• Posted August 2, 2023

Pill to Counter Postpartum Depression Looks Good in Trial, May Gain FDA Approval

All eyes are on the U.S. Food and Drug Administration this week as the agency weighs approval of a new pill that may quickly treat and ease severe postpartum depression.

Approval of the drug could help millions of women regain their emotional equilibrium following childbirth. The FDA's decision is expected by Friday.

Taken as a pill once a day for two weeks, zuranolone showed “rapid, significant and sustained” reductions in depressive symptoms when compared to a placebo, or dummy pill, according to a recent study of nearly 200 women.

These improvements occurred in as few as three days and were still evident 28 and 45 days later, said study author Dr. Kristina Deligiannidis. She is a professor at the Institute of Behavioral Science at the Feinstein Institutes for Medical Research in Manhasset, N.Y.

As many as 1 in 8 women in the United States develops depression immediately before or after giving birth. “Women report severe sadness or loss of interest in pleasurable activities and relationships, have significant guilt, often about not being a good enough mother or partner, low energy, poor concentration and indecisiveness, loss of appetite and irritability," Deligiannidis said. Many also say they feel overwhelmed and are anxious, especially over the baby's well-being, she added.

Some women may start to believe that their family would be better off if they were dead, she said.

Sahar McMahon, 39, of New York City, participated in the clinical trial of zuranolone after the birth of her second daughter. She never wanted to hurt herself, she told CNN, but she felt she "just was existing."

"There were points where my kids would be screaming. I would leave them screaming in the living room. I'd go in my room, close the door, scream into a pillow, and then I'd think, ‘What are we doing this for?'" McMahon said. “My whole thought process was very pessimistic, and that's not who I am at all."

After taking zuranolone, "I immediately just started feeling more like me,” she recalled.

Women like McMahon need more treatment options. “Standard of care antidepressants, while effective, take a few weeks to start to show benefit, with maximal benefit often not seen until after 8-12 weeks of treatment,” Deligiannidis said.

Moreover, these pills must be taken for months or years and can have chronic side effects.

The FDA approval of Zulresso (brexanolone) in 2019 for postpartum depression was a breakthrough, Deligiannidis said. “However, there have been barriers in getting this lifesaving medication to women, so the development of a related, oral option may increase treatment access,” she said.

Both brexanolone and zuranolone are versions of allopregnanolone, a neuroactive steroid that is a by-product of the hormone progesterone. Levels of allopregnanolone can rise dramatically during pregnancy and then crash after childbirth, potentially contributing to postpartum depression.

"Although it is not yet known exactly how zuranolone has rapid antidepressant effects, research suggests that neurosteroids like zuranolone work to support brain health by rapidly reducing stress and restoring healthy brain network connections,” Deligiannidis said.

Brexanolone is given via a 60-hour IV infusion in a health care setting. It has been associated with a loss of consciousness in some women.

There have been no reports of loss of consciousness with zuranolone use, Deligiannidis said. The most common side effects with zuranolone were sleepiness, dizziness, sedation and headache.

“Since zuranolone is an acute, 14-day treatment course, the medication is not taken chronically, and side effects should be confined to the short treatment course,” Deligiannidis said.

The study was recently published in the American Journal of Psychiatry. It was funded by zuranolone maker Sage Therapeutics and Biogen.

Women's health experts are excited about the possibility of a new option to treat postpartum depression.

“This could be a big deal,” said Dr. Misty Richards. She is an assistant clinical professor of child and adolescent psychiatry and obstetrics and gynecology at the University of California, Los Angeles.

Brexanolone can be prohibitively expensive, and requires an inpatient stay, which has been a barrier for many, Richards said.

“Zuranolone is taken by mouth, and we hope that will make it more affordable, and you see benefits as soon as three days,” she said.

Timing is of the essence when treating postpartum depression, Richards added.

“Symptoms can compromise the bonding of parents to the baby and the attachment of babies to the parent,” she said.

“If it is approved by the FDA, this medication will, to a great degree, have a very positive impact on the treatment of postpartum depression," agreed Dr. Nirmaljit Dhami, a psychiatrist at El Camino Health in Mountain View, Calif.

Postpartum depression symptoms can be chronic, and many women will experience relapses, she said.

“The hope is that this medication will lead to permanent remission of symptoms and that the patient will not need to take it on an ongoing basis," Dhami said.

Women experiencing symptoms of postpartum depression should not suffer in silence, she said. “Let your support system know if you are having these feelings and symptoms,” Dhami said. “You are not alone and not at fault. This condition is treatable so there is hope."

More information

Learn more about postpartum depression at the American College of Obstetricians and Gynecologists.

SOURCES: Kristina Deligiannidis, MD, professor, Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset N.Y.; Misty Richards, MD, assistant clinical professor, child and adolescent psychiatry, obstetrics and gynecology, University of California, Los Angeles; Nirmaljit Dhami, MD, psychiatrist, El Camino Health, Mountain View, Calif., American Journal of Psychiatry, July 26, 2023; CNN