ModifiedmhnPolicy CP.PMN.199

Esketamine (Spravato) — Coverage and prior authorization criteria

Coverage and prior authorization criteria for esketamine (Spravato) for treatment-resistant depression and major depressive disorder with acute suicidal ideation/behavior for members of Centene-affiliated health plans (Commercial, HIM/ICHRA, Medicaid).

Policy Summary

Payermhn

PolicyEsketamine (Spravato) — Coverage and prior authorization criteria

Policy CodePolicy CP.PMN.199

Change TypeMaterial revisions to TRD requirements, approval durations, device limits, and HCPCS coding

Effective Date06.01.19

Next Review Date

Key ActionSubmit prior authorization with documentation showing diagnostic criteria, severity scores, prior medication/augmentation failures, and REMS enrollment/monitoring.

SourceLink

POLICY UPDATE CHANGES

Revised TRD requirement for failure of antidepressant augmentation therapies from two to one and revised continued approval duration from 6 months to 12 months; updated HCPCS code.

Revised TRD initial approval duration to 3 months and up to 48 nasal spray devices and added ICHRA line of business.

Updated HCPCS coding: added J0013 (Esketamine) and removed S0013.

Reduced trial duration of antidepressants for TRD from at least 8 weeks to 4 weeks.

3 monthsinitial approval period for TRD

48maximum nasal spray devices (TRD initial)

168 mgmax induction weekly dose

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Coverage Criteria

Initial Therapy - Treatment-Resistant Depression

Covered when ALL of the following are met:

TRD Initial Approval: 1. Diagnosis of treatment‑resistant depression (TRD). 2. Prescribed by or in consultation with a psychiatrist. 3. Age ≥ 18 and < 65 years. 4. Documented baseline PHQ‑9 score ≥ 15 within the previous 4 weeks. 5. Member meets one of the following (a or b): (a) Request is for a member in a state with limitations on step therapy in certain mental health settings; OR (b) For all other requests, both (i) failure of TWO antidepressants from at least two different classes each used ≥ 4 weeks at therapeutic doses (unless contraindicated or intolerant) AND (ii) failure of ONE antidepressant augmentation therapy used ≥ 4 weeks (unless contraindicated or intolerant). 6. Either no prior history of Spravato OR documentation of prior positive response to Spravato defined as ≥ 50% reduction in PHQ‑9. 7. Dose limits not exceeded during induction and maintenance: induction ≤ 168 mg/week (6 devices) and ≤ 24 nasal spray devices for 4 weeks; maintenance ≤ 84 mg/week (3 devices) and ≤ 24 devices for 8 weeks.

Approval duration: 3 months (up to 48 nasal spray devices)

Initial Therapy - MDD with Suicidal Ideation or Behavior

Covered when ALL of the following are met:

MDD with Suicidality Initial Approval: 1. Diagnosis of major depressive disorder (MDD). 2. Prescribed by or in consultation with a psychiatrist. 3. Age ≥ 18 years. 4. Prescribed in combination with initiation or optimization of an oral antidepressant. 5. Member is recently (within 5 days) discharged from or currently in acute/subacute inpatient care for suicidality. 6. Either no prior history of Spravato OR documentation of prior positive response to Spravato. 7. Severity meets one of: MADRS ≥ 20 OR HAMD ≥ 17 OR PHQ‑9 ≥ 15. 8. Dose does not exceed 168 mg/week and 24 nasal spray devices for 4 weeks.

Re‑authorization not permitted; members must meet initial approval criteria

Continuation Therapy

Covered for continuation when ALL of the following are met:

TRD Reauthorization: 1. Member is currently receiving Spravato via the Centene benefit or documentation supports member has received Spravato for at least 30 days. 2. Member is responding positively with ≥ 50% reduction in PHQ‑9 score from baseline. 3. If request is for a dose increase, the new dose does not exceed 84 mg (3 nasal spray devices) per week.

Approval duration: 12 months

Coverage criteria for Esketamine

Covered when ALL of the following are met for TRD or MDD with acute suicidal ideation/behavior as indicated:

Indication and dosing: Patient has TRD or depressive symptoms in MDD with acute suicidal ideation/behavior and will receive esketamine per indicated dosing: Induction—56 mg or 84 mg nasally twice weekly for weeks 1–4; Maintenance—as specified thereafter (56 mg or 84 mg once weekly for weeks 5–8 then every 2 weeks or once weekly thereafter as clinically indicated).

Indication‑specific dosing per Section V

REMS and monitoring: Administration must occur in a REMS‑certified healthcare setting; patient must be enrolled in the Spravato REMS; administration must be directly observed and the patient monitored for at least 2 hours post administration for sedation, dissociation, and respiratory depression.2 hours observation

Boxed warnings and REMS requirements

Prior treatment requirements: For TRD, prior failure of required antidepressant therapy and failure of one antidepressant augmentation therapy used ≥ 4 weeks unless contraindicated; trial durations reduced from 8 to 4 weeks per 2022 update. State redirection exceptions may apply.

Non‑FDA approved indications for Spravato that are not specifically addressed in this policy are not authorized unless the provider supplies sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace/ICHRA), or CP.PMN.53 (Medicaid), or unless coverage is supported by the member’s evidence of coverage document.

Contraindications to Spravato include: aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels) or arteriovenous malformation; a history of intracerebral hemorrhage; and hypersensitivity to esketamine, ketamine, or any excipients. Note that Spravato is not indicated for bipolar depression.

