ModifiedmhnPolicy CP.PMN.284

Clinical Policy: Dextromethorphan/Bupropion (Auvelity)

Medical necessity and prior authorization criteria for Auvelity (dextromethorphan/bupropion) for treatment of major depressive disorder in adults across Centene-affiliated lines of business.

Policy Summary

Payermhn

PolicyDextromethorphan/Bupropion (Auvelity) coverage criteria

Policy CodePolicy CP.PMN.284

Change TypeState bypasses and step therapy clarifications (IL bypass addedpreferred formulary antidepressant requirement clarified)

Effective DateDec 1, 2022

Next Review DateN/A

Key ActionSubmit prior authorization with documentation showing diagnosis of MDD, age ≥18, required prior therapy trials (unless exception), dosing within specified limits, and response for continuation.

SourceLink

POLICY UPDATE CHANGES

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

Clarified that required two prior antidepressant trials must be preferred formulary antidepressants.

Removed redirection to individual Auvelity components from step therapy/redirection language.

Added redirection bypass for members in a State with limitations on step therapy in certain mental health settings and included Appendix D (Texas requirements for single drug redirection).

2failed prior antidepressant trials

12approval duration (months)

90 mg / 210 mg

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max dextromethorphan / bupropion

TX, ILstate bypasses present

Coverage Criteria for Auvelity (dextromethorphan/bupropion)

Initial Therapy — Major Depressive Disorder

Covered when ALL of the following are met:

Initial MDD criteria: 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 in certain mental health settings (see Appendix D); OR (b) failure of TWO preferred formulary antidepressants (SSRI, SNRI, bupropion, or mirtazapine), each tried ≥ 4 weeks at up to maximally indicated doses unless clinically significant adverse effects or contraindications are present. 4. Dose does not exceed both of the following: (a) 90 mg dextromethorphan and 210 mg bupropion per day; AND (b) 2 tablets per day.

Approval duration: 12 months

Continuation Therapy — Major Depressive Disorder

Covered when ALL of the following are met:

Continued MDD criteria: 1. Member meets one of the following: (a) currently receiving medication via Centene benefit or previously met initial approval criteria; OR (b) member is currently receiving medication and is enrolled in a state/product with continuity of care regulations (see state-specific addendums for CC.PHARM.03A and CC.PHARM.03B). 2. Member is responding positively to therapy. 3. If request is for a dose increase, the new dose does not exceed both of the following: (a) 90 mg dextromethorphan and 210 mg bupropion per day; AND (b) 2 tablets per day.

Approval duration: 12 months

Other Diagnoses/Indications

If requested use is not covered under primary criteria:

Other diagnoses/indications: 1. If the drug has undergone a label change within the last 6 months that is not yet reflected in this policy (e.g., new indication, age expansion, new dosing), follow the formulary/no-coverage or non-formulary policy for the relevant line of business as applicable. 2. If the requested use (diagnosis, age, dosing) is not specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) and criterion 1 does not apply, refer to the off-label use policy for the relevant line of business (commercial, HIM, or Medicaid).

Follow relevant formulary and off-label policies: CP.CPA.190, HIM.PA.33, CP.PMN.255, HIM.PA.103, CP.PMN.16, CP.CPA.09, HIM.PA.154, CP.PMN.53 as applicable.

Utilization Management and State Bypass Provisions

Policy includes utilization management requiring trials of preferred formulary antidepressants and step therapy with state-specific redirection/bypass provisions.

State-specific step therapy logic: Step therapy generally requires failure of TWO preferred formulary antidepressants (each used ≥ 4 weeks at up to maximally indicated doses) unless clinically significant adverse effects or contraindications exist. A redirection/bypass exists for members in States with limitations on step therapy in certain mental health settings; Texas (see Appendix D) allows single-drug redirection for HIM requests. As of 1/1/2026, Illinois HIM requests are bypassed per IL HB 5395. The policy clarifies that the two antidepressants must be preferred formulary agents and removed redirection to individual Auvelity components.

Apply Health Plan prior authorization and step therapy processes; see Appendix D and state addenda for details.

Requests for indications that are not FDA-approved and are not specifically addressed in this policy are excluded from coverage unless the provider submits sufficient documentation of efficacy and safety consistent with the applicable off‑label use policies (see CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid) or the member’s evidence of coverage permits such use.

If a state Medicaid program’s coverage provisions conflict with this clinical policy, the state Medicaid provisions take precedence over the policy. Coverage decisions remain subject to the member’s contract terms, applicable law, and Health Plan‑level administrative policies and procedures.

Auvelity is not approved for use in pediatric patients. The product labeling contains a boxed warning noting an increased risk of suicidal thoughts and behaviors in pediatric and young adult patients treated with antidepressants; all patients started on antidepressant therapy should be closely monitored for clinical worsening, suicidal ideation, or unusual changes in behavior.

This policy is intended to provide guidance on medical necessity determinations for Auvelity and the criteria used for prior authorization and coverage. It is not a contract or a guarantee of payment and does not, by itself in this excerpt, constitute the exhaustive list of statements that would be defined as Not Medically Necessary for all circumstances.

Coding and Dosage Limits

No explicit codes listed in this document portionmixed

No codes listed

Maximum daily dose — Auvelity

Maximum daily dextromethorphan dose90 mg per day

Maximum daily bupropion dose210 mg per day

Maximum tablets per day2 tablets per day

Typical dosing regimen (first week)1 tablet PO once daily for first 3 days, then 1 tablet PO twice daily (at least 8 hours apart)

Thresholds — none present

Thresholds in this document portionNo numerical thresholds or limits beyond dosing/step therapy details are present in this excerpt

Related policy updates

Provider Actions and Prior Authorization Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Requests must include documentation demonstrating the member meets the medical necessity criteria for Major Depressive Disorder (MDD) and all other applicable policy requirements.

