Ketamine vs. Esketamine (Spravato®): Why IV Ketamine Is the Gold Standard for Treatment-Resistant Depression

Adam O'Neill
May 13
2 min read

Rocky tunnel road with "No Entry" and "Right Turn" signs. Surrounded by lush greenery and red-brown rocks, creating a calm, scenic view.

If you or a loved one has been diagnosed with treatment-resistant depression (TRD), you’ve likely come across two leading options in advanced psychiatric care: IV ketamine infusions and esketamine nasal spray (Spravato®).

At Mosaic Infusions & Wellness, we specialize in IV ketamine therapy because it offers a greater level of precision, flexibility, and evidence-backed effectiveness—especially for those who haven’t found relief through traditional medications or therapies.

Here’s what you should know about the key differences between IV ketamine and Spravato—and why more people are choosing infusions for TRD relief.

The Short Answer: Why We Prefer IV Ketamine

Feature	IV Ketamine (What We Offer)	Spravato® (Esketamine Nasal Spray)
Form	Racemic ketamine (R- and S-enantiomers)	Esketamine only (S-enantiomer)
Administration	IV infusion (highly customizable)	Fixed-dose nasal spray
FDA Approval	Off-label for TRD (clinically supported)	FDA-approved for TRD
Onset	Rapid relief (often within hours)	Also fast, but less consistent
Coverage	Self-pay or out-of-network though increasingly more covered	Can be insurance covered
Experience	Calmer, deeper therapeutic sessions	Variable, often lighter sessions
Setting	Quiet infusion suite, monitored by clinical staff	REMS-certified facility with 2+ hour monitoring

What Is Ketamine Therapy?

Ketamine is a powerful NMDA receptor antagonist originally used as an anesthetic. In recent years, it’s become a breakthrough option for rapid symptom relief in depression, anxiety, and PTSD—particularly when other treatments have failed.

At Mosaic Infusions & Wellness, we use racemic ketamine, which contains both:

The S-enantiomer (used in Spravato)
And the R-enantiomer, which research suggests may have longer-lasting antidepressant effects

What Is Spravato®?

Spravato® (esketamine) is a nasal spray version of ketamine’s S-enantiomer, approved by the FDA for:

Treatment-resistant depression (TRD)
Major depressive disorder with suicidal thoughts

While it has the benefit of insurance coverage in many cases, it’s limited to a specific dose range, must be used alongside a traditional antidepressant, and requires REMS-certified administration.

Many patients find the delivery method less consistent and the results less durable than with infusions.

Why IV Ketamine Offers More Control—and Better Outcomes

Unlike Spravato’s one-size-fits-all nasal dose, IV ketamine infusions are fully customizable to your:

Weight
Symptom severity
Response rate
Co-occurring conditions

This allows for more precise titration, smoother experiences, and longer-lasting relief—particularly when administered as part of a structured series (often 6 infusions over 2–3 weeks).

Maintenance and Long-Term Relief

Both ketamine and Spravato often require ongoing maintenance or “booster” treatments, but IV ketamine allows:

More flexibility in frequency
No requirement to remain on oral antidepressants
A more introspective experience that many patients prefer for deeper healing

Patient Experience at Mosaic Infusions & Wellness

At our Fairfax, VA clinic, IV infusions take place in a calm, spa-like setting with individualized monitoring. Each session lasts about 60–90 minutes, including recovery time.

Patients frequently report:

Feeling deeply relaxed or emotionally open
Dramatic symptom reduction within hours or days
Improved emotional clarity and reduced negative thought loops

So… Which Is Better?

So while we understand not every patient is the same, we feel IV ketamine is superior:

Want...	Consider IV Ketamine
Customizable dosing	✅
Whole-molecule effect (R+S)	✅
Flexible scheduling	✅
More introspective or therapeutic experiences	✅
Non-insurance-based care with faster access	✅