CurrentCentenePolicy CP PMN.296

Ketamine (Ketalar) clinical coverage

Defines medical necessity, prior authorization requirements, and coverage criteria for Ketamine (Ketalar) including FDA-approved anesthetic uses and specified off-label psychiatric uses (MDD, TRD) for members across Commercial, HIM, and Medicaid lines of business.

Policy Summary

PayerCentene

PolicyKetamine (Ketalar) clinical coverage

Policy CodePolicy CP PMN.296

Change TypeNo material clinical or coverage changes

Effective DateSep 1, 2024

Next Review DateN/A

Key ActionSubmit prior authorization with documentation showing diagnosis, trials of required therapies, prescriber specialty, and dosing consistent with policy.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

0.5 mg/kgtypical IV off-label infusion dose for MDD/TRD

1 mg/kgmaximum off-label IV single dose

Commercial,HIM,Medicaidlines of business covered

J3490billing code implication

Coverage Criteria

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Initial approval: 1) Diagnosis: request is for an FDA‑approved anesthetic indication OR for a specified off‑label psychiatric indication (treatment‑resistant depression [TRD] or major depressive disorder [MDD]). 2) If brand Ketalar is requested, member must use generic ketamine unless contraindicated or clinically significant adverse effects are experienced. 3) Request is for intravenous (IV) ketamine when indicated for psychiatric use. 4) For TRD/MDD: prescribed by or in consultation with a psychiatrist. 5) For TRD/MDD: member meets age requirements (≥18 years unless state limitations apply) and step therapy requirements (failure of first‑line antidepressants and failure of one augmentation therapy) unless contraindicated or clinically significant adverse effects occur. 6) Dose does not exceed 1 mg/kg IV as a single dose and dosing is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence).dose <= 1 mg/kg per single IV dose

Provider must submit documentation (e.g., office chart notes, lab results) demonstrating criteria are met.

Off‑label evidence requirements

When the request is for an off‑label psychiatric indication, evidence requirements must be met:

Off‑label evidence: 1) Use must be supported by Micromedex DrugDex with strength of recommendation Class I or IIa OR by evidence from at least two high‑quality published studies or evidence‑based clinical practice guidelines that: a) adequately represent the prescribed drug regimen; b) adequately represent the member's clinical characteristics, age, and diagnosis; and c) demonstrate clinically meaningful outcomes; 2) Appropriate experimental design or peer‑reviewed literature must support dosing and use; 3) Case reports alone are inadequate; randomized controlled trials or nonrandomized trials with a significant number of subjects are preferred.

See Appendix D for details on evidence strength and study design.

Requests for indications that are not FDA‑approved and are not specifically addressed in this policy are excluded from coverage unless the provider supplies sufficient documentation demonstrating efficacy and safety in accordance with applicable off‑label use policies (for example, CP.CPA.09 for commercial, HIM.PA.154 for marketplace, or CP.PMN.53 for Medicaid).

This policy recognizes use of ketamine for certain off‑label psychiatric indications (for example, low‑dose IV regimens for MDD/TRD), but specific off‑label requests must be evaluated against the plan’s medical necessity criteria and the policy’s evidentiary requirements. Providers should submit supporting literature and dosing rationale consistent with the policy when requesting coverage for off‑label psychiatric uses.

Coding and Dosing

Coding — no explicit codes listedmixed

NDC or CPT not listed in this section

No explicit CPT/HCPCS/NDC codes provided in this document portion.

Coding implicationsHCPCS

J3490

Unclassified drugs

IV Ketamine Infusion Dose — dosing and regimen

IV ketamine infusion dose0.5 mg/kg IV administered over 40 minutes; may repeat 1–3 times weekly; dose may be increased to 0.75–1 mg/kg based on response and tolerability; maximum 1 mg/kg per dose.

Typical courseCourse commonly given as 4–6 infusions administered 2–3 times per week.

Use contextOff‑label use for TRD/MDD as subanesthetic IV infusion per policy dosing guidance.

Infusion Dose Threshold — TRD/MDD

Typical infusion threshold (TRD/MDD)0.5 mg/kg IV administered over 40 minutes (typical protocol).

Maximum per‑doseMaximum single dose 1 mg/kg IV.

Dose escalationMay increase to 0.75–1 mg/kg based on response and tolerability.

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization required. Prior authorization requires submission of documentation demonstrating the member meets initial approval criteria, including diagnosis, prior treatment history, and supporting clinical evidence.

Submit office chart notes, relevant lab results, medication history, and any supporting peer-reviewed literature or guidelines when requesting coverage.
Requests for brand Ketalar require trial of generic ketamine unless contraindicated or clinically significant adverse effects are documented.

Documentation Required

Required Documentation

Provider must submit documentation (such as office chart notes, lab results, or other clinical information) supporting that the member has met all approval criteria. Coverage decisions are subject to plan-level administrative policies, coverage documents, and state/federal requirements.

