Brexanolone for Postpartum Depression

I’m sure everyone has read the announcement for brexanolone, the first medication indicated for the treatment of postpartum depression. I was asked to share my professional opinion on this medication since it will inevitably be used in lactating individuals. It’s important to discuss postpartum depression and the information we currently have regarding brexanolone so you understand my opinion.

Postpartum depression is characterized as a major depressive episode occurring during pregnancy or within 4 weeks of delivery. It is different from the “baby blues” in that the symptoms are more debilitating and persistent. Postpartum depression can be life-threatening depending on its severity. It can have significant and/or lifelong social, financial, emotional, and physical impacts on a person’s life and their family life. The prevalence of postpartum depression varies from state to state, but it can be as high as 1 in 5 women according to the CDC. 

It is great that the postpartum period is being researched in terms of drug development. I strongly feel that postpartum care with our current healthcare model is lacking, and I believe individuals go undiagnosed and untreated because of it. Oral antidepressants are the current medication of choice for postpartum depression, but they can take 4-8 weeks to become effective. It can also take time to find the right medication and the right dose, and some individuals do not have time. The ability of a medication to decrease or eliminate depression within days is unheard of and would be a serious breakthrough for depression in general.

Brexanolone will be released under the trade name of Zulresso. Brexanolone is chemically equivalent to allopregnanolone, which is a metabolite of progesterone. Allopregnanolone concentrations are high in the last trimester of pregnancy and then decrease rapidly after childbirth and the delivery of placenta. This decrease is thought to play a role in the development of postpartum depression in susceptible women. Allopregnanolone crosses the blood brain barrier rapidly and binds to GABA-A receptors, resulting in antidepressant and anti-anxiety effects among other effects. The goal of brexanolone is to bind to the same receptors that allopregnanolone would if allopregnanolone were still present and reduce or eliminate the symptoms of depression in patients with postpartum depression. Brexanolone is given as a continuous intravenous infusion over 60 hours or 2.5 days. Patients will have to be monitored for sedation and sedation-related events, and only specific facilities and specific providers will be able to administer brexanolone. In the clinical trials, brexanolone was administered in a variety of healthcare settings with some settings allowing infants or older babies to stay overnight. Three placebo-controlled, randomized, double-blind clinical trials were able to show that brexanolone was superior to placebo in rapidly improving clinical symptoms of postpartum depression at the end of the 60 hour treatment. These results were still present at 30 days post-treatment.

Brexanolone will be very expensive - current quotes are $34,000 - but I would expect the manufacturer to offer financial assistance as manufacturers often do for expensive name brand medications. I would also anticipate that insurance companies will only cover this medication if other treatments have failed, such as oral antidepressant medications. 

The manufacturer has studied brexanolone in lactating women, but brexanolone has not been studied in breastfed infants. Clinical trial participants were asked to wean or postpone breastfeeding while receiving brexanolone. Breastmilk was collected from twelve women and analyzed to determine milk:plasma ratio and relative infant dose. Brexanolone rapidly diffuses between plasma and breastmilk in a nearly 1-to-1 ratio. The relative infant dose was calculated to be 1.3%. Brexanolone has demonstrated poor oral bioavailability (<5%). All of this together indicates that the amount of brexanolone an infant or older baby receives will probably be clinically insignificant since it will likely be destroyed in the infant’s gut. The manufacturer states the half-life to be 40 minutes with a terminal half-life of 12 hours, which is also favorable for use in lactation. The effects of brexanolone have not been studied in breastfed infants, but the briefing document released by the FDA states, “Patients can be treated with a single 2.5-day infusion of brexanolone IV without having to discontinue breastfeeding” on page 29. This document is listed in the references. This is just my opinion, but I would expect to see case reports of the use of brexanolone in lactating individuals in the near future based on the data released from the manufacturer.

Overall, I am tentatively excited about this medication. Brexanolone could be a miracle drug to some. The data indicates brexanolone is probably compatible with lactation, but it hasn’t been specifically studied in a breastfeeding dyad. I don’t see a reason that brexanolone would decrease milk supply since it is chemically equivalent to a breakdown product of progesterone and not progesterone itself, but I will reserve judgment until I see it used in practice. I’m really curious to see how hospitals or infusion centers accommodate the lactating individual and his/her baby. Lactation consultants will need to be involved in this treatment. The lactating individual needs to be with his/her baby to maintain milk supply and if not, a pumping schedule needs to be created. A plan needs to be in place if the lactating individual has the adverse effect of sedation and can’t nurse or pump himself/herself. If the lactating individual decides to abruptly wean from breastfeeding, lactation consultants need to be there to help with the emotional and physical effects of weaning. 

Postpartum depression is a complex condition and treatment has to be chosen based on the individual and the severity of depression. Brexanolone won’t be any provider’s “go-to” medication unless it’s an emergency situation. Insurance companies will probably make providers complete multiple steps before approving the medication. If an individual requires brexanolone, lactation and the breastfeeding relationship will be low priority compared to the individual’s health and safety. The conversation regarding brexanolone and lactation needs to occur regardless of whether an individual chooses to wean, interrupt lactation, or continue lactation through treatment. 

I’m a community pharmacist in practice, so this won’t be a medication I dispense. If you have any personal or professional experience with brexanolone after it hits the market, please reach out to me. I would so enjoy hearing your experiences and thoughts on the medication.

References:

1) Depression Among Women - CDC: https://www.cdc.gov/reproductivehealth/depression/index.htm

2) Allopregnanolone - ScienceDirect: https://www.sciencedirect.com/topics/neuroscience/allopregnanolone

3) Brexanolone Injection, for Intravenous Use: Sponsor Briefing Document - FDA: https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM624646.pdf

4) FDA approves first treatment for post-partum depression - FDA: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm633919.htm

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