Rexulti (brexpiprazole)

Rexulti (brexpiprazole) is a second-generation atypical antipsychotic that modulates the action of dopamine and serotonin, neurotransmitters in the brain that influence mood and cognition. The FDA has approved Rexulti for the following indications:

1. Adjunctive treatment of major depressive disorder (MDD) in adults
2. Treatment of schizophrenia in adults and pediatric patients ages 13 years and older
3. Treatment of agitation associated with dementia due to Alzheimer's disease

Limitations of Use: Rexulti (brexpiprazole) is not indicated as an as needed ("prn") treatment for agitation associated with dementia due to Alzheimer's disease

Rexulti is part of the larger class of second-generation antipsychotics, which includes drugs like aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone. These medications all work in somewhat similar ways, but individual patient response and tolerance can vary. This means that if a patient does not respond well to one antipsychotic, they may still benefit from trying another. Selection of an antipsychotic often depends on multiple factors, including patient response to previous treatments, safety and tolerability of the drug, and individual patient considerations such as coexisting health conditions and potential drug interactions.

Definitions

• Adjunct Therapy is a treatment used together with the primary treatment. Its purpose is to assist the primary treatment.
• Agitation is a state of excessive restlessness or emotional distress often characterized by behaviors such as pacing, yelling, or resistance.
• Atypical Antipsychotic is a class of medications, also known as second-generation antipsychotics, that are primarily used to treat psychiatric conditions. Unlike the first-generation antipsychotics, these drugs are less likely to produce extrapyramidal side effects but more likely to cause weight gain and metabolic abnormalities.
• Major depressive disorder (MDD), is a psychiatric condition characterized by persistent low mood, low energy, or loss of interest in enjoyable activities causing substantial impairment in daily life. MDD is thought to be caused by a combination of genetic, environmental and psychological factors. Risk factors include family history, major life changes, certain medications, chronic health problems, and substance use disorders.
• Neuropsychiatric symptoms are symptoms that originate from a disturbance in the brain and influence both neurological and psychiatric functionality. In the context of Alzheimer's disease, it may include symptoms such as agitation, depression, apathy, and psychosis.
• Neurotransmitter is a molecule that sends signals from neurons to different parts of the body (e.g., muscles).
• Schizophrenia is a psychiatric disorder involving chronic or recurrent psychosis and is commonly associated with impairments in social and occupational functioning.

Clinical Indications

The Plan considers Rexulti (brexpiprazole) medically necessary when ALL the following criteria are met for the applicable indication listed below:

Agitation associated with dementia due to Alzheimer's disease

Medical Necessity Criteria for Initial Authorization

1. Prescribed by a specialist in Alzheimer's disease or a psychiatrist; AND
2. The member is 18 years of age or older; AND
3. The member has a confirmed diagnosis of Alzheimer's disease with documented agitation; AND

To ensure member access to appropriate pharmacotherapy when clinical criteria are met but specialist availability is limited, an exception to the Rexulti (brexpiprazole) specialist requirement may be considered if there is inadequate access to specialists in the member's location. In such cases, Rexulti may be prescribed by the member's primary care provider or other qualified clinician experienced in safely using this medication for agitation in Alzheimer's dementia, provided all other clinical criteria are documented and met.

4. The member exhibits sufficient agitation behaviors (i.e., symptoms are severe, dangerous, and/or cause significant distress) warranting pharmacotherapy; AND
5. Rexulti (brexpiprazole) is NOT being used as an "as needed" treatment; AND
6. Clinical chart documentation is provided for review to substantiate the above listed requirements.

If the above prior authorization criteria are met, Rexulti (brexpiprazole) will be approved for 12 weeks.

Medical Necessity Criteria for Reauthorization

Reauthorization for 6-months will be granted if ALL of the following are met:

1. Recent chart documentation (within the last 3 months) shows the member has experienced clinical response to Rexulti (brexpiprazole) as evidenced by one of the following since starting therapy:
   • a. Reduction in intensity or frequency of agitation episodes; or
   • b. Stability in agitation symptoms (e.g., no worsening of agitation episodes); AND
2. IF the member’s behavior stabilizes for 3 months OR there is no response to treatment, the prescriber has reassessed the necessity for pharmacotherapy and there is a valid clinical justification to continue therapy; AND
3. The member maintains adherence to the prescribed dosing regimen as evidenced by pharmacy claims record.

Major depressive disorder

Medical Necessity Criteria for Initial Authorization

1. The member is 18 years of age or older; AND
2. The member has a diagnosis of major depressive disorder; AND
3. The member has demonstrated an inadequate response to at least 8-weeks of antidepressant therapy (e.g., delayed-release duloxetine, escitalopram, fluoxetine, extended-release paroxetine, sertraline, or extended-release venlafaxine); AND
4. Rexulti (brexpiprazole) is being prescribed for use as an adjunct to an antidepressant (e.g., delayed-release duloxetine, escitalopram, fluoxetine, extended-release paroxetine, sertraline, or extended-release venlafaxine); AND
5. The member is unable to use or has tried and failed TWO (2) of the following:
   • a. Aripiprazole; and/or
   • b. Olanzapine; and/or
   • c. Quetiapine; AND
6. Clinical chart documentation is provided for review to substantiate the above listed requirements.

