CurrentPremera BluecrossPolicy N/A

Antipsychotics (Pharmacy Policy - 5.01.659)

Defines medical necessity criteria and documentation requirements for coverage of brand and specific antipsychotic oral products under the pharmacy benefit for Premera Bluecross members.

Policy Summary

PayerPremera Bluecross

PolicyAntipsychotics (Pharmacy Policy - 5.01.659)

Policy CodePolicy N/A

Change TypeMaterial revisions (moved criteriaupdated prior‑trial requirements)

Effective DateJun 1, 2026

Next Review DateN/A

Key ActionObtain prior authorization with documentation of required prior trials or clinical justification and submit office visit notes showing medication history and inadequate response or intolerance.

SourceLink

POLICY UPDATE CHANGES

Moved coverage criteria for all second‑generation antipsychotic brands from policy 5.01.605 to new policy 5.01.659 and added new formulary sections.

Updated Symbyax criteria to require trial of generic fluoxetine‑olanzapine prior to brand Symbyax.

Updated Vraylar criteria for bipolar depression to require prior trial of quetiapine, lurasidone, or olanzapine‑fluoxetine combination.

~18brand agents listed with criteria

12 monthsapproval length (initial/re-auth)

≥18min age where specified

125 mg/30 mg BIDCobenfy max dose

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Coverage Criteria for Brand Second‑Generation Antipsychotics

Initial coverage — Brand SGAs

Brand second‑generation antipsychotics — covered when ALL of the following are met:

General brand SGA requirement: The individual has tried 1 generic second‑generation antipsychotic (e.g., aripiprazole, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone) and had an inadequate response or intolerance.1 trial

Applies to listed brand SGAs unless otherwise specified.

Cobenfy (xanomeline and trospium chloride)

Cobenfy (xanomeline and trospium chloride) — covered when ALL of the following are met:

Age: The individual is aged 18 years or older.>=18 years

Diagnosis: Diagnosed with schizophrenia based on the most updated Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria.DSM diagnosis

Prior trials: Has tried 3 generic second‑generation antipsychotics (e.g., aripiprazole, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone) and had an inadequate response or intolerance.3 trials

Examples listed in policy.

Prescriber: Prescribed by or in consultation with a psychiatrist.psychiatrist involvement

Dose limited to 125 mg/30 mg capsule twice daily.125 mg/30 mg BID

Latuda (lurasidone HCL) — bipolar depression

Latuda (lurasidone HCL) — covered when ALL of the following are met:

Prior trial: The individual has tried generic lurasidone and had an inadequate response or intolerance.1 trial

Opipza (aripiprazole oral film)

Opipza (aripiprazole oral film) — covered when ANY of the following are met:

Prior trial or clinical necessity: Either 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).1 trial or clinical justification

Rexulti (brexpiprazole)

Rexulti — covered when ALL of the following are met:

Prior trial: The individual has tried aripiprazole and had an inadequate response or intolerance.prior aripiprazole

Rexulti dose limit specified for agitation in dementia due to Alzheimer’s: 3 mg once daily.

Rexulti — agitation with Alzheimer's dementia

Rexulti for agitation associated with dementia due to Alzheimer's disease — covered when ALL of the following are met:

Clinical condition: Documentation of agitation associated with dementia due to Alzheimer's disease (examples: pacing, gesturing, profanity, shouting, shoving, hitting).documented agitation

Dose limited to 3 mg once daily.3 mg daily

Symbyax (fluoxetine‑olanzapine)

Symbyax — covered when ALL of the following are met:

Prior trial: The individual has tried generic fluoxetine‑olanzapine and had an inadequate response or intolerance.prior generic fluoxetine‑olanzapine trial

Updated requirement per policy history.

Vraylar (cariprazine) — bipolar depression

Vraylar — covered for bipolar depression when ALL of the following are met:

Age: Individual is aged 18 years or older.>=18 years

Diagnosis: Has been diagnosed with bipolar depression.DSM diagnosis

Prior trials: Has tried quetiapine, lurasidone, or olanzapine‑fluoxetine combination and had an inadequate response or intolerance.prior trial of one of listed agents

Updated prior‑trial requirements per policy history.

