Treatment-resistant depression can leave people feeling as though they have exhausted every option. At The Invictus Clinic in Marietta, Georgia, we offer SPRAVATO®, or esketamine nasal spray, for qualifying adults with treatment-resistant depression. Treatment-resistant depression is commonly used to describe depression that has not responded adequately to at least two antidepressant trials of appropriate dose and duration, although definitions vary across studies (Gaynes et al., 2020).
If you have cycled through antidepressants without lasting relief, SPRAVATO® may represent an FDA-approved treatment option worth discussing with your provider.
What Is SPRAVATO®?
SPRAVATO® is a nasal spray containing esketamine, the S-enantiomer of ketamine. It is a non-competitive NMDA receptor antagonist and is FDA-approved for treatment-resistant depression in adults, either as monotherapy or in conjunction with an oral antidepressant. It is also approved, in conjunction with an oral antidepressant, for depressive symptoms in adults with major depressive disorder and acute suicidal ideation or behavior (U.S. Food and Drug Administration [FDA], 2025).
These are FDA-approved uses, not off-label uses. However, SPRAVATO® has not been shown to prevent suicide or reduce suicidal ideation or behavior, and hospitalization may still be clinically necessary even when depressive symptoms improve after treatment begins (FDA, 2025).
Because SPRAVATO® can cause sedation, dissociation, respiratory depression, and changes in blood pressure, it must be administered under direct healthcare-provider supervision through the SPRAVATO® REMS program. Patients are monitored for at least two hours after each treatment session, and SPRAVATO® cannot be taken home (FDA, 2025).
At The Invictus Clinic, every SPRAVATO® session takes place in our Marietta office under clinical supervision.
How SPRAVATO® Works: The Glutamate Connection
Like our treatments and therapies, SPRAVATO® works through the glutamatergic system rather than the monoamine pathways primarily targeted by traditional antidepressants such as SSRIs and SNRIs.
Glutamate is the brain’s primary excitatory neurotransmitter, and NMDA receptors are one type of glutamate receptor involved in neural signaling. Esketamine acts on these receptors, although the precise mechanism by which it produces antidepressant effects is not fully known (FDA, 2025).
Research into ketamine and related treatments has identified downstream pathways involving AMPA receptor signaling, BDNF, and synaptic plasticity. These pathways may help explain why glutamate-based treatments can have a different time course than conventional antidepressants, though individual response varies (Zanos & Gould, 2018).
Clinical trials of esketamine in treatment-resistant depression have found improvement in depressive symptoms for some participants during the early stages of treatment, but no treatment can predict an individual outcome in advance (Popova et al., 2019). To understand more about how these mechanisms compare, our blog on how ketamine affects the brain provides helpful background.
The SPRAVATO® Treatment Protocol
For treatment-resistant depression, SPRAVATO® is generally administered twice weekly during the first four weeks. During weeks five through eight, treatment is generally once weekly. After week nine, treatment may continue weekly or every two weeks, with frequency individualized to maintain response or remission (FDA, 2025).
Each appointment includes self-administration of the nasal spray under direct supervision and at least two hours of post-administration monitoring. You will need transportation home after every session and should not drive, operate machinery, or engage in other potentially hazardous activities until the next day after a restful sleep (FDA, 2025).
For adults with major depressive disorder and acute suicidal ideation or behavior, SPRAVATO® follows a separate four-week dosing schedule and is used with an oral antidepressant (FDA, 2025).
Insurance Coverage: A Critical Difference
One important difference between SPRAVATO® and IV ketamine therapy is insurance coverage. Because SPRAVATO® is FDA-approved for specific depressive-disorder indications, it may be covered by insurance for qualifying patients.
At The Invictus Clinic, we work with Anthem BCBS, Aetna, and Medicare for qualifying SPRAVATO® patients. Prior authorization and coverage verification may be required, and our team will help clarify the process before treatment begins.
IV ketamine infusion therapy for psychiatric conditions is used off-label and is not widely covered by insurance. At our clinic, individual IV ketamine infusions range from $400 to $1,000, depending on the protocol. We offer a 15% discount for upfront payment of an initial infusion series, a 25% discount for active military personnel, veterans, and first responders, and CareCredit financing.
For some patients, insurance coverage may make SPRAVATO® a more accessible option. Our team can help you compare SPRAVATO® and IV ketamine therapy based on your history, diagnosis, goals, and coverage.
Addressing Fear: What to Expect During a SPRAVATO® Session
We understand that beginning a new psychiatric treatment, especially one that may cause dissociation, can feel daunting. The most common concern we hear is whether patients will feel panicked or lose control.
SPRAVATO® can cause dissociative or perceptual changes, dizziness, nausea, sedation, and temporary increases in blood pressure. These effects are why every treatment is monitored closely in a clinical setting (FDA, 2025).
Our clinical team is with you throughout the session to help you feel informed, supported, and safe. We encourage you to discuss any history of anxiety, panic disorder, dissociation-related distress, substance-use concerns, or prior medication reactions during consultation so we can determine whether SPRAVATO® is appropriate for you.
You may also find our post on what to look for in a ketamine clinic helpful before deciding on treatment.
