CurrentPremera BluecrossPolicy 5.01.659

Antipsychotics (Second‑generation antipsychotic pharmacy coverage)

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Defines pharmacy benefit medical necessity criteria, age limits, quantity and duration limits, and documentation requirements for oral second‑generation (atypical) antipsychotics and select other antipsychotic products for Premera Bluecross members.

Policy Summary

PayerPremera Bluecross

PolicyAntipsychotics (Second‑generation antipsychotic pharmacy coverage)

Policy CodePolicy 5.01.659

Change TypeMaterial updates (added Bysantirevised Cobenfy quantity limit)

Effective DateAug 1, 2026

Last ReviewAug 1, 2026

Next Review DateAug 1, 2026

Key ActionObtain prior authorization and submit medical records demonstrating diagnosis, medication history, and prior trials of generic SGAs as required by the drug-specific criteria.

SourceLink

POLICY UPDATE CHANGES

Added coverage criteria for Bysanti (milsaperidone).

Updated criteria for Cobenfy (xanomeline and trospium chloride) to add a quantity limit of 60 capsules per 30 days.

Removed brand clozapine and brand clozapine ODT because they are no longer on the market.

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CurrentPremera BluecrossPolicy 5.01.659

Antipsychotics (Second‑generation antipsychotic pharmacy coverage)

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Policy Summary

PayerPremera Bluecross

PolicyAntipsychotics (Second‑generation antipsychotic pharmacy coverage)

Policy CodePolicy 5.01.659

Change TypeMaterial updates (added Bysantirevised Cobenfy quantity limit)

Effective DateAug 1, 2026

Last ReviewAug 1, 2026

Next Review DateAug 1, 2026

Key ActionObtain prior authorization and submit medical records demonstrating diagnosis, medication history, and prior trials of generic SGAs as required by the drug-specific criteria.

SourceLink

POLICY UPDATE CHANGES

Added coverage criteria for Bysanti (milsaperidone).

Updated criteria for Cobenfy (xanomeline and trospium chloride) to add a quantity limit of 60 capsules per 30 days.

Removed brand clozapine and brand clozapine ODT because they are no longer on the market.

Coverage Criteria

Brand second‑generation antipsychotics — general rule

Brand second‑generation antipsychotics may be considered medically necessary when the drug‑specific trial requirements are met.

General brand SGA requirement: The individual has tried the required number of generic second‑generation antipsychotics and had an inadequate response or intolerance as specified by the requested brand product; applies to individuals not previously treated with the requested therapy when noted.varies by product (see product-specific nodes)

Applies to most brand SGAs listed in policy

Bysanti (milsaperidone)

Bysanti may be considered medically necessary for schizophrenia or acute manic/mixed episodes of bipolar I when ALL are met:

Bysanti criteria: The individual is aged 18 years or older AND has tried 2 generic second‑generation antipsychotics and had an inadequate response or intolerance AND the dose is limited to 24 mg daily.dose ≤ 24 mg/day

Bysanti specific prior trial = 2 generics

Cobenfy (xanomeline and trospium chloride)

Cobenfy may be considered medically necessary for schizophrenia when ALL are met:

Cobenfy criteria: The individual is aged 18 years or older AND has been diagnosed with schizophrenia based on DSM criteria AND has tried 3 generic second‑generation antipsychotics and had an inadequate response or intolerance AND the prescription is by or in consultation with a psychiatrist AND dose is limited to 125 mg/30 mg capsule twice daily AND quantity is limited to 60 capsules per 30 days.125 mg/30 mg twice daily; 60 capsules/30 days

Contraindications include urinary retention, moderate/severe kidney or liver disease, gastric retention, untreated narrow‑angle glaucoma, or hypersensitivity to components.

Latuda (lurasidone HCl)

Latuda for bipolar depression

Latuda for bipolar depression: Latuda (lurasidone HCl) may be considered medically necessary for the treatment of bipolar depression when the individual has tried generic lurasidone and had an inadequate response or intolerance.prior trial of generic lurasidone

Drug‑specific prior trial requirement

Nuplazid (pimavanserin)

Parkinson's disease psychosis

Nuplazid criteria: Nuplazid (pimavanserin) may be considered medically necessary for hallucinations and delusions associated with Parkinson's disease psychosis; use is restricted to individuals with Parkinson's disease psychosis and Nuplazid is not subject to the other brand SGA criteria in this policy.PD psychosis diagnosis

Nuplazid limited to Parkinson's disease psychosis indication

Opipza (aripiprazole oral film) and Rexulti (brexpiprazole)

Formulation and indication‑specific rules

Opipza criteria: Opipza (aripiprazole oral film) may be considered medically necessary when the individual has tried 1 generic second‑generation antipsychotic and had an inadequate response or intolerance OR documentation is provided that the oral film is clinically necessary (e.g., trouble swallowing); the dose is limited to 30 mg per day.30 mg/day

Swallowing difficulty exception allowed

Rexulti criteria: Rexulti (brexpiprazole) may be considered medically necessary when the individual has tried aripiprazole and had an inadequate response or intolerance. For agitation associated with dementia due to Alzheimer's disease, documentation of agitation is required AND the dose is limited to 3 mg once daily.3 mg once daily for dementia agitation

Rexulti is not approved for dementia‑related psychosis without agitation (boxed warning)

Symbyax (fluoxetine‑olanzapine) and Vraylar (cariprazine)

Indication‑specific prior trials

Symbyax criteria: Symbyax (fluoxetine‑olanzapine) may be considered medically necessary when the individual has tried generic fluoxetine‑olanzapine and had an inadequate response or intolerance.prior trial of generic fluoxetine‑olanzapine

Updated to require prior trial

Vraylar for bipolar depression: Vraylar (cariprazine) may be considered medically necessary for bipolar depression when the individual is aged 18 years or older AND has been diagnosed with bipolar depression AND has tried quetiapine, lurasidone, or olanzapine‑fluoxetine combination and had an inadequate response or intolerance.prior trial of one of specified agents

Vraylar prior trial requirement updated

Use of drugs for conditions not listed in this policy are considered investigational.