Schizophrenia

Medical Necessity Criteria for Initial Authorization

1. The requested medication is prescribed by or in consultation with a psychiatrist; AND
2. The member is 13 years of age or older; AND
3. The member has a diagnosis of schizophrenia; AND
4. The member is unable to use or has adequately tried and failed at least a one month trial to THREE (3) of the following:
   • a. Aripiprazole; and/or
   • b. Olanzapine; and/or
   • c. Quetiapine; and/or
   • d. Risperidone; and/or
   • e. Ziprasidone; AND
5. Clinical chart documentation is provided for review to substantiate the above listed requirements.

If the above prior authorization criteria are met, Rexulti (brexpiprazole) will be approved for 12 months.

Medical Necessity Criteria for Reauthorization:

Reauthorization for 12 months will be granted if BOTH of the following are met:

1. Recent chart documentation (within the last 3 months) shows the member has experienced clinical response to the requested therapy as evidenced by one of the following:
   • a. clinical improvement (e.g., reduction in intensity or severity of symptoms) since starting the requested medication; or
   • b. stability in condition (e.g., stabilizing mood, return to normal psychosocial functioning) since starting the requested medication; AND
2. The member maintains adherence to the prescribed dosing regimen as evidenced by pharmacy claims record.

Experimental or Investigational / Not Medically Necessary

Rexulti (brexpiprazole) for any other indication is considered not medically necessary by the Plan, as it is deemed to be experimental, investigational, or unproven.

Non-covered indications include, but are not limited to, the following:

• Acute Mania / Bipolar 1 Disorder
• Alcohol Use Disorders (AUD)
• Attention Deficit Hyperactivity Disorder (ADHD)
• Borderline Personality Disorder (BPD)
• Irritability Associated With Autism Spectrum Disorder (ASD)
• Post Traumatic Stress Disorder (PTSD)

References

1. American Psychiatric Association (APA). Practice guideline for the treatment of patients with major depressive disorder. 3rd ed. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf Published October 2010. Accessed July 2022.
2. American Psychological Association (APA). Clinical practice guideline for the treatment of depression across three age cohorts. https://www.apa.org/depression-guideline/guideline.pdf. Published February 16, 2019. Accessed June 21, 2022.
3. Daniel Lee, Emily D. Clark, Inga M. Antonsdottir & Anton P. Porsteinsson (2023) A 2023 update on the advancements in the treatment of agitation in Alzheimer’s disease, Expert Opinion on Pharmacotherapy, 24:6, 691-703, DOI: 10.1080/14656566.2023.2195539
4. Grossberg, George T., et al. “Efficacy and Safety of Brexpiprazole for the Treatment of Agitation in Alzheimer’s Dementia: Two 12-Week, Randomized, Double-Blind, Placebo-Controlled Trials.” The American Journal of Geriatric Psychiatry, vol. 28, no. 4, Apr. 2020, pp. 383–400, https://doi.org/10.1016/j.jagp.2019.09.009.
5. Keepers GA, Fochtmann LJ, Anzia JM, et al. The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2020;177(9):868-872. doi:10.1176/appi.ajp.2020.177901
6. National Institute for Health and Clinical Excellence (NICE), National Collaborating Centre for Mental Health. Psychosis and schizophrenia in children and young people: recognition and management. 2013. https://www.nice.org.uk/guidance/cg155[PubMed 26065063]
7. Reus VI, Fochtmann LJ, Eyler AE, et al. The American Psychiatric Association practice guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia. Am J Psychiatry. 2016;173(5):543-546. doi:10.1176/appi.ajp.2015.173501
8. Rexulti (brexpiprazole) [prescribing information]. Rockville, MD: Otsuka America Pharmaceutical Inc; May 2023.
9. Stroup TS, Marder S. Schizophrenia in adults: maintenance therapy and side effect management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 21, 2022.
10. The Department of Veterans Affairs and the Department of Defense Evidence-Based Practice Working Group. VA/DoD Clinical Practice Guidelines for the Management of Major Depressive Disorder, version 3.0. 2016 April. Website: https://www.healthquality.va.gov/guidelines/MH/mdd/VADoDMDDCPGFINAL82916.pdf. Available from Internet. Accessed April 9, 2021.

Clinical Guideline Revision / History Information

Original Date: 11/05/2020
Reviewed/Revised: 06/24/2021, 12/01/2021, 9/15/2022, 10/27/2023