FDA Approved First Pill Designed For Postpartum Depression

The Food and Drug Administration on Friday approved the first-ever pill specifically designed to treat postpartum depression. Taken once a day for two weeks, the drug, called zuranolone and marketed as Zurzuvae, can rapidly and effectively relieve symptoms of postpartum depression, a mental health condition that affects as many as 17% of people who’ve recently given birth.

“This will be a game changer,” Jennifer Payne, director of the Reproductive Psychiatry Research Program at the University of Virginia School of Medicine, told Wired earlier this week.

During pregnancy and childbirth, the brain undergoes significant chemical changes that make it more susceptible to stress, and, as a result, depression. Other factors, such as pregnancy complications, social isolation and underlying illness, can contribute to the mood disorder, too. Postpartum depression commonly includes symptoms like mood swings, anxiety, extreme fatigue, aches or pains, and difficulty sleeping.

Until now, the go-to treatments for PPD have been standard antidepressants, which take weeks to kick in, psychotherapy and/or an injection called brexanolone that’s fast-acting and effective but takes 60 hours to administer in a medical setting.

There’s been an urgent need for an oral pill that can swiftly improve depressive symptoms in new moms, and the approvals process for Zurzuvae was given priority review and fast-track status by the FDA. Zuranolone helps restore chemicals and neuronal networks in the brain that may have become depleted during pregnancy and childbirth, according to researchers. This resets brain functions related to mood, arousal, behavior and cognition, and helps the brain cope with stress again.

“This new medication is exciting because of the rapid onset, and it can be taken orally,” said Dr. Jennifer McMahon, an assistant professor of psychiatry at Yale School of Medicine and a clinician at Yale Medicine.

Here’s how the pill works and why it’s such a big deal for people with postpartum depression.

Postpartum depression can trigger feelings of sadness, anxiety, guilt, low energy, poor concentration and indecisiveness. The condition affects mother-infant bonding, and some women develop suicidal ideation.

“Suicide is the leading cause of direct maternal mortality in the first postpartum year with one in seven deaths due to suicide,” Dr. Kristina M. Deligiannidis, the principal investigator on zuranolone’s clinical trials and a professor at the Feinstein Institutes for Medical Research in Manhasset, New York, told HuffPost.

The causes of postpartum depression are multi-factorial and include everything from genetics and hormonal changes to a strained social support system, pregnancy complications and financial stress. Having a personal or family history of a mental health issue like depression or bipolar disorder can increase a person’s risk, as can having a baby with a health complication, going through with an unwanted pregnancy, experiencing difficulty with breastfeeding, or having problems with a partner.

It’s also known that certain brain functions become dysregulated and imbalanced when someone is experiencing postpartum depression. For example, in an otherwise healthy person, the brain produces neuroactive steroids that help manage stress and keep brain network function — particularly related to behavior and cognition — in good shape. With postpartum depression, the production of those neuroactive steroids becomes impaired, causing the brain to become more sensitive to stress (which there’s no shortage of during pregnancy and after childbirth).

Zuranolone is a neuroactive steroid that affects the primary neurotransmitter in the brain, binding to receptors and boosting activity that can restore dysregulated networks. “That’s the hypothesis of why it could be impacting depression in the perinatal period,” says McMahon.

The phase 3 clinical trial, which was funded by the drug manufacturers Sage Therapeutics and Biogen, evaluated the safety and efficacy of zuranolone in a relatively small sample size of 196 women who had given birth less than 12 months prior and had experienced a major depressive episode either in the third trimester of pregnancy or within four weeks postpartum.

The women were split up into two groups: 98 took 50 milligrams of zuranolone once daily for 14 days and the other 98 took a placebo. By day 15, 57% of those who took the pill said their depressive symptoms had improved by at least 50%, and 26.9% achieved remission.

The study monitored the women for 30 days after they completed their treatment and found that the effects were lasting. By the 45th day, nearly 62% of the women who had taken zuranolone reported a 50% improvement in their depressive symptoms, compared to 54% of those who took the placebo.

The pill kicked in quickly — some women reported improvements after taking just two doses of the medication — and was also well-tolerated. The main side effects reported were drowsiness, dizziness and sedation. Some people developed a headache, and a handful had gastrointestinal issues like diarrhea and nausea.

The drug wasn’t tested in people who were breastfeeding, so future research would need to examine zuranolone’s effects on those who are nursing. This exclusion isn’t unusual; many research studies often exclude lactating people since it’s unknown how a drug could affect the baby.

The treatment course is short, lasting only two weeks. According to McMahon, more research is needed to understand the long-term effects of zuranolone and how postpartum depression affects people once their two-week treatment ends. Some may recover and be able to function normally again after the two-week treatment, whereas others may need to continue to take a standard antidepressant or do psychotherapy for maintenance treatment.

One in eight women develop perinatal depression, or depression that begins either in pregnancy or after delivery, yet only 10% of people with the condition receive adequate treatment. Many women aren’t screened for mental health conditions during pregnancy or after delivery, said Deligiannidis, and of those who are identified as having symptoms, most are never connected with mental health care.

Plus, the treatments that have previously been available for postpartum depression, though effective, have shortcomings. Psychotherapies and selective serotonin reuptake inhibitor antidepressants take weeks to kick in. It takes a couple of weeks for SSRIs to start working, and around two months for them to reach their full effect.

Brexanolone, another neurosteroid that received FDA approval in 2019, is the only other drug specifically designed and approved for postpartum depression. It works phenomenally well, and quickly, but it’s not easy to administer. It’s given via an infusion that lasts 60 hours, or two and a half days. It must be done in a medical setting, which means that soon after childbirth, women must go back to the hospital for a multi-day stay.

“Some women may not be able to access that rapid-acting, lifesaving medication,” said Deligiannidis. It may also cause serious side effects, like loss of consciousness or severe sedation. All this is to say: There are major limitations to the currently available postpartum depression treatments.

Zuranolone can change the way doctors treat postpartum depression.

“An oral, rapid-acting antidepressant has the potential to quickly alleviate depressive symptoms so that women can regain functioning,” said Deligiannidis. While zuranolone targets one very crucial piece of the postpartum puzzle, other contributing factors — including a history of trauma or domestic violence and life stressors — can’t be ignored. “But this is potentially a very helpful tool of one of many things to help women,” McMahon said.

Sage Therapeutics is not yet providing cost and other market information. A company report from May said it anticipates that zuranolone could be commercially available in “late 2023” in accordance with the post-approval Drug Enforcement Administration scheduling period.

If you or someone you know needs help, call or text 988 or chat 988lifeline.org for mental health support. Additionally, you can find local mental health and crisis resources at dontcallthepolice.com. Outside of the U.S., please visit the International Association for Suicide Prevention.