CurrentmhnPolicy CP.PMN.65

Clinical Policy: Vortioxetine (Trintellix)

Clinical coverage policy defining medical necessity criteria, prior authorization requirements, dosing limits, continuation criteria, exclusions, therapeutic alternatives, and administration details for vortioxetine (Trintellix) for Centene-affiliated health plans (HIM, Medicaid).

Policy Summary

Payermhn

PolicyClinical Policy: Vortioxetine (Trintellix)

Policy CodePolicy CP.PMN.65

Change TypeClarified and revised coverage criteria; reference updates

Effective DateMay 1, 2015

Next Review Date

Key ActionProvider must submit office chart notes, lab results or other clinical information supporting that member meets all approval criteria.

POLICY UPDATE CHANGES

Shortened trial durations of alternative agents from 8 weeks to 4 weeks (3Q2021) and added bupropion and mirtazapine as trial options.

Added redirection bypass for members in States with limitations on step therapy and Appendix D listing Texas and notes (3Q2023).

Revised continued therapy to allow continuity of care for antidepressants and updated therapeutic alternatives (3Q2024).

References and appendix updates through 2025 (Trintellix PI Aug 2023; Clinical Pharmacology 2025).

1Covered Indication (FDA-approved)

4Therapeutic alternative classes listed

20 mg/dayMaximum daily dose

Coverage Summary

Vortioxetine (Trintellix) is covered with criteria for the treatment of major depressive disorder (FDA‑approved). Coverage requires documentation that the member meets the policy’s initial or continuation criteria, including age ≥ 18 and specified prior antidepressant trial(s) or applicable step‑therapy exceptions. The policy includes a boxed warning for increased suicidal thinking and behavior in pediatric and young adult patients, lists contraindications (hypersensitivity; concomitant MAOI use within specified washout periods; linezolid or IV methylene blue), and enforces therapeutic alternatives and dose limits. Dose limits are ≤ 20 mg/day and ≤ 1 tablet/day. Prior authorization is required and renewal is allowable for 12 months when continuation criteria are met.

Quick facts

Maximum daily dose≤ 20 mg/day

Maximum tablets per day≤ 1 tablet/day

Trial duration of alternative antidepressants≥ 4 weeks at up to maximally indicated doses

Minimum prior exposure for continuation≥ 30 days

Approval duration12 months

Initial Therapy Criteria

I. Initial Approval Criteria - Major Depressive Disorder

Provider must submit documentation supporting that member has met all approval criteria. Trintellix is medically necessary when ALL of the following are met:

ALL of the following

Diagnosis of major depressive disorder
Age ≥ 18 years
Member meets one of the following (a, b, or c)
- a: Request is for the treatment of a member in a State with limitations on step therapy in certain mental health settings (see Appendix D) (bypasses step therapy)

Continuation / Renewal Criteria

II. Continued Therapy / Renewal Criteria - Major Depressive Disorder

For continuation, must meet all:

ALL of the following

Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Trintellix for a covered indication and has received the medication for at least 30 days≥ 30 days
Member is responding positively to therapy
If request is for a dose increase, new dose limits (must meet both)
- a: New dose does not exceed 20 mg per day≤ 20 mg/day

Other Indications / Not Authorized

III. Other Diagnoses/Indications

If use not covered by primary criteria:

ANY of the following

If drug label changed within last 6 months not reflected in policy, follow formulary/no-coverage or non-formulary policies as specified (HIM.PA.33, CP.PMN.255, HIM.PA.103, CP.PMN.16)
If requested use is NOT specifically listed under section III and above does not apply, refer to off-label use policy (HIM.PA.154 for marketplace; CP.PMN.53 for Medicaid)

IV. Diagnoses/Indications Not Authorized

Non-FDA approved indications not addressed in this policy are not authorized unless there is sufficient documentation of efficacy and safety according to off-label use policies HIM.PA.154 or CP.PMN.53 or evidence of coverage documents

Provider Actions & Prior Authorization

Prior Authorization

Prior authorization required with step therapy exceptions

Prior authorization is required. The policy requires documentation of prior antidepressant trial failures per the criteria: either the single-agent option for Fidelis Ambetter (NY Exchange) — failure of ONE agent tried ≥ 4 weeks at up to maximally indicated doses (SSRI, SNRI, bupropion, mirtazapine, vilazodone) — or failure of TWO antidepressants from at least two different classes, each tried ≥ 4 weeks at up to maximally indicated doses. Exceptions/bypasses: members in states with limitations on step therapy (see Appendix D) bypass step therapy requirements; Fidelis Ambetter allows the single-agent option; Illinois HIM step therapy bypass was added per IL HB 5395.

