CurrentBlue Cross Blue Shield - North CarolinaPolicy N/A

Esketamine (Spravato) Nasal Spray Coverage Criteria

Defines medical necessity, initial and continuation coverage criteria, dosing limits, administration and REMS requirements for esketamine nasal spray for Blue Cross NC members age 18+.

Policy Summary

PayerBlue Cross Blue Shield - North Carolina

PolicyEsketamine (Spravato) Nasal Spray Coverage Criteria

Policy CodePolicy N/A

Change TypeAdded REMS use-timing requirementclarified dosing/coding

Effective DateJan 1, 2026

Next Review DateN/A

Key ActionObtain prior authorization with documentation that initial or continuation criteria are met and confirm product will be used for the named patient within 14 days of receipt at a REMS-certified facility.

SourceLink

POLICY UPDATE CHANGES

Added requirement that the requested product be administered to the individual patient for whom it has been specifically prescribed and ordered, and within 14 days after receipt by the REMS-certified treatment facility.

Minor adjustments made to dosing table and coding description for clarity according to FDA label.

18+minimum patient age for coverage

MADRS ≥28required baseline depression severity

90 daysinitial approval duration

180 days

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Coverage Criteria for Esketamine (Spravato)

Dosing and Maximum Units

FDA-labeled dosing and programmatic maximums

TRD dosing (induction/maintenance): Induction (Weeks 1-4): Administer twice weekly starting Day 1 with 56 mg dose, may increase to 84 mg; Maintenance (Weeks 5-8): Administer once weekly (56 mg or 84 mg); Maintenance (Weeks 9+): Administer every 2 weeks or once weekly (56 mg or 84 mg), individualized to the least frequent dosing that maintains response. Evaluate evidence of benefit at the end of the 4-week induction phase to determine need for continued treatment.Maximum units: Initial 2,016; Continuation 4,032

See HCPCS mapping for billing

Esketamine nasal spray must not be administered in combination with ketamine of any formulation or route for the same indication. Requests that propose concurrent use of esketamine and ketamine for the same clinical indication are excluded from coverage and are at risk for denial.

For initial medical necessity, the patient must have baseline depression severity of ≥ 28 on the MADRS or a comparable standardized rating scale that reliably measures depressive symptoms. Treatment initiation when baseline severity is below this threshold does not meet initial medical necessity criteria.

Billing Codes and Code-related Criteria

Applicable HCPCS codes and descriptionsHCPCS

S0013	Esketamine nasal spray drug HCPCS code (drug supplied/dispensed)
G2082	Visit with provision of up to 56 mg esketamine nasal self-administration including 2 hours observation
G2083	Visit with provision of greater than 56 mg esketamine nasal self-administration including 2 hours observation

inv-07: Baseline MADRS score — threshold value displayed

Baseline MADRS threshold≥ 28 on the Montgomery‑Åsberg Depression Rating Scale (MADRS) or comparable standardized depression rating

PurposeRequired at initiation to meet initial medical necessity for esketamine therapy

Alternative scoringA comparable standardized rating scale that reliably measures depressive symptoms may be used

Prior Authorization, Documentation, and Billing Requirements

Prior Authorization

Prior Authorization & Coding

Prior authorization is required for esketamine (Spravato) therapy. Submit requests using the combined G-codes when the drug is supplied and administered at the same site: G2082 (up to 56 mg, includes 2-hour post‑administration observation) or G2083 (greater than 56 mg, includes 2-hour post‑administration observation). If the drug is dispensed by a different site (e.g., specialty pharmacy) than the administration site, submit S0013 for the drug and the appropriate E/M CPT code for the administration/monitoring visit. Ensure the REMS-certified facility administers the dose within 14 days of receipt and that dosing/quantity requested is within FDA‑labeled limits.

Use combined G-codes (G2082/G2083) when drug is supplied/dispensed AND administered with monitoring at the same site.
If supply and administration occur at separate sites, bill S0013 for the drug and the appropriate E/M CPT code for the service.
Ensure REMS-certified facility administers within 14 days of receipt.

