Blue Cross Blue Shield MA Esketamine Prior Auth

Coverage Criteria for Esketamine and IV Ketamine

Initial Therapy

Covered for Treatment-Resistant Depression when ALL of the following are met:

TRD initial therapy criteria: Individual is ≥18 years old

[[chunk 6]]

DSM-5 diagnosis: Meets DSM-5 criteria for a major depressive episode by a structured clinical interview

[[chunk 6]]

Severity: Current depressive episode is severe with MADRS ≥28 OR HAM-D ≥17MADRS ≥28 or HAM-D ≥17

[[chunk 6]]

Prior treatment failure: Inadequate response to four antidepressant agents from at least two different classes AND at least one augmentation agent trial

[[chunk 6]]

Adequate trial definition: Each antidepressant trial ≥6 weeks at generally accepted doses with ≥80% adherence≥6 weeks; ≥80% adherence

[[chunk 6]]

Concurrent therapy: Esketamine or IV ketamine to be administered in conjunction with an oral antidepressant

[[chunk 6]]

Contraindications absent: No hypersensitivity to esketamine, ketamine, or excipients; not pregnant or breastfeeding; no aneurysmal vascular disease/AVM; no intracerebral hemorrhage; no current episode of delirium

[[chunk 6]]

Setting and monitoring: Administration in a provider office or hospital setting with monitoring by a specialist (e.g., psychiatrist)

[[chunk 6]]

Reauthorization / Continuation Therapy

Reauthorization (Continuation) when ALL of the following are met:

Improvement: Individual has had improvement in depression symptoms as evaluated with an appropriate depression rating scale (e.g., PHQ-9, CUDOS, QIDS-SR16, MADRS, HAM-D)

[[chunk 7]]

Concurrent therapy maintained: Esketamine or IV ketamine continued in conjunction with an oral antidepressant

[[chunk 7]]

Substance use disorder: Individuals with a substance use disorder have remained in remission (complete abstinence)

[[chunk 7]]

Contraindications absent: No development of FDA-labeled contraindications (e.g., aneurysmal vascular disease, intracerebral hemorrhage, hypersensitivity)

Acute Suicidal Ideation Therapy

Covered for Major Depressive Disorder with acute suicidal ideation when ALL of the following are met:

Age and setting: Individual is ≥18 years and currently hospitalized and at imminent risk for suicide

[[chunk 9]]

Imminent risk documented: Structured assessment indicates imminent suicide risk AND clinical confirmation by a mental health professional/psychiatrist

[[chunk 9]]

Severity: Current depressive episode is moderate or severe with MADRS ≥28 OR HAM-D ≥17MADRS ≥28 or HAM-D ≥17

[[chunk 9]]

Concurrent standard-of-care:

Esketamine (Spravato) nasal spray and intravenous ketamine are not authorized when the individual has any FDA-labeled contraindication or other exclusion listed in the policy. Specifically, authorization is denied for members with hypersensitivity to esketamine, ketamine, or any excipients, those who are pregnant or breastfeeding, individuals with aneurysmal vascular disease or arteriovenous malformation (including thoracic/abdominal aorta, intracranial and peripheral arterial vessels), or a history of intracerebral hemorrhage. Current delirium is also an exclusion. For esketamine nasal spray, the product must be used consistent with the FDA label and the Spravato REMS program; presence of FDA REMS contraindications precludes authorization.

Requests that do not meet all listed clinical criteria for treatment-resistant depression or for major depressive disorder with acute suicidal ideation are not supported as medically necessary unless an approved clinical exception (letter of medical necessity/individual consideration) is provided. Providers should submit clinical documentation that supports medical necessity (structured clinical interview for DSM-5, depression rating scales, prior treatment history) and, when criteria are unmet, include a clear rationale in the request for a clinical exception.

Coding and Severity Thresholds

Esketamine HCPCS codesHCPCSCovered

G2082	Office or other outpatient visit for evaluation and management of an established patient that requires supervision 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 evaluation and management of an established patient that requires supervision and provision of greater than 56 mg esketamine nasal self-administration; includes 2 hours post-administration observation

Relevant ICD-10 diagnosis codesICD-10

F33.2

Major Depressive Disorder; Severe

MADRS / HAM-D severity thresholds

Scale namesMontgomery-Asberg Depression Rating Scale (MADRS) or Hamilton Rating Scale for Depression (HAM-D)

ApplicationApplies to both treatment-resistant depression and MDD with acute suicidal ideation per coverage criteria

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for esketamine (Spravato) and intravenous ketamine for treatment‑resistant depression. Initial requests are authorized for up to 28 days. Use Authorization Manager to submit initial authorization requests, attach required clinical documentation, and check case status. For out-of-network providers, fax requests to 1-888-641-5199.