Fidelis Ambetter (NY Exchange) single-agent option: failure of ONE of SSRI, SNRI, bupropion, mirtazapine, or vilazodone tried ≥ 4 weeks at up to maximally indicated doses
Standard step therapy: failure of TWO antidepressants from at least two different classes (SSRI, SNRI, bupropion, mirtazapine, vilazodone), each tried ≥ 4 weeks at up to maximally indicated doses
State limitations/redirection bypass: members in States with limitations on step therapy (Appendix D) bypass step therapy requirements (e.g., Texas noted; IL HIM step therapy bypass added per IL HB 5395)
Single step redirection allowance for Fidelis Ambetter (NY Exchange) per policy updates

Applicable Codes

Policy Reference Numbermixed

CP.PMN.65

Clinical Policy Reference Number for Vortioxetine (Trintellix)

Clinical Evidence & References

Primary evidence sources cited in the policy include the Trintellix Prescribing Information (Aug 2023) and the Clinical Pharmacology database; practice guideline sources referenced include the American Psychiatric Association and American College of Physicians guidelines. The policy explicitly notes the boxed warning for increased suicidal thinking and behavior in pediatric and young adult patients and lists contraindications such as hypersensitivity to vortioxetine, concomitant MAOI use within specified timeframes, and use with linezolid or intravenous methylene blue.

Evidence sourcesTrintellix Prescribing Information (Aug 2023); Clinical Pharmacology database; APA and ACP guidelines

Guideline-based trial change (3Q2021)Shortened alternative agent trials from 8 to 4 weeks and added bupropion and mirtazapine as options

Therapeutic alternatives listedSSRI, SNRI, bupropion, mirtazapine, vilazodone

Dosage form / dosing rangeTablets: 5 mg, 10 mg, 20 mg; usual titration to max 20 mg/day

Background

Vortioxetine is an FDA‑approved antidepressant indicated for the treatment of major depressive disorder. This policy defines initial and continuation coverage criteria for Centene‑affiliated plans (HIM, Medicaid), including prior authorization requirements, dose limits (≤ 20 mg/day, ≤ 1 tablet/day), contraindications (hypersensitivity; prohibited/limited use with MAOIs, linezolid, IV methylene blue), and the boxed warning regarding increased suicidal thoughts and behaviors in pediatric and young adult patients. Therapeutic alternatives listed in the policy include SSRI and SNRI class agents, bupropion (including Wellbutrin XL and SR), mirtazapine, and vilazodone (Viibryd). The policy scope applies to Centene‑affiliated health plans and includes step‑therapy details and state‑specific redirection/step therapy bypass provisions.

Definitions: SSRI = selective serotonin reuptake inhibitor; SNRI = serotonin norepinephrine reuptake inhibitor; MAOI = monoamine oxidase inhibitor.

Revision History

3Q2021 (05.27.21 / P&T 08.21)policy update

Shortened trial durations of alternative agents from 8 weeks to 4 weeks; added bupropion and mirtazapine as additional options; combined trial requirements to allow trying any two among SSRI, SNRI, bupropion, and mirtazapine.

3Q2023 (04.18.23 / P&T 08.23)policy update

Added redirection bypass for members in a State with limitations on step therapy in certain mental health settings and added Appendix D noting Texas with requirements for single drug redirection for HIM requests.

3Q2024 (05.29.24 / P&T 08.24)policy update

Revised continued therapy to allow continuity of care for antidepressants; in Appendix B added Wellbutrin SR to therapeutic alternatives and clarified that fluvoxamine used in depression is off-label.