The newly approved drug brexanolone simulates a natural steroid to alleviate symptoms
Approval of the first and only treatment in the United States specifically targeting postpartum depression offers hope for millions of women each year who suffer from the debilitating mental health disorder after giving birth.
The new drug brexanolone — marketed under the name Zulresso and approved on March 19 by the U.S. Food and Drug Administration — is expected to become available to the public in late June. Developed by Sage Therapeutics, based in Cambridge, Mass., the drug is costly and treatment is intensive: It’s administered in the hospital as a 60-hour intravenous drip, and a treatment runs between $20,000 and $35,000. But researchers say that it could help many of the estimated 11.5 percent of U.S. new moms each year who experience postpartum depression, which can interfere with normal bonding between mothers and infants and lead to feeling hopeless, sad or overly anxious.
Here’s a closer look at the drug, its benefits and some potential drawbacks.
How does the new drug work?
How exactly brexanolone works is not known. But because the drug’s chemical structure is nearly identical to the natural hormone allopregnanolone, it’s thought that brexanolone operates in a similar way.
Allopregnanolone enhances the effects of a neurochemical called gamma-aminobutyric acid, or GABA, which stops nerve cells in the brain from firing. Ultimately this action helps quell a person’s anxiety or stress.
During pregnancy, the concentration of allopregnanolone in a woman’s brain spikes. This leads some neurons to compensate by temporarily tuning out GABA so that the nerve cells don’t become too inactive. Levels of the steroid typically return to normal quickly after a baby is born, and the neurons once again responding to GABA shortly thereafter. But for some women, this process can take longer, possibly resulting in postpartum depression.
Brexanolone temporarily elevates the brain’s allopregnanolone levels again, which results in a patient’s mood improving. But it’s still not clear exactly why the drug has this effect, says Samantha Meltzer-Brody, a reproductive psychiatrist at the University of North Carolina School of Medicine in Chapel Hill and the lead scientist of the drug’s clinical trials. Nor is it clear whether allopregnanolone’s, and thus possible brexanolone’s, influence on GABA is affecting only postpartum depression. But the drug clearly “has this incredibly robust response,” she says, “unlike anything currently available.”
How effective was the drug in clinical trials?
Brexanolone went through three separate clinical trials in which patients were randomly given either the drug or a placebo: one Phase II trial, which tests the drug’s effectiveness and proper dosage, and two Phase III trials, which tested the drug’s effects on moderate or severe postpartum depression and were necessary to gain approval for the drug’s commercial use in people.
Of 234 people who completed the trials, 94 received the suggested dosage of brexanolone. About 70 of those patients, or 75 percent, had what Meltzer-Brody described as a “robust response” to just one course of treatment. And of those patients with positive responses, 94 percent continued to feel well 30 days after the treatment. The results suggest that the drug may be most effective for those with severe postpartum depression; among those with moderate symptoms, the drug and the placebo had a fairly similar impact.
Can people take the drug again?
“There’s nothing prohibiting” a second course of brexanolone, but the effects of a repeat course have not been studied, Meltzer-Brody says. The drug was designed to be taken in tandem with the start of antidepressants, which take effect after about two to four weeks. So by the time the brexanolone wears off, the antidepressants would have kicked in.
It’s not clear yet if some patients could need a second dose. The clinical trials compared a group of women taking both antidepressants and brexanolone with another group taking only brexanolone and found no difference in the two group’s response 30 days after tests ended, Meltzer-Brody says. Because the study ended at 30 days, it’s unclear if the effects of brexanolone on its own last longer.
Can women breastfeed while taking brexanolone?
As a precaution, treated women did not breastfeed until six days after taking the drug. But in tests of breastmilk from 12 treated, lactating women, concentrations of brexanolone in breastmilk were negligible — less than 10 nanograms per millileter — in most of the women 36 hours after they received the infusion, according to Sage’s briefing document for the FDA. The FDA has yet to issue guidance on breast feeding.
Are there side effects?
About a third of the trial patients experienced sleepiness, sedation or headaches. The possibility of drowsiness led to the FDA’s requirement that the drug be administered by IV drip in a supervised setting. “If someone isn’t supervised, then there would be the risk that someone could get sleepy and pass out,” Meltzer-Brody says.
Are there plans for different versions of the drug?
Sage Therapeutics is developing a pill version of a drug called SAGE-217. It’s chemically similar to brexanolone and has similar antidepressant effects. Early results from a Phase III trial reported by the company in January show that, of 78 women treated with the pill, 72 percent responded favorably within two weeks, and 53 percent had not experienced a recurrence of symptoms four weeks later.
Is it worth the price and time?
Setting aside 60 hours to be hospitalized for an expensive drug could be discouraging for some. “It’s going to be very important for insurance to cover it in order for it be accessible,” Meltzer-Brody says. “I’m hoping that will be the case.” But based on the reaction of women with severe postpartum depression who participated in the trials, “two-and-a-half days seems like nothing if your debilitating, depressive symptoms will be gone.”
U.S. Food and Drug Administration. FDA approves first treatment for postpartum depression. March 19, 2019.
Sage Therapeutics. Sage therapeutics announces SAGE-217 meets primary and secondary endpoints in phase 3 clinical trial in postpartum depression. January 7, 2019.
U.S. Food and Drug Administration. Brexanolone injection, for intravenous use. November 2, 2018.
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