CurrentmhnPolicy CP.PMN.296

Clinical Policy: Ketamine (Ketalar)

Defines medical necessity and coverage criteria for Ketalar (ketamine) including FDA indications and specified off-label uses (treatment‑resistant depression, major depressive disorder) for Commercial, HIM, and Medicaid lines of business. Applies to prior authorization decisioning and formulary considerations.

Policy Summary

Payermhn

PolicyClinical Policy: Ketamine (Ketalar)

Policy CodePolicy CP.PMN.296

Change TypeAnnual review (no material changes)

Effective DateSep 1, 2024

Next Review Date

Key ActionProvider must submit documentation supporting that the member meets all approval criteria and ensure requests meet the policy's initial criteria (diagnosis, prescriber specialty, age, prior therapy, dosing limits).

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

3Primary covered diagnostic categories listed (FDA indication, Micromedex-supported, specified off-label)

2Antidepressant trials required for TRD before ketamine (number of agents)

0.5 mg/kgTypical IV ketamine dose recommended for TRD/MDD

1 mg/kgMaximum IV dose allowed per single dose for TRD/MDD

Medical Necessity Criteria for Ketamine (Ketalar)

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Initial Approval Criteria

Ketamine (Ketalar) is medically necessary when ALL of the following are met:

ALL of the following

One of
- An FDA-approved indication for ketamine
- ALL of the following
  - Micromedex DrugDex strength = Class I or IIa
  - Evidence from >= 2 high-quality published studies or evidence-based clinical practice guidelines
  - Studies/guidelines must provide adequate representation of member's clinical characteristics, age, and diagnosis
  - Adequate representation of the prescribed drug regimen in the evidence
  - Clinically meaningful outcomes as a result of the drug therapy demonstrated
  - Appropriate experimental design and methods to address research questions
- Specified off-label indications (Appendix E)
  - Treatment-resistant depression (TRD)
  - Major depressive disorder (MDD)
If request is for brand Ketalar, member must use generic ketamine unless contraindicated or clinically significant adverse effects are experienced
ALL of the following
- Request is for intravenous (IV) ketamine
- Prescribed by or in consultation with a psychiatrist
- Age >= 18 years
- ANY of the following
  - Otherwise
    Failure of TWO antidepressants (each tried >= 4 weeks at up to maximally indicated doses) from: SSRI, SNRI, bupropion, mirtazapine, vilazodone, unless adverse effects or contraindicated
    Failure of ONE antidepressant augmentation therapy (each used >= 4 weeks): second-generation antipsychotic, lithium, thyroid hormone, or buspirone, unless adverse effects or contraindicated
ALL of the following
- ANY of the following
  - Dose does not exceed 0.5 mg/kg IV for up to 8 doses
  - Dose does not exceed 1 mg/kg IV as a single dose
  - Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)

ref”:

Other diagnoses/indications

If requested use is not listed in Section III and label changes do not apply, follow one of the business-line referral rules:

ANY of the following

ALL of the following
- Commercial/formulary or PDL: CP.CPA.190
- HIM/formulary or PDL: HIM.PA.33
- Medicaid/formulary or PDL: CP.PMN.255
- Commercial non-formulary: CP.CPA.190
- HIM non-formulary: HIM.PA.103

Diagnoses/Indications Not Authorized

Coverage is NOT authorized for:

ALL of the following

Non-FDA approved indications that are not addressed in this policy, unless there is sufficient documentation per the referenced off-label use policies or evidence of coverage documents

ref":

What Providers Must Do

Prior Authorization

Prior authorization required with criteria

Requests must meet the policy's initial approval criteria, including diagnosis, prescriber specialty, age, prior therapy requirements, and dosing limits. Re-authorization is not permitted; members must meet the initial approval criteria for coverage.

Documentation Required

Submit supporting clinical documentation

Submit documentation such as office chart notes, laboratory results, or other clinical information that demonstrates the member meets all approval criteria.

Step Therapy

Antidepressant and augmentation trial requirements for TRD/MDD

For TRD or MDD, prior to IV ketamine (unless the member is in a state with step therapy limitations), document failure of two antidepressants and one augmentation therapy; each antidepressant and the augmentation must be tried for ≥ 4 weeks at up to maximally indicated doses unless contraindicated or clinically significant adverse effects occur. Illinois HIM requests have a statutory bypass of these step therapy requirements effective 1/1/2026 per IL HB 5395.

Failure of TWO antidepressants (each ≥ 4 weeks) from SSRI, SNRI, bupropion, mirtazapine, vilazodone unless adverse effects or contraindicated.
Failure of ONE antidepressant augmentation therapy (≥ 4 weeks): second-generation antipsychotic, lithium, thyroid hormone, or buspirone unless adverse effects or contraindicated.

Documentation Required

Dose justification for higher-than-standard dosing

If the prescribed IV dose exceeds 0.5 mg/kg (or exceeds the single-dose 1 mg/kg limit), the prescriber must submit supporting practice guideline or peer‑reviewed literature evidence that justifies the higher dose for the off-label use.

Clinical Background

Ketamine is a non-selective, non-competitive NMDA receptor antagonist originally developed and used as an anesthetic. At lower, subanesthetic intravenous doses it has been used off-label for severe and treatment-resistant depression (TRD) and major depressive disorder (MDD).

The typical protocol for IV subanesthetic ketamine used in studies and practice is 0.5 mg/kg given over 40 minutes, often administered as a single infusion or as a course of repeated infusions (commonly 1–3 times per week for a total of 4–8 infusions). Evidence supports rapid antidepressant effects following these subanesthetic IV infusions.

Clinical guidance (for example CANMAT and VA/DoD) recognizes IV ketamine as an option for patients who have not responded to multiple adequate pharmacologic trials; per CANMAT IV ketamine is considered a third-line recommendation for adults with TRD when treatment resistance exceeds minimum criteria. Policy criteria therefore restrict use to appropriate adult patients with prior treatment failures and require prescriber specialty, dosing limits, and supporting documentation.

Policy Metadata & Scope

Policy metadata

Policy numberCP.PMN.296

Scope summaryDefines medical necessity and coverage criteria for Ketalar (ketamine) including FDA indications and specified off-label uses (TRD, MDD) for Commercial, HIM, and Medicaid lines of business. Applies to prior authorization decisioning and formulary considerations.

SubjectKetamine (Ketalar) clinical coverage

StatusCURRENT

Effective date2024-09-01

Last review date2024-08-25

Next review date

3Primary covered diagnostic categories

2Antidepressant trials required for TRD before ketamine

0.5 mg/kgTypical IV ketamine dose recommended for TRD/MDD

1 mg/kgMaximum IV single dose allowed for TRD/MDD

Policy Summary

Payermhn

PolicyClinical Policy: Ketamine (Ketalar)

Policy CodePolicy CP.PMN.296

Change TypeAnnual review (no material changes)

Effective DateSep 1, 2024

Next Review Date

SourceLink

On This Page

OpenPayer

Clinical Policy: Ketamine (Ketalar)

Medical Necessity Criteria for Ketamine (Ketalar)

Relevant Billing Codes and Coding Notes

What Providers Must Do

Numeric and Clinical Thresholds

Clinical Background

Defined Terms

Policy Metadata & Scope

Clinical Policy: Ketamine (Ketalar)

Medical Necessity Criteria for Ketamine (Ketalar)

Relevant Billing Codes and Coding Notes

What Providers Must Do

Numeric and Clinical Thresholds

Clinical Background

Defined Terms

Policies to Read With This One

Policy Metadata & Scope