Nuplazid (pimavanserin)

Nuplazid — covered when ALL of the following are met:

Indication: For treatment of hallucinations and delusions associated with Parkinson's disease psychosis.PD psychosis indication

Nuplazid is restricted to Parkinson's disease psychosis and is not subject to the general brand SGA criteria.

Cobenfy (xanomeline and trospium chloride) has specific contraindications and warnings that must be considered prior to authorization. The product label contraindicates use in individuals with urinary retention, moderate or severe kidney or liver disease, gastric retention, untreated narrow‑angle glaucoma, or a history of hypersensitivity to Cobenfy or its components. Prescribers should review these conditions when assessing eligibility for treatment and document absence of contraindications in the medical record.

Uses of drugs not specifically listed in this policy are considered investigational and are not covered. For the agents included, coverage is determined by the drug‑specific medical necessity criteria; all prescribing should follow the product FDA dosing and administration information unless the policy explicitly states otherwise. Initial and re‑authorization approvals for listed drugs may be granted for up to 12 months when the applicable criteria are met and documentation demonstrates continued clinical benefit.

Coding and Dose Limits

Coding statementneutral

No codes listed

Cobenfy dose limit — numeric dose limit information

Dose limit125 mg/30 mg capsule twice daily (maximum per policy)

FrequencyTwice daily (BID)

Formulation125 mg/30 mg combination capsule (xanomeline 125 mg + trospium chloride 30 mg)

Applies toCobenfy (xanomeline and trospium chloride) when used for schizophrenia in adults

Prior Authorization, Step Therapy, and Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for all brand-name second-generation antipsychotics and other listed agents per this policy. Submit a prior authorization request before initiating therapy to avoid claim denials or delays.

Applies to listed brand products and select formulations (see Policy Coverage Criteria).
Initial and re-authorization requests may be approved up to 12 months when criteria are met.

Step Therapy

Step Therapy Requirements

Step therapy requirements must be met where specified in the Policy Coverage Criteria. If the policy requires trial(s) of one or more generic second‑generation antipsychotics or specific branded agents, documentation of those trials (drug name, dose, dates, and reason for discontinuation or inadequate response) must be provided.

General requirement: Try 1 generic second‑generation antipsychotic (e.g., aripiprazole, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone) and document inadequate response or intolerance before brand coverage.

Definitions

Second‑generation antipsychotics (SGAs) — key definition of SGAs

DefinitionSecond‑generation antipsychotics (SGAs), also called atypical antipsychotics, are agents with generally lower risk of extrapyramidal symptoms and tardive dyskinesia compared to first‑generation antipsychotics.

Common examplesAripiprazole, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone (examples listed in policy)

Clinical usesTreat acute psychosis, schizophrenia, bipolar mania, acute agitation, and other psychiatric conditions as described in policy

Cobenfy (xanomeline and trospium chloride) — drug definition and notes

Drug class / compositionCobenfy is an oral combination of xanomeline (M1/M4 muscarinic receptor agonist) and trospium chloride (muscarinic antagonist)

Indication

Background

Antipsychotic medications are used to treat acute psychosis and chronic psychotic disorders such as schizophrenia, and are also employed for behavioral symptoms including agitation and for mood disorders such as bipolar mania. Second‑generation (atypical) antipsychotics generally have a lower risk of extrapyramidal symptoms and tardive dyskinesia than first‑generation agents but carry distinct metabolic and other adverse‑event profiles. Cobenfy is a novel, oral muscarinic agent approved for schizophrenia in adults; because its mechanism differs from traditional antipsychotics, it does not carry antipsychotic class boxed warnings but has a different adverse‑event profile and specific contraindications that must be considered when selecting therapy.

Revision History and Policy Changes

2026-06-01Interim review / formatting updateLatest

Interim review approved May 12, 2026: removed references to specific formulary section labels (Section 1/2/3) and non‑formulary exception reviews; updated formatting across the policy.

2026-02-01Annual review – clinical criteria updates

Annual review approved January 13, 2026: updated Symbyax criteria to require trial of generic fluoxetine‑olanzapine prior to brand Symbyax, and updated Vraylar criteria for bipolar depression to require prior trial of quetiapine, lurasidone, or olanzapine‑fluoxetine combination.

2026-01-01