Spravato vs Ketamine: What’s Covered by Insurance and What’s Not?

Quick answer



• Spravato (esketamine) - more likely to be covered by insurance for treatment-resistant depression or certain labeled indications because it is FDA-approved for those uses and provided under a REMS (safety) program. Coverage usually requires prior authorization and is commonly billed through the medical benefit (clinic/office administration), though specifics vary by insurer.

• Ketamine (racemic or other formulations) given for depression (IV, IM, oral, compounded intranasal) is generally off-label for psychiatric indications. Most commercial and government payers treat ketamine for depression as experimental/ investigational and do not routinely cover it, so patients commonly pay out-of-pocket. Exceptions can occur on a case-by-case basis.

Below is a patient-friendly but practical breakdown to help you understand the differences, benefits, and when each option might be preferred.

How insurers think about these two treatments

1. FDA approval & labeling (big insurer signal)

• Spravato (esketamine): FDA-approved specifically for treatment-resistant depression (and for depressive symptoms in certain cases). Because it’s approved and regulated (REMS), payers have a clear precedent for coverage policies — though they still typically require documentation of prior treatment attempts and a prior authorization.

• Ketamine (IV/IM/oral/compounded intranasal): Ketamine as an anesthetic is FDA-approved, but not specifically approved for depression except for esketamine. Using ketamine for depression is off-label, so most insurers label it “investigational” and don’t cover it routinely.

2. Delivery setting & billing pathway

• Spravato: Administered in a certified clinic with monitoring (because of REMS). Charges are generally billed under the medical benefit (clinic visit/drug administration/observation). In some systems, parts may route through the pharmacy/medical split — check your plan.

• Ketamine: Often given via IV infusion in outpatient infusion clinics/medical offices. Since this use is off-label, some insurers will not cover the drug or the infusion visit; even when they do, coverage is inconsistent. Ketamine given for anesthesia (unrelated uses) is covered in its approved context, but that does not imply coverage for depression treatment.

3. Evidence & guidelines

• Spravato has randomized trials, an FDA label, and published REMS safety requirements — this strengthens the case for insurer coverage.

• Ketamine has growing evidence showing rapid antidepressant effects but lacks a universal regulatory approval for depression (outside esketamine), so guidelines and payer policies are uneven.

Benefits of each treatment (clinical perspective)

Spravato (esketamine)

• Standardized, FDA-approved formulation and dose.
• REMS program requires safe administration and monitoring, which some insurers view positively.
• Good evidence for treatment-resistant depression and a clear pathway for prior authorization.
• Administered under supervision with structured follow-up — easier to document for insurers.

Ketamine (IV/IM/oral/compounded)

• Flexible routes of administration (IV, IM, oral, intranasal) — IV infusions may produce rapid effects.
• Often faster & flexible protocols in experienced clinics (some patients respond when other treatments fail).
• Potentially lower direct drug cost (depending on formulation), but overall cost can still be high because of clinic fees and repeat sessions.
• Clinical experience: Many providers and clinics report beneficial outcomes, particularly for acute suicidal ideation or rapid symptom relief; however, standardization and long-term data vary.
  

What insurers are likely to pay for (and what they won’t)

Likely covered (with prior authorization and documentation):

• Spravato treatment for patients who meet payer criteria (e.g., a documented trial of multiple antidepressants/therapies and a diagnosis of treatment-resistant depression). Coverage will usually require: documented prior treatment failures, psychiatric evaluation, and REMS-compliant administration at the clinic.

• Associated clinic/observation fees for Spravato when billed via the medical benefit are commonly covered if the drug administration itself is authorized.

Rarely covered / often self-pay:

• Off-label ketamine infusions or compounded intranasal ketamine for depression — most payers consider these experimental.
• Ancillary costs which insurers may deny separate coverage for, e.g., video production for therapy integration, non-medical amenities, or certain integration psychotherapy billed separately (coverage varies).
• Repeated maintenance infusions of ketamine without strong insurer policy support — even if a payer covers a trial, ongoing coverage is uncommon.

When one treatment might be preferred over the other

Choose Spravato when:

• The patient meets the FDA-approved indication (e.g., treatment-resistant depression) and insurance coverage is available or likely.
• You want a treatment with standardized dosing, safety protocols, and predictable billing/ prior-authorization pathways.
• Having REMS oversight and formalized clinic procedures is important for monitoring or liability reasons.

Choose ketamine (off-label) when:

• Spravato is not effective, not tolerated, or not accessible, and the patient can tolerate and afford an off-label option.
• The patient and provider prioritize flexibility in formulation or dosing (IV infusions, for example), or there is a specific clinical rationale for IV/IM ketamine (e.g., prior positive response).
• The clinic has experience and protocols for ketamine therapy, and the patient understands the out-of-pocket cost and risk.
  

Practical steps to check coverage & improve chances of approval

1. Verify benefit type (medical vs pharmacy): Ask the insurer whether Spravato is billed under the medical benefit (clinic administration) or pharmacy benefit, and confirm prior authorization requirements.
2. Gather documentation: clinical diagnosis, symptom severity scales (PHQ-9/GAD-7/etc,), history of prior antidepressant trials and outcomes, rationale for using Spravato/ketamine, and planned monitoring.
3. Prior authorization: for Spravato, this is typical. For ketamine, request a case-by-case review with thorough documentation if you want to pursue coverage.
4. Ask about in-network providers: in-network clinics mean lower patient out-of-pocket costs.
5. Get an itemized estimate: confirm whether the drug, facility fee, monitoring/observation time, and any follow-up visits are covered.
6. Appeal if denied: submit a peer-to-peer or medical necessity appeal with documented prior treatment failures and a clear treatment plan.