ModifiedMass General Brigham Health PlanPolicy 031

Intravenous Ketamine for Treatment-Resistant Depression

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This policy governs medical-necessity and prior-authorization determinations for intravenous ketamine used for treatment-resistant major depressive disorder or severe suicidal ideation, with individual-case consideration for primary PTSD with severe depressive symptoms. It applies across Medicare Advantage, Mass General Brigham ACO, One Care/SCO, Commercial, and Qualified Health Plan members.

Policy Summary

PayerMass General Brigham Health Plan

PolicyIntravenous Ketamine for Treatment-Resistant Depression

Policy CodePolicy 031

Change TypeModified

Effective DateOctober 1, 2026

Last ReviewOct 1, 2026

Next Review DateNot specified

Key ActionObtain prior authorization before providing intravenous ketamine for eligible members.

SourceLink

POLICY UPDATE CHANGES

The October 1, 2026 annual review reformatted the policy and removed the statement that intravenous ketamine is experimental and investigational in all other situations because the service is covered in other cases.

The January 2026 ad hoc review added a variation for One Care and Senior Care Options members and updated the prior-authorization table.

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ModifiedMass General Brigham Health PlanPolicy 031

Intravenous Ketamine for Treatment-Resistant Depression

Customize your policy alerts

Sign up for Mass General Brigham Health Plan Policy 031 alerts

Get alerted when Policy 031 changes without checking for updates manually.

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Policy Summary

PayerMass General Brigham Health Plan

PolicyIntravenous Ketamine for Treatment-Resistant Depression

Policy CodePolicy 031

Change TypeModified

Effective DateOctober 1, 2026

Last ReviewOct 1, 2026

Next Review DateNot specified

Key ActionObtain prior authorization before providing intravenous ketamine for eligible members.

SourceLink

POLICY UPDATE CHANGES

The January 2026 ad hoc review added a variation for One Care and Senior Care Options members and updated the prior-authorization table.

18+Minimum age for initial treatment

28 daysInitial authorization period

1 yearReauthorization period

4Required treatment attempts

0.5 mg/kgStarting IV ketamine dose

Medical Necessity and Coverage Criteria

Initial Treatment

Initial IV ketamine treatment may be considered medically necessary for members age 18 or older with treatment-resistant major depressive disorder or severe suicidal ideation requiring rapid onset when all criteria are met.

Initial treatment

Diagnosis and treatment plan: The member meets DSM-5 criteria for unipolar major depressive disorder and will receive IV ketamine together with an oral antidepressant and/or mood stabilizer.Age 18 or older
Severe current depressive episode: Within the past 30 days, the member has a qualifying score on HAMD, MADRS, QIDS-SR 16-item, or PHQ-9.HAMD ≥17; MADRS ≥28; QIDS-SR 16-item qualifying score; or PHQ-9 ≥15
Prior treatment failure: The member tried and had an inadequate therapeutic response in the current episode to a combination of four antidepressants, including augmentation when appropriate, or psychotherapy, from different classes; antidepressants must include at least two classes.Each medication trial generally lasts at least 6 weeks or a sufficient duration at generally accepted doses, with at least 80% adherence
Augmentation may include lithium, an atypical antipsychotic, or thyroid hormone T3.
Specialist evaluation and administration: A psychiatrist evaluated the patient and documented candidacy for IV ketamine. Administration occurs in a hospital or provider office and is monitored by a psychiatrist or other specialist with expertise in IV ketamine; the prescriber is a specialist in the diagnosis or consulted one.

Reauthorization Guidelines

IV ketamine may be reauthorized for one year when all medical-necessity criteria are met.

Reauthorization

Concomitant medication: The member receives IV ketamine together with an oral antidepressant or mood stabilizer.
Clinical improvement: The member has improved depression symptoms on a proper depression rating scale or has significantly improved functionally.Examples include CGI, QIDS-SR 16-item, PHQ-9, HAM-D, or MADRS
The policy states AND/OR between symptom-scale improvement and functional improvement.
Substance-use-disorder status: The member does not have a substance use disorder, is in remission with complete abstinence for one month, or is receiving maintenance treatment for substance use disorder.Complete abstinence for 1 month when remission is used

Primary PTSD

Administration of IV ketamine for primary PTSD with severe depressive symptoms is considered on an individual case basis.

Primary PTSD individual-case review: Primary PTSD with severe depressive symptoms may be considered individually; the policy does not provide a separate standardized criteria set in this section.

