mhn Esketamine (Spravato) Coverage Update

Coverage Criteria for Esketamine (Spravato)

Initial Therapy

Initial Approval — Covered when ALL of the following are met for each indication group

A. Treatment-Resistant Depression (TRD) initial criteria: 1. Diagnosis of 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) request is for a member in a state with limitations on step therapy in certain mental health settings OR (b) failure of TWO antidepressants from at least two different classes each used ≥ 4 weeks AND failure of ONE antidepressant augmentation therapy used ≥ 4 weeks (second-generation antipsychotic, lithium, thyroid hormone, or buspirone), unless contraindicated or not tolerated; 6. Either no prior history of Spravato OR documentation of prior positive response to Spravato (≥ 50% reduction in PHQ-9); 7. Dose during the 4-week induction does not exceed both: (a) 168 mg (6 devices) per week AND (b) 24 nasal spray devices for four weeks.

B. Major Depressive Disorder with Suicidal Ideation or Behavior initial criteria: 1. Diagnosis of MDD; 2. Prescribed by or in consultation with a psychiatrist; 3. Age ≥ 18 years; 4. Spravato prescribed in combination with initiation or optimization of oral antidepressant therapy; 5. Member is recently (within the last 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. Baseline severity meets one of: MADRS ≥ 20 OR HAMD (HAM-D) ≥ 17 OR PHQ-9 ≥ 15; 8. Dose during the 4-week induction does not exceed both: (a) 168 mg (6 devices) per week AND (b) 24 nasal spray devices for four weeks.

Continuation / Re-authorization

Re-authorization / Continuation criteria

A. TRD continuation: 1. Member is currently receiving Spravato via the benefit or has received Spravato for at least 30 days with documentation; 2. Positive response defined as ≥ 50% reduction in PHQ-9 score compared to baseline; 3. If request is for a dose increase, the new dose must not exceed 84 mg (3 nasal spray devices) per week.

Approval duration: 12 months.

B. MDD with Suicidal Ideation or Behavior continuation: Re-authorization is not permitted. Members requiring ongoing therapy must meet initial approval criteria for a new authorization.

Approval duration: Not applicable.

Initial therapy — TRD specific

Covered when criteria for indication and administrative requirements are met

TRD indication initial therapy (as revised): TRD indication allows use as monotherapy or in conjunction with an oral antidepressant. TRD initial criteria updated to permit monotherapy; requirement for failure of antidepressant augmentation therapies reduced to ONE (2Q 2025); initial authorization aligned to 4-week induction and initial approval maximum revised to allow up to 24 nasal spray devices per 4-week induction.see dosing and limits

Refer to dosing schedule for induction/maintenance and to prior authorization documentation requirements.

Continued therapy — TRD

Continuation/maintenance therapy criteria

Continued therapy: Continued approval duration for TRD revised to allow up to 12 months authorization for members responding to therapy (response defined as ≥ 50% reduction in PHQ-9). Prior requirement for mandatory combination with an oral antidepressant for continued TRD therapy was removed in updates; monitor clinical response with standardized rating scales.duration: 12 months

If dose escalation is requested, do not exceed 84 mg (3 devices) per week.

Administration/Monitoring

Administration and monitoring requirements

Administration/REMS: Spravato must be dispensed and administered only in healthcare settings certified in the Spravato REMS program; patients must be enrolled in REMS; administration must be by or under the direct observation of a healthcare provider; monitor patients for at least 2 hours after each administration for sedation, dissociation, and respiratory depression; pharmacies must be REMS-certified and dispense only to certified healthcare settings.2 hours observation

Consider risks of abuse and monitor for signs of misuse; Spravato is not approved for pediatric patients.

Requests for Spravato to treat indications that are not FDA-approved and are not specifically addressed in this policy will not be authorized unless the provider supplies sufficient documentation of efficacy and safety consistent with the payer's off-label use policies. See off-label use policy references: CP.CPA.09 (commercial), HIM.PA.154 (health insurance marketplace), and CP.PMN.53 (Medicaid) for requirements and acceptable evidence to support non‑FDA uses.

Spravato is not indicated for the treatment of bipolar depression and should not be used for that diagnosis. Contraindications include: history of aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels) or arteriovenous malformation; prior intracerebral hemorrhage; and hypersensitivity to esketamine, ketamine, or any excipients. The product carries boxed warnings for risks of sedation, dissociation, respiratory depression, and potential for abuse/misuse; these safety concerns inform limits on use and monitoring.

Spravato use in pediatric patients is not approved. The labeling notes an increased risk of suicidal thoughts and behaviors in pediatric and young adult patients treated with antidepressants; all antidepressant‑treated patients should be closely monitored for clinical worsening and emergence of suicidal ideation or behavior. Because Spravato is not FDA‑approved for pediatric use, requests for patients <18 years require off‑label justification per the payer's off‑label policies.

Coding and Dosing Details

Coding referencedHCPCS

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

PHQ-9 baseline threshold

PHQ-9 baseline requirementBaseline PHQ-9 score ≥ 15 within the previous 4 weeks

Use case in indicationsRequired for TRD initial approval and acceptable as one of the baseline scores for MDD with suicidal ideation/behavior

PurposeDocument severity (moderately severe major depression) for eligibility and to measure treatment response

MADRS baseline threshold

MADRS baseline requirementMADRS score ≥ 20

Clinical roleReferenced as a baseline severity measure for MDD with suicidal ideation/behavior and TRD eligibility

Provider Actions, Documentation, and Billing

Prior Authorization

Prior Authorization Required

Prior authorization (PA) is required. Submit documentation demonstrating that the member meets all approval criteria for the requested indication; incomplete documentation or requests for non-covered indications may be denied.