Prior authorization required for Auvelity (dextromethorphan/bupropion) per this clinical policy.
Approval decisions subject to member’s contract, benefit limitations, and Health Plan-level administrative policies and procedures.

Step Therapy

Prior Authorization and Step Therapy Requirements

This policy implements utilization management including prior authorization and step therapy requirements for Major Depressive Disorder. Generally, initial approval requires failure of two preferred formulary antidepressants (each tried ≥ 4 weeks at up to maximally indicated doses) unless the member qualifies for an exception or a state-level bypass/redirection applies. For continuation therapy, members must be responding to treatment or meet continuity-of-care provisions.

Step therapy: failure of TWO preferred formulary antidepressants (SSRI, SNRI, bupropion, or mirtazapine), each for ≥ 4 weeks at up to maximally indicated doses, unless clinically significant adverse effects or contraindications.

Pharmacotherapy

Pharmacotherapy — Auvelity

Pharmacotherapy (Auvelity): Auvelity (dextromethorphan/bupropion) is indicated for MDD in adults; contraindications and boxed warning apply (see Appendix C). Dosing and administration per product labeling and Appendix B; do not exceed 90 mg dextromethorphan and 210 mg bupropion per day or 2 tablets per day.

Dosing per Appendix and product labeling; monitor for boxed warning risks.

Pharmacotherapy (Auvelity)

Preferred antidepressant trial requirement: Clarification: the required two antidepressant trials referenced for initial approval must be preferred formulary antidepressants. Redirection to individual components of Auvelity has been removed from criteria.

Policy revision history documents this clarification and removal of component redirection.

Definitions and Drug Information

Auvelity (dextromethorphan/bupropion)

Product descriptionAuvelity is an extended-release, fixed-dose combination of dextromethorphan hydrobromide and bupropion hydrochloride

FDA-approved indicationIndicated for the treatment of major depressive disorder (MDD) in adults

Maximum approved MDD dosingMaximum dose: 2 tablets/day (dextromethorphan 90 mg / bupropion 210 mg)

Definition: Health Plan

Defined term'Health Plan' means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan's affiliates

Scope of definitionApplies to Health Plans that have adopted this clinical policy and their affiliates

Policy Summary

Payermhn

PolicyDextromethorphan/Bupropion (Auvelity) coverage criteria

Policy CodePolicy CP.PMN.284

Change TypeState bypasses and step therapy clarifications (IL bypass addedpreferred formulary antidepressant requirement clarified)

Effective DateDec 1, 2022

Next Review DateN/A

SourceLink

On This Page

Document notes state-specific redirection/bypass and Appendix updates but does not add numeric thresholds

Action for reviewersRefer to full policy Appendices for dosing of therapeutic alternatives and state appendices for redirection rules

Continuation/renewal: member must be responding positively to therapy; prior approval continuity allowed if member currently receiving medication via the Centene benefit or previously met initial criteria.

Step Therapy

Step Therapy Requirements and State Exceptions

Step therapy requirements are implemented consistent with applicable state laws and the policy’s Appendix D. Some states and product lines have limits on redirection or require fewer trial failures; when applicable, the state-specific provisions supersede the general step therapy requirement.

Appendix D lists states with limitations on redirection/step therapy in certain mental health settings (example: Texas — see Appendix D notes).
Illinois: As of 1/1/2026, IL HB 5395 provides a step therapy bypass for HIM requests; 4Q 2025 updates added IL HIM bypass per HB 5395.

Documentation Required

Required Documentation

Providers must submit supporting clinical documentation with authorization requests. Required materials include office chart notes, medication trials (dates, doses, and reasons for discontinuation if applicable), and relevant laboratory or diagnostic information demonstrating the member meets approval criteria.

Submit office notes documenting diagnosis of MDD and age ≥ 18.
Document prior antidepressant trials: drug name, start/stop dates, dose, duration (≥ 4 weeks each unless adverse effect/contraindication), and reason for failure if applicable.
If request is for continuation or dose increase, provide documentation of positive response and details of dosing.

Denial Risk

Non‑FDA Indications

Requests for non–FDA‑approved (off‑label) indications that are not addressed in this policy will be denied unless sufficient evidence of efficacy and safety is provided per the applicable off‑label use policies.

Off‑label requests must follow referenced off‑label policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), CP.PMN.53 (Medicaid) or evidence of coverage documentation.
If adequate supportive literature and rationale are submitted, coverage may be considered per those off‑label policies.

Note

Health Plan Administrative Requirements

Providers must follow applicable Health Plan‑level administrative policies and the member’s contract terms when submitting requests. This clinical policy is a guide to medical necessity and does not override contract provisions, state/federal law, or Health Plan procedures.

Coverage decisions are subject to all terms, conditions, exclusions, and limitations of the member’s evidence of coverage or contract documents.
Health Plan retains the right to change, amend, or withdraw this clinical policy; legal/regulatory requirements govern if discrepancies exist.

Policy roleDefinition used to clarify applicability and administrative responsibilities for implementation of this clinical policy

Auvelity is a fixed‑dose, extended‑release combination of dextromethorphan and bupropion. Dextromethorphan acts as an uncompetitive N‑methyl‑D‑aspartate (NMDA) receptor antagonist and a sigma‑1 receptor agonist, while bupropion is an aminoketone antidepressant that serves as a CYP2D6 inhibitor in this combination. The pharmacologic pairing is designed to provide antidepressant effects and is FDA‑approved for the treatment of major depressive disorder in adults.