ModifiedCentenePolicy CP.PMN.65

Vortioxetine (Trintellix) coverage

Defines medical necessity and prior authorization criteria for vortioxetine (Trintellix) for treatment of major depressive disorder and continuity/renewal requirements for members under Centene-affiliated health plans. Affects prescribers and prior authorization reviewers for HIM and Medicaid lines of business.

Policy Summary

PayerCentene

PolicyVortioxetine (Trintellix) coverage

Policy CodePolicy CP.PMN.65

Change TypeMaterial clinical updates (step therapy, trial durations, redirect options)

Effective DateMay 1, 2015

Next Review Date

Key ActionSubmit prior authorization demonstrating diagnosis of major depressive disorder, age ≥18, required prior antidepressant trials or applicable step-therapy exception, and dose within limits.

SourceLink

POLICY UPDATE CHANGES

Clarified failure of two antidepressants must be from at least two different drug classes.

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

Shortened alternative agent trial duration from 8 weeks to 4 weeks and added bupropion and mirtazapine as redirect options.

20max daily dose (mg)

12 moapproval duration

≥18minimum age

4 wks

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yesMedicaid precedence

Coverage Criteria for Vortioxetine (Trintellix)

Initial Therapy

Covered when ALL of the following are met for Initial Approval (Major Depressive Disorder):

Initial Approval - MDD: 1. Diagnosis of major depressive disorder; 2. Age ≥ 18 years; 3. Member meets one of the following (a, b, or c): For Illinois HIM requests, the step therapy requirements do not apply per IL HB 5395 (effective 1/1/2026). a. Request is for treatment of a member in a State with limitations on step therapy in certain mental health settings (see Appendix D); b. Fidelis Ambetter (New York Exchange): failure of ONE of the following, tried ≥4 weeks at up to maximally indicated doses unless clinically significant adverse effects or contraindicated: SSRI, SNRI, bupropion, mirtazapine, vilazodone (generic Viibryd); c. Failure of TWO antidepressants from at least two different classes, each tried ≥4 weeks at up to maximally indicated doses unless clinically significant adverse effects or contraindicated: SSRI, SNRI, bupropion, mirtazapine, vilazodone (generic Viibryd); 4. Dose does not exceed both: a) 20 mg per day; and b) 1 tablet per day.

Approval duration: 12 months

Continuation Therapy

Covered when ALL of the following are met for Continued Therapy (Major Depressive Disorder):

Continued Therapy - MDD: 1. Member is currently receiving medication via the Centene benefit, or documentation supports current receipt of Trintellix for a covered indication for at least 30 days; 2. Member is responding positively to therapy; 3. If request is for a dose increase, the new dose does not exceed both: a) 20 mg per day; and b) 1 tablet per day.

Approval duration: 12 months

Non‑FDA approved indications for vortioxetine (Trintellix) that are not specifically addressed by this policy are not authorized unless the provider submits sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies: HIM.PA.154 for Health Insurance Marketplace lines of business or CP.PMN.53 for Medicaid, or unless coverage is supported by the member’s evidence of coverage documents.

Coverage determinations for vortioxetine are made using this clinical policy as a medical necessity guide but remain subject to all terms, conditions, exclusions, and limitations of the member’s coverage documents (for example, evidence of coverage, certificate of coverage, policy or contract) and to applicable state and federal requirements. The Health Plan’s administrative policies and procedures and any legal or regulatory requirements take precedence where applicable.

Use of vortioxetine for off‑label indications without adequate supporting documentation is not authorized under this policy; such requests must meet the documentation standards set forth in the referenced off‑label use policies (HIM.PA.154 or CP.PMN.53) to be considered.

Policy Identifier and Dosing Key Data

Policy Identifiermixed

CP.PMN.65

Policy reference number for vortioxetine clinical policy

Maximum daily dose — vortioxetine (Trintellix)

Maximum daily dose20 mg/day

Dose frequency limit1 tablet per day

Typical titrationStart 10 mg orally daily then increase to 20 mg/day as tolerated

Prior Authorization, Documentation, and Step Therapy

Prior Authorization

Prior Authorization Required

Prior authorization is required for Trintellix (vortioxetine). Requests must include diagnosis and supporting clinical documentation. Coverage is governed by this policy's clinical criteria and by the member's evidence of coverage; if plan documents or applicable laws limit coverage, those limits apply.

Drug: Trintellix (vortioxetine)
Policy Number: CP.PMN.65
Effective Date: 2015-05-01

Prior Authorization

Trintellix approval criteria — key points

For Major Depressive Disorder, prior authorization approvals require: diagnosis of major depressive disorder, age ≥ 18 years, and meeting the step-therapy or redirection requirements (see step therapy callout). Dose limits: ≤ 20 mg per day and 1 tablet per day. Initial approvals are for 12 months.

