Clinical Policy: Esketamine (Spravato)
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Defines Meridian Health Plan medical necessity and prior authorization criteria for esketamine (Spravato) for treatment-resistant depression and MDD with acute suicidal ideation/behavior for Illinois Medicaid line of business.
No material clinical or coverage changes in this revision.
Coverage Criteria
Initial Therapy — Treatment-Resistant Depression
Covered when ALL of the following are met for Treatment-Resistant Depression (initial approval):
Approval duration: 6 months
Initial Therapy — MDD with Suicidal Ideation or Behavior
Covered when ALL of the following are met for Major Depressive Disorder with Suicidal Ideation or Behavior (initial approval):
Approval duration: 4 weeks (up to 23 nasal spray devices)
Continued Therapy
Continued therapy coverage criteria:
Approval duration: 12 months
Coverage criteria for esketamine (Spravato)
Covered when ALL of the following are met
See Dosage and Administration section for schedule specifics.
Coverage for non‑FDA indications is not authorized unless the requested use is specifically addressed by this policy or the provider supplies sufficient clinical documentation supporting safety and efficacy in accordance with Meridian’s off‑label use guidance (see policy CP.PMN.53). Requests for off‑label uses should include pertinent literature or evidence and meet the same standards for medical necessity as FDA‑approved indications; otherwise the request may be denied.
This policy’s covered indications include: Treatment‑Resistant Depression (TRD) and Major Depressive Disorder (MDD) with acute suicidal ideation or behavior when all indication‑specific criteria are met (see Initial Therapy sections). All approvals require documentation of baseline severity using validated scales (PHQ‑9, MADRS, or HAM‑D17) and the treatment plan submitted with prior authorization must demonstrate adherence to dosing, monitoring, and REMS program requirements.
Requests for continuation of therapy for members who previously met initial approval criteria or who are continuing treatment under continuity‑of‑care provisions must demonstrate ongoing clinical benefit (for TRD this is defined as ≥50% reduction in PHQ‑9 from baseline) and continued concomitant use of an oral antidepressant as specified in the continued therapy criteria. Continued approvals also require documentation of REMS enrollment, adherence to maintenance dosing schedules, and monitoring.
Spravato is not indicated for the treatment of bipolar depression and must not be used in patients with specified vascular or bleeding risks. Contraindications include aneurysmal vascular disease or arteriovenous malformation, a history of intracerebral hemorrhage, and hypersensitivity to esketamine, ketamine, or any excipient. These contraindications should be verified in the medical record prior to authorization.
Spravato carries boxed warnings that require monitoring for sedation and dissociation with at least 2 hours of post‑administration observation, and warnings about the potential for abuse and misuse. The product is available only through the Spravato REMS program; lack of REMS enrollment for the patient, administering site, or dispensing pharmacy may result in denial or noncompliance.
Additionally, requests for indications not addressed in this policy remain subject to denial unless the off‑label request is supported per Meridian’s off‑label policy (CP.PMN.53). Use in pediatric patients is not approved; Spravato is not indicated for pediatric use and antidepressants carry increased risk of suicidal thoughts in children and young adults.
Spravato is not approved as an anesthetic agent. The safety and effectiveness of esketamine when used as an anesthetic have not been established, and such uses are outside the scope of this coverage policy and will be considered not medically necessary.
Clinical trial data show limited evidence of benefit for geriatric patients with TRD aged 65–74. In the TRANSFORM‑3 study (ages 65–74) Spravato plus oral antidepressant did not achieve a statistically significant improvement versus placebo plus antidepressant on the primary efficacy endpoint (change in MADRS at Week 4). Safety outcomes in that trial were generally consistent with previous studies, but treatment‑emergent adverse events were frequent.
Because of the TRANSFORM‑3 results, the policy requires standard indication criteria and evidence of clinical benefit for geriatric members and notes that utility in the 65–74 subgroup may be limited. Providers should document expected benefit and monitor closely for adverse events; REMS enrollment and the required post‑dose observation period remain mandatory for older adults as for all patients.
For completeness, clinicians should recognize that Spravato’s dosing and monitoring requirements — induction/maintenance schedules (56 mg or 84 mg dosing options), dosing caps during induction, REMS‑certified administration setting, and ≥2 hour post‑dose monitoring — apply to geriatric patients in the same manner as younger adults and must be reflected in prior authorization documentation.
Coding
| 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 |
| S0013 | Esketamine, nasal spray, 1 mg |
Provider Actions and Requirements
Prior authorization requirement
Prior authorization is not required for members currently prescribed/taking Spravato when one of the following continuity conditions is met: member changed providers (including inpatient to outpatient), member changed insurance providers, or a prior authorization was previously approved and the new prescription only modifies dosage and/or frequency. For all other situations, prior authorization is required and initial approval criteria must be met.