Use of the medications listed in this policy for indications or conditions that are not specifically included in this document is considered investigational and not medically necessary.

Coding

Codingmixed

No codes listed

Cobenfy quantity limit

Quantity limit60 capsules per 30 days

Bysanti dose limit

Maximum daily dose24 mg daily

Opipza dose limit

Maximum daily dose30 mg per day

Rexulti dose limit for agitation in dementia

Maximum dose for agitation in dementia

Provider Actions & Requirements

Prior Authorization

Prior authorization required for brand SGAs

Prior authorization is required for brand second‑generation antipsychotics. Approvals are subject to the drug‑specific prior trial and dosing/quantity limits described in the drug criteria (see product‑specific rules).

Step Therapy

Documented trials of generic SGAs required (step therapy)

Many brand antipsychotics require documented failure or intolerance to one or more generic second‑generation antipsychotics prior to approval; the required number of generic trials varies by product (see product‑specific criteria).

Example: Bysanti requires trials of 2 generic SGAs.
Example: Cobenfy requires trials of 3 generic SGAs.
Example: Opipza requires trial of 1 generic SGA (unless oral film is clinically necessary).

Background

Antipsychotic medications are used to treat acute psychosis and chronic psychotic disorders such as schizophrenia, and for other indications including acute agitation and bipolar disorder. Second‑generation antipsychotics (SGAs) are generally associated with a lower risk of extrapyramidal symptoms and tardive dyskinesia compared with first‑generation agents. This policy defines pharmacy benefit medical necessity criteria for oral SGAs and select other antipsychotic products, specifying age limits, required prior trials of generic SGAs for brand products, product‑specific dosing and quantity limits, authorization durations (up to 12 months), and documentation requirements to support medical necessity.

Definitions

First‑generation antipsychotics (FGAs)

DefinitionOriginal ('typical') antipsychotics associated with higher risk of movement-related side effects such as extrapyramidal symptoms and tardive dyskinesia.

ExamplesChlorpromazine, haloperidol (representative FGAs listed as 'first-generation antipsychotics').

Clinical noteHigher risk of EPS and tardive dyskinesia compared to second‑generation agents.

Second‑generation antipsychotics (SGAs)

DefinitionAtypical ('second‑generation') antipsychotics generally associated with lower risk of EPS and tardive dyskinesia compared to FGAs.

ScopeThis policy covers brand second‑generation antipsychotics and select other antipsychotic agents.

Initial Therapy Criteria

Initial therapy approval

Initial authorization rules

Initial authorization duration: Initial approvals for drugs listed in this policy may be approved up to 12 months if coverage criteria are met.up to 12 months

Applies to all listed drugs

Continuation Criteria

Continuation criteria

Re-authorization

Re-authorization: Re‑authorization may be approved up to 12 months if drug‑specific coverage criteria are met and chart notes document continued positive clinical response to therapy.up to 12 months

Continuing clinical benefit required

Step Therapy / Prior Trials

Requirement	Details
General prior trial requirement for most brand SGAs
The individual has tried 1 generic second-generation antipsychotic (e.g., aripiprazole, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone) and had an inadequate response or intolerance; applies to individuals not previously treated with the requested therapy.
Bysanti (milsaperidone) specific prior trial
The individual is aged ≥18 AND has tried 2 generic second-generation antipsychotics and had an inadequate response or intolerance (dose limited to 24 mg/day).
Cobenfy (xanomeline and trospium chloride) specific prior trial
The individual is aged ≥18 AND has tried 3 generic second-generation antipsychotics and had an inadequate response or intolerance; prescribed by or in consultation with a psychiatrist; dose limited to 125 mg/30 mg capsule twice daily; quantity limited to 60 capsules per 30 days.
Opipza (aripiprazole oral film) specific prior trial
The individual has tried 1 generic second-generation antipsychotic and had an inadequate response or intolerance OR documentation that oral film is clinically necessary (e.g., trouble swallowing); dose limited to 30 mg/day.
Rexulti (brexpiprazole) specific prior trial
The individual has tried aripiprazole and had an inadequate response or intolerance. For agitation associated with dementia due to Alzheimer's disease, documentation of agitation is required and dose limited to 3 mg once daily.

Quantity Limits

Cobenfy (xanomeline and trospium chloride)

Drug and componentsCobenfy (xanomeline and trospium chloride)

Indication coveredSchizophrenia for individuals aged 18 years or older when drug‑specific criteria are met.

Dose and formulation125 mg/30 mg capsule, twice daily (dose limited as specified in criteria).

Quantity limit60 capsules per 30 days

Safety/contraindicationsLabel contraindications include urinary retention, moderate/severe kidney or liver disease, gastric retention, untreated narrow‑angle glaucoma, or hypersensitivity to components.

Site of Care

Note

Site of care: pharmacy benefit

The oral antipsychotic drugs in this policy are managed through the pharmacy benefit.