Documentation must demonstrate diagnostic criteria, prior therapies tried, durations and doses, treatment response, and rationale for ketamine use.
Providers are expected to supply supporting evidence for off‑label uses consistent with the plan's off‑label use policies.

Step Therapy

Step Therapy for Psychiatric Indications

Step therapy applies for TRD and MDD requests. Prior to approval, documentation must show trials of first‑line antidepressants at therapeutic doses for an adequate duration and failure of one augmentation therapy when applicable.

Trials of SSRI, SNRI, bupropion, mirtazapine, or vilazodone at maximally tolerated/therapeutic doses for an adequate duration (typically several weeks) unless contraindicated or discontinued for clinically significant adverse effects.
Failure of one antidepressant augmentation (e.g., second‑generation antipsychotic, lithium, thyroid hormone, or buspirone) used for ≥4 weeks unless contraindicated.
For TRD/MDD, prescriber must document consultation with or prescribing in coordination with a psychiatrist as specified in the criteria.

Note

Step Therapy Bypass Note

Step therapy bypass: Illinois Health Insurance Marketplace (HIM) requests are exempt from the step therapy requirements per Illinois HB 5395 effective 01/01/2026. Operational details and implementation follow plan procedures.

When applicable, indicate that the member is an IL HIM enrollee to apply the bypass.
All other prior authorization and documentation requirements remain applicable even when step therapy is bypassed.

Billing Rule

Billing/Coding

Ketamine billing: ketamine is associated with HCPCS code J3490 (Unclassified drugs). Ensure billing and claims submission comply with plan prior authorization and coding guidance.

Use J3490 for ketamine-related drug charges where applicable and include prior authorization references on claims per plan instructions.

Background

Ketalar (ketamine) is a non‑selective N‑methyl‑D‑aspartate (NMDA) receptor antagonist approved for use as an anesthetic agent for induction and maintenance of anesthesia and as a supplement to other anesthetic agents. The policy also references lower, subanesthetic IV regimens that have been used off‑label for psychiatric indications such as treatment‑resistant depression and major depressive disorder (typical regimen: 0.5 mg/kg IV over 40 minutes, with a maximum single dose of 1 mg/kg).

Definitions

TRD — definition

DefinitionTreatment‑resistant depression (TRD) is often defined as failure of at least two adequate trials of first‑line antidepressants.

Clinical roleTRD identifies patients considered for third‑line options such as low‑dose ketamine per CANMAT guidance.

Appendix referenceSee Appendix D for CANMAT and VA‑DoD guideline context on TRD and ketamine use.

Ketalar (ketamine) — drug description

Drug classKetalar (ketamine) is a non‑selective, non‑competitive NMDA receptor antagonist.

Approved useApproved as an anesthetic agent for induction and maintenance of anesthesia and as a supplement to other anesthetic agents.

Off‑label psychiatric useUsed off‑label in low, subanesthetic IV doses for severe and treatment‑resistant major depressive disorder (MDD/TRD).

TRDt / MDDt — infusion regimen

Regimen label (TRDt/MDDt)TRD/MDD infusion regimen: 0.5 mg/kg IV over 40 minutes; may repeat 1–3 times weekly; may increase to 0.75–1 mg/kg based on response; maximum 1 mg/kg per dose.

Administration frequencyMay be administered 1–3 times per week for a course of infusions (commonly 4–6 total).

Dose thresholdPolicy threshold specifies per‑dose maximum of 1 mg/kg for TRD/MDD infusions.

Treatment Modalities

IV ketamine infusion for MDD/TRD

IV ketamine regimen for MDD/TRD: Typical regimen: 0.5 mg/kg IV administered over 40 minutes; may be repeated 1–3 times weekly for a course (commonly 4–6 infusions); dose may be increased to 0.75–1 mg/kg based on response and tolerability; maximum 1 mg/kg per dose.0.5–1 mg/kg

Prescriber must document dosing plan and supporting evidence; see CANMAT and VA‑DoD guidance in Appendix D.

Ketamine IV infusion for treatment-resistant depression

IV infusion regimen for TRD/MDD: 0.5 mg/kg IV administered over 40 minutes; may repeat 1–3 times weekly; may increase to 0.75–1 mg/kg based on response/tolerability; maximum 1 mg/kg per dose.0.5–1 mg/kg

Dosing and maximum per dose follow the policy's Dosage and Administration section.

Visit Limits and Authorization Duration

Ketamine Therapy — re‑authorization

Re‑authorization policyRe‑authorization is not permitted; members must meet the initial approval criteria for each request.

Approval durationNot applicable — each request requires meeting initial criteria rather than ongoing re‑authorization.

Provider implicationProviders should submit required documentation for each new request since continuing approvals are not allowed.