- PA not required if member changed providers (including inpatient to outpatient).
- PA not required if member changed insurance providers.
- PA not required if prior PA approved and new prescription only modifies dose or dosage frequency.
Prior authorization: HCPCS codes and REMS enrollment
Include the applicable HCPCS codes and document REMS enrollment on the prior authorization. Use HCPCS G2082 for administrations up to 56 mg, G2083 for administrations greater than 56 mg, and S0013 for the product (Esketamine, nasal spray, 1 mg). Ensure dosing (56 mg or 84 mg options) and that the healthcare setting and patient are enrolled in the Spravato REMS are documented.
- HCPCS: G2082 — up to 56 mg administration (includes 2-hour post-administration observation).
- HCPCS: G2083 — greater than 56 mg administration (includes 2-hour post-administration observation).
- HCPCS: S0013 — Esketamine, nasal spray, 1 mg.
- Document Spravato REMS enrollment of the healthcare setting and patient.
Required prior therapy
For Treatment-Resistant Depression prior authorization requests must document failure of two antidepressants from at least two different classes each used for ≥8 weeks at therapeutic doses, and failure of two augmentation therapies each used ≥4 weeks unless contraindicated or not tolerated.
- Antidepressant trials: ≥2 agents from different classes (e.g., SSRI, SNRI, TCA, bupropion, mirtazapine) used ≥8 weeks each.
- Augmentation trials: ≥2 strategies (second-generation antipsychotic, lithium, thyroid hormone, buspirone) used ≥4 weeks each.
Combination with oral antidepressant
Spravato must be administered in conjunction with an oral antidepressant for TRD and MDD with suicidal ideation/behavior per the policy. Document concurrent oral antidepressant therapy at initiation and during ongoing therapy.
- Induction and maintenance dosing are specified with Spravato given alongside an oral antidepressant.
- For TRD, member must be stabilized on an oral antidepressant at least two weeks (not one previously failed).
Documentation requirement
Submit supporting clinical documentation with the prior authorization: office chart notes, lab results, or other clinical information that demonstrates the member meets all approval criteria.
- Include records that verify diagnosis, prior therapy history, baseline rating scale scores, and REMS enrollment as applicable.
Depression rating scales and response documentation
Document baseline and follow-up depression rating scales and treatment response: baseline PHQ-9 (for TRD baseline must be ≥15 within 4 weeks), and as applicable MADRS or HAM-D17. For continued therapy, provide evidence of response such as ≥50% reduction in PHQ-9 from baseline.
- Baseline PHQ-9 ≥15 within prior 4 weeks for TRD.
- MADRS ≥20 or HAM-D17 ≥17 may be used for MDD with suicidality.
- Continued therapy requires ≥50% reduction in PHQ-9 from baseline to show response.
Non‑FDA indications — off‑label requests handling
Requests for indications that are not FDA‑approved and are not addressed in this policy may be denied unless sufficient documentation of efficacy and safety is provided per the Off‑Label Use policy (CP.PMN.53) or other evidence of coverage documents. Include supportive literature or documentation when seeking coverage for non‑FDA indications.
- Non‑FDA indications must have sufficient documentation per off‑label use policy CP.PMN.53 (Medicaid) or evidence of coverage documents.
- If policy does not address the indication, provide efficacy and safety evidence to support the request.
REMS and monitoring noncompliance — denial risk and requirements
Failure to ensure REMS requirements or to monitor patients as required may result in denial or noncompliance. The healthcare setting and pharmacies must be REMS‑certified, patients must be enrolled in the Spravato REMS, Spravato must be administered under direct observation, and patients must be monitored for at least 2 hours after each administration.
- Healthcare settings and dispensing pharmacies must be certified in the Spravato REMS.
- Patients must be enrolled in the REMS and administered Spravato under direct observation.
- Monitor patients for at least 2 hours post‑administration; lack of REMS compliance or monitoring may trigger denial.
Background
Esketamine (Spravato) is a non‑competitive N‑methyl‑D‑aspartate (NMDA) receptor antagonist formulated as an intranasal spray. It is FDA‑approved for use in adults as an adjunct to an oral antidepressant for treatment‑resistant depression (TRD) and for adults with major depressive disorder with acute suicidal ideation or behavior, when administered in a REMS‑certified healthcare setting. Administration must be under direct healthcare professional supervision with monitoring for at least 2 hours after each dose, and Spravato is available only through the Spravato REMS program.
Definitions
Level of Care Criteria
Treatment Modalities
Visit Limits and Supply
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