Initial authorizations: up to 28 days
Submission method: Authorization Manager (available 24/7); out-of-network fax 1-888-641-5199
Enter servicing provider NPI (surgeon/provider) and facility NPI where services are performed

Step Therapy

Step Therapy / Prior Treatment Requirement

Patient must have an inadequate response to an adequate trial of four antidepressant agents from at least two different classes and at least one augmentation trial before esketamine or IV ketamine will be authorized.

Inadequate response to four antidepressant agents from at least two different classes (examples: SSRI, SNRI, tricyclic, bupropion, mirtazapine)

Background

Esketamine nasal spray (Spravato) and intravenous ketamine are treatment options for adults with treatment-resistant major depressive episodes and for adults with major depressive disorder complicated by acute suicidal ideation. Use for treatment-resistant depression requires documentation of a DSM-5 major depressive episode and severity meeting standardized scales (e.g., MADRS ≥ 28 or HAM-D ≥ 17), plus failure of prior therapies. Specifically, patients must have had inadequate response to four antidepressant agents from at least two different classes and at least one adequate augmentation trial, with each antidepressant trial generally ≥6 weeks at accepted doses and ≥80% adherence. Esketamine or IV ketamine must be administered in a monitored provider office or hospital setting under the supervision of a specialist (for esketamine, consistent with the FDA label and REMS requirements) and is given in conjunction with an oral antidepressant. For acute suicidal ideation, use is intended for adults who are hospitalized and documented to be at imminent suicide risk by structured assessment and clinician confirmation; treatment must be combined with standard-of-care therapies and monitored appropriately.

Definitions and REMS

Treatment-resistant depression (TRD) definition

DefinitionFailure to respond to at least four antidepressant agents from at least two different classes plus at least one augmentation agent trial

Classes specifiedExamples include SSRIs, SNRIs, tricyclics, bupropion, or mirtazapine

REMS and FDA label compliance

REMS requirementEsketamine (Spravato) must be used consistent with the FDA-approved label and the Spravato Risk Evaluation and Mitigation Strategy (REMS) program requirements

ContraindicationsMust not have FDA-labeled contraindications to esketamine (e.g., aneurysmal vascular disease, intracerebral hemorrhage, hypersensitivity)

Prescriber and settingPrescriber should be a specialist or consult one; administration in provider office or hospital with specialist monitoring

Level of Care

Outpatient or Inpatient (per indication)

Level of care applicability: Treatment may be provided in outpatient or inpatient settings per indication: TRD typically outpatient; acute suicidal ideation requires hospitalization and documented imminent risk

[[chunk 9],[6]]

Monitoring and setting: Administration must occur in a provider office or hospital setting with monitoring by a specialist (e.g., psychiatrist)

[[chunk 7],[6]]

Authorization periods: Initial requests authorized up to 28 days; reauthorization may be granted for up to 1 year when continuation criteria are metinitial 28 days; reauthorization up to 1 year

[[chunk 6],[7]]

Treatment Modalities Covered

Esketamine nasal spray (Spravato) or Intravenous Ketamine

Modality selection: Esketamine nasal spray (Spravato) OR Intravenous Ketamine may be used as the treatment modality

[[chunk 6],[9]]

Concurrent oral therapy requirement: Esketamine or IV ketamine must be administered in conjunction with an oral antidepressant (and, for acute suicidality, may be combined with atypical antipsychotic or mood stabilizer as indicated)

[[chunk 6],[9]]

REMS and FDA contraindications for Spravato: Esketamine (Spravato) must be used consistent with the FDA-approved label and Spravato REMS program and must not be used if FDA-labeled contraindications are present

[[chunk 7],[9]]

Treatment Session Limits and Authorization Durations

Treatment session authorization limits

Authorization period (initial)Initial authorizations: up to 28 days

Reauthorization periodReauthorization/continuation: up to 1 year when reauthorization criteria are met

Service specificationNumber of treatment sessions requested must be specified on the authorization request

Applies toEsketamine (Spravato) nasal spray and intravenous ketamine treatment sessions

OpenPayer

Esketamine Nasal Spray (Spravato) and Intravenous Ketamine for Mental Health Conditions Prior Authorization

Coverage Criteria for Esketamine and IV Ketamine

Coding and Severity Thresholds

Provider Actions, Prior Authorization, and Documentation

Background

Definitions and REMS

Level of Care

Treatment Modalities Covered

Treatment Session Limits and Authorization Durations