CurrentMass General Brigham Health PlanPolicy 031

intravenous_ketamine_policy

Defines medical necessity criteria, authorization requirements, dosing, exclusions, reauthorization requirements, and coding information for intravenous (IV) ketamine for treatment-resistant major depressive disorder and severe suicidal ideation for Mass General Brigham Health Plan members (Commercial, MassHealth/ACO, Medicare Advantage variations noted).

Policy Summary

PayerMass General Brigham Health Plan

Policyintravenous_ketamine_policy

Policy CodePolicy 031

Change TypeAnnual/ad hoc editorial updates (2021-2025)

Effective DateApr 1, 2021

Next Review Date

Key ActionTreating specialist must request prior authorization for IV ketamine.

SourceLink

POLICY UPDATE CHANGES

Annual and ad hoc updates listed (2021-2025) with editorial clarifications and additions (e.g., Medicare/MassHealth variations, summary of evidence).

2Covered indications (TRD and severe suicidal ideation)

16Exclusion criteria listed

28Initial authorization days

1Reauthorization duration (years)

This policy (Policy Number: 031) defines medical necessity criteria, authorization requirements, dosing, exclusions, reauthorization, and coding information for intravenous ketamine for treatment‑resistant major depressive disorder (TRD) and severe suicidal ideation. Effective date originally 2021-04-01 with last review on 2025-10-01. Coverage stance: covered_with_criteria. Prior authorization is required for Commercial, MassHealth/ACO, and Medicare Advantage members. The intent is to permit IV ketamine for selected adults meeting strict clinical criteria (including DSM-5 diagnosis and severity thresholds) and to require careful monitoring and specialist involvement.

Key thresholds and authorization durations

HAM-D threshold>= 17

MADRS threshold>= 28

QIDS threshold (16-item)Score >=16 indicates severe depression

Medication trial duration>= 6 weeks at generally accepted doses (or sufficient duration per treating physician)

Medication adherence during trial>= 80% adherence throughout the trial

Uncontrolled hypertension exclusionSystolic BP >160 mm Hg or diastolic BP >90 mm Hg (requires cardiology clearance)

Initial authorization duration28 days

Reauthorization durationUp to 1 year (when reauthorization criteria met)

Initial Treatment (Initial authorization for 28 days)

Intravenous ketamine may be considered medically necessary when ALL of the following are met:

ALL of the following

Eligibility: Member is 18 years of age or older
Diagnostic criteria: Member meets DSM-5 criteria for unipolar major depressive disorder (see Table A)
Concomitant therapy: IV ketamine will be given together with an oral antidepressant and/or mood stabilizer
Depression severity (one of)
- HAM-D: Hamilton Rating Scale for Depression (HAM-D) score ≥ 17>= 17
  See Table B
- MADRS: Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 28>= 28
  See Table C
- QIDS: Quick Inventory of Depressive Symptomatology-Self Report (QIDS) score indicating severe depression (QIDS 16+)QIDS ≥ 16
  See Table D
Prior treatment (TRD) and satisfactory medication trial
- Medication trial duration: Length of trial at least 6 weeks at generally accepted doses or sufficient duration as defined by treating physician>= 6 weeks
- Medication adherence: Member was at least 80% adherent to the medication throughout the trial>= 80% adherence
Psychiatrist evaluation: A psychiatrist has evaluated the patient and documented that the patient qualifies as a candidate for IV ketamine
Administration and prescriber: Administration must occur in a hospital setting or provider's office and must be monitored by a psychiatrist or other specialist with expertise in IV ketamine administration; prescriber must be a specialist in area of member's diagnosis or have consulted with such specialist

Reauthorization Guidelines (up to 1 year)

IV ketamine may be reauthorized for one year when ALL of the following are met:

ALL of the following

Concomitant therapy: Member receives IV ketamine together with an oral antidepressant or mood stabilizer
Clinical improvement: Member experienced improvement in depression symptoms as evaluated with an appropriate depression rating scale (e.g., CGI, QIDS-16, PHQ-9, HAM-D, MADRS) and/or significant functional improvement
Substance use disorder status: Member does not have substance use disorder OR is in remission (complete abstinence for one month) OR is in maintenance treatment for substance use disorderremission = complete abstinence for one month

Exclusions (Not medically necessary / Contraindications)

IV ketamine is excluded when ANY of the following are present (some require specialist clearance):

