Zuranolone for the Treatment of Postpartum Depression

  • Practice Advisory PA
  • August 2023

This Practice Advisory was developed by the American College of Obstetricians and Gynecologists with the assistance of Tiffany A. Moore Simas, MD, MPH, MEd; M. Camille Hoffman, MD, MSc; Kay Roussos-Ross, MD; Emily S. Miller, MD, MPH; Manisha Gandhi, MD; and Andrea Shields, MD, MS.

The Society for Maternal-Fetal Medicine endorses this Practice Advisory.

This Practice Advisory serves as an update to Clinical Practice Guideline No. 5, Treatment and Management of Mental Health Conditions During Pregnancy and Postpartum, originally published in 2023 1 .

This Practice Advisory is provided to address the August 4, 2023, decision by the U.S. Food and Drug Administration (FDA) to approve zuranolone. Zuranolone is a neuroactive steroid gamma-aminobutyric acid (GABA) A receptor positive modulator, and the first oral medication indicated to treat postpartum depression in adults 2 .

Perinatal mental health conditions via suicide and overdose/poisoning are the leading cause of overall and preventable maternal mortality 3 4 , and thus understanding, discussing, and recommending treatment, including pharmacotherapy when indicated and needed, is within the scope of the obstetrician–gynecologist’s practice 1 . Perinatal depression affects approximately one in seven women (14%)  5 . While SSRIs are commonly utilized to treat major depressive disorder including perinatal depression, the only FDA approved treatment specifically for postpartum depression before zuranolone was brexanolone 6. While effective, brexanolone consists of a 60-hour in-hospital intravenous infusion and may not be readily accessible. The FDA approval of zuranolone provides another treatment option for severe postpartum depression that had onset within the third trimester of pregnancy or within 4 weeks postpartum, that is orally administered for 14 days.

Zuranolone efficacy has been demonstrated in two phase 3 randomized, double-blind, placebo-controlled, multicenter studies 7 8 . The primary endpoint of both studies was the change in depressive symptoms using the total score from the 17-item Hamilton depression rating scale (HAMD-17), measured at day 15. In both studies, patients in the zuranolone groups showed significantly more improvement in their symptoms compared to those in the placebo groups. The treatment effect was maintained at day 42—four weeks after the last dose of zuranolone 7 8 . The HAMD-17 is used more commonly in research settings. It is anticipated that other validated tools (eg, EPDS or PHQ9) will be used in clinical settings.

ACOG recommends consideration of zuranolone in the postpartum period (ie, within 12 months postpartum) for depression that has onset in the third trimester or within 4 weeks postpartum. The decision to use zuranolone should balance the benefits (eg, significantly improved and rapidly resolved symptoms) with the risks and challenges (eg, potential suicidal thoughts or behavior, sedation that precludes performing some activities of daily living like driving, and lack of efficacy data beyond 42 days).

Considerations for zuranolone therapy:

  • The daily recommended dose of zuranolone is generally 50 mg. It is taken in the evening with a fatty meal (eg, 400 to 1,000 calories, 25% to 50% fat), for 14 days. Dosage may be reduced to 40 mg if central nervous system (CNS) depressant effects occur. In the case of severe hepatic or moderate to severe renal impairment, dosing should be initiated at 30 mg. Dose adjustments will also be needed if patients are taking medications that are strong CYP3A4 inhibitors and concomitant use with CYP3A4 inducers should be avoided.*
  • If an evening dose is missed, take the next dose at the regular time the following evening; do not take extra doses on the same day. Complete 14 days of treatment total.
  • Zuranolone can be used alone or as an adjunct to other oral antidepressant therapy like SSRIs and SNRIs.
  • Patients should use effective contraception during the 14-day treatment course and for 1-week after the final dose. Zuranolone may cause fetal harm 2 . If pregnancy does occur, there is a registry.**
  • Patients should be warned and given precautions about adverse reactions including:
    • Impaired ability to drive or engage in other potentially hazardous activities,
    • CNS depressant effects including somnolence and confusion, and
    • Increased suicidal thoughts and behaviors.
  • Patients should not drive or engage in activities requiring complete mental alertness until at least 12 hours after each dose for the duration of the full treatment course. Patients may not be able to accurately assess their own degree of impairment during the treatment cycle.
  • Other CNS depressing substances should be avoided (eg, alcohol, benzodiazepines, opioids, tricyclic antidepressants). If unable to avoid, a dose reduction may be necessary.
  • The most common side effects include dizziness, fatigue, drowsiness, diarrhea, common cold-like symptoms, and urinary tract infections.
  • Zuranolone passes into breast milk, although with a RID lower than that of SSRIs. There are no data on effects on a breastfed infant and limited data on milk production. The patient’s clinical need for zuranolone and the developmental and health benefits of breastfeeding should be balanced through a shared decision-making process that considers continuation, pumping and discarding milk through 1-week past treatment completion, and cessation.

ACOG recommends that a validated screening tool be used to monitor for response to treatment or remission of depression symptoms 1 . For information on validated depression screening tools, and more information on screening and diagnosis of perinatal mental health conditions, refer to Clinical Practice Guideline No. 4, Screening and Diagnosis of Mental Health Conditions During Pregnancy and Postpartum 9 .

* Potent inhibitors of CYP3A4 include clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal, and grapefruit. Inducers of CYP3A4 include phenobarbital, phenytoin, rifampicin, St. John's wort, and glucocorticoids.

** National Pregnancy Registry for Antidepressants (1-844-405-6185 and

Please contact [email protected] with any questions.


  1. 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.
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  6. U.S. Food and Drug Administration. Zulresso (brexanolone). Approved Risk Evaluation and Mitigation Strategies (REMS). Available at: Accessed August 14, 2023
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  7. Deligiannidis KM, Meltzer-Brody S, Maximos B, Peeper EQ, Freeman M, Lasser R, et al. Zuranolone for the treatment of postpartum depression. Am J Psychiatry. Published online July 26, 2023. doi: 10.1176/appi.ajp.20220785
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  8. Deligiannidis KM, Meltzer-Brody S, Gunduz-Bruce H, Doherty J, Jonas J, Li S, et al. Effect of zuranolone vs placebo in postpartum depression: a randomized clinical trial [published errata appear in JAMA Psychiatry 2022;79:740; JAMA Psychiatry 2023;80:191]. JAMA Psychiatry 2021;78:951-9. doi: 10.1001/jamapsychiatry.2021.1559
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  9. Screening and diagnosis of mental health conditions during pregnancy and postpartum. Clinical Practice Guideline No. 4. American College of Obstetricians and Gynecologists. Obstet Gynecol 2023;141:1232-61. doi: 10.1097/AOG.0000000000005200
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