAVATO® varies by insurance plan, clinical indication, treatment setting, and plan requirements. Individual clinics may also have different participation and authorization requirements.
What Can Affect Coverage?
- Insurance plan
- FDA-approved indication
- Prior authorization requirements
- Treatment setting
- Clinic participation
Before You Schedule
Confirm benefits, authorization requirements, and expected costs directly with your insurer and the clinic.
Before scheduling, confirm coverage directly with your insurance company and the clinic.
Compare insurance information listed by clinicsFind Clinics Offering SPRAVATO®
Search MDDCare’s directory for clinics that list SPRAVATO® treatment and compare location, insurance information, and other available clinic details.
SPRAVATO® Treatment Locations
Browse clinics that list SPRAVATO® among their treatment options.
Treatment Modalities
See other treatments and services a clinic lists.
Location
Browse clinics by city, state, or nearby location where available.
Insurance Information
Review insurance plans listed by the clinic and confirm coverage with the clinic and your insurer.
Directory note: MDDCare lists clinics and does not provide treatment. REMS certification, treatment availability, and insurance information can change. Confirm current details directly with the clinic and your insurance company.
Frequently Asked Questions About SPRAVATO®
Educational answers about FDA-approved uses, treatment visits, monitoring, and coverage.
What is SPRAVATO®?
SPRAVATO® is a prescription esketamine nasal spray. It is FDA-approved for adults with treatment-resistant depression, alone or with an oral antidepressant, and, with an oral antidepressant, for depressive symptoms in adults with major depressive disorder and acute suicidal ideation or behavior.
How is SPRAVATO® different from ketamine?
SPRAVATO® is an FDA-approved prescription product with specific labeled indications, dosing, and monitoring requirements. Ketamine products may be used in other clinical contexts that are not covered by the SPRAVATO® labeling.
How is SPRAVATO® administered?
Patients self-administer the nasal spray in a certified healthcare setting under the direct supervision of a healthcare provider. SPRAVATO® is not taken home.
How long does a treatment visit take?
Patients are monitored for at least two hours after dosing. The overall visit can take longer depending on the clinic and individual circumstances.
Why is monitoring required after treatment?
SPRAVATO® can cause sedation, dissociation, respiratory depression, increases in blood pressure, and other effects. Monitoring for at least two hours allows the healthcare team to assess these effects until it is safe to leave.
Can I drive after SPRAVATO®?
No. Patients should not drive or operate machinery until the next day after a restful sleep, so transportation home should be arranged in advance.
How often is SPRAVATO® given?
Treatment frequency depends on the indication and treatment phase. For treatment-resistant depression, the FDA-approved schedule begins with twice-weekly treatment and becomes less frequent during maintenance, with frequency individualized based on response and tolerability. A qualified healthcare professional determines whether SPRAVATO® is appropriate and sets the schedule.
Is SPRAVATO® covered by insurance?
Coverage varies by plan, clinical indication, and treatment setting. Confirm coverage directly with your insurance company and the clinic. MDDCare does not determine coverage.
Is SPRAVATO® FDA-approved for treatment-resistant depression?
Yes. Under the current FDA labeling, SPRAVATO® is approved for adults with treatment-resistant depression, either alone or with an oral antidepressant.
Is SPRAVATO® approved for depressive symptoms with acute suicidal ideation or behavior?
SPRAVATO® is approved, with an oral antidepressant, for depressive symptoms in adults with major depressive disorder and acute suicidal ideation or behavior. It has not been established to prevent suicide or reduce suicidal ideation or behavior, and its use does not replace hospitalization when clinically warranted.
Medical information: MDDCare is a clinic directory and does not provide SPRAVATO® or medical care. This page is for educational purposes and is not a substitute for professional medical advice, diagnosis, or treatment. FDA-approved indications, safety information, and prescribing details may change. Discuss treatment decisions with a qualified healthcare professional.
Clinical Sources: SPRAVATO® Prescribing Information (DailyMed, current FDA labeling)SPRAVATO® REMSPopova et al., 2019 (TRANSFORM-2)Daly et al., 2019 (SUSTAIN-1)Fu et al., 2020 (ASPIRE I)Ionescu et al., 2021 (ASPIRE II)