Spravato® vs Ketamine Infusion Therapy
By Charles Miller, CRNA, CMO, Founder/Owner of Scenic City Neurotherapy
If you’ve been researching ketamine therapy for enough time, chances are you’re curious about the comparison between Spravato® vs ketamine infusion therapy. One of the most common misconceptions in mental health treatment is that Spravato® and ketamine infusion therapy are interchangeable.
They are not.
Both treatments are derived from ketamine. Both can help patients with treatment-resistant depression. Both have an important role in psychiatric care. But they are not the same treatment, and patients should not expect identical outcomes.
Why Spravato® vs Ketamine Infusion Therapy Matters
When someone tells me they “tried ketamine and it didn’t work,” one of my first questions is: “Did you receive intravenous ketamine infusion therapy or intranasal esketamine (Spravato®)?” Many patients are surprised to learn that these are different treatments.
Spravato® is an intranasal medication that contains esketamine, one component of the ketamine molecule. Ketamine infusion therapy delivers ketamine directly into the bloodstream through a carefully controlled intravenous infusion. The route of administration matters. In medicine, how a medication reaches the body can dramatically influence its effectiveness.
Looking at the Numbers
The TRANSFORM-2 trial, one of the landmark studies supporting Spravato®, reported:
- Response rate: 69%
- Remission rate: 36%
Those are meaningful outcomes. Many patients improve with Spravato®, and for some patients it can be life-changing.
But those numbers also tell another story.
If 1,000 patients receive Spravato®, approximately:
- 690 will experience significant improvement.
- 310 will not.
In our recent retrospective analysis of 252 patients treated with a standardized neuroplasticity-focused ketamine infusion protocol, we observed:
- Response rate: 82%
- Remission rate: 55%
Applied to the same 1,000-patient example:
- 820 would experience significant improvement.
- 180 would not.
That difference represents approximately 130 additional patients achieving meaningful relief. For those individuals, the choice of treatment may determine whether they improve or continue to struggle.
The Wrong Conclusion
One of the most concerning misconceptions is the belief that failure to respond to Spravato® means a patient has “failed ketamine.” That conclusion is not supported by the available evidence. A patient who does not respond to intranasal esketamine has not necessarily failed intravenous ketamine therapy. They have failed one ketamine-derived treatment delivered through one route of administration. Those are not the same thing.
Insurance Coverage & Clinical Outcomes are Not the Same
Many patients choose Spravato® because it is covered by insurance while ketamine infusion therapy often requires out-of-pocket payment. That decision is understandable.
Unfortunately, insurance coverage is determined by regulatory approval and reimbursement policy – not by which treatment produces the highest response and remission rates. Patients deserve to know that distinction.
The treatment most likely to be covered is not always the treatment most likely to help.
The Bottom Line
Spravato® can work. For many patients, it works well. But the evidence suggests that ketamine infusion therapy produces meaningfully higher response and remission rates than intranasal esketamine. Patients should not assume these therapies are equivalent, and they should not assume that a lack of response to Spravato® means ketamine therapy has failed.
The question should not be: “Did I try ketamine?”
The better question is: “Did I receive the form of ketamine treatment most likely to help me achieve recovery?”
References
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. The American journal of psychiatry, 176(6), 428–438. https://doi.org/10.1176/appi.ajp.2019.19020172
Jones, B. D. M., Razza, L. B., Weissman, C. R., Karbi, J., Vine, T., Mulsant, L. S., Brunoni, A. R., Husain, M. I., Mulsant, B. H., Blumberger, D. M., & Daskalakis, Z. J. (2021). Magnitude of the Placebo Response Across Treatment Modalities Used for Treatment-Resistant Depression in Adults: A Systematic Review and Meta-analysis. JAMA network open, 4(9), e2125531. https://doi.org/10.1001/jamanetworkopen.2021.25531
Miller, C., Lopes, B., McCurdy, A., & Diller, T. (2026). Analysis of standardized neuroplasticity-focused ketamine therapy in treatment-resistant depression: A longitudinal retrospective study [Manuscript under review].
About Scenic City Neurotherapy
At Scenic City Neurotherapy, we help people find real answers and lasting relief through advanced, evidence-based treatments designed to address the root of mental health and chronic pain challenges, not just the symptoms.
Founded in 2019 by Charles Miller, CRNA, our clinic leads the way in Minimally Stimulated Ketamine Infusion Therapy (MSKIT®) and Transcranial Magnetic Stimulation (TMS) – two cutting-edge therapies proven to safely and effectively restore healthy brain communication.
Our approach is evidence-backed, informed by research, and focused on helping you feel clear, resilient, and capable of moving forward.
If you’re ready for treatment that’s built on proof, not trial and error, contact us today.
📞 (423) 228-0579
