The U.S. Food and Drug Administration (FDA) has announced the first-ever approval of a drug specifically meant to treat postpartum depression. The drug, called brexanolone (brand name Zulresso), needs to be given in a health care facility under medical supervision and is delivered intravenously over the course of 60 hours (2.5 days), the FDA said.
Brexanolone is “unlike anything else we have currently approved for depression,” said Dr. Kristina Deligiannidis, director of women’s behavioral health at Zucker Hillside Hospital in New York, who was involved with the clinical trials of the drug leading up to its approval.
But how exactly does the drug work, and what makes it different from other medications for depression?
The drug is a synthetic version of a steroid called allopregnanolone, which people make naturally in their bodies. Allopregnanolone is a breakdown product of the sex hormone progesterone, and is produced in the brain and ovaries, as well as in the placenta during pregnancy.
It’s known that blood levels of allopregnanolone increase during pregnancy and drop rapidly after childbirth. And it’s thought that fluctuations in levels of the steroid may trigger changes in the brain that contribute to depression and anxiety in some women, according to Sage Therapeutics Inc., the company that makes brexanolone.
It’s unclear exactly how brexanolone works to treat postpartum depression. But it’s thought that the drug modifies the body’s stress response, which is abnormal in women with postpartum depression, Deligiannidis said. The drug binds to GABA receptors, which play a role in many brain functions.
The binding may work to reverse or “reset” the brain activity tied to postpartum depression symptoms, the company said.
A different type of treatment
Brexanolone works in a different way than other drugs for depression, which typically don’t bind to GABA receptors, Deligiannidis said. A class of drugs called benzodiazepines, sometimes referred to as tranquilizers, also bind to GABA receptors, but they bind to a different type of GABA receptor than brexanolone and have a different function, she said.
Studies of brexanolone found that the drug had quick and effective results. Two clinical trials of about 250 women with postpartum depression showed that within 60 hours, 50 percent of the women who received brexanolone were no longer clinically depressed, compared with 25 percent of women who received a placebo, Deligiannidis said. (Clinical depression was assessed using a questionnaire that gave women a depression score.)
It’s still unclear how brexanolone works so quickly compared with other drugs for depression, which can take weeks to have an effect, she said.
The effects from a single drug infusion of brexanolone appeared to last at least 30 days, the maximum time the women were followed during the studies. As doctors prescribe the drug, they’ll get a better understanding of how long the effects last beyond 30 days, Deligiannidis said. But a monthlong period also gives doctors a chance to start other treatments for depression, such as talk therapy, she added.
Because some women who received brexanolone experienced excessive sedation and sudden loss of consciousness, the drug needs to be administered under supervision, the FDA said.
Sage Therapeutics is also working on a similar drug for postpartum depression that can be taken as a pill once a day. That drug is currently in clinical trials and is not yet FDA-approved.
But the new drug also requires a lot of women: their time and money. And ultimately, brexanolone’s costs may be too prohibitive to reach the moms who’d benefit most.
The drug costs $34,000 per patient without insurance, according to Sage Therapeutics. Even if a woman prescribed the drug can find a way to pay for it, or her insurance company decides to cover it, she would need to check herself into a hospital or clinic that’s certified to deliver brexanolone, and stay connected to an infusion drip for 60 hours under medical supervision. Brexanolone also has side effects, including passing out. So women need to be constantly accompanied by someone else if they bring their newborns with them.
Still, for the subset of women with very severe postpartum depression, the drug could be a “game changer,” said Lucy Puryear, medical director of Center for Reproductive Psychiatry at Texas Children’s Pavilion for Women in Houston, who was not involved with any clinical studies of the drug. “These are women who often are thinking about dying,” she said. “They aren’t able to function, aren’t getting out of bed.” Let’s walk through what we know about brexanolone and why it’s garnered a mixed reception.
Postpartum depression is very common — but people don’t like to talk about it
Postpartum depression is believed to be the most common complication of childbirth, affecting 15 percent of new moms shortly before or within a year after delivery. While the disorder can manifest differently in each woman, the National Institutes of Health describes symptoms including feeling sad and hopeless, crying for no reason, anxiety, over- or under-sleeping, and experiencing changes in appetite.
What sets PPD apart, however, is that new moms are recovering from a majorly stressful physical event — delivering a baby — and they’re also suddenly charged with caring for a new life. So symptoms of PPD can also include having trouble bonding with the baby and thinking about harming oneself or the child.
Moms who experience these feelings don’t always want to report them, since they may feel shame or stigma. Couple that with the fact that access to mental health care in this country is already abysmal, and it helps explain why the treatment rate for women with PPD can be so absurdly low: less than 15 percent.
To date, women with depression during pregnancy, or in the months after, have only had the treatments available to everybody with depression — counseling and antidepressants. But the drugs have come with some big question marks: Patients and doctors have never had clear answers on their efficacy and safety for moms, since they haven’t been studied in randomized controlled trials involving pregnant and breastfeeding women. And sometimes, antidepressant drugs fail to help women with PPD, or to help them fast enough.
Even more frustrating: Though PPD is so pervasive — like many women’s health questions, doctors still don’t know precisely what causes it. Their best guess is that the massive drop in estrogen and progesterone hormones, which happens after childbirth, triggers changes in brain chemistry. And in some women, that can darken their mood.
“There’s a subset of women — nobody understands why yet — and their brains are susceptible to that drop in hormones that occurs for all women,” Puryear said.
“What this drug adds,” said Yale University psychiatrist Kimberly Yonkers, “is that it’s a different mechanism than most of the medicines we currently have. So it may be for people who have not had an adequate response to one of the existing medications.” But the drug’s benefits need to be weighed against the costs and risks.
Sage says that in determining the price of brexanolone, it considered the fact that postpartum depression represents an unmet medical need, and that it’s a one-time treatment with the opportunity rapid relief. Each insurance company will have to determine whether the drug gets covered.
“It’s important to have a medication that was developed specifically for the treatment of [postpartum] depression,” Yonkers said. “But we have concerns about the mode of administration — it’s burdensome to patients and our health system. … I think people would be happier if it didn’t cost $34,000.”