The effectiveness of Spravato in preventing suicide or in reducing suicidal ideation or behavior as a demonstrated preventive measure has not been demonstrated. Spravato does not replace the need for hospitalization when clinically indicated, and it is not approved as an anesthetic agent.

Spravato is only available through the Spravato REMS. Administration must occur in healthcare settings certified in the REMS program, patients must be enrolled in the REMS, and dosing must be administered under direct observation with monitoring by a healthcare provider for at least 2 hours after administration. Dispensing or administration outside REMS‑certified settings or without the required monitoring (including dispensing by non‑certified pharmacies to non‑certified settings) is not compliant with REMS requirements and may be considered non‑covered.

Coding and Measurement

Relevant visit and drug HCPCS/CPT codesmixed

G2082	Office or other outpatient visit for the evaluation and management of an established patient that requires the supervision of a physician or other qualified health care professional and provision of up to 56 mg of esketamine nasal self-administration, includes 2 hours post administration observation.
G2083	Office or other outpatient visit for the evaluation and management of an established patient that requires the supervision of a physician or other qualified health care professional and provision of greater than 56 mg esketamine nasal self-administration, includes 2 hours post administration observation.
J0013	Esketamine, nasal spray, 1 mg

Depression severity scales — thresholds

PHQ-9 thresholdPHQ-9 ≥ 15 (baseline within previous 4 weeks)

MADRS thresholdMADRS ≥ 20

HAMD (HAM-D17) thresholdHAMD ≥ 17

Dosing limits — induction

Maximum induction weekly dose≤ 168 mg per week (6 nasal spray devices)

Maximum induction device limit (4 weeks)≤ 24 nasal spray devices for 4 weeks

Induction period

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required for TRD

Prior authorization is required for treatment-resistant depression (TRD). Requests must include documentation that the member meets diagnostic, prescriber, age, severity, prior medication and augmentation requirements. For TRD, initial approval duration is 3 months (up to 48 nasal spray devices). Prior authorization will be denied or redirected for indications that are non‑FDA approved unless sufficient off‑label documentation is provided per applicable off‑label policies.

TRD initial approval: 3 months, up to 48 nasal spray devices
HCPCS code updates noted in policy history (see Coding Implications)

Step Therapy

Step Therapy / Medication-Failure Requirements and Redirection Bypass

For TRD requests outside of states with step‑therapy redirection limits, the member must have failed two antidepressants from at least two different classes, each used ≥ 4 weeks at therapeutic doses, and failed ONE antidepressant augmentation therapy used ≥ 4 weeks (unless contraindicated). In states with limitations on step therapy in certain mental health settings (see Appendix F), a single‑drug redirection bypass may apply per state-specific rules.

Background

Esketamine (Spravato) is an N‑methyl‑D‑aspartate (NMDA) receptor antagonist FDA‑approved for adults with treatment‑resistant depression (TRD) and for adults with major depressive disorder (MDD) who have acute suicidal ideation or behavior, used in conjunction with an oral antidepressant as indicated. Due to risks of sedation, dissociation, respiratory depression, and potential for abuse, Spravato is distributed only through the Spravato REMS, and patients must be monitored for at least 2 hours post‑administration. The effectiveness of Spravato to prevent suicide has not been established.

Definitions

Treatment-Resistant Depression (TRD) — policy definition

Policy definition of TRDAdults with a diagnosis of treatment‑resistant depression (TRD) meeting prior treatment failure requirements as specified in the criteria (failure of two antidepressants from ≥2 classes each ≥4 weeks and failure of one augmentation therapy used ≥4 weeks, unless state exceptions apply)

Age requirementAge ≥ 18 and < 65 years for TRD initial approval (see Appendix E)

Severity requirementBaseline PHQ-9 ≥ 15 within previous 4 weeks

REMS — Spravato REMS requirements

REMS program requirementSpravato is available only through the Spravato REMS; healthcare settings and pharmacies must be certified in the REMS program

Administration and dispensing

Level of Care Criteria

Treatment Modalities

Esketamine (Spravato)

Spravato use: Used as monotherapy or in conjunction with an oral antidepressant for TRD; used in conjunction with an oral antidepressant for MDD with acute suicidal ideation/behavior; Spravato is not an anesthetic and its effectiveness in preventing suicide has not been demonstrated.

Esketamine nasal spray (Spravato)

Induction dosing: Induction for TRD and for MDD with acute suicidal ideation/behavior: administer 56 mg or 84 mg nasally twice per week for weeks 1–4.weeks 1–4 twice weekly

Section V dosing

Monitoring and REMS: Administration must occur in a REMS‑certified setting with patient enrollment in REMS; monitor patients for at least 2 hours after administration for sedation, dissociation, and respiratory depression. Pharmacies and administering sites must be REMS certified.

Visit Limits and Quantity Limits

Esketamine nasal spray devices — initial authorization limits

TRD initial authorization device allowance (2Q2026)Up to 48 nasal spray devices for TRD initial authorization (approval duration: 3 months)

Previous device limits referencedPrior criteria limited to 24 devices for 4 weeks during induction and 24 devices for eight weeks of maintenance (see dosing limits)

Policy revision note2Q2026 revision updated TRD initial approval duration to 3 months and device limit to up to 48 devices