A Novel Drug for Severe Postpartum Depression: Who Might Benefit?

Arefa Cassoobhoy, MD, MPH; Elizabeth Fitelson, MD


June 20, 2019

This transcript has been edited for clarity.

Until now, we've managed women with postpartum depression pretty much the same as any patient with depression: lifestyle modification, psychotherapy, and time-tested antidepressants. But now we have a new option for severe postpartum depression. The novel drug brexanolone was developed specifically to counteract the unique physiologic changes that can induce postpartum depression in vulnerable women. WebMD's Arefa Cassoobhoy spoke about what we can expect from this new treatment with Elizabeth Fitelson, MD, director of the Women's Program in the Department of Psychiatry at Columbia University. (For more on perinatal depression and its treatment, see The Perils of Dismissing Depression as Just the 'Baby Blues.')

Arefa Cassoobhoy, MD: What can we expect from brexanolone, and why should it work better than everything else we've tried for postpartum depression?

Elizabeth Fitelson, MD: Brexanolone was based on research that helped us understand more about hormones in pregnancy and the postpartum period. We've known for a while that the hormonal changes taking place during pregnancy can actually have a significant impact on some women and their risk for postpartum depression. The sudden hormone changes during pregnancy—the levels of estrogen and progesterone, for example—skyrocket in the second and third trimesters, and then as soon as the baby and the placenta are delivered, they plummet to essentially postmenopausal levels within 48 hours.

That's a huge hormonal shift. Think about how sensitive some women are to the relatively more subtle hormonal changes during the menstrual cycle, and imagine how sensitive those women might be to the massive hormonal shifts in the perinatal period. When researchers looked at the source of these mood changes, they found that in some women, the levels of allopregnanolone (a metabolite of progesterone) seemed to be involved in regulating mood and anxiety.

This makes sense because allopregnanolone (the main ingredient of brexanolone) is an allosteric GABAA modulator. It binds to that receptor and has an anxiolytic or inhibitory function in the brain. It's been known for a while that the sudden drop in allopregnanolone levels may be involved in the emergence of postpartum depression in some women. Brexanolone was developed through research, asking: If we give back allopregnanolone, would that help correct the big hormonal shift and reverse postpartum depression?

What's exciting about brexanolone is that it is a novel compound. Allopregnanolone has not been studied in other kinds of depression. It's targeted for postpartum depression, and there isn't anything else out there that is targeted for perinatal mood and anxiety disorders, which are so prevalent and can be devastating. It seems to work, based on the preliminary studies. A good response was seen in a number of women, and it seemed to work rapidly, which is very exciting.

Cassoobhoy: Which women are expected to benefit from brexanolone?

Fitelson: Brexanolone seems to be more effective for severe depression and we don't really know about moderate depression. The threshold for who will benefit is still fairly high because of the restrictions on the drug's use. It would be great if over time we could figure out which women would benefit from it. Is it that hormone-sensitive cohort who will benefit most? Once it's out there, because there's so much excitement and hope about it, I'm concerned that if a woman is treated with brexanolone and doesn't recover, she might feel hopeless or think "maybe there is really something wrong with me," and that shouldn't be the message. There are many different ways to recover from perinatal mood and anxiety disorders. This is one new and exciting treatment, but it's certainly not the only treatment.

There are other questions about women with bipolar depression. Is brexanolone safe to use in bipolar disorder? In the studies, it was used concurrently with other medications. If a woman isn't on another medication, such as an SSRI antidepressant, how long do the benefits from brexanolone last? Is it a persisting effect? There are a lot of questions, but it's very exciting to have a new medication that's really for perinatal mood and anxiety disorders. It's also bringing a lot of attention to this really important issue, but we will have to gather a lot more information after the medication is released.

The studies were done in moderate to severe perinatal depression, which is defined as depression emerging during pregnancy or within the first 4 weeks postpartum. The indication for brexanolone is postpartum depression, and women can be up to 6 months postpartum at the time they get the treatment, although that may change with the FDA labeling.

Cassoobhoy: I understand that brexanolone will be available in a restricted inpatient program. Tell us more about this. How does it work? How will it be administered?

Fitelson: Brexanolone is administered as an infusion. It has to be given over 60 hours, which is 2.5 days, which is one of the major limitations of the medication. The patient needs to have an intravenous line for 60 hours. At this point, it needs to be done in a monitored setting. Because it won't be a mother-baby unit, that means that for most women, the mom will be separated from the baby for at least a significant portion of those 60 hours.

Because of a few adverse events involving excessive sedation, the FDA is requiring that the infusion be given in a monitored setting. For most patients, that would be at a medical center where they can be monitored throughout the entire 60 hours of the infusion, to make sure they're not excessively sedated. Their blood oxygen levels will be monitored and they'll be checked every 2 hours.

The inpatient monitoring is imposed by the FDA for safety because of the excessive sedation. Not only does that post a risk potentially for the patients, but if you can imagine someone taking care of a newborn baby, the concern is that that might put the baby at risk as well. All of the patients in the study recovered very quickly after it was discovered that they were excessively sedated.

Cassoobhoy: How about safety for the infant of a mother who is breastfeeding?

Fitelson: Brexanolone hasn't been studied in breastfeeding women. The women in the studies stopped breastfeeding at least for the duration of the infusion. There's no real information about breastfeeding; however, my understanding is that it's a large molecule and doesn't pass readily into the breast milk. It may be safe in breastfeeding; I just don't have the information to say one way or the other.


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