IV ketamine is excluded when the member is pregnant, breastfeeding, or at risk of becoming pregnant; has current or historical primary psychotic disorder, dementia, hypersensitivity to ketamine, esketamine, or excipients; has an active untreated substance use disorder; previously received adequate-dose IV ketamine without symptom or functional improvement; experienced delirium within the past 7 days; or has current or previous ketamine misuse. Psychotic features associated with severe depression may be considered case by case.

Treatment is also excluded or requires the specified clearance when relevant medical risks are present. These include uncleared aneurysmal vascular disease; intracerebral hemorrhage within the past 6 months or an older hemorrhage without neurology or neurovascular clearance; uncontrolled hypertension, defined as systolic blood pressure >160 mm Hg or diastolic blood pressure >90 mm Hg, cardiac arrhythmia, or unstable or symptomatic cardiovascular disease without cardiology clearance; cerebrospinal-fluid obstructive states without neurology clearance; intraocular-pressure pathology without ophthalmology clearance; uncontrolled hyperthyroidism without medical clearance; porphyria; and active pulmonary infection or severe pulmonary disease.

The member must remain under the ongoing care of a psychiatrist, APRN, or PCP and must be willing to sign a release of information for communication with the primary treatment team and family. Requests may also be excluded when required specialist or medical clearance has not been obtained.

Coding and Clinical Thresholds

Authorized Codemixed

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

HAMD threshold

Qualifying scoreHAMD score ≥ 17

Assessment windowWithin the past 30 days

Clinical useSupports documentation of a severe current depressive episode for initial IV ketamine treatment

MADRS threshold

Qualifying scoreMADRS score ≥ 28

Assessment windowWithin the past 30 days

Clinical useSupports documentation of a severe current depressive episode for initial IV ketamine treatment

Authorization, Documentation, and Denial Risks

Prior Authorization

Prior Authorization Required

Prior authorization is required for IV ketamine for members in all listed lines of business. The treating specialist must submit the request before treatment; coverage determinations follow the applicable CMS, MassHealth, or plan medical-necessity criteria.

Medicare Advantage: CMS guidance and Medicare manuals apply; plan criteria are used when CMS guidance is unavailable.
Mass General Brigham ACO: MassHealth Drug List criteria for Ketalar (IV ketamine) apply.
One Care and SCO: CMS criteria apply first; MassHealth criteria apply when CMS criteria are unavailable or not met.
Commercial and Qualified Health Plans: Prior authorization is required.

Step Therapy

Treatment-Resistant Depression Requirement

Initial IV ketamine authorization requires treatment-resistant major depressive disorder or severe suicidal ideation requiring rapid onset, with an inadequate response to four prior treatment attempts in the current episode. The attempts must include antidepressants, with augmentation when appropriate, or psychotherapy, and antidepressants must represent at least two different classes.

Clinical Background

Intravenous racemic ketamine is a mixture of R- and S-ketamine molecules and is administered by intravenous infusion. It is an NMDA-receptor antagonist and dissociative anesthetic used off-label for treatment-resistant depression and related severe depressive presentations.

The policy cites evidence of short-term efficacy for selected patients with severe, treatment-resistant depression or suicidal ideation, while noting that long-term efficacy and safety data remain limited. Accordingly, treatment requires careful patient selection, controlled administration, and close monitoring. During induction, the recommended starting dose is 0.5 mg/kg over 40 minutes, administered 2–3 times weekly with adjustment for tolerability and clinical response.

Definitions and Assessment Instruments

Treatment-resistant depression

Current episodeInadequate therapeutic response to four antidepressant treatments in the current depressive episode

Treatment typesTreatments may include antidepressants with augmentation when appropriate or psychotherapy from different classes

Antidepressant classesThe four-treatment history must include antidepressants from at least two different classes

Satisfactory medication trial

Expected durationAt least 6 weeks, or a sufficient duration defined by the treating physician

DoseGenerally accepted doses

Covered Treatment Modality

Intravenous Ketamine

When IV ketamine is covered, administration must follow the policy's specified induction and response-monitoring approach.

