Currentsierra health and lifePolicy 2026D0069Q

Ketalar (Ketamine) and Spravato (Esketamine) — Coverage Criteria

Defines medical necessity, coverage criteria, and investigational exclusions for Spravato (esketamine) nasal spray and ketamine injections for UnitedHealthcare Commercial and Individual Exchange plans; affects providers prescribing or administering these agents for depression, suicidal ideation, anesthesia, and pain.

Policy Summary

Payersierra health and life

PolicyKetalar (Ketamine) and Spravato (Esketamine) — Coverage Criteria

Policy CodePolicy 2026D0069Q

Change TypeTemplate transfer and reference updates

Effective DateMay 1, 2026

Next Review DateN/A

Key ActionObtain prior authorization and document at least two failed antidepressant trials (each ≥ 8 weeks) and REMS enrollment before Spravato administration.

SourceLink

POLICY UPDATE CHANGES

Transferred content to shared policy template that applies to both UnitedHealthcare Commercial and Individual Exchange benefit plans.

Updated References section to reflect the most current information.

≥2antidepressant trials required for TRD

12 monthsmax authorization period

J0013, J3490listed drug HCPCS codes

REMSREMS monitoring requirement

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05/01/2026policy revision date

Coverage Criteria

Initial Therapy (TRD)

Covered when ALL of the following are met

Spravato for TRD - Initial: Diagnosis of major depressive disorder (treatment-resistant) according to DSM by a mental health professional; baseline clinical assessment score documented on at least one of: BDI, HAMD, MADRS, PHQ-9, or QIDS; history of failure of at least two different antidepressants or treatment regimens (each >= 8 weeks; document medication, date, duration); provider and/or healthcare setting certified in the Spravato REMS program; prescribed by or in consultation with a psychiatrist; Spravato dosing in accordance with FDA-approved labeling; initial authorization up to 12 months.all conditions required

Submit medical records documenting baseline scoring and prior antidepressant trials.

Continuation of Therapy (TRD)

Covered when ALL of the following are met

Spravato for TRD - Continuation: Documentation of remission or positive clinical response to Spravato with recent (within last month) assessment scores demonstrating improvement on BDI, HAMD, MADRS, PHQ-9, or QIDS; provider and/or healthcare setting REMS certified; prescribed by or in consultation with a psychiatrist; Spravato dosing in accordance with FDA-approved labeling; reauthorization up to 12 months.all conditions required

Submit recent assessment scores and maintenance of REMS certification.

Spravato — MDD with acute suicidal ideation/behavior

Covered when ALL of the following are met

Spravato for MDD with acute SI/behavior - Initial: Diagnosis of major depressive disorder according to DSM by a mental health professional; patient is experiencing acute suicidal ideation or behavior; patient will receive Spravato in conjunction with a newly initiated or optimized oral antidepressant; provider and/or healthcare setting certified in the Spravato REMS program; Spravato dosing in accordance with FDA-approved labeling; initial authorization up to 12 months.all conditions required

In ASPIRE trials Spravato was given with comprehensive standard of care including newly initiated or optimized oral antidepressant and initial inpatient care as indicated.

Ketamine injection — Covered and Not Medically Necessary

Covered when ALL of the following are met (anesthesia indications) or Not Covered for specified indications

Ketamine injection - Covered Indications: Anesthesia for diagnostic and surgical procedures that do not require skeletal muscle relaxation; induction of anesthesia prior to administration of other general anesthetic agents; supplemental anesthesia for low-potency agents (e.g., nitrous oxide).any of these

Covered when used as indicated for anesthesia.

Ketamine injection - Not medically necessary: Use of ketamine injection for psychiatric disorders (including but not limited to depression, bipolar disorder, PTSD), chronic pain (including but not limited to fibromyalgia, neuropathic pain, complex regional pain syndrome, reflex sympathetic dystrophy), and migraine headaches is investigational and not medically necessary.any of these

FDA has warned about risks of compounded ketamine products for psychiatric disorders; Spravato is not approved as an anesthetic.

Spravato (esketamine) and ketamine injection are explicitly limited in their covered uses. Spravato is unproven and not medically necessary as an anesthetic agent, and both agents are not covered for a set of specified non‑approved indications. The policy lists chronic pain (including nonmalignant pain, fibromyalgia, neuropathic pain, complex regional pain syndrome, and reflex sympathetic dystrophy) and migraine headaches among uses that are considered investigational or not medically necessary. Use of ketamine injection for psychiatric disorders (including but not limited to depression, bipolar disorder, and PTSD) is also considered investigational and not medically necessary.

