ModifiedCentenePolicy CP.PMN.284

Dextromethorphan/Bupropion (Auvelity)

Medical necessity and prior authorization criteria for Auvelity (dextromethorphan/bupropion) for treatment of major depressive disorder and agitation associated with Alzheimer's disease for members covered by Centene-affiliated plans.

Policy Summary

PayerCentene

PolicyDextromethorphan/Bupropion (Auvelity)

Policy CodePolicy CP.PMN.284

Change TypeAdded AD agitation indicationIL step therapy bypasscontinued therapy revisions

Effective Date12.01.22

Next Review Date

Key ActionSubmit prior authorization with documentation showing diagnosis, age ≥18, required step therapy history (or state bypass), and dosing within limits.

SourceLink

POLICY UPDATE CHANGES

Added new indication for treatment of agitation associated with dementia due to Alzheimer's disease (AD).

Added step therapy bypass for Illinois HIM per IL HB 5395 (1/1/2026) for HIM requests.

Revised continued therapy criteria to allow continuity of care for MDD.

Clarified that step therapy requires failure of TWO preferred formulary antidepressants (SSRI, SNRI, bupropion, mirtazapine) each tried >=4 weeks unless contraindicated.

12 monthsApproval duration

≥18Minimum age

2Required failed antidepressants

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90/210 mgMax daily dose

IL HB 5395State law (IL)

Coverage Criteria

Initial Therapy - Major Depressive Disorder

Covered when ALL of the following are met

MDD Initial: 1. Diagnosis of major depressive disorder (MDD); 2. Age ≥ 18 years; 3. Member meets one of the following: (a) request is for a member in a State with limitations on step therapy (see Appendix D), OR (b) failure of TWO preferred formulary antidepressants (SSRI, SNRI, bupropion, mirtazapine), each tried ≥ 4 weeks at up to maximally indicated doses unless clinically significant adverse effects or contraindications exist (note: for Illinois HIM requests the step therapy requirements do not apply per IL HB 5395); 4. Dose does not exceed BOTH: (a) 90 mg dextromethorphan and 210 mg bupropion per day; AND (b) 2 tablets per day.

Approval duration: 12 months

Initial Therapy - Alzheimer's Disease Related Agitation

Covered when ALL of the following are met

AD Agitation Initial: 1. Diagnosis of agitation associated with dementia due to Alzheimer disease (AD); 2. Age ≥ 18 years; 3. Auvelity is not prescribed as an as needed ('prn') treatment; 4. Dose does not exceed BOTH: (a) 90 mg dextromethorphan and 210 mg bupropion per day; AND (b) 2 tablets per day.

Approval duration: 12 months

Continued Therapy

Covered when ALL of the following are met

Continued Therapy: 1. Member meets one of the following: (a) currently receiving medication via Centene benefit or previously met initial approval criteria; (b) documentation supports that member is currently receiving Auvelity for MDD and has received medication for at least 30 days; (c) member is currently receiving medication and is enrolled in a state/product with continuity of care regulations; 2. Member is responding positively to therapy; 3. If request is for a dose increase, the new dose does not exceed BOTH: (a) 90 mg dextromethorphan and 210 mg bupropion per day; AND (b) 2 tablets per day.

Approval duration: 12 months

Updated Indications and Continued Therapy

Policy revisions noted (no full criteria text in this excerpt).

Revisions Announced: Added new indication for treatment of agitation associated with dementia due to Alzheimer disease; revised continued therapy criteria to allow continuity of care for major depressive disorder (MDD).

Full criteria details not present in this document excerpt.

Requests for uses that are not FDA‑approved and are not otherwise addressed in this policy will be excluded unless the provider supplies sufficient documentation of efficacy and safety consistent with the Health Plan's off‑label use policies. See off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), and CP.PMN.53 (Medicaid) for the documentation standards required to consider coverage of non‑FDA indications.

Within the document excerpt provided there are no additional explicit exclusions listed beyond the general statement that non‑FDA indications not addressed here require off‑label documentation. The revision history and change log do not add other exclusion clauses in this excerpt.

Uses for indications that are not FDA‑approved and that lack adequate supporting documentation per the Health Plan's off‑label use policies are not authorized for coverage. Providers should reference the applicable off‑label policies (CP.CPA.09, HIM.PA.154, CP.PMN.53) when submitting requests for such indications.

The excerpt contains no explicit statements labeling any additional uses as 'not medically necessary.' The policy revision notes focus on added indications and continuity‑of‑care changes; no explicit not‑medically‑necessary language appears in this selection.

Coding and Dosing Limits

Policy Identifiermixed

CP.PMN.284

Clinical policy identifier

Maximum daily dose

Maximum daily dextromethorphan dose90 mg per day

Maximum daily bupropion dose210 mg per day

Maximum tablets per day2 tablets/day

Provider Actions and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior Authorization Required: Auvelity (dextromethorphan/bupropion) requests require prior authorization and must meet applicable initial or continuation therapy criteria, including diagnosis, age, dosing limits, and step therapy when applicable.

Approval duration: 12 months
Dose limits: ≤ 90 mg dextromethorphan and ≤ 210 mg bupropion per day; ≤ 2 tablets/day

Step Therapy

Step Therapy Prior Authorization

Step therapy applies for Major Depressive Disorder (MDD): member must have failed TWO preferred formulary antidepressants (each tried ≥ 4 weeks at up to maximally indicated doses) unless contraindicated or clinically significant adverse effects occur. Preferred classes include SSRI, SNRI, bupropion, or mirtazapine. Exceptions or state-specific redirection provisions (see Appendix D) may modify this requirement.