Who Qualifies for SPRAVATO®?
SPRAVATO® may be an option for adults with treatment-resistant depression or for adults with major depressive disorder and acute suicidal ideation or behavior, depending on diagnosis, medical history, current medications, and safety considerations.
A comprehensive psychiatric and medical evaluation is required before beginning treatment. Certain medical conditions, including uncontrolled hypertension, aneurysmal vascular disease, arteriovenous malformation, or a history of intracerebral hemorrhage, may affect eligibility. A history of psychosis or substance-use disorder also requires careful clinical consideration (FDA, 2025).
Results vary by individual, and not every patient will experience the same response to SPRAVATO®. For context on the range of depressive conditions that may be candidates for advanced treatment, see our overview of what are the different types of depression.
Frequently Asked Questions
Is SPRAVATO® the same as IV ketamine infusion therapy?
No. SPRAVATO® is esketamine nasal spray administered under direct supervision and is FDA-approved for specific depressive-disorder indications. IV ketamine uses racemic ketamine administered intravenously and is used off-label for psychiatric conditions, including depression. Both involve glutamate-based mechanisms, but they are distinct treatments with different delivery methods, monitoring requirements, and regulatory status.
Does insurance cover SPRAVATO®?
Coverage may be available for qualifying patients. At The Invictus Clinic, we work with Anthem BCBS, Aetna, and Medicare for SPRAVATO® treatment. Prior authorization and eligibility requirements may apply, so our team verifies coverage before treatment begins.
How long does a SPRAVATO® session take?
Each session includes nasal spray administration and at least two hours of post-administration monitoring. Your total time in the clinic may be longer depending on your individual needs and clinical stability after treatment (FDA, 2025).
How quickly might I notice improvement with SPRAVATO®?
Some clinical trials have found early symptom improvement for some patients, while others experience more gradual changes across the treatment schedule. We cannot predict your individual response in advance, and results vary by person (Popova et al., 2019).
Can I drive after a SPRAVATO® session?
No. You must arrange transportation home after treatment. Do not drive, operate machinery, or engage in activities requiring full alertness until the next day after a restful sleep (FDA, 2025).
Key Takeaways
- SPRAVATO® is FDA-approved for treatment-resistant depression in adults, either alone or with an oral antidepressant, and for depressive symptoms in adults with major depressive disorder and acute suicidal ideation or behavior when used with an oral antidepressant.
- SPRAVATO® is administered under direct supervision in a certified healthcare setting, with at least two hours of monitoring after every treatment.
- Esketamine acts on NMDA receptors in the glutamatergic system, though its exact antidepressant mechanism is not fully known.
- SPRAVATO® may be covered by insurance for qualifying patients, including patients we treat through Anthem BCBS, Aetna, and Medicare.
- A comprehensive psychiatric and medical evaluation is required before beginning treatment, and individual results vary.
At The Invictus Clinic, we believe that insurance coverage should not be the barrier that keeps a patient from exploring a clinically appropriate treatment option. If you are living with treatment-resistant depression or major depressive disorder with acute suicidal ideation or behavior and want to explore SPRAVATO®, please call us at 770-580-1042 or schedule a consultation at our Marietta, GA office.
References
Gaynes, B. N., Lux, L., Gartlehner, G., Asher, G., Forman-Hoffman, V., Green, J., Boland, E., Weber, R. P., Randolph, C., Bann, C., Coker-Schwimmer, E., Viswanathan, M., & Lohr, K. N. (2020). Defining treatment-resistant depression. Depression and Anxiety, 37(2), 134–145. DOI: 10.1002/da.22968. https://pubmed.ncbi.nlm.nih.gov/31638723/
Popova, V., Daly, E. J., Trivedi, M., Cooper, K., Lane, R., Lim, P., Mazzucco, C., Hough, D., Thase, M. E., Shelton, R. C., Molero, P., Vieta, E., Bajbouj, M., Manji, H., Drevets, W. C., & Singh, J. B. (2019). Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: A randomized double-blind active-controlled study. American Journal of Psychiatry, 176(6), 428–438. DOI: 10.1176/appi.ajp.2019.19020172. https://pubmed.ncbi.nlm.nih.gov/31109201/
U.S. Food and Drug Administration. (2025). SPRAVATO® (esketamine) nasal spray: Prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/211243s016lbl.pdf
Zanos, P., & Gould, T. D. (2018). Mechanisms of ketamine action as an antidepressant. Molecular Psychiatry, 23(4), 801–811. DOI: 10.1038/mp.2017.255. https://pubmed.ncbi.nlm.nih.gov/29532791/
Medical Disclaimer
The information in this blog is for educational purposes only and does not constitute medical advice. SPRAVATO® and IV ketamine infusion therapy should only be pursued under the supervision of a licensed provider familiar with your full medical and psychiatric history. Individual results vary. SPRAVATO® is FDA-approved for specific indications, while IV ketamine for psychiatric conditions is used off-label. If you are experiencing a mental health crisis or thoughts of self-harm, call or text 988 to reach the Suicide & Crisis Lifeline or go to your nearest emergency room.