Spravato is approved by the FDA for treatment‑resistant depression and for depressive symptoms in adults with MDD with acute suicidal ideation or behavior when used with an oral antidepressant, but it is not approved as an anesthetic agent. The FDA‑approved prescribing information and the policy note that the safety and effectiveness of Spravato as an anesthetic have not been established.

The FDA has issued a warning regarding the use of compounded ketamine products for psychiatric disorders; the advisory highlights potential safety risks associated with compounded formulations (including oral ketamine). Providers and payers should exercise caution and consider this advisory when evaluating requests involving compounded ketamine for psychiatric indications.

The policy specifies several unproven/not medically necessary uses for Spravato and ketamine injection. Spravato is regarded as not medically necessary when used as an anesthetic or for chronic pain and migraine. Ketamine injection is considered investigational and not medically necessary for psychiatric disorders, chronic pain conditions, and migraine headaches. Requests for these indications may be denied consistent with policy.

Coding

Applicable HCPCS/CodesHCPCS

J0013	Esketamine, nasal spray, 1 mg.
J3490	Unclassified drugs

Applicable ICD-10 CodesICD-10

F33.0	Major depressive disorder, recurrent, mild.
F33.1	Major depressive disorder, recurrent, moderate.
F33.2	Major depressive disorder, recurrent severe without psychotic features.
F33.3	Major depressive disorder, recurrent, severe with psychotic symptoms.
F33.40	Major depressive disorder, recurrent, in remission, unspecified.
F33.41	Major depressive disorder, recurrent, in partial remission.
F33.42	Major depressive disorder, recurrent, in full remission.
F33.8	Other recurrent depressive disorders.
F33.9	Major depressive disorder, recurrent, unspecified

Minimum antidepressant trial duration — >= 8 weeks each

Minimum required duration>= 8 weeks each for each antidepressant trial (document medication, date, and duration)

Acceptable trial typesTrials may include SSRIs, SNRIs, bupropion, TCAs, mirtazapine, MAOIs, serotonin modulators, or augmentation with antipsychotics/lithium/thyroid hormone

Documentation neededMedical record must list medication name, start/stop dates, and duration of each ≥8-week trial

ContextRequired as part of establishing treatment-resistant depression (TRD) prior to Spravato authorization

Provider Actions and Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required for Spravato (esketamine) nasal spray when the policy criteria for treatment-resistant depression are met. Providers must obtain authorization before initiating therapy and note that initial and reauthorization approvals are limited to no longer than 12 months per authorization.

Affected drug: Spravato (esketamine) nasal spray
Initial and continuation authorizations limited to ≤ 12 months per approval
Verify authorization requirements prior to dispensing/administration

Note

Verify Member-Specific Plan and Benefits

Check the member-specific benefit plan for prior authorization and coverage determination before providing Spravato. This policy is intended to assist interpretation of UnitedHealthcare standard benefit plans but member-specific plan documents, and any applicable federal or state mandates, govern coverage decisions in the event of a conflict.

Background

Major depressive disorder (MDD) is a common and disabling condition; a substantial proportion of patients do not respond adequately to first‑line therapies. Treatment‑resistant depression (TRD) generally refers to failure to achieve clinically meaningful improvement after treatment with at least two different antidepressant regimens. Esketamine (Spravato) is an NMDA receptor antagonist approved for adults with TRD and for adults with MDD with acute suicidal ideation or behavior when used per FDA labeling and the REMS requirements; by contrast, ketamine injection is an anesthetic agent that is not FDA‑approved for psychiatric disorders.

Definitions

TRD — treatment-resistant depression definition (failure after ≥2 antidepressants)

TRD definition (policy)Failure to achieve clinically meaningful improvement after treatment with at least two different antidepressant agents

Clinical significance threshold (phase 3 studies)Defined in phase 3 studies as ≤25% improvement (lack of clinically meaningful improvement) after treatment with ≥2 different AD agents at adequate dose/duration

Population notePatients who have failed at least two antidepressant trials generally comprise the TRD population; definition is not fully standardized

Spravato (esketamine) — S-enantiomer description and FDA approvals

Molecular descriptionSpravato (esketamine) is the S‑enantiomer of racemic ketamine and is a non-selective, non-competitive NMDA receptor antagonist

Regulatory approvals

Level of Care Criteria

Treatment Modalities

Spravato (esketamine nasal spray) — modality criteria

Spravato modality requirements: Administered in a REMS-certified healthcare setting; dispensed and administered only to patients enrolled in the Spravato REMS; administered under direct observation with monitoring for at least 2 hours after dosing; prescribed by or in consultation with a psychiatrist; dosing in accordance with FDA-approved labeling; initial and reauthorization durations up to 12 months.all conditions required

Pharmacies must be REMS-certified and dispense only to certified healthcare settings.

