CurrentCentenePolicy CP.PMN.296

Ketamine (Ketalar) (PDF)

Defines medical necessity criteria, initial approval requirements, re-authorization policy, allowed indications (FDA and specified off-label uses for TRD and MDD), dosing limits, step therapy requirements and therapeutic alternatives for Ketalar/ketamine across Commercial, HIM, and Medicaid lines of business.

Policy Summary

PayerCentene

PolicyKetamine (Ketalar) (PDF)

Policy CodePolicy CP.PMN.296

Change TypeClarified; Revised

Effective Date09.01.24

Next Review Date08.25.25

Key ActionProvider must submit documentation (office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.

SourceLink

POLICY UPDATE CHANGES

Added step therapy bypass for IL HIM per IL HB 5395.

Policy created and P&T approval recorded.

2Allowed Off-label Indications

0Re-authorizations Permitted

1Required prescriber specialty (psychiatrist for TRD/MDD)

J3490Referenced billing code

Coverage Summary

Coverage stance: covered_with_criteria. Scope: Defines medical necessity criteria, initial approval requirements, re-authorization policy, allowed indications (FDA and specified off-label uses for TRD and MDD), dosing limits, step therapy requirements and therapeutic alternatives across Commercial, HIM, and Medicaid. Subject: Ketamine (Ketalar) coverage and medical necessity criteria. Policy number: CP.PMN.296. Effective date: 2024-09-01. Status: CURRENT.

Key thresholds & quick facts

Typical IV dose0.5 mg/kg IV infused over 40 minutes; may repeat 1–3 times per week for a total course of 4–8 infusions

Max doseDose does not exceed 0.5 mg/kg IV for up to 8 doses (typical course); single-dose maximum 1 mg/kg IV

Antidepressant trial durationEach prior antidepressant trial ≥ 4 weeks at up to maximally indicated doses

Augmentation trial durationPrior antidepressant augmentation therapy trial ≥ 4 weeks

Prescriber requirementPrescribed by or in consultation with a psychiatrist for TRD/MDD requests

Initial Therapy Criteria

Initial Approval Criteria

Provider must submit documentation supporting that member has met all approval criteria. Ketalar and ketamine are medically necessary when the following criteria are met:

For TRD and MDD specific requirements

Diagnosis
- Uses supported by evidence
  - Micromedex support: Supported by Micromedex DrugDex with strength of recommendation Class I or IIa
    See Appendix D
  - High-quality evidence: Evidence from at least two high-quality, published studies in reputable peer-reviewed journals or evidence-based clinical practice guidelines that provide adequate representation of the member's characteristics, regimen, clinically meaningful outcomes, and appropriate experimental design
    See Appendix D
- Allowed off-label indications
  - TRD: Treatment-resistant depression (TRD)
    Appendix E
  - MDD: Major depressive disorder (MDD)
    Appendix E
Brand vs generic requirement: If request is for brand Ketalar, member must use generic ketamine, unless contraindicated or clinically significant adverse effects are experienced
TRD/MDD additional requirements
- Route: Request is for intravenous (IV) ketamine
- Prescriber specialty: Prescribed by or in consultation with a psychiatrist
- Age ≥ 18 years
- Step therapy exception or requirements
  - State limitation: Request is for the treatment of a member in a State with limitations on step therapy in certain mental health settings (see Appendix E)
  - For all other requests

Other Indications / Not Authorized

Other diagnoses/indications

If requested use is not listed under approved/allowed indications

Other diagnoses/indications routing: If drug underwent a recent label change within last 6 months not reflected in policy, refer to no coverage or non-formulary policy per line of business; if requested use is NOT specifically listed under section III AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09; HIM.PA.154; CP.PMN.53

Diagnoses/Indications not authorized

Diagnoses/Indications not authorized: Non-FDA approved indications which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to off-label use policies CP.CPA.09; HIM.PA.154; CP.PMN.53

Provider Actions / Authorization Requirements

Prior Authorization

Prior authorization required and re-authorization not permitted

Initial approval requires prior authorization per policy criteria. Re-authorization is not permitted; members must meet the initial approval criteria for each request (approval duration: Not applicable).

