Dextromethorphan/Bupropion (Auvelity) (PDF)

Coverage Summary

Scope: This policy defines medical necessity, prior authorization, and continuation criteria for Auvelity (dextromethorphan/bupropion) for the treatment of major depressive disorder (MDD) in adults across Centene lines of business (Commercial, HIM, Medicaid). Coverage stance: covered_with_criteria. FDA indication: Treatment of major depressive disorder (MDD) in adults. Effective date: 12.01.22; Last review/ P&T approval: 11.25.25. Approval duration: 12 months for both initial and continued therapy when criteria are met. Background safety highlights: Auvelity is an extended-release fixed-dose combination of dextromethorphan hydrobromide and bupropion hydrochloride; it carries a boxed warning for an increased risk of suicidal thoughts and behavior in pediatric and young adult patients and is not approved for pediatric use. Key contraindications include history of seizure disorder, current or prior bulimia/anorexia nervosa, abrupt discontinuation of alcohol/benzodiazepines/barbiturates/antiepileptics, use with an MAOI or within 14 days of stopping an MAOI, and hypersensitivity to components. Dosing limits and administration are summarized in the approval criteria (see criteria for specific thresholds).

Initial Approval Criteria - Major Depressive Disorder

Covered when ALL of the following are met:

ALL of the following

Diagnosis of major depressive disorder (MDD)
Age ≥ 18 years>= 18 years
ONE of
- Request is for the treatment of a member in a State with limitations on step therapy in certain mental health settings (see Appendix D)
- Failure of TWO preferred formulary antidepressants (each tried for ≥ 4 weeks at up to maximally indicated doses) from SSRI, SNRI, bupropion, or mirtazapine, unless clinically significant adverse effects or contraindicationsEach tried >= 4 weeks
  Preferred formulary antidepressants required
ALL of the following
- ≤ 90 mg dextromethorphan and ≤ 210 mg bupropion per dayMax daily dextromethorphan 90 mg; Max daily bupropion 210 mg
- ≤ 2 tablets per dayMax tablets per day = 2

Initial Approval Criteria - Other diagnoses/indications

If not covered under main criteria or recent label change:

ANY of the following

If drug has recently (within last 6 months) undergone a label change not yet reflected in this policy, follow the relevant formulary/no-coverage/non-formulary policy for the applicable line of business
Commercial: CP.CPA.190; Marketplace: HIM.PA.33 (no-coverage) or HIM.PA.103 (non-formulary); Medicaid: CP.PMN.255 (no-coverage) or CP.PMN.16 (non-formulary)
If requested use (diagnosis, age, dosing) is not listed under section III and criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business
Commercial: CP.CPA.09; Marketplace: HIM.PA.154; Medicaid: CP.PMN.53

Continued Therapy - Major Depressive Disorder

Covered for continuation when ALL of the following are met:

ALL of the following

ANY of the following
- Member currently receiving medication via Centene benefit or member has previously met initial approval criteria
- Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to CC.PHARM.03A and CC.PHARM.03B)
Member is responding positively to therapy
Provider must document positive response
ALL of the following

Not Authorized Indications

Coverage is NOT authorized for:

ALL of the following

Non-FDA approved indications not addressed in this policy, unless sufficient documentation of efficacy and safety per off-label use policies
Commercial: CP.CPA.09; Marketplace: HIM.PA.154; Medicaid: CP.PMN.53

Applicable Codes

Product NDC / CodesNDC

No codes listed

Provider Actions & Authorization Rules

Prior Authorization

Prior authorization required

Authorization is required for Auvelity. When criteria are met, approval duration is 12 months for both initial and continued therapy.

Approval duration: 12 months

Documentation Required

Submit supporting documentation

Submit office chart notes, laboratory results, or other clinical information demonstrating the member meets all approval criteria (e.g., diagnosis, prior antidepressant trials, dosing limits, response to therapy).

Clinical Evidence & References

Evidence: FDA approved indication — Treatment of major depressive disorder (MDD) in adults (Auvelity Prescribing Information, Axsome Therapeutics, June 2024). Primary reference: Auvelity Prescribing Information, Axsome Therapeutics, June 2024. Boxed warning summary: increased risk of suicidal thoughts and behavior in pediatric and young adult patients; monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors; Auvelity is not approved for pediatric patients. Note: This policy is applicable to adults only (age ≥ 18 years) per the approval and criteria.

Background & Definitions

Background: Auvelity is an extended-release, fixed-dose combination tablet containing dextromethorphan hydrobromide (an uncompetitive NMDA receptor antagonist and sigma-1 receptor agonist) and bupropion hydrochloride (an aminoketone and CYP2D6 inhibitor). It is indicated for the treatment of major depressive disorder (MDD) in adults. Recommended dosing: 1 tablet once daily for the first 3 days, then 1 tablet twice daily (at least 8 hours apart); maximum 2 tablets/day (total daily dose dextromethorphan 90 mg / bupropion 210 mg). Contraindications include: seizure disorder; current or prior diagnosis of bulimia or anorexia nervosa; abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs; concomitant use with an MAOI or within 14 days of stopping/starting an MAOI; and hypersensitivity to bupropion, dextromethorphan, or other components. Boxed warning: increased risk of suicidal thoughts and behavior in pediatric and young adult patients; not approved for pediatric use and all antidepressant-treated patients should be closely monitored.

Term	Definition
{"text":"MDD","status":""},{"text":"Major depressive disorder","status":""}
{"text":"MAOI","status":""},{"text":"Monoamine oxidase inhibitor","status":""}

Policy Thresholds

Age≥ 18 years

Antidepressant trial durationEach preferred antidepressant tried for ≥ 4 weeks at up to maximally indicated doses

Maximum daily dextromethorphan90 mg/day

Revision History

11.25.25revisedLatest

4Q 2025 annual review: added step therapy bypass for IL HIM per IL HB 5395; references reviewed and updated. (Material change)

07.30.24revised

4Q 2024 annual review: no significant changes; updated dosing regimen for therapeutic alternatives per Clinical Pharmacology; references reviewed and updated.

09.06.23revised

4Q 2023 annual review: clarified that the two antidepressants must be preferred formulary antidepressants; removed redirection to individual Auvelity components; references reviewed and updated. (Material change)