There’s Now An Oral Treatment for Postpartum Depression

Treating depression is complex and time-consuming, since matching patients to the right drug treatment is a matter of trial and error that can take weeks or even months. And post partum depression, which affects up to 20% of new mothers in the first six weeks after giving birth, is no different.

On August 4, the U.S. Food and Drug Administration (FDA) approved zuranolone, or Zurzuvae, for treating postpartum depression. The drug, developed by Massachusetts-based biotechs Sage Therapeutics and Biogen, is a pill that women take once a day for 14 days and is the first oral treatment for the major depressive condition.

“It’s amazing that we are starting to think about postpartum depression more and more, and starting to create novel treatments that for a long time went under recognized,” says Dr. Samantha Latorre, assistant professor of psychiatry at the University of Maryland School of Medicine, who was not involved in the zuranolone studies.

The companies had requested that the FDA approve zuranolone for both post partum and major depressive disorder, and provided data supporting both indications. The agency, however, only announced approval for treating post partum and did not provide an explanation for that decision in its announcement. One study of the drug in several hundred people with major depressive disorder showed early and rapid improvement of symptoms, but that change wasn't sustained; by the end of the treatment period, there was little difference from the start of the study in patients' depression symptoms as measured by standard tests.

The FDA reviewed a series of separate studies involving both people with postpartum depression and major depressive disorder, two related forms of depression. Among people with a major episode of postpartum depression, those who were randomly assigned the drug showed statistically significant improvements in depression scores after two weeks compared to those receiving placebo. And the effect seemed to be persistent through at least a month after the women stopped taking the pills.

Some women showed improvements as early as the third day of treatment, and the fast-acting effect of the drug could be a game-changer in the treatment of depression. Currently, many people continue to experience symptoms for months after starting existing antidepressant therapies that rely on the brain chemicals serotonin, noradrenalin, or dopamine. Zuranolone promises to relieve those symptoms within days. That, in turn, could help people to be more receptive to other interventions such as psychotherapy.

For women with postpartum depression, rapid reduction in symptoms could transform the relationship women have with their babies. “I see this as a tool to get a woman feeling better, and restore her function so she can start feeling herself again, and start taking care of herself and interacting with her baby,” says Dr. Kristina Deligiannidis, director of women’s behavioral health at Zucker Hillside Hospital of Northwell Health and one of the researchers who led the zuranolone trials in women with the condition. “It may even reduce the long-lasting effects of postpartum depression on the neurodevelopment of babies.”

The drug’s quick action may be due to how it works in the brain. Zuranolone targets a receptor called GABA-A, which plays a key role in how the brain calms down nerve activity. In women with postpartum depression, this response isn’t regulated as well as it should be, and the stress responses, including those due to hormonal changes caused by pregnancy, aren’t modulated as well, which can lead to imbalances in brain chemicals that contribute to depression. Zuranolone restores the function of these GABA-A receptors, modulating the brain’s inhibitory response.

Zuranolone is the second drug approved to treat postpartum depression, and represents a major improvement in convenience for patients. Brexanolone, or Zulressa, approved in 2019, also works on the GABA-A system. But the drug is given as an intravenous infusion over 60 hours, and requires women to stay in a hospital-like setting to be monitored during the nearly three day infusion. Only a few centers in the U.S. administer brexanolone, so access has been extremely limited for women who might benefit from the drug.

One reason doctors need to monitor patients while they are given brexanolone is the risk of losing consciousness or passing out during administration. About 26% of the women taking zuranolone in one of the trials experienced drowsiness and 11% became sedated, but Deligiannidis says none lost consciousness. “There’s a striking difference,” she says between the side effects seen with brexanolone and zuranolone. “I don’t know if it’s because of the different molecules or because [zuranolone] is taken by mouth and not through the vein, but we have not seen to my knowledge any loss of consciousness among people taking zuranolone.” The FDA's approval for zuranolone includes a warning about the risk of drowsiness and driving or operating heavy machinery up to 12 hours after taking the medication. The label also alerts patients that they may experience cold symptoms, diarrhea and suicidal thoughts.

New mothers who are breastfeeding may also be worried about how the drug might affecting their babies, and the FDA advises that the medication "may cause fetal harm." There isn't much data on how zuranolone may affect developing babies, since in the studies reviewed by the FDA, women were asked to stop breastfeeding during the 14 days they took zuranolone, and for seven days after that, and were provided breast pumps and donor milk to feed their babies during that time. But in a separate study of lactating women taking zuranolone, Deligiannidis says the amounts of drug in the breast milk after five days of treatment were very low, although more research on the effects of even this exposure will be needed.

While it’s not clear yet how lasting the effects of zuranolone might be, or if it’s changing brain signaling in more than a transient way, treating depression early like this could potentially lead to better and more durable outcomes, says Deligiannidis. And having another effective option for treating postpartum depression could help more women to feel comfortable about reporting symptoms so they can start taking advantage of treatments, whether its drugs like zuranolone or something more like talk therapy. Women “should not try to push through or suffer alone, since in many cases they won’t resolve on their own,” says Deligiannidis. “There are effective treatments available.”