If you’ve been researching treatment-resistant depression, you’ve likely come across both Spravato and IV ketamine. Because both are ketamine-based treatments, it’s easy to assume they’re interchangeable.

They’re not.

While they share similarities, they differ in structure, insurance coverage, dosing flexibility, and clinical context. Understanding when each option makes sense can help you make a more informed decision.

Spravato (esketamine) is an FDA-approved nasal spray for:

• Treatment-resistant depression
• Major depressive disorder with acute suicidal ideation

It must be administered in a REMS-certified clinic under supervision, and it’s typically used alongside an oral antidepressant.

Because it is FDA-approved for specific diagnoses, it is often covered by insurance when eligibility criteria are met.

IV ketamine uses intravenous infusion of ketamine in a clinical setting.

Unlike Spravato:

• It is not FDA-approved specifically for depression
• It is often considered off-label for mood disorders
• Insurance coverage is less common

However, IV ketamine offers more flexibility in dosing and administration.

Spravato may be the better fit when:

• You meet criteria for treatment-resistant depression
• You prefer insurance coverage when possible
• You’re comfortable with a structured, protocol-based schedule
• You want FDA-approved treatment specifically for depression

Because of insurance coverage, Spravato is often more financially accessible for long-term treatment.

IV ketamine may be appropriate when:

• A patient does not qualify for Spravato
• Insurance approval is not possible
• Greater dosing flexibility is clinically appropriate
• Rapid titration or protocol adjustments are needed

IV administration allows providers to adjust dose more precisely in real time.

One of the biggest distinctions is flexibility.

Spravato follows a standardized dosing schedule:

• Fixed dosing levels
• Structured frequency
• REMS-required monitoring

IV ketamine allows:

• Weight-based dosing
• Adjustments session by session
• Broader protocol variation

Neither approach is inherently “better.” The right choice depends on clinical goals and patient history.

Spravato:

• Often covered by insurance when criteria are met
• May require prior authorization
• Typically involves copays or coinsurance

IV Ketamine:

• Frequently self-pay
• Insurance coverage is uncommon
• Cost per session varies by provider

For some patients, insurance coverage makes Spravato the practical choice. For others, clinical flexibility outweighs cost considerations.

Spravato:

• Nasal spray
• Self-administered under supervision
• Two-hour monitoring window

IV Ketamine:

• Administered via infusion
• Continuous medical oversight during infusion
• Monitoring during and after infusion

Both are supervised treatments, but the patient experience differs slightly.

Some patients begin with Spravato and later transition to IV ketamine. Others explore IV ketamine if they do not qualify for Spravato.

The goal isn’t to choose a “winner.” It’s to determine which option aligns with:

• Diagnosis
• Treatment history
• Safety considerations
• Insurance coverage
• Long-term care goals

The decision between Spravato and IV ketamine should be clinical, not marketing-driven.

A proper evaluation considers:

• Prior antidepressant response
• Cardiovascular health
• Risk factors
• Financial considerations
• Long-term maintenance plans

Both treatments can be effective in the right context.

If you’re exploring ketamine-based treatment for depression, a structured evaluation can help determine which approach fits your situation best.

You can learn more about Spravato treatment at Therapeutic Infusions on our Spravato treatment page, or explore how IV ketamine therapy is administered in a supervised setting.