ZURANOLONE CAP,ORAL

Clinical Criteria Summary

Diagnosis of postpartum unipolar depression without psychosis
Patient is 12 months or less postpartum
Rapid response needed due to suicidality or homicidality
The prescriber is a VA/VA Community Care Mental Health Provider
Patient has been counseled about lack of data in human pregnancy and has made an informed decision about whether to use contraception during the 14-day treatment course and for 1 week following the completion of therapy
Patient agrees not to drive or engage in other potentially hazardous activities until at least 12 hours after administration for the duration of the 14-day treatment course

Take with fat-containing food (e.g., 400 to 1,000 calories, 25-50% fat) for optimal absorption
Patient counseling required regarding passage into breast milk; shared decision-making needed to balance clinical need against developmental and health benefits of breastfeeding (consider continuation, pumping and discarding milk through 1 week past treatment completion, or cessation)

• Treatment of postpartum depression (PPD) in adults
• PPD defined as a perinatal major depressive episode with onset during pregnancy or within 4 weeks of delivery
• Severe depression indicated by baseline 17-item Hamilton Rating Scale for Depression (HAM-D 17) score >26

• Oral capsules available in 20 mg, 25 mg, and 30 mg strengths
• Administered once daily in the evening with fat-containing food for a 14-day treatment course
• Food effect: Low-fat meal (400-500 calories, 25% fat) increases Cmax 3.5-fold and AUC ~1.8-fold; high-fat meal (800-1000 calories, 50% fat) increases Cmax 4.3-fold and AUC ~2-fold compared to fasted conditions

• Concomitant use of existing oral antidepressants permitted if patient maintained a stable dose for at least 30 days prior to baseline
• Avoid concomitant use with CYP3A4 inducers
• Avoid concomitant use with other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) due to increased risk of psychomotor impairment, somnolence, cognitive impairment, and respiratory depression

• Boxed warning for impaired ability to drive or engage in other potentially hazardous activities due to CNS depressant effects
• Patients must be advised not to drive or engage in hazardous activities until at least 12 hours after administration for the duration of the 14-day treatment course; patients may be unable to self-assess driving competence or impairment degree
• Increased risk of falls may impact ability to care for an infant or other children
• May cause fetal harm; advise pregnant women of potential risk to exposed infants
• Advise females of reproductive potential to use effective contraception during treatment and for one week after the final dose
• Present in low levels in human milk; limited data on effects on breastfed infants or milk production
• Dose-dependent abuse potential comparable to alprazolam

• Use is strictly limited to a 14-day treatment course
• Evidence suggests benefit primarily in individuals with severe PPD
• Determination of step/place in therapy is difficult as studies compared zuranolone only to placebo, not treatment as usual
• Use must be weighed against other effective treatment options (e.g., interpersonal psychotherapy, cognitive-behavioral therapy, antidepressant medications) and safety considerations
• Maintenance management of PPD will likely require usual care (oral antidepressant and/or evidence-based psychotherapy)