Last Friday, a breaking news alert lit up phone screens: the US Food and Drug Administration had approved zuranolone (sold under the brand name Zurzuvae), the first oral medication created specifically to target postpartum depression. Considering that the news cycle more commonly focuses on the tragic consequences of the rarest and most extreme circumstances of postpartum mental health issues (as it would for many New Yorkers the very next day), the announcement felt like a dramatic shift. And a necessary one: one in five mothers will experience a mood or anxiety disorder (or PMAD) during pregnancy or postpartum, around one in seven women may develop postpartum depression, and women of color are at a notably higher risk of both.
But can zuranolone be a fix for these wide-ranging issues? First, though it’s being touted as a first for postpartum depression (which, admittedly, makes for a very compelling headline), that’s not exactly true. In 2019, the FDA approved brexanolone, which works in a very similar way but is administered via IV instead of orally. “You can imagine all of the procedural as well as logistical complications involved in going in for an IV when you’re in the postpartum period,” says New York-based reproductive psychiatrist Lucy Hutner, MD. “It’s just not the most feasible thing to do postpartum.”
Zuranolone, on the other hand, appears to be a far more practical option. The pill works by controlling the brain’s GABA neurotransmitters, acting, Hutner points out, in the same way as our reproductive hormones. The fact that the pill works very rapidly—zuranolone is administered over the course of 14 days and in the study, results were seen after only three days—and that it’s effective on the most severe symptoms are the biggest positive takeaways, says Hutner, who sees it as a precision medicine for postpartum depression. One challenge will be determining which people will benefit from it the most. For Hutner, they will be her patients whose moods tend to fall off a cliff after giving birth in a manner that’s clinically distinct from others with PPD. “There is a subgroup of people who are particularly sensitive to reproductive hormone transitions, and giving birth is one of the biggest ones—because the levels of hormones in our brains go from sky high at the end of pregnancy, down to almost menopausal levels within 24 hours,” Hutner explains.
The scientists conducting the study measured the depression scores of participants (women with children under a year who were all suffering from severe PPD) at various points, starting at three days when they first saw positive results (impressive considering most antidepressants take two weeks to have an impact), and after they had ceased taking the medication at 15 and then 45 days. The improvements, even at day 45, were significant.
But what about after that? There’s no indication, yet at least, of how the efficacy of zuranolone holds up a year or two down the line, as well as no indication of how it might work on those with underlying conditions like bipolar disorder. “There is still research that needs to be done about if zuranolone is safe to be used while breastfeeding,” adds Veerle Bergink, MD, director of the women’s mental health program at New York’s Mt. Sinai Hospital and a professor of psychiatry, pointing to the fact that the study’s participants ceased breastfeeding during treatments. “A number of current antidepressants are well-investigated and very safe to use while breastfeeding as the dose in breast milk is really low.”
The FDA was specific in its approval of the drug solely for PPD and not major depressive orders as its efficacy was not great enough compared to products already on the market (a decision that actually drove the drug companies stock down in the days afterwards). But while Bergink sees zuranolone, particularly its rapid onset, as a positive step, she wants to see more data about its efficacy as compared to other SSRIs currently being prescribed for PPD. “Right now we do not know how this compares to other antidepressant treatments we have, and we do not know if it lasts—and these are things that need to be investigated so that we know how to include this treatment in our current treatment protocols,” Bergink explains.
Bergink sees stigma as a big roadblock. “The main problem with PPD is that it goes undetected or untreated,” says Bergink, adding that this is especially true among women of color and women in lower socioeconomic classes. “There is a stigma around admitting that you’re not well and that your life feels upside down when there are expectations that you’re going to be super happy. Getting people who need it to a mental health care professional who has the experience to help them is hard.” For these women, a drug with a rapid onset like zuranolone could be a great option if it becomes widely accessible (and with no sense yet of price or availability this remains to be seen). It could also, adds Hutner, offer peace of mind to the many patients she sees who now fear PPD, because of how widespread it is, as an inevitability. “To the extent that we can reduce this feeling of bracing for impact we can make people feel more empowered,” she says.
The idea of a pill you can take to make all your problems disappear is tempting (I mean, who wouldn’t want that?), but what’s crucial to remember is that one of the root causes of PPD isn’t hormonal or biological, it’s societal. “We give birth in a social context and in our country we’re giving birth in a situation where we have a deeply frayed social safety net,” says Hutner. There is the marked lack of postpartum support more broadly (whether for mental health issues, or simply for matters like lactation and breastfeeding), the absence of affordable child care, and no standardized parental leave—something the U.S. is in the shameful position of being the only high-income nation not to have (one in four women here are back at work two weeks postpartum). While zuranolone holds real promise, a generous mandated paid family leave for all would feel like more of a magic bullet. As Hutner says: “A pill is not a policy.”