IV ketamine administration and dosing: During induction weeks 1–4, administer IV ketamine 2–3 times per week, starting at 0.5 mg/kg over 40 minutes and adjusting for tolerability and clinical response. Evaluate therapeutic benefit at the end of induction to determine continued treatment and dosage; subsequently adjust maintenance or discontinuation frequency based on the empirically determined duration of response.0.5 mg/kg per 40 minutes starting dose; 2–3 administrations weekly during weeks 1–4

Authorization Periods

Initial IV ketamine treatment

TreatmentInitial intravenous ketamine treatment

Authorization period28 days

Applicable stageInitial authorization

Continuation IV ketamine treatment

TreatmentContinuation intravenous ketamine treatment

Reauthorization periodOne year

Applicable stageReauthorization after initial treatment

Policy Summary

PayerMass General Brigham Health Plan

PolicyIntravenous Ketamine for Treatment-Resistant Depression

Policy CodePolicy 031

Change TypeModified

Effective DateOctober 1, 2026

Last ReviewOct 1, 2026

Next Review DateNot specified

Key ActionObtain prior authorization before providing intravenous ketamine for eligible members.

SourceLink

On This Page

QIDS-SR threshold

Qualifying resultA qualifying severe-depression score on the 16-item QIDS-SR

Assessment windowWithin the past 30 days

Numeric thresholdA numeric threshold is not stated in this section of the policy

PHQ-9 threshold

Qualifying scorePHQ-9 score ≥ 15

Assessment windowWithin the past 30 days

Clinical useSupports documentation of a severe current depressive episode for initial IV ketamine treatment

Uncontrolled hypertension

Systolic blood pressureGreater than 160 mm Hg

Diastolic blood pressureGreater than 90 mm Hg

DefinitionEither value constitutes current uncontrolled hypertension

Intracerebral hemorrhage

Recent historyIntracerebral hemorrhage occurring less than 6 months ago

Older historyA history longer than 6 months ago requires neurology or neurovascular clearance

Clearance requirementRequired clearance applies before treatment when the hemorrhage history is older than 6 months

HAM-D severity

0–7Normal

8–16Mild depression

17–23Moderate depression

≥24Severe depression

MADRS severity

0–6No depression

7–19Mild depression

20–34Moderate depression

35–60Severe depression

QIDS severity

1–5No depression

6–10Mild depression

11–15Moderate depression

16–20Severe depression

21–27Very severe depression

PHQ-9 severity

5–9Mild depression

10–14Moderate depression

15–19Moderately severe depression

20–27Severe depression

The member must be at least 18 years old.
A satisfactory medication trial generally requires at least 6 weeks at generally accepted doses, or the duration defined by the treating physician, with at least 80% adherence.
Potential antidepressant classes include tricyclic antidepressants, SSRIs, SNRIs, mirtazapine, and bupropion.
Augmentation may include lithium, an atypical antipsychotic, or thyroid hormone T3.

Documentation Required

Initial Treatment Documentation

Document that the member meets DSM-5 criteria for unipolar major depressive disorder and has a severe current depressive episode, demonstrated within the past 30 days by an accepted depression scale. The record must also support concurrent therapy, psychiatric evaluation, treatment resistance, and the planned monitored administration setting.

Provide a qualifying severity score: HAMD ≥17, MADRS ≥28, QIDS-SR-16 qualifying score, or PHQ-9 ≥15.
Document that IV ketamine will be given with an oral antidepressant and/or mood stabilizer.
Include the four treatment attempts, medication classes, trial duration, doses, adherence, and inadequate response.
A psychiatrist must evaluate the patient and document that the patient is an appropriate IV ketamine candidate.
Treatment must occur in a hospital or provider office under monitoring by a psychiatrist or other specialist experienced in IV ketamine administration.
The prescriber must specialize in the diagnosis, such as psychiatry, or document consultation with an appropriate specialist.

Documentation Required

Reauthorization Documentation

Reauthorization may be granted for one year only when ongoing treatment and clinical benefit are documented. Submit evidence of continued pharmacologic therapy, symptom or functional improvement, and the member’s substance-use status.

Document that IV ketamine continues with an oral antidepressant or mood stabilizer.
Document improvement on an appropriate scale, such as CGI, QIDS-SR-16, PHQ-9, HAM-D, or MADRS, and/or significant functional improvement.
Document that the member has no substance use disorder, is in remission with complete abstinence for one month, or is receiving maintenance treatment.

Documentation Required

Safety Screening and Required Clearances

Screen for medical conditions that require exclusion or specialist clearance before IV ketamine. Include the relevant clearance documentation in the authorization submission when required.