PA must demonstrate member meets full clinical criteria for the requested indication.
Provide office chart notes, baseline and follow-up depression rating scale scores (PHQ-9, MADRS, or HAM-D17), prior treatment history, and prescriber specialty documentation.
Requests lacking required documentation or for non-covered indications per policy (see Diagnoses/Indications not authorized) are at high risk for denial.

Documentation Required

REMS and Monitoring Requirements

Providers must enroll and comply with the Spravato REMS program. Treatment and dispensing are restricted to certified healthcare settings and pharmacies; patients must be enrolled and directly observed during administration with monitoring for at least 2 hours post-dose.

Background

Esketamine nasal spray (Spravato) is an N-methyl D-aspartate (NMDA) receptor antagonist approved for adults with treatment‑resistant depression (TRD)—either as monotherapy or in conjunction with an oral antidepressant—and for adults with major depressive disorder (MDD) presenting with acute suicidal ideation or behavior when used alongside an oral antidepressant. Spravato is not an anesthetic and its use is restricted by a REMS program because of risks including sedation, dissociation, respiratory depression, and potential for abuse; administration must occur in REMS‑certified healthcare settings with direct observation and monitoring for at least 2 hours after each dose.

Definitions and Rating Scales

TRD definition as used in the policy

TRD definition in policyTreatment-resistant depression (TRD) defined as a diagnosis of TRD with required prior treatment failures per criteria (e.g., failed antidepressant trials and required augmentation failure), with TRD initial therapy dosing and administrative requirements applied

Age requirementApplies to adults aged ≥ 18 and < 65 years for TRD initial criteria

Prior therapy requirement (current policy revision note)Policy requires failure of two antidepressants from at least two classes and failure of one antidepressant augmentation therapy (revised to one augmentation failure in 2Q 2025 updates)

PHQ-9 definition/reference

PHQ-9 (term)Patient Health Questionnaire - 9 item (PHQ-9)

Use in policy

Level of Care and Setting Requirements

Inpatient-related initiation / Outpatient administration setting

Criteria regarding initiation location and setting

Inpatient-related initiation / Outpatient administration setting: For MDD with acute suicidal ideation or behavior, Spravato may be initiated for members recently (within 5 days) discharged from or currently in acute/subacute inpatient care and continued in outpatient certified REMS settings when prescribed in combination with initiation or optimization of an oral antidepressant; prescriber must be or consult a psychiatrist; baseline severity requirements apply.

Initial authorization duration aligns with induction (4 weeks).

Outpatient administration / Certified REMS setting

Certified REMS facility requirements for outpatient administration

Outpatient administration / Certified REMS setting: Outpatient administration is allowed only in REMS-certified healthcare settings; facility and staff must be enrolled/certified in the Spravato REMS program; patients must be monitored for at least 2 hours post-dose and the drug dispensed only to certified settings by certified pharmacies.

Treatment Modalities and Product References

Esketamine (Spravato)

Esketamine (Spravato) general treatment modality node

FDA approved uses: Spravato is indicated for TRD in adults (as monotherapy or adjunct to an oral antidepressant) and for depressive symptoms in adults with MDD with acute suicidal ideation or behavior when used in conjunction with an oral antidepressant; effectiveness in preventing suicide has not been demonstrated; Spravato is not approved as an anesthetic.

Follow indication-specific dosing and monitoring requirements.

Esketamine nasal spray (Spravato)

Esketamine nasal spray (Spravato) specific modality node

Esketamine nasal spray (Spravato) dosing and device limits: Induction for TRD: Weeks 1–4, administer 56 mg or 84 mg nasally twice weekly. Maintenance: Weeks 5–8 once weekly; Week 9 and after every 2 weeks or once weekly as clinically indicated. For MDD with acute suicidal ideation/behavior: 56 mg or 84 mg nasally twice weekly for 4 weeks in conjunction with an oral antidepressant. Maximum per-dose esketamine = 84 mg; each nasal spray device contains 28 mg; induction limits: not to exceed 168 mg/week and 24 devices per 4-week induction (per recent updates).

Visit Limits and Observation Time

G2082/G2083 office visit with esketamine administration — includes 2 hours post-administration observation per visit

G2082/G2083 visit descriptionG2082/G2083 are office/outpatient visit codes for esketamine administration that include up to 2 hours post-administration observation per visit

G2082 specificsG2082 covers provision of up to 56 mg esketamine nasal self-administration and includes 2 hours observation

G2083 specificsG2083 covers provision of greater than 56 mg esketamine nasal self-administration and includes 2 hours observation

Revision History

2026-01-06HCPCS update

HCPCS code J0013 (Esketamine, nasal spray, 1 mg) was added and S0013 was removed.

2025-05-25Annual review (2Q 2025)

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 and references.

2025-02-13RT4 update

Updated TRD indication to include monotherapy option; removed stabilization and mandatory future combination with an oral antidepressant for TRD initial therapy; removed requirement for combination with an oral antidepressant for TRD continued therapy; initial approval maximum adjusted to allow 24 nasal spray devices.

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Esketamine (Spravato) — Coverage Criteria