On March 19, 2019, the FDA approved brexanolone (Zulresso), the first medication for postpartum depression (PPD). Delivered by intravenous injection, brexanolone is an analogue of the hormone allopregnanolone. Allopregnanolone levels fall abruptly after childbirth, which is thought to contribute to PPD by destabilizing GABAA receptors.
We covered brexanolone’s mechanism in our January 2019 issue and have some practical updates for readers who want to start using it.
How is it delivered?
As a one-time, 60-hour IV infusion at 60–90 µg/kg/hour.
How effective is it?
To achieve remission, the number needed to treat with brexanolone is 5–8. The efficacy is based on three positive randomized, double-blind, placebo-controlled trials involving 267 women with moderate or severe PPD (Meltzer-Brody S et al, Lancet 2018;392:1058–1070).
Are the effects long lasting?
We only have data up to 30 days, and 94% of patients who responded maintained their response at that point.
Are there side effects?
The main risk is excessive sedation (2%–4%) and loss of consciousness. Otherwise, side effects were similar in the placebo and brexanolone groups and included dry mouth, loss of consciousness, and flushing.
Can women breastfeed during the infusion?
Possibly. We have data on only 12 women, and brexanolone had a low rate of transfer to the infant in that group (1%–2% of maternal weight-adjusted dosage).
Who can administer it?
Brexanolone is a schedule IV controlled substance and requires both the patient and health care provider to enroll in a REMS program (see www.thecarlatreport.com/REMS). Because of the risk of excessive sedation, brexanolone must be administered with continuous pulse oximetry during the 60-hour infusion. If hypoxia occurs, the infusion should be stopped and not restarted. Patients can engage with their children during the infusion, but they are required to be accompanied by another adult because of the risk of sedation.
What is the cost?
$34,000 for the drug without insurance, plus costs associated with administration and monitoring. Insurers have not developed their coverage policies yet, but it’s likely they will require failure of antidepressant trials before authorizing it.
How can I find a brexanolone center for my patient?
Sage Therapeutics keeps a list of certified providers at 844-472-4379.
Brexanolone’s main advantage is speed. Each month of depression takes a toll on infant development and maternal attachment, so a medication that works within a few days is worth considering. The main drawback is the cost and lengthy infusion period. While the one-time treatment will be appealing to some patients, we need more research to know if these recoveries can last beyond 30 days.
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