Exclusions

Pregnancy/breastfeeding: Member is pregnant or breastfeeding or at risk of becoming pregnant
Psychotic disorder: Current or past history of primary psychotic disorder (e.g., schizophrenia); presence of psychotic features in context of severe depression considered case-by-case
Dementia: Member has dementia
Active SUD unwilling to be treated: Member has an active substance use disorder and is unwilling to receive treatment for it
Prior nonresponse: Member underwent previous IV ketamine at adequate doses and it did not reduce symptoms or improve function
Recent delirium: Member has a current episode (within 7 days) of deliriumwithin 7 days
Aneurysmal vascular disease (any of)
- Thoracic/abdominal aorta aneurysm: Thoracic and abdominal aorta aneurysmal disease
- Intracranial/peripheral aneurysm: Intracranial and peripheral arterial vessel aneurysms
- Arteriovenous malformation
Aneurysm clearance: If aneurysmal vascular disease or AVM present, member must be cleared by cardiovascular or neurovascular specialist
Recent intracerebral hemorrhage: Recent (<6 months) intracerebral hemorrhage — excluded; if history >6 months, neurology or neurovascular clearance required< 6 months excluded
Uncontrolled hypertension/cardiac: Current uncontrolled hypertension (systolic >160 mm Hg or diastolic >90 mm Hg), cardiac arrhythmia, or unstable/symptomatic cardiovascular disease — requires cardiology clearancesystolic >160 mm Hg or diastolic >90 mm Hg
Requires cardiology clearance
CSF obstructive states: Cerebrospinal fluid (CSF) obstructive states (e.g., severe head injury, central congenital or mass lesions) — requires neurology clearance
Intraocular pressure pathology (e.g., uncontrolled glaucoma, acute globe injury) — requires ophthalmology clearance
Uncontrolled hyperthyroidism — requires medical clearance
Porphyria: Diagnosis of porphyria (risk of triggering acute porphyria reaction)
Pulmonary infection/severe pulmonary disease: Active pulmonary infection or severe pulmonary disease (increased risk for apnea, hypoxia)
Lack of ongoing care: Member is not under ongoing care of psychiatrist/APRN/PCP or unwilling to sign release to allow communication with primary team and family
Misuse history: Current or previous misuse of ketamine

Provider Actions and Documentation Requirements

Prior Authorization

Prior authorization required

Treating specialist must request prior authorization for IV ketamine (applies to Commercial, Qualified Health Plans, MassHealth, Medicare Advantage as indicated in header).

Documentation Required

Documentation of prior treatment trials and assessment

Document DSM-5 diagnosis, depression rating scale scores (e.g., HAM-D, MADRS, QIDS, PHQ-9, or CGI), evidence of four antidepressant trials from at least two different classes including augmentation when appropriate, the duration of each trial (at least 6 weeks at generally accepted doses or sufficient duration as defined by treating physician), and documentation of at least 80% adherence during each trial.

Documentation Required

Specialist evaluation and monitoring documentation

Document that a psychiatrist has evaluated the patient and determined the patient qualifies as a candidate for IV ketamine, and document that administration will occur in an appropriate monitored setting (hospital or provider office) and that the prescriber is a specialist in the area of the member’s diagnosis or has consulted with such a specialist.

Documentation Required

Clearance requirements for certain comorbidities

Obtain and document required medical clearances per exclusion criteria: cardiology clearance for uncontrolled hypertension (systolic >160 mm Hg or diastolic >90 mm Hg), cardiac arrhythmia, or unstable/symptomatic cardiovascular disease; neurology or neurovascular clearance for aneurysmal vascular disease or history of intracerebral hemorrhage >6 months; neurology clearance for CSF obstructive states; ophthalmology clearance for uncontrolled intraocular pressure/pathology (e.g., uncontrolled glaucoma); and other medical clearance as specified for hyperthyroidism, severe pulmonary disease, or other listed exclusions.

Billing Rule

Coding disclaimer

Codes listed are informational and inclusion does not constitute coverage or reimbursement. J3490 is an unclassified drug code and must be coupled with the appropriate National Drug Code (NDC) when used.

Background, Evidence & Definitions

IV racemic ketamine is used off‑label for TRD and for rapid reduction of severe suicidal ideation. Randomized and controlled trials and reviews show evidence of short‑term efficacy (including rapid remission at 24 hours and studies demonstrating noninferiority to ECT in induction), but longer‑term efficacy and safety remain uncertain. Because of the need for safety precautions and limited long‑term data, the policy limits treatment to selected individuals, requires administration in monitored settings, specialist evaluation, and ongoing monitoring.

Study	Key finding
RCT Anand et al. 2023	Ketamine noninferior to ECT; remission rates ~55% vs 41%; 6-month relapse 35% vs 56%
Cochrane review (Dean et al. 2021)	Ketamine may result in remission at 24 hours; evidence very low certainty

Revision History

2021-04-01policy_effective

Policy became effective on April 1, 2021 (initial effective date).

2022-10-01annual_update

October 2022 annual update: Coverage guidelines clarified to remove language requiring patient be considered for electroconvulsive therapy; references updated (editorial changes).

2023-10-01annual_update

October 2023 annual update: Medicare Advantage added to table; minor editorial refinements to overview section; language moved to coverage guidelines; Medicare Variation language added; intent unchanged.

2024-03-04ad_hoc_update

March 4, 2024 ad hoc update: Table changed to reflect coverage for MassHealth members.

2024-09-01ad_hoc_update

September 2024 ad hoc update: MassHealth Variation added (editorial/variation language added).

2024-10-01annual_update

October 2024 annual update: Clarified Medicare Variation language (evidence/variation language added).

2025-03-01ad_hoc_update

March 2025 ad hoc update: Summary of evidence added and references updated (evidence language added).

2025-10-01annual_updateLatest

October 2025 annual update: Code disclaimer fixed; typographical fixes and hyperlinks to tables added; many editorial updates; stated intent remained unchanged.

J3490	Unclassified drugs (Must be coupled with the appropriate National Drug Code [NDC] number)
96365	Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug); initial, up to 1 hour

OpenPayer

intravenous_ketamine_policy

Coverage Summary

Initial Treatment (Initial authorization for 28 days)

Reauthorization Guidelines (up to 1 year)

Administration, Setting & Monitoring

Exclusions (Not medically necessary / Contraindications)

Provider Actions and Documentation Requirements

Coding

Background, Evidence & Definitions

Medicare Determinations

Revision History