If you have been researching ketamine-based treatments for depression or other mental health conditions, you have likely encountered both SPRAVATO® and IV ketamine — and if you are wondering which one might be appropriate for your situation, you are asking exactly the right question. Many clinical definitions of treatment-resistant depression require inadequate response to at least two antidepressant trials of adequate dose and duration (Gaynes et al., 2020). Both SPRAVATO® and IV ketamine target the glutamate system rather than serotonin, but they differ in meaningful ways — including FDA approval status, method of delivery, and the populations they are specifically indicated for. At Allevate Health in Princeton, NJ, we help patients navigate this choice through a complimentary consultation.
Understanding the Basics: What Are These Two Treatments?
Both SPRAVATO® and IV ketamine are related to the same chemical family, but they are distinct medications administered in distinct ways. SPRAVATO® (esketamine) is a nasal spray containing the S-enantiomer of ketamine, while IV ketamine infusions deliver racemic ketamine — containing both R- and S-enantiomers — directly into the bloodstream through an intravenous line. Our overview of ketamine methods explains how these approaches differ in a clinical setting.
Key differences at a glance:
SPRAVATO® is self-administered as a nasal spray under clinical supervision; patients remain at the clinic for at least two hours after each dose for monitoring.
IV ketamine is administered intravenously in a clinical setting, with a treatment session typically lasting 40–60 minutes plus a recovery period.
SPRAVATO® is FDA-approved for specific depressive-disorder indications; IV ketamine for psychiatric conditions is off-label.
Insurance coverage is more commonly available for SPRAVATO® due to its FDA-approved status; IV ketamine coverage varies widely.
SPRAVATO® is available only through certified healthcare settings under a REMS program; IV ketamine is administered in a medically supervised clinical setting.
Understanding these distinctions upfront helps set realistic expectations and allows for a more informed conversation with your provider.
FDA Approval Status — A Critical Distinction
This is perhaps the most important difference between the two treatments. SPRAVATO® is FDA-approved for treatment-resistant depression in adults and for depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior (U.S. Food and Drug Administration, 2025). This means SPRAVATO® can be prescribed within those labeled indications when a patient meets the appropriate criteria.
IV ketamine for psychiatric conditions — including depression, OCD, bipolar depression, PTSD, and others — is off-label use. Ketamine injection is FDA-approved as an anesthetic, but it has not gone through the same formal FDA approval process for psychiatric indications (DailyMed, n.d.). There is a substantial evidence base supporting IV ketamine’s antidepressant effects in treatment-resistant depression, including randomized controlled trial data (Murrough et al., 2013). Off-label prescribing is common and legal in clinical medicine, but it does carry different implications for insurance coverage and patient consent. Discuss with your provider what off-label status means for your situation and rights. Results vary by individual for both treatments.
Who Is Each Treatment Designed For?
A second barrier to making this decision is understanding the clinical criteria each treatment is designed to address. SPRAVATO® is specifically indicated for:
Adults with treatment-resistant depression who have not responded adequately to prior antidepressant treatment.
Adults with depressive symptoms in major depressive disorder with acute suicidal ideation or behavior, where fast-acting treatment may be clinically urgent.
IV ketamine is commonly considered for:
Treatment-resistant depression, including cases where SPRAVATO® has not been effective, tolerated, or clinically appropriate.
Bipolar depression with a significant depressive burden.
OCD, PTSD, and other mood or anxiety conditions, all off-label.
Chronic pain conditions including complex regional pain syndrome and neuropathic pain.
Situations where IV delivery may offer more precise dosing flexibility.
Neither treatment is a first-line intervention — both are most appropriate when standard therapies have not produced sufficient relief. One barrier many patients face is not having clear documentation of prior antidepressant trials even when they have been suffering significantly. This is worth discussing with your provider so your treatment history can be accurately reviewed.
Administration and the In-Office Experience
The logistics of treatment differ meaningfully between SPRAVATO® and IV ketamine. For SPRAVATO®, you self-administer the nasal spray under the supervision of a clinical team, and you are monitored for a required two-hour observation period at each visit. The treatment schedule typically begins twice weekly during the induction phase, then moves into weekly or every-other-week maintenance depending on your response and treatment plan (U.S. Food and Drug Administration, 2025). The experience is generally milder than IV infusions in terms of dissociative effects, although individual responses vary.
IV ketamine infusions deliver medication directly into the bloodstream, producing a more rapid and often more intense in-session experience. Some patients describe heightened perceptual awareness, dream-like imagery, or a sense of mental distance during infusions — effects that typically resolve fully within the recovery period. To understand what that in-session experience is actually like, our post on what it feels like to get a ketamine infusion offers a firsthand perspective. A standard initial course for depression, anxiety, and PTSD at Allevate Health is typically six infusions over two to four weeks. At our Princeton location, IV ketamine is provided in a medically supervised setting designed to support safety, comfort, and monitoring throughout the session.
Insurance and Cost Considerations
For many patients in Princeton, NJ, insurance coverage is a practical consideration that influences the treatment decision. SPRAVATO® is covered by many commercial insurance plans and Medicare for patients who meet FDA-labeled indications, though prior authorization requirements vary by plan. IV ketamine for psychiatric indications is typically not covered by insurance due to its off-label status, though some plans may handle specific pain-related diagnoses differently.
Our team discusses financial considerations during your complimentary consultation and can help clarify what your insurance may or may not cover. We also recommend reviewing our guide to insurance coverage for treatment-resistant depression before your visit so you can come prepared with the right questions.