Intranasal esketamine (Spravato) — modality-specific node

Intranasal esketamine (Spravato) modality: Indicated for TRD as monotherapy or with an oral antidepressant and for depressive symptoms in adults with MDD with acute suicidal ideation or behavior when given with an oral antidepressant; dosing per FDA labeling (twice weekly induction then weekly or every other week for maintenance); administered in REMS-certified settings with required monitoring.

Visit Limits

Spravato administration — frequency

Induction frequency (first 4 weeks)Twice weekly during the first 4 weeks (induction phase)

Post‑induction frequencyFor maintenance, administered weekly for 4 weeks post‑induction, then either weekly or every other week as ongoing maintenance (per trials and FDA labeling)

SourceDosing schedules derived from phase 3 studies and FDA approved labeling (MADRS‑based trials with twice‑weekly induction)

Revision History

05/01/2026Template update & policy transferLatest

Content transferred to a shared policy template and applicability updated to include UnitedHealthcare Commercial and Individual Exchange benefit plans; Application section and References were updated and prior policy versions 2026D0069P and IEXD0069.10 were archived.

Policy Summary

Payersierra health and life

PolicyKetalar (Ketamine) and Spravato (Esketamine) — Coverage Criteria

Policy CodePolicy 2026D0069Q

Change TypeTemplate transfer and reference updates

Effective DateMay 1, 2026

Next Review DateN/A

Key ActionObtain prior authorization and document at least two failed antidepressant trials (each ≥ 8 weeks) and REMS enrollment before Spravato administration.

SourceLink

On This Page

Confirm member plan type (Commercial, Individual Exchange, Medicare Advantage) and any plan-specific requirements

If discrepancy exists between this policy and the member's plan, the member's plan prevails

Denial Risk

Denial Triggers — Unproven Indications

Spravato must not be used for unproven indications. Claims or requests for Spravato for non-covered uses may be denied as not medically necessary.

Do not submit Spravato for use as an anesthetic agent
Do not submit Spravato for chronic pain (including fibromyalgia, neuropathic pain, CRPS/RSD)
Do not submit Spravato for migraine headaches
Ketamine injections for psychiatric disorders or chronic pain are investigational and not covered

Documentation Required

REMS-Related Administration Requirements

Spravato is available only through the Spravato REMS program. Providers, healthcare settings, and dispensing pharmacies must be certified in the REMS and follow REMS administration and monitoring requirements.

Provider and/or healthcare setting must be certified in the Spravato REMS program prior to dispensing or administration
Spravato must be dispensed and administered only in certified healthcare settings
Patients must be enrolled in the REMS program
Patients must be administered Spravato under direct observation and monitored by a healthcare provider for at least 2 hours after dosing
Pharmacies must be REMS-certified and may only dispense to certified healthcare settings

Documentation Required

Required Clinical Documentation and Treatment-Resistance Verification

Submit complete clinical documentation to support medical necessity and coverage decisions. Documentation requirements include treatment-resistance verification, baseline and follow-up assessment scores, and evidence of REMS certification and prescribing clinician qualifications.

Initial therapy: medical records documenting DSM diagnosis of MDD (treatment-resistant) by a mental health professional
Initial therapy: documentation of baseline scoring prior to starting Spravato on at least one validated scale (BDI, HAMD, MADRS, PHQ-9, QIDS)
Initial therapy: documentation of failure of at least two different adequate antidepressant regimens (each ≥ 8 weeks); include medication name, dates, and duration
Continuation therapy: documentation of remission or positive clinical response with baseline and recent (within last month) scores on the same validated scales demonstrating improvement
Document that prescriber is a psychiatrist or that treatment is prescribed in consultation with a psychiatrist when required
Document REMS certification for the provider/setting and that dosing conforms to FDA-approved labeling

Documentation Required

Documentation and Plan-Governed Coverage

When determining coverage, reference member-specific plan documents and applicable mandates. In case of conflict between this policy and the member-specific benefit plan, the member's plan governs. Clinical judgment and supporting documentation should be included with prior authorization requests.

