Spravato vs. Ketamine Infusions: Which Is Better for Treatment-Resistant Depression?

Is Spravato Better Than Ketamine Infusions for Depression Treatment?

Many patients with treatment-resistant depression are faced with a difficult decision: Should I choose Spravato or IV ketamine infusions? While both therapies originate from the same compound, there are important differences in administration, side effects, cost, insurance coverage, and safety that can help determine the best choice for your needs.

At Axis Integrated Mental Health, we believe Spravato offers several advantages that make it the better option for most patients. Here's why.

How Spravato and IV Ketamine Work Differently

Spravato (esketamine) and ketamine affect the brain in similar ways by targeting the NMDA receptor, stimulating glutamate release, and promoting neuroplasticity. However, Spravato is a more selective isomer and has recently been FDA-approved not just as an add-on therapy but as a standalone treatment for treatment-resistant depression (TRD).

IV ketamine is used off-label, meaning it's not FDA-approved for depression. While it can be effective, it lacks the rigorous oversight and safety infrastructure that accompanies Spravato.

Ease of Administration: Nasal Spray vs. IV Line

Spravato is self-administered as a nasal spray under clinical supervision. No needles, no IVs. This is a big relief for many patients who experience anxiety around invasive procedures.

Ketamine infusions require an intravenous line, continuous monitoring, and a more intensive setup. This can be a deterrent for patients uncomfortable with needles or clinical equipment.

Safety and Abuse Risk: Why Spravato Wins

Spravato is available only through certified treatment centers that participate in the FDA Risk Evaluation and Mitigation Strategy (REMS) program. Patients are supervised for at least two hours post-treatment, and the drug cannot be taken home.

IV ketamine has no such federal oversight. This opens the door to potential overuse or misuse, especially at clinics without psychiatric oversight.

While many people think that the psychedelic experience many have while being treated with either Spravato or ketamine, neuroplasticity occurs regardless if this side effect occurs. What is true is that ketamine tolerance is inevitable. We've seen many people develop a psychological dependence on ketamine because they stop feeling the psychedelic experience and keep asking for higher doses because they know they can with an unregulated treatment. With Spravato, the dose is predetermined so it's less likely to result on dependence.

Side Effects: A Gentler Experience with Spravato

Both treatments can cause dissociation and dizziness, but IV ketamine has more intense side effects such as nausea, vomiting, injection site pain, and temporary hallucinations.

Spravato, by contrast, typically causes only mild nasal discomfort, fatigue, or a sense of floating. Many patients describe it as a "guided mental journey" compared to the more jarring experience of ketamine infusions.

Insurance and Affordability: A Clear Advantage for Spravato

Spravato is covered by most major insurance companies, including Medicare, Medicaid (in many states, including Colorado), Anthem/BCBS, Aetna, Cigna, and United Healthcare.

Additionally, patients with commercial insurance may be eligible for the Spravato Savings Card, which can reduce costs to as low as $10 per visit. This program can contribute over $8,000 annually toward deductibles and copays.

On the other hand, ketamine infusions are never covered by insurance due to their off-label status. Patients typically pay hundreds of dollars out-of-pocket per session.

You can read more about Spravato costs and Ketamine costs on our website for more details.

FDA Approval and Long-Term Viability

Spravato is the only ketamine-derived therapy approved by the FDA as both an add-on and a standalone treatment for TRD. This distinction gives Spravato an edge in safety, credibility, and insurance support.

IV ketamine, though effective in some cases, remains off-label and unregulated. While it may work faster in some cases, it also carries more clinical and financial risks.

Efficacy Studies: What the Research Says

A Cambridge study published in CNS Spectrums showed that Spravato and ketamine had similar remission rates, but ketamine required fewer treatments to achieve a response.

Other research suggests Spravato is just as effective, especially when used consistently and paired with other therapies like oral antidepressants or TMS.

Spravato vs. TMS: Why You Don’t Have to Choose Just One

TMS (Transcranial Magnetic Stimulation) and Spravato both promote neuroplasticity, but through different mechanisms. TMS uses magnetic pulses to stimulate underactive brain regions, while Spravato enhances glutamate signaling and synaptic growth.

At Axis, we've seen the best outcomes when patients use both together. It's not a competition—it's a combination.

What Real Patients Say

One of our patients recently shared:

"I'm living proof. I'm a testament to that. I am profoundly a different person today than I was a year and a half ago. I know who to thank for that. I know what work I did that I can thank myself for. I know who I can look at and say, you created something that finally helped me, and it doesn't just happen. I know that I did it, but man, I don't take any aspect of this for granted any day that I've ever been here, any day that I've ever reflected upon what I experienced the day before. I'm so excited to continue this process. I'm so excited to see who I can be in this world moving forward, and it all ties back to one common denominator, and that's what Axis has created for me to take part of." - Axis Patient Interview

Hearing patient stories like these reminds us why expanding access to FDA-approved, insurance-covered treatments is so important.

How to Get Started with Spravato at Axis

If you're struggling with depression that hasn’t improved after multiple medications, Spravato may be a great fit. At Axis Integrated Mental Health, we provide:

• Free benefits verification to see if your insurance covers Spravato
• Comprehensive psychiatric evaluation to assess eligibility
• A certified REMS clinic and highly trained staff

You don’t have to figure this out alone. Let us help you take the next step toward recovery.

Still wondering, "Is Spravato better than ketamine infusions?" For many patients, the answer is yes, because safety, affordability, and accessibility matter just as much as symptom relief.

Ready to explore your options? Contact Axis Integrated Mental Health by calling us at 720-400-7025 or book with us online.

People Also Ask

1. What is the main difference between Spravato and ketamine infusions?
Spravato (esketamine) is an FDA-approved nasal spray used to treat treatment-resistant depression under clinical supervision through the REMS safety program. Ketamine infusions are IV-based and used off-label, meaning they are not FDA-approved for depression. Spravato offers more oversight, insurance coverage, and safety regulation, while IV ketamine can be more intense and lacks standardization.

2. Is Spravato covered by insurance, and how much does it cost?
Yes. Spravato is covered by most commercial insurance plans, as well as Medicare and Medicaid in Colorado. Many patients pay as little as $10 per session with the Spravato Savings Card, which can contribute up to $8,150 annually toward copays and deductibles. In contrast, ketamine infusions are rarely if ever covered by insurance and typically cost $400–$650 per session out of pocket.

3. Which treatment is safer: Spravato or IV ketamine?
Spravato is generally considered safer due to its FDA approval, REMS monitoring requirements, and strict in-clinic administration with at least two hours of supervision. IV ketamine, while potentially effective, lacks federal oversight and is more prone to variation in dosing, monitoring, and clinical quality, especially in non-psychiatric or cash-based clinics.

4. Does Spravato work as well as IV ketamine for depression?
Studies show esketamine vs ketamine have comparable efficacy for treatment-resistant depression. While ketamine may produce faster initial results, Spravato’s consistent administration, insurance coverage, and safety monitoring make it a more sustainable long-term option for many patients. Combining Spravato with therapy or TMS can also enhance outcomes.

5. Can I switch from IV ketamine to Spravato if I’m already in treatment?
Yes. Many patients transition from IV ketamine to Spravato, especially if cost or clinic accessibility is a concern. At Axis Integrated Mental Health, our psychiatric team evaluates your history and guides you through switching to Spravato safely and effectively, ensuring continuity of care and insurance support.