Documentation Required

Prior Antidepressant Trials Required

Clinical Background

Esketamine nasal spray (Spravato®) is FDA-approved for adults with treatment-resistant depression and for depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior when used with an oral antidepressant as specified. Administration must occur under direct supervision at a treatment facility certified through the Spravato REMS program, with observation per the REMS requirements and programmatic dosing schedules. For TRD, the FDA-labeled dosing includes an induction phase (Weeks 1–4) of twice-weekly administration starting at 56 mg with optional increase to 84 mg, followed by maintenance dosing (Weeks 5–8) once weekly (56 mg or 84 mg) and thereafter every 2 weeks or once weekly individualized to the least frequent dosing that maintains response. Evidence of therapeutic benefit should be assessed at the end of the 4‑week induction phase. Billing and supply are reflected by HCPCS codes S0013, G2082, and G2083.

Key Definitions

inv-13: TRD — definition entry (treatment-resistant depression)

DefinitionTreatment‑resistant depression (TRD): Major depressive disorder with inadequate response (≤25% improvement) in the current episode to at least two antidepressants from at least two different classes at adequate dose and duration (typically 6 weeks).

Applicable populationAdults (age ≥ 18) with MDD meeting TRD criteria

Policy implicationDocumentation of ≥2 antidepressant trials from ≥2 classes with inadequate response is required for TRD coverage

inv-14: REMS — REMS-certified administration requirement

REMS requirementPrescribed dose must be administered under direct supervision at a treatment facility certified through the Spravato (esketamine) REMS program

Use timeframe

Level of Care / Setting

Outpatient

Outpatient/clinic administration admission: Patient eligible for outpatient supervised administration at a REMS-certified facility when initial criteria are met (age >= 18, qualifying diagnosis, required prior antidepressant trials for TRD or oral antidepressant for suicidal indication, baseline MADRS >= 28).

Continued outpatient therapy: Continued outpatient treatment permitted if continuation criteria are met including >=50% reduction in depressive symptoms from baseline on a standardized scale and ongoing supervised administration at a REMS-certified facility with product used for the prescribed individual within 14 days of receipt.

Treatment Modalities

Esketamine nasal spray (Spravato)

Esketamine modality: Administration under direct supervision at a REMS-certified facility with observation per REMS requirements. Used in conjunction with an oral antidepressant for the suicidal indication and either as monotherapy (where FDA allows for TRD) or with an oral antidepressant for TRD per FDA label. Not approved as an anesthetic and not to be combined with ketamine for the same indication.

Supervised Administration and Visit Billing

inv-17: Supervised administration visits billed with G2082/G2083 or S0013 + E/M as applicable — dosing schedule

Induction dosing frequencyTwice weekly during induction (Weeks 1–4), starting Day 1 at 56 mg and may increase to 84 mg

Maintenance frequency (Weeks 5–8)Once weekly (56 mg or 84 mg)

Maintenance frequency (Weeks 9+)Every 2 weeks or once weekly (56 mg or 84 mg), individualized to the least frequent dosing that maintains response

Billing guidanceSupervised administration visits billed with G2082/G2083 or S0013 plus appropriate E/M as applicable per HCPCS descriptions

Documentation Required

Required Documentation for Authorization

Include the following baseline and ongoing documentation with the prior authorization request: patient age (≥18), diagnosis (TRD or MDD with suicidal ideation/behavior), confirmation of MDD subtype where applicable, baseline depression severity score (MADRS ≥28 or comparable scale), details of prior antidepressant history (names, classes, doses, durations, responses), planned concomitant oral antidepressant, REMS facility documentation, contraindications check (e.g., aneurysmal vascular disease, intracerebral hemorrhage), and proposed dosing schedule within FDA labelling. For continuation requests, include baseline and on‑therapy standardized rating scale scores showing ≥50% reduction in symptoms compared to baseline.

Patient age ≥ 18 documented.
Diagnosis: TRD (with MDD confirmation) or MDD with imminent suicidal ideation/behavior.
Baseline MADRS ≥ 28 (or comparable scale) at initiation; for continuation, ≥50% reduction from baseline.
Detailed prior antidepressant history with at least two adequate trials from two classes.
Confirmation patient will continue an oral antidepressant while receiving esketamine.
Evidence REMS‑certified facility involvement and supervised administration.
Documentation that requested dose and quantity are within FDA‑labeled dosing and maximum units.