Aneurysmal vascular disease involving the thoracic or abdominal aorta, intracranial or peripheral arterial vessels, or an arteriovenous malformation requires cardiovascular or neurovascular clearance.
A prior intracerebral hemorrhage more than 6 months ago requires neurology or neurovascular clearance; a hemorrhage within the prior 6 months is excluded.
Uncontrolled hypertension, cardiac arrhythmia, or unstable or symptomatic cardiovascular disease requires Cardiology clearance.
Cerebrospinal fluid obstructive states require Neurology clearance.
Intraocular pressure pathology, including uncontrolled glaucoma or acute globe injury, requires Ophthalmology clearance.
Uncontrolled hyperthyroidism requires medical clearance.

Denial Risk

Clinical Exclusions

IV ketamine may be denied when an exclusion applies, unless the policy specifically allows case-by-case consideration or the required clearance is obtained. Review all psychiatric, medical, substance-use, and care-coordination exclusions before submitting the request.

Pregnancy, breastfeeding, or risk of becoming pregnant.
Current or prior primary psychotic disorder, such as schizophrenia; psychotic features in severe depression are considered case by case.
Dementia; hypersensitivity to esketamine, ketamine, or an excipient; or porphyria.
Active substance use disorder when the member is unwilling to receive treatment; or current or previous misuse of ketamine.
Prior adequate-dose IV ketamine that failed to reduce symptoms or improve function.
Delirium within the prior 7 days.
Recent intracerebral hemorrhage, defined as within 6 months, or an older hemorrhage without required neurology or neurovascular clearance.
Uncontrolled hypertension, cardiac arrhythmia, unstable or symptomatic cardiovascular disease, or other cardiovascular condition without required clearance.
Cerebrospinal fluid obstructive states, intraocular pressure pathology, or uncontrolled hyperthyroidism without required specialist or medical clearance.
Active pulmonary infection or severe pulmonary disease.
The member is not under ongoing care of a psychiatrist, APRN, or PCP, or will not sign a release to permit communication with the primary team and family.

Denial Risk

Initial Criteria Not Met

An initial request is at risk for denial when the member does not satisfy every applicable medical-necessity requirement for the 28-day initial authorization. Confirm that the diagnosis, severity, treatment resistance, specialist evaluation, concurrent medication, and monitored administration plan are all documented.

The member is younger than 18 or does not meet DSM-5 criteria for unipolar major depressive disorder.
The current episode is not severe under an accepted depression-rating threshold documented within the past 30 days.
The member has not failed four qualifying treatment attempts in the current episode, lacks trials from at least two antidepressant classes, has inadequate trial duration, or has less than 80% adherence.
IV ketamine is not planned with an oral antidepressant and/or mood stabilizer.
A psychiatrist has not evaluated and documented candidacy, or the required specialist involvement and monitored hospital or office administration are not established.

Denial Risk

Reauthorization Criteria Not Met

Continuation treatment is at risk for denial when the reauthorization request does not meet every required criterion for the one-year authorization period. Submit current evidence rather than relying only on the initial authorization record.

IV ketamine is not being continued with an oral antidepressant or mood stabilizer.
There is no documented improvement on an appropriate depression rating scale and no significant functional improvement.
The member has an active substance use disorder without remission through complete abstinence for one month or without maintenance treatment.

At least 80% adherence throughout the medication trial

Racemic ketamine

CompositionA mixture of R- and S-ketamine molecules

AdministrationMost often given by infusion into the bloodstream, also called intravenous or IV ketamine

Depression useUsed off-label to treat depression

Unipolar major depressive episode

Symptom countFive or more symptoms

DurationPresent for 2 weeks

Required core symptomAt least one symptom must be depressed mood or anhedonia

Clinical impactSymptoms cause clinically significant distress or functional impairment and are not attributable to a substance or another medical condition

HAM-D

Instrument typeClinician-rated scale

PurposeAssesses depression severity before, during, and after treatment

Total score range0 to 52

MADRS

Instrument type10-item questionnaire used by psychiatrists

PurposeEvaluates the efficacy of antidepressant treatment by assessing depressive symptom severity

Total score range0 to 60

QIDS

Instrument typeSelf-report measure of depression

DomainsCovers sleep disturbance, sad mood, appetite or weight, concentration, self-criticism, suicidal ideation, interest, energy or fatigue, and psychomotor agitation or retardation

Score interpretationSeverity categories range from no depression through very severe depression

PHQ-9

Diagnostic thresholdFive or more of the nine depressive symptom criteria

Assessment periodSymptoms present at least more than half the days during the past 2 weeks

Core symptomOne symptom must meet the required core symptom criteria