Making the Decision in Princeton, NJ
At our Princeton, NJ location, your care begins with a complimentary consultation in which we review your diagnosis, treatment history, medications, safety considerations, and goals. For many patients with well-documented treatment-resistant depression or depressive symptoms with acute suicidal ideation or behavior, SPRAVATO® treatment may be a natural starting point given its FDA approval and insurance coverage potential. For those with conditions beyond the SPRAVATO® label or who need the flexibility that IV ketamine therapy provides, IV ketamine may make more clinical sense.
In some cases, a patient may transition from one option to the other based on response, tolerability, cost, or diagnosis. The right choice is not determined by which treatment sounds more advanced; it is determined by your clinical profile, your prior treatment history, your safety considerations, and what you are realistically able to access and sustain.
To learn more or schedule a consultation, visit our Princeton location page or call 640-252-9785.
Frequently Asked Questions
Q: Can I try both SPRAVATO® and IV ketamine?
A: In some clinical circumstances, patients may receive one after the other — for example, if SPRAVATO® does not produce adequate response, IV ketamine may be considered, or vice versa. This decision depends on your clinical history, diagnosis, response, tolerability, and provider judgment. We discuss sequencing options with you during consultation.
Q: Is one treatment more effective than the other?
A: Head-to-head comparative trials are limited, and results vary by individual. SPRAVATO® has FDA approval and clinical trial evidence for treatment-resistant depression, while IV ketamine has randomized controlled evidence supporting rapid antidepressant effects in treatment-resistant depression (Popova et al., 2019; Murrough et al., 2013). The “better” option for you depends on your diagnosis, treatment history, safety profile, and practical considerations such as insurance coverage.
Q: Do I need a referral to come to Allevate Health Princeton for a consultation?
A: No referral is required. You can contact us directly to schedule your complimentary consultation. We recommend bringing any documentation of prior treatment trials — medication names, doses, duration, side effects, and outcomes — to your first appointment.
Q: How long do effects from either treatment last?
A: Both treatments can produce acute relief that may diminish over time without ongoing treatment. Maintenance schedules vary by individual. Relapse-prevention research supports ongoing SPRAVATO® treatment for some patients with treatment-resistant depression, while IV ketamine maintenance planning is individualized based on response and clinical judgment (Daly et al., 2019). We discuss realistic expectations and maintenance options during your consultation.
Q: Is SPRAVATO® just a form of ketamine?
A: SPRAVATO® (esketamine) is chemically related to ketamine but is a distinct pharmaceutical product — the S-enantiomer of ketamine, formulated as a nasal spray and delivered at different doses through a different route than IV ketamine. The two treatments share overlapping glutamate-related mechanisms but are not identical in their clinical profile, FDA status, dosing, or insurance landscape.
Key Takeaways
SPRAVATO® is FDA-approved for treatment-resistant depression and depressive symptoms in adults with MDD with acute suicidal ideation or behavior; IV ketamine for psychiatric conditions is off-label, though supported by clinical evidence.
The two treatments are related but differ in delivery route, dosing flexibility, session experience, FDA status, and insurance coverage landscape.
SPRAVATO® is generally better suited for patients whose clinical history fits its FDA-labeled indications; IV ketamine offers broader off-label flexibility across multiple conditions.
Insurance coverage is more commonly available for SPRAVATO® than for IV ketamine for psychiatric indications; financial options should be discussed during a complimentary consultation.
At Allevate Health in Princeton, NJ, we evaluate your full history and help guide the most appropriate treatment choice. Results vary by individual.
References
Daly, E. J., Trivedi, M. H., Janik, A., Li, H., Zhang, Y., Li, X., Lane, R., Lim, P., Duca, A. R., Hough, D., Thase, M. E., Zajecka, J., Fava, M., Elad, I., Mangano, R. M., & Goodman, W. K. (2019). Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: A randomized clinical trial. JAMA Psychiatry, 76(9), 893–903. https://doi.org/10.1001/jamapsychiatry.2019.1189
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. https://doi.org/10.1002/da.22968
Murrough, J. W., Iosifescu, D. V., Chang, L. C., Al Jurdi, R. K., Green, C. E., Perez, A. M., Iqbal, S., Pillemer, S., Foulkes, A., Shah, A., Charney, D. S., & Mathew, S. J. (2013). Antidepressant efficacy of ketamine in treatment-resistant major depression: A two-site randomized controlled trial. American Journal of Psychiatry, 170(10), 1134–1142. https://doi.org/10.1176/appi.ajp.2013.13030392
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. https://doi.org/10.1176/appi.ajp.2019.19020172
Rush, A. J., Trivedi, M. H., Wisniewski, S. R., Nierenberg, A. A., Stewart, J. W., Warden, D., Niederehe, G., Thase, M. E., Lavori, P. W., Lebowitz, B. D., McGrath, P. J., Rosenbaum, J. F., Sackeim, H. A., Kupfer, D. J., Luther, J., & Fava, M. (2006). Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report. American Journal of Psychiatry, 163(11), 1905–1917. https://doi.org/10.1176/ajp.2006.163.11.1905
U.S. Food and Drug Administration. (2025). SPRAVATO® (esketamine) nasal spray, CIII prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/211243s016lbl.pdf
Medical Disclaimer
The information in this blog is for educational purposes only and does not constitute medical advice. Ketamine therapy, SPRAVATO®, and ketamine treatment should only be pursued under the supervision of a licensed provider familiar with your full medical and psychiatric history. Individual results vary. If you are experiencing a mental health crisis or thoughts of self-harm, please call or text 988 to reach the Suicide and Crisis Lifeline or go to your nearest emergency room.