Check for applicable federal or state mandates that may affect coverage
Include clinical rationale and supporting records with requests to facilitate timely review
UnitedHealthcare may use external criteria (e.g., InterQual) to assist in administration

Step Therapy

Step Therapy Requirement

Step therapy requirement: prior to Spravato, the patient must have an inadequate response to at least two different antidepressant regimens of adequate dose and duration in the current depressive episode.

Each failed antidepressant trial should be an adequate dosage and duration (policy documents specify ≥ 8 weeks; phase 3 studies defined adequate duration as ≥ 6 weeks)
Document agents tried (examples: SSRIs, SNRIs, bupropion, TCAs, mirtazapine, MAOIs, serotonin modulators, or augmentation with antipsychotics/lithium/thyroid hormone)
Provide dates and clinical response documentation for each trial

FDA‑approved for treatment‑resistant depression (TRD) in adults as monotherapy or with an oral antidepressant, and for depressive symptoms in adults with MDD with acute suicidal ideation or behavior (with an oral antidepressant)

Labeling noteSpravato is not approved as an anesthetic agent; safety and effectiveness as an anesthetic have not been established

Treatment-resistant depression (TRD) — phase 3 study definition details

Phase 3 TRD enrollment criteriaPatients met DSM-5 criteria for MDD and were required to have failed ≥2 different antidepressant agents prescribed in adequate dosages for an adequate duration

Operational definition used in trialsLack of clinically meaningful improvement defined as ≤25% improvement in the current depressive episode after ≥2 adequate AD trials

Assessment toolsStudies used standardized diagnostic verification (MINI) and measured outcomes primarily with the MADRS administered by blinded remote raters

Spravato REMS — REMS program description and requirements

REMS purposeSpravato is available only through the Spravato REMS because of risks of sedation, dissociation, and abuse/misuse

Certified settings requirementHealthcare settings must be certified in the REMS and Spravato may only be dispensed to and administered in certified settings

Administration and monitoringPatients must be enrolled in the REMS, administered under direct observation, and monitored by a healthcare provider for at least 2 hours after dosing

Pharmacy rolePharmacies must be certified in the REMS and may only dispense Spravato to certified healthcare settings

Esketamine/ketamine therapies — summary of intranasal and infusion investigational uses

Intranasal esketamine (Spravato)Investigated and FDA‑approved for TRD and for depressive symptoms with acute suicidal ideation/behavior (administered intranasally under REMS)

Intravenous ketamine infusionsIV ketamine has been studied for rapid antidepressant effects with pooled response rates reported (evidence variable; often transient effects) and is not FDA‑approved for psychiatric disorders

Evidence limitationsStudies of ketamine for psychiatric disorders are of variable quality, with concerns about sample size, duration, and safety (abuse, psychiatric events, BP rise, respiratory depression)

Compounded ketamine safety warning — FDA warning about compounded ketamine products

FDA safety advisoryFDA warns patients and health care providers about potential risks associated with compounded ketamine products, including oral formulations, for the treatment of psychiatric disorders

ImplicationCompounded ketamine products for psychiatric use carry safety risks and are cautioned against by the FDA

all conditions required

Initial treatment often twice weekly for first 4 weeks per clinical trials.

Intravenous ketamine — infusion modality node

Intravenous ketamine — evidence and modality: IV ketamine demonstrates rapid antidepressant effects (hours to days) with pooled response rates reported (e.g., ~67% in pooled data); effects may be transient and repeat infusions may be more effective than single infusion. Evidence is variable and IV ketamine for psychiatric disorders remains investigational per this policy.any conditions

IV ketamine is not FDA-approved for psychiatric indications; use for these indications is considered investigational/not medically necessary.

Esketamine/ketamine (intranasal and infusion) — combined modalities node

Esketamine/ketamine combined modalities: Clinical use of intranasal esketamine (Spravato) follows REMS requirements and FDA labeling for TRD and MDD with acute suicidal ideation/behavior; ketamine infusion shows rapid but often transient antidepressant effects and is considered investigational for psychiatric disorders. Spravato is not approved as an anesthetic; compounded ketamine products carry FDA safety warnings.all conditions required

Documentation of treatment history and assessments required for coverage decisions; refer to member-specific plan for prior authorization.