Documentation Required

Submit supporting documentation

Submit office chart notes, lab results, or other clinical information demonstrating the member meets all approval criteria (diagnosis, prior medication/augmentation trials or step therapy exception, prescriber specialty, dosing limits, and any supporting literature when applicable).

Step Therapy

Step therapy requirements for TRD/MDD

For TRD/MDD requests (unless the request qualifies under a State limitation on step therapy, see Appendix E), the member must have failed TWO antidepressants (each tried ≥ 4 weeks at up to maximally indicated doses) and ONE antidepressant augmentation therapy (trial ≥ 4 weeks), unless clinically significant adverse effects occur or all are contraindicated. Note: for Illinois HIM requests, these step therapy requirements do not apply as of 1/1/2026 per IL HB 5395 (see Appendix E).

Documentation Required

Brand vs generic requirement

If the request is for brand Ketalar, the member must use generic ketamine unless contraindicated or clinically significant adverse effects are experienced.

Documentation Required

Prescriber specialty requirement for TRD/MDD

Prescriptions for IV ketamine for TRD/MDD must be written by or in consultation with a psychiatrist as a condition of approval.

Clinical Evidence & Dosing

Ketamine is an NMDA receptor antagonist approved for anesthesia and used off-label at subanesthetic IV doses for treatment-resistant depression and major depressive disorder; clinical guidance from CANMAT and the VA/DoD recognize IV ketamine as an option for refractory MDD/TRD with typical protocols (e.g., 0.5 mg/kg infused over 40 minutes, repeated 2–3 times weekly for 4–8 infusions).

Evidence — quantitative metrics

Typical IV TRD dose per referenced trials/guidelines0.5 mg/kg infused over 40 minutes; course may be repeated 1–3 times weekly for total of 4–8 infusions (CANMAT and referenced trials)

Max dose per policyMaximum per dose = 1 mg/kg IV; typical course dose limit: 0.5 mg/kg for up to 8 doses

Background & Definitions

Ketamine has been used in low (subanesthetic) IV doses for severe and treatment-resistant depression (TRD often defined as failure of ≥2 adequate antidepressant trials). Per CANMAT and VA/DoD guidance, IV ketamine is considered an option for adults with TRD/MDD who have not responded to adequate trials; the typical IV protocol is 0.5 mg/kg infused over 40 minutes given as a single infusion or repeated infusions administered 2 to 3 times per week for a total of 4 to 8 infusions, with dosing allowed to increase up to a maximum of 1 mg/kg per dose based on response and tolerability.

Definitions

TRDTreatment-resistant depression: often defined as failure of at least 2 trials of first-line antidepressants given in adequate dosage and duration

MDDMajor depressive disorder

Revision History

2024-05-07policy_created

Policy created.

2024-08-24pt_review

P&T approval recorded.

2025-06-30material_changeLatest

Added step therapy bypass for Illinois HIM requests per IL HB 5395; documentation notes that step therapy requirements do not apply for Illinois HIM as of 01/01/2026.

2025-08-25references_review

3Q 2025 annual review: references reviewed and updated; no significant clinical changes identified.

Policy Summary

PayerCentene

PolicyKetamine (Ketalar) (PDF)

Policy CodePolicy CP.PMN.296

Change TypeClarified; Revised

Effective Date09.01.24

Next Review Date08.25.25

Key ActionProvider must submit documentation (office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.

SourceLink

On This Page

Dose limits for TRD/MDD

Typical course limit: Dose does not exceed 0.5 mg/kg IV for up to 8 dosesUp to 8 doses at 0.5 mg/kg
Single dose max: Dose does not exceed 1 mg/kg IV as a single doseMaximum 1 mg/kg per dose
Guideline-supported dosing: Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)

OpenPayer

Ketamine (Ketalar) (PDF)

Coverage Summary

Initial Therapy Criteria

Continuation / Re-authorization

Other Indications / Not Authorized

Provider Actions / Authorization Requirements

Applicable Codes

Clinical Evidence & Dosing

Background & Definitions

Revision History