Failure of TWO preferred formulary antidepressants: each ≥ 4 weeks at up to maximally indicated doses

Level of Care Criteria

Treatment Modalities

Pharmacologic (Auvelity)

Auvelity pharmacologic treatment: Dosing per indication: MDD dosing starts 45/105 mg PO QAM for first 3 days then increase to BID (at least 8 hours apart) based on tolerability; agitation in AD titration begins 30/105 mg QAM for first 7 days then increase to BID and to 45/105 mg BID by day 15 as tolerated. Maximum: 2 tablets/day (dextromethorphan 90 mg / bupropion 210 mg).

Prescribe within maximum dose limits.

Pharmacologic (dextromethorphan/bupropion)

Active ingredients (dextromethorphan/bupropion): Auvelity contains dextromethorphan and bupropion; maximum combined daily dose is dextromethorphan 90 mg and bupropion 210 mg (2 tablets/day). Dosing regimens vary by indication as specified for MDD and agitation associated with AD.

Do not exceed specified maximums.

Definitions

Major Depressive Disorder (MDD)

DefinitionMajor depressive disorder (MDD)

FDA‑approved indicationAuvelity is indicated for the treatment of MDD in adults.

Minimum age for coverage≥ 18 years

Alzheimer's disease related agitation

DefinitionAgitation associated with dementia due to Alzheimer’s disease (AD)

Use restrictionAuvelity is not indicated as an as‑needed ('prn') treatment for agitation associated with dementia due to AD.

Minimum age for coverage

Background

Auvelity is described as a fixed‑dose combination product containing dextromethorphan and bupropion. Dextromethorphan acts via NMDA receptor antagonism and sigma‑1 agonism, while bupropion serves as a CYP2D6 inhibitor and aminoketone antidepressant; together they are indicated for adult major depressive disorder and, per recent revision, for agitation associated with dementia due to Alzheimer disease. Dosing and titration differ by indication and the product carries standard safety considerations including age‑related warnings.

Policy Summary

PayerCentene

PolicyDextromethorphan/Bupropion (Auvelity)

Policy CodePolicy CP.PMN.284

Change TypeAdded AD agitation indicationIL step therapy bypasscontinued therapy revisions

Effective Date12.01.22

Next Review Date

Key ActionSubmit prior authorization with documentation showing diagnosis, age ≥18, required step therapy history (or state bypass), and dosing within limits.

SourceLink

On This Page

Preferred classes: SSRI, SNRI, bupropion, mirtazapine

See Appendix D for states with limitations on step therapy/redirection

Prior Authorization

Prior Authorization Updated for Illinois (IL)

Illinois Step Therapy Bypass: For Illinois Health Insurance Marketplace (HIM) requests, step therapy bypass for MDD has been added per IL HB 5395 and is effective 01/01/2026; therefore, the two-drug step requirement does not apply for IL HIM requests. Operational systems and PA workflows should reflect this state-specific bypass.

IL HB 5395: step therapy bypass for IL HIM effective 01/01/2026
4Q2025 policy update added IL bypass — update PA processes accordingly

Documentation Required

Documentation and State Precedence

Documentation Required and State Precedence: Providers must submit supporting documentation (office notes, labs, medication history, prior trial details) to demonstrate that the member meets all applicable criteria. For Medicaid members, state Medicaid coverage provisions take precedence over this clinical policy when there is a conflict; follow the applicable state Medicaid manual and product-specific addendums for continuity-of-care or redirection rules.

Submit office chart notes, lab results, and documentation of prior antidepressant trials (drug, dose, duration, reason for discontinuation)
For Medicaid, follow state Medicaid provisions when they conflict with this policy

Denial Risk

Non‑FDA Indications

Non‑FDA (Off‑Label) Indications: Requests for indications not FDA‑approved and not addressed in this policy will be denied unless sufficient off‑label evidence and documentation are provided in accordance with applicable off‑label policies (CP.CPA.09 for commercial, HIM.PA.154 for HIM, CP.PMN.53 for Medicaid) or evidence of coverage documents.

Off‑label requests require clinical evidence per referenced off‑label policies
Refer to product-specific off‑label coverage rules for the relevant line of business

Note

Removal of Individual Component Criteria

Removal of Individual Component Criteria: Prior policy language redirecting trials to individual Auvelity components has been removed; prior authorization decisions will no longer accept trials of individual dextromethorphan or bupropion components in lieu of the required preferred formulary antidepressant trials.

Do not accept prior trials of individual dextromethorphan or bupropion products as meeting step therapy requirements
Policy clarifications made in 4Q2023 and corrected 01/10/24 removed component‑level redirection

Revision / round identifier

Revision identifierRT4

Revision summaryRT4 added a new indication for agitation associated with dementia due to AD and revised continued therapy criteria to allow continuity of care for MDD.

Revision date noted in log05.06.26 (RT4)

Legislative reference

Legislative referenceIL HB 5395

Effect on policyStep therapy requirements do not apply to Illinois HIM requests per IL HB 5395 (effective 1/1/2026).

Recorded in revision logAdded in 4Q 2025 annual review and referenced in RT4 revisions.