Initial therapy: age ≥ 18, documented MDD
Dose limit: 20 mg/day and 1 tablet/day

Pharmacotherapy Considerations

pharmacotherapy

Pharmacotherapy options and operational note: Allowed alternative antidepressants for required step trials include SSRIs, SNRIs, bupropion, mirtazapine, and vilazodone (generic Viibryd). Trials are generally ≥4 weeks at maximally indicated doses unless clinically significant adverse effects or contraindications exist; specific agent dosing is listed in Appendix B.≥ 4 weeks

Trials generally ≥4 weeks at maximally indicated doses unless contraindicated or intolerable adverse effects; maximum vortioxetine dose limit: 20 mg/day and 1 tablet/day.

Definitions and Terms

vortioxetine (Trintellix) — key facts

Generic/BrandVortioxetine (Trintellix)

FDA indication referencedTreatment of major depressive disorder in adults

Typical starting dose10 mg orally daily

Maximum dose20 mg/day

MAOI — definition and timing (relative to vortioxetine)

DefinitionMonoamine oxidase inhibitor (MAOI)

Contraindication timing with vortioxetineDo not use MAOIs intended to treat psychiatric disorders within 21 days of stopping vortioxetine; do not start vortioxetine within 14 days of stopping an MAOI

Background — Drug Information

Vortioxetine (brand name Trintellix) is an oral antidepressant approved by the FDA for the treatment of major depressive disorder in adults. Typical dosing begins at 10 mg once daily with the option to increase to a maximum recommended dose of 20 mg per day. Clinicians should be mindful of contraindications and drug interactions (for example, monoamine oxidase inhibitors) and the boxed warning regarding increased risk of suicidal thinking and behavior in pediatric and young adult patients when making treatment decisions.

Policy Summary

PayerCentene

PolicyVortioxetine (Trintellix) coverage

Policy CodePolicy CP.PMN.65

Change TypeMaterial clinical updates (step therapy, trial durations, redirect options)

Effective DateMay 1, 2015

Next Review Date

SourceLink

On This Page

Approval duration: 12 months

Step Therapy

Step Therapy Requirements and Exceptions

Step therapy requires failure of two antidepressants from at least two different classes (SSRI, SNRI, bupropion, mirtazapine, or vilazodone) each tried ≥ 4 weeks at up to maximally indicated doses unless contraindicated or intolerable. Alternate pathway: for Fidelis Ambetter (NY Exchange) only, failure of one agent tried ≥ 4 weeks is required. Illinois HIM requests: per IL HB 5395 (effective 1/1/2026) the step therapy requirements do not apply (HIM bypass).

Required trial duration: ≥ 4 weeks at adequate dose
Classes: SSRI, SNRI, bupropion, mirtazapine, vilazodone (generic Viibryd)
Fidelis Ambetter NY: single-agent failure option
IL HIM: step therapy bypass per IL HB 5395

Documentation Required

Required Supporting Documentation

Providers must submit supporting documentation with the prior authorization request. Acceptable documentation includes office chart notes, medication history, progress notes demonstrating treatment attempts and response, and relevant laboratory or diagnostic test results.

Examples: office chart notes, medication administration records, lab results, progress notes, prior authorization forms showing prior trials

Denial Risk

Documentation Insufficiency May Result in Denial

If the documentation submitted does not sufficiently demonstrate that the member meets all policy criteria (including diagnosis, prior trials, dose limits, or continuity criteria), the request may be denied. Providers may be asked to supply missing records prior to a final determination.

Insufficient documentation triggers denial or request for additional information
Non‑FDA indications require evidence per off‑label use policies (HIM.PA.154 or CP.PMN.53) or evidence of coverage

Note

Coverage Governed by Plan Documents and Law

Coverage decisions are guided by this clinical policy but remain subject to the member's evidence of coverage, certificate of coverage, plan contract terms, and applicable state or federal law. Even if policy criteria are met, benefits may be limited or denied per those documents.

Follow the member's evidence of coverage/certificate and state/federal law
Plan administrative policies and procedures also govern coverage decisions

Other interaction warningsDo not start vortioxetine in a patient being treated with linezolid or intravenous methylene blue due to serotonin syndrome risk

Health Plan — definition and policy context

DefinitionHealth Plan: 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 affiliates.

Policy contextThis clinical policy provides a guide to medical necessity to assist coverage decisions but is not a contract or guarantee of payment

Document limitationsCoverage decisions are subject to the terms, exclusions, and limitations in the member's coverage documents and applicable law