First-ever pill for postpartum depression is up for FDA approval this week

The Food and Drug Administration is expected to decide by Saturday whether to approve the first-ever pill for postpartum depression.

The medication, called zuranolone, is taken daily for two weeks. In a pair of clinical trials involving women who experienced severe depression after having a baby, the drug improved symptoms — such as anxiety, trouble sleeping, loss of pleasure, low energy, guilt or social withdrawal — as early as three days after the first pill.

The medication was jointly developed by pharmaceutical companies Biogen and Sage Therapeutics. If approved, it will become the first treatment for postpartum depression that can be taken at home. The only other available option is an intravenous injection that the FDA approved in 2019. It requires patients to stay in a hospital for two-and-a-half days.

Dr. Samantha Meltzer-Brody, director of the University of North Carolina’s Center for Women’s Mood Disorders and an investigator on both zuranolone trials, said the data so far are "incredibly encouraging and very exciting."

But she cautioned that the trials only followed patients for 45 days.

“We know that it works quickly and that you have a durable effect out to day 45, but what happens after that remains to be seen," Meltzer-Brody said.

Women who breastfed or had mild or moderate depression weren't included in the trials.

"At the moment, we can’t recommend this for people who are breastfeeding until we have more data," said Dr. Lauren Osborne, a reproductive psychiatrist at NewYork-Presbyterian/Weill Cornell Medicine.

The FDA is simultaneously considering whether to approve zuranolone for clinical depression, so the pill could be approved for one or both indications.

Postpartum depression is common among new mothers

Around 1 in 8 women report symptoms of postpartum depression after recently giving birth, a Centers for Disease Control and Prevention report found.

Overall, mental health conditions are an underlying cause of around 9% of deaths among women during or within a year after pregnancy, according to the CDC.

Postpartum depression is more intense and lasts longer than the typical worries, sadness or tiredness that many women experience after giving birth. The condition can make it harder for mothers to bond with their babies and may increase the likelihood of developmental delays in infants.

Amy Bingham, a 33-year-old resident of Burlington, North Carolina, started feeling depressed shortly after giving birth to her son, Benjamin, in 2018. With her parents overseas in England and her husband at work, she was left to care for the baby alone, she said.

“It was very overwhelming. I was very scared that I wasn’t doing the right thing for my child,” Bingham said.

Bingham enrolled in UNC Chapel Hill’s zuranolone trial after seeing an advertisement on Facebook. After five days on the medication, she said, she started feeling less anxious and more in tune with her son’s emotional cues.

“I was able to enjoy my time with him,” Bingham said. “It allowed me to get to know him. I was able to bond with him.”

Bingham said her depression returned after the trial ended, however.

Osborne said researchers still aren't sure whether people may need follow-up doses.

Zuranolone is a neuroactive steroid — a synthetic hormone that gets synthesized in the brain and helps regulate mood and behavior. The drug acts on GABA receptors, chemical messengers thought to play a role in regulating fear, anxiety and stress. Studies have shown that people with depression have abnormally low GABA levels.

Osborne said the receptors that stimulate the release of GABA change significantly during the postpartum period, in part because the body produces lots of reproductive hormones.

How zuranolone compares to the existing postpartum depression treatment

Zuranolone offers several advantages over the existing treatment for postpartum depression, called Zulresso, according to the experts interviewed.

Although 70% of women see an improvement in their symptoms within 24 hours of receiving the Zulresso injection, Meltzer-Brody said, it takes 60 hours to administer.

The treatment is “not convenient to say the least, but pretty transformative,” she said.

Zulresso also carries a risk of excessive sedation or sudden loss of consciousness — side effects that were not observed in trials of zuranolone.

Nor did the zuranolone trials find the classic side effects of antidepressants, like sexual dysfunction, weight gain, sleep disturbance or an increased risk of suicidal thoughts, according to Anita Clayton, the national principal investigator for two zuranolone trials in people with clinical depression.

The main side effects included drowsiness, dizziness, sedation, headache, nausea and diarrhea.

For people with mild or moderate postpartum depression, however, psychotherapy is still the go-to treatment. Some are prescribed antidepressants, but Meltzer-Brody said zuranolone may be preferable because it seems to improve symptoms more quickly.

“If you asked any new mother who’s having postpartum depression, ‘Would you like something that can work in days, or would you rather take weeks to months?’ most people really don’t have to think about that very long,” she said.

The new pill may also get approved for clinical depression

Clayton said she expects the FDA to approve zuranolone for both postpartum and clinical depression.

Six zuranolone trials have focused on patients with clinical depression, and five showed positive results, she said. But in one trial, the drug was no better than a placebo at improving symptoms at the 15-day mark. It did improve symptoms at other time points, however.

“Five out of six were positive, so that’s pretty impressive,” said Clayton, who is chair of psychiatry and neurobehavioral sciences at the University of Virginia School of Medicine.

In one of the zuranolone trials, 80% of patients who responded to the initial treatment required an additional treatment course over a one-year period. A small group with persistent symptoms required three, four or five courses.

But Clayton said ending just one depressive episode early can improve a person's long-term prospects.

"What you want to do is get people to remission and feeling normal, without symptoms, and it's more likely for people to then stay well for a longer period of time," she said.