Spravato vs Ketamine: Which Depression Treatment?

If you're exploring breakthrough treatments for treatment-resistant depression (TRD), you've likely encountered both Spravato and ketamine infusions. While they're related compounds, they differ in important ways that affect your treatment experience, cost, and outcomes. Let's break down everything you need to know.

Understanding the Basics

What Is Spravato?

Spravato (esketamine) is an FDA-approved nasal spray for treatment-resistant depression and major depressive disorder with suicidal ideation. It contains esketamine—the "S" enantiomer of ketamine, which is the more potent version of the molecule.

What Is Ketamine (IV Infusion)?

Ketamine infusions use racemic ketamine—the original compound containing both S and R enantiomers—delivered intravenously. While ketamine has been FDA-approved as an anesthetic since 1970, its use for depression is "off-label," meaning providers can prescribe it but it wasn't specifically approved for this purpose.

Key Differences at a Glance

Factor	Spravato	IV Ketamine
FDA Approved for Depression	✅ Yes (2019)	❌ No (off-label)
Administration	Nasal spray	IV infusion
Insurance Coverage	Often covered	Rarely covered
Cost per Session	$20-150 (with insurance)	$400-800 (out of pocket)
Setting	Certified REMS clinic only	Various clinics
Monitoring Time	2 hours	1-2 hours
Standardized Protocol	Yes	Varies by provider

FDA Approval: Why It Matters

The FDA approval distinction is significant for several reasons:

Spravato (FDA Approved)

• Underwent rigorous clinical trials specifically for depression
• Standardized dosing based on research
• Required safety monitoring protocols
• Insurance more likely to cover
• REMS program ensures quality control

IV Ketamine (Off-Label)

• Evidence is strong but less standardized
• Dosing protocols vary by clinic
• No required safety certification
• Insurance rarely covers
• Quality varies significantly by provider

Insurance Coverage: The Biggest Practical Difference

For many patients, insurance coverage is the deciding factor. Here's the reality:

Spravato Insurance Coverage

• Most commercial insurance plans cover Spravato with prior authorization
• Medicare Part D typically covers it
• Many Medicaid plans provide coverage
• Patient copays often range from $20-150 per session
• Manufacturer assistance available for eligible patients

IV Ketamine Insurance Reality

• Almost never covered by insurance for depression
• Full out-of-pocket cost: $400-800 per infusion
• Initial series (6 infusions): $2,400-4,800
• Maintenance infusions add ongoing costs
• HSA/FSA may be used but doesn't reduce total cost

"Many patients come to us after being quoted $4,000-5,000 for ketamine infusion treatment. When we tell them Spravato may cost them just a copay through their insurance, it's a game-changer."

How Do They Compare in Effectiveness?

Both Spravato and ketamine infusions have shown effectiveness for treatment-resistant depression. Here's what the research shows:

Spravato Clinical Trial Results

• Significant reduction in depression symptoms vs. placebo
• Many patients respond within the first 1-4 weeks
• Sustained benefit with maintenance treatment
• Particularly effective for depression with suicidal thoughts

IV Ketamine Research

• Numerous studies show rapid antidepressant effects
• Some patients report improvement within hours
• Effects may be slightly faster than Spravato initially
• Long-term effectiveness similar when maintained properly

Head-to-head comparisons are limited, but both treatments work through similar mechanisms and show comparable effectiveness. The choice often comes down to practical factors like cost, access, and personal preference.

The Treatment Experience

Spravato Experience

Self-administered nasal spray under supervision
Non-invasive—no needles or IV lines
2-hour monitoring after each session
Dissociative effects typically mild to moderate
Standardized protocol at all certified centers

IV Ketamine Experience

Intravenous infusion over 40-60 minutes
Requires IV placement—minor needle stick
1-2 hour monitoring typically
Dissociative effects can be more intense
Protocols vary between different clinics

Safety Considerations

Both treatments have similar safety profiles, but Spravato's regulatory framework provides additional safeguards:

Spravato REMS Program

All Spravato providers must be certified through the FDA's Risk Evaluation and Mitigation Strategy (REMS) program. This ensures standardized safety protocols, monitoring requirements, and quality control across all treatment centers.

IV Ketamine Variability

Ketamine clinics operate with more variability. Quality depends heavily on the specific provider. Some clinics have excellent protocols; others may have less rigorous standards. Research your provider carefully.

Which Should You Choose?

Here's a practical decision framework:

Spravato May Be Better If:

✓ You have insurance that covers it
✓ Cost is a significant concern
✓ You prefer non-invasive treatment (no needles)
✓ You want FDA-approved, standardized protocols
✓ You need ongoing maintenance treatment
✓ Your provider is a certified Spravato center

IV Ketamine May Be Better If:

✓ You can afford out-of-pocket costs
✓ You don't have insurance or Spravato isn't covered
✓ You haven't responded to Spravato
✓ You prefer IV administration or have nasal issues
✓ You've found a reputable ketamine provider

Our Recommendation

For most patients with treatment-resistant depression, we recommend starting with Spravato if insurance coverage is available. Here's why:

Similar effectiveness to ketamine in clinical practice
Dramatically lower cost with insurance coverage
FDA approval provides regulatory oversight and safety standards
Sustainable long-term because of lower ongoing costs
Standardized quality through REMS certification

If Spravato doesn't work or isn't an option, IV ketamine remains a valuable alternative worth exploring.

Spravato vs Ketamine: Which Depression Treatment Is Right for You?