Postpartum Depression (PPD)

Postpartum depression (PPD) is a major depressive disorder that occurs during pregnancy or within 4 weeks after delivery, affecting approximately 14% of postpartum women. It is one of the most common complications of childbirth and a leading cause of maternal mortality.

First-line treatments for PPD include psychotherapy such as cognitive behavioral therapy (CBT) and antidepressant medications like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). However, response with standard antidepressants can be delayed by weeks. Prior to zuranolone, the only FDA-approved medication specifically for PPD was brexanolone, which requires a 60-hour continuous IV infusion and restricted distribution program.

Zurzuvae (zuranolone)

Zurzuvae (zuranolone) is a neuroactive steroid gamma-aminobutyric acid (GABA)A receptor positive allosteric modulator indicated for the treatment of postpartum depression (PPD) in adults. It is the first FDA-approved oral antidepressant specifically for PPD. Zurzuvae (zuranolone) offers rapid improvement in depressive symptoms within 3 days and continued efficacy over the 2-week treatment course.

Definitions

• Antidepressant refers to a medication used to treat depression and other mental health conditions. Common classes include SSRIs, SNRIs, and atypical antidepressants.
• Edinburgh Postnatal Depression Scale (EPDS) is a 10-item self-rated depressive symptom severity scale specific to the perinatal period. Each item is rated on a 4-point scale from 0 to 3. The total score ranges from 0 to 30 points, calculated by summing the 10 individual item scores. Higher total scores indicate more severe depression.
• Patient Health Questionnaire-9 (PHQ-9) is a 9-item self-rated depressive symptom severity scale used to monitor depression treatment over time. Each item is scored from 0 to 3 based on symptom frequency over the past 2 weeks. The total score ranges from 0 to 27 calculated by summing the 9 item scores. Higher scores indicate more severe depression.
• Peripartum onset refers to the onset of mood symptoms during pregnancy or within 4 weeks postpartum.
• Postpartum depression (PPD) refers to major depressive disorder with peripartum onset, defined as depression with onset during pregnancy or within 4 weeks after delivery.
• Psychotherapy refers to treatment involving counseling and therapeutic techniques to address psychological, emotional, and behavioral issues. Common forms used for PPD include cognitive behavioral therapy (CBT) and interpersonal therapy.
• Selective serotonin reuptake inhibitor (SSRI) refers to a class of antidepressants that work by blocking the reabsorption (reuptake) of serotonin in the brain, increasing levels of this neurotransmitter. Examples include fluoxetine, sertraline, and paroxetine.
• Serotonin-norepinephrine reuptake inhibitor (SNRI) refers to a class of antidepressants that block the reuptake of both serotonin and norepinephrine. Examples include duloxetine and venlafaxine.

Medical Necessity Criteria for Initial Authorization

The Plan considers Zurzuvae (zuranolone) medically necessary when ALL of the following criteria are met:

1. Prescribed by or in consultation with a psychiatrist or OB/GYN; AND
2. Age ≥18 years old; AND
3. Diagnosis of postpartum depression (PPD) with onset during pregnancy or within 4 weeks postpartum; AND
4. Documentation of current depressive symptoms consistent with a diagnosis of major depressive disorder with peripartum onset; AND
5. Baseline assessment using a validated depression rating scale indicates at least moderate severity depression (e.g., PHQ-9 score ≥10, EPDS score ≥14); AND
6. Documentation provided confirms that the member:
   • is not actively suicidal, homicidal, or an imminent danger to self or others based on clinical assessment; and
   • is not currently pregnant; and
   • does not have a history of seizures, bipolar disorder, schizophrenia, or schizoaffective disorder; and

agrees to use effective contraception during treatment and for at least 7 days after final dose; AND

7. Dosage does not exceed 50 mg orally once daily for 14 days.

If the above prior authorization criteria are met, Zurzuvae (zuranolone) will be authorized for one 14- day course.

Medical Necessity Criteria for Reauthorization

Reauthorization for one additional 14-day course in a 12-month period will be granted if the member has recent (within the last 30 days) clinical chart documentation demonstrating ALL of the following criteria:

1. Prescribed by or in consultation with a psychiatrist or OB/GYN; AND
2. The member has completed the initial 14-day treatment course of Zurzuvae (zuranolone); AND
3. The initial 14-day treatment course did not adequately resolve patient's PPD symptoms as evidenced by validated rating scale (e.g. EPDS, PHQ-9); AND
4. At least 8 weeks have elapsed since completion of the prior Zurzuvae (zuranolone) treatment course.

Experimental or Investigational / Not Medically Necessary

Zurzuvae (zuranolone) for any other indication or use 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:

3. Treatment of non-FDA approved indications (e.g. anxiety, bipolar depression, major depressive disorder).
4. Members with a suicidal or homicidal risk factor or who are deemed unsafe to self or others.

References

1. American College of Obstetricians and Gynecologists Committee on Obstetric Practice: ACOG Committee Opinion No. 757: screening for perinatal depression. Obstet Gynecol. 132(5):e208-12, 2018
2. American College of Obstetricians and Gynecologists. "Zuranolone for the Treatment of Postpartum Depression." www.acog.org, Aug. 2023, www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2023/08/zuranolone-for-the-treatment-of-postpartum-depression.
3. American Psychiatric Association: Depressive disorders. In: Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Text Revision. American Psychiatric Association; 2022:178-215
4. Centers for Disease Control and Prevention, Division of Reproductive Health. (2020). Pregnancy Risk Assessment Monitoring System (PRAMS). Washington, DC: Centers for Disease Control and Prevention. Retrieved from: https://www.cdc.gov/prams/prams-data/mch-indicators/states/pdf/2020/All-Sites-PRAMS-MCH-Indicators-508.pdf.
5. Centers for Disease Control and Prevention. "Depression among Women." Centers for DiseaseControl and Prevention , 23 May 2022, www.cdc.gov/reproductivehealth/depression/index.htm#Postpartum.
6. Earls MF et al: Incorporating recognition and management of perinatal and postpartum depression into pediatric practice. Pediatrics. 126(5):1032-9, 2010
7. Oates MR: Psychiatric disorders of childbirth. In: Symonds I et al, eds: Essential Obstetrics andGynecology. 5th ed. Elsevier; 2013:207-19
8. Office on Women's Health. "Postpartum Depression." Womenshealth.gov, U.S. Department of Health and Human Services, 17 Feb. 2021, www.womenshealth.gov/mental-health/mental-health-conditions/postpartum-depression.
9. Siu AL; US Preventive Services Task Force (USPSTF), Bibbins-Domingo K, et al. Screening for depression in adults: US Preventive Services Task Force recommendation statement. JAMA. 2016;315(4):380-387. PMID: 26813211 pubmed.ncbi.nlm.nih.gov/26813211/.
10. Treatment and management of mental health conditions during pregnancy and postpartum. Clinical Practice Guideline No. 5. American College of Obstetricians and Gynecologists. Obstet Gynecol 2023;141:1262-88. doi: 10.1097/AOG.0000000000005202.

Clinical Guideline Revision / History Information

Original Date: 11/29/2023
Reviewed/Revised: 4