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Hosted by Editor in Chief Lorenzo Norris, MD, Psychcast features mental health care professionals discussing the issues that most affect psychiatry.

Dec 18, 2019

Ruta Nonacs, MD, PhD, conducts a Masterclass lecture on treating women with postpartum depression from the Psychopharmacology Update in Cincinnati. The meeting was sponsored by Global Academy for Medical Education and Current Psychiatry.

Dr. Nonacs is a staff psychiatrist with the Perinatal and Reproductive Psychiatry Clinical Research Program at Massachusetts General Hospital in Boston. 

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Features of postpartum depression 

  • Postpartum depression (PPD) affects 10%-15% of women after delivery. For many women, their depression starts in the third trimester and worsens after delivery.
  • Unique symptoms of PPD include difficulties bonding with the baby, feeling like an inadequate mother, and experiencing severe sleep disturbance with anxiety and edginess. In a common scenario, the mother will not be able to sleep at night, though her baby is sleeping well. Anxiety is a common comorbidity, especially obsessive thoughts about the baby’s safety.

Treatment of PPD

  • Treatment in this population is complicated by many demands placed on a mother as the primary caregiver of an infant. The medication chosen must target depression and anxiety, improve sleep, yet not be too sedating.
  • The concentration of antidepressants in breast milk is low, but many women will defer treatment for their depression until they’ve stopped breastfeeding.
  • Treatment of mild PPD includes recruiting more support to help the mother with care of the infant and psychotherapy to identify stressors and coping skills. In moderate to severe PPD, antidepressants are needed. Selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs) are the preferred treatments, and studies support the use of sertraline, fluoxetine, paroxetine, and venlafaxine at their standard dosages. SSRIs and SNRIs are compatible with breastfeeding, because the medications are detected in the breast milk at very low levels.
  • Brexanolone (Zulresso) is the only Food and Drug Administration–approved medication for postpartum depression. It is a neurosteroid and derivative of allopregnanolone, which is a positive allosteric modulator of the gamma-aminobutyric acid receptor. Brexanolone has low oral bioavailability and is administered only as a 60-hour infusion in a certified medical setting with continuous monitoring. The trials for brexanolone included women with moderate to severe PPD, and Hamilton Depression Rating Scale scores (HAM-D) scores ranging from 20 to 25. After the 60-hour infusion, 45% of the subjects with severe PPD in the brexanolone group achieved remission by the end of treatment, compared with 23% in the placebo group. Women retained the antidepressant effect at the 30-day follow-up. The results in the moderate PPD group were not as impressive; these women had a decrease in their depression HAM-D scores, but the antidepressant effect did not continue to the 30-day follow-up.
  • The FDA approval came with a Risk Evaluation Mitigation Strategy in place.


Currently, approximately 100 sites are ready to administer brexanolone; however, some obstacles remain:

Obstacles to using brexanolone

  • The medication costs more than $30,000 per infusion, and it is uncertain how much insurance will cover.
  • Since brexanolone is administered in hospital settings, women must be separated from their children for several days.
  • Breastfeeding must be stopped while women are on the medication because of the lack of data about excretion in breast milk.
  • Brexanolone is labeled as a Schedule IV medication because it has a similar mechanism of action to midazolam and diazepam. Likelihood of diversion is low, but some women with substance abuse histories might be concerned about this treatment. 


Leader LD et al. Brexanolone for postpartum depression: Clinical evidence and practical considerations. Pharmacotherapy. 2019 Nov;39(11):1105-12.

Meltzer-Brody S et al. Brexanolone injection in postpartum depression: Two multicenter, double-blind, randomized, placebo-controlled, phase 3 trials. Lancet. 2018 Sep 22;392(10152):1058-70.

Nonacs R. A Deeper Shade of Blue: A Woman’s Guide to Recognizing and Treating Depression in Her Childbearing Years. New York, NY: Simon & Schuster; 2006.

Massachusetts General Hospital Center for Women’s Mental Health.

National Institutes of Health. Drugs and Lactation Database (LactMed).

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