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.
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
- 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
- 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
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
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
- 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
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.
A Deeper Shade of Blue: A Woman’s Guide to Recognizing and Treating
Depression in Her Childbearing Years. New York, NY: Simon &
Massachusetts General Hospital Center for Women’s Mental Health.
National Institutes of Health. Drugs and Lactation Database
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