New pill Zuranolone for postpartum depression could change treatment

The apathy started almost immediately after Sahar McMahon gave birth to her second daughter, Lenora, in November 2020. When they returned home, she never took Lenora anywhere like she did with her first daughter, Ophelia. At the time, she rationalized that the COVID-19 pandemic was reason to do nothing.

“I could walk around. I could stay in my garden with friends. I (could) go to the playground and I didn’t do any of that,” the 39-year-old from New York City told TODAY.com. “My husband came home and said, ‘Why haven’t you dressed? The girls are not dressed. What have you been eating today?’ I say, ‘I don’t know.’

McMahon began to wonder what the meaning of life was.

“It started to scare me that I would have crying spells or periods where I would go into my room and close the door while my children were screaming when they clearly needed me,” she says. “(I’d) be by myself and think, ‘What is any of this? Why?'”

Often she would put on Disney+ for her kids while she was alone in her room. This was a huge difference from all the playgroups and mommy and me classes Ophelia enjoyed. McMahon began looking online for explanations as to why she felt so “meh.” She didn’t think it was postpartum depression at first because she didn’t feel like she was going to hurt herself or Lenora, and that’s what she thought the symptoms were.

“I wasn’t in touch with her,” she says. “I knew I loved her, but I resented her nursing. I resented her crying. We just existed.”

She signed up for a clinical trial for a new drug treatment for postpartum depression. At the time, she did not know whether she had received the drug, the zuranolone or the placebo. (The study was double-blind, meaning that neither patients nor researchers knew who got the drug or the placebo until after the trial ended.)

After one dose, McMahon noticed a difference and later had confirmation that she was taking zuranolone. Sage Therapeutics, the drug’s manufacturer, has applied to the US Food and Drug Administration for approval of zuranolone, which is expected in early August.

“I woke up the next day and I’m like, OK, I’ve got things to do like the dishes aren’t done. The laundry is started but not moved into the dryer. I’ve got to figure out how to take care of this kid ,” she recalls. “I felt like myself. I felt clearer.”

She took the pill for a full two week course of treatment and felt even better when she finished. “This was life-changing for me,” she says.

Postpartum depression and its treatment

That US Centers for Disease Control and Prevention estimates that one in eight people experience postpartum depression, which can start during pregnancy and last at least nine months after birth, says Dr. Kristina Deligiannidis, principal investigator of zuranolone clinical trials.

Symptoms of postpartum – also called perinatal depression – mirror the symptoms of clinical depression and can include:

• Severe grief
• Loss of interest
• Increased guilt
• Loss of energy
• Lost appetite
• Increased anxiety and irritability
• Feeling overwhelmed
• An inability to bond with the child

“Their biggest complaint is that they feel overwhelmed and anxious,” Deligiannidis, a behavioral science professor at the Feinstein Institutes for Medical Research, told TODAY.com. Deligiannidis has acted as a consultant for and received grants from Sage Therapeutics for the clinical trials with zuranolone.

In a recent study published in American Journal of Psychiatry, Deligiannidis and her colleagues randomly assigned 196 patients to two groups. One group received zuranolone for 14 days; the other received a placebo. Both groups underwent depression screening before and after the experiment. Those taking zuranolone experienced fewer symptoms on day 15 than those taking placebo.

What’s more, many patients reported a “rapid reduction in depressive symptoms” on day three of taking zuranolone, Deligiannidis notes, whereas SSRIs can take weeks or even months to make a noticeable difference in mood.

The study found that the improvement in depression symptoms lasted for 45 days, Deligiannidis adds.

“We didn’t see any return of the depressive symptoms,” she explains. “Even though they’ve stopped the medication … they continue to do well.”

The drug continues to work even after a patient stops taking it because the neuroactive steroids can actually “shift brain networks to a healthy … state that is more stable,” Deligiannidis says, adding that there is a need more research to fully understand why.

According to the paper, the most notable side effects include feeling dizzy or lethargic, and people did not experience withdrawal symptoms or suicidal thoughts after stopping the medication.

Deligiannidis says the pill could change the treatment of postpartum depression.

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“Some women may only need an acute course of treatment,” she says. “There may be some other women who have other psychiatric illnesses, such as chronic anxiety disorders or other types of mental health problems, who may need a longer course.”

Dr. Katherine Taljan, a perinatal psychiatrist at the Cleveland Clinic who was not involved in the study, says zuranolone is a “very exciting, new treatment.”

She agrees that because the study only looks at participants after 45 days, it is unclear whether some patients may need longer intervention.

“We may see the symptoms return. We don’t know yet,” says Taljan. “The strength of a treatment like this is that we can break the real downward cycle that can happen with severe symptoms, and we can get a reset for the patients – even if that means they will be engaged in ongoing treatment with a psychiatrist or therapist.”

She notes that current PPD treatment often lasts months. “I really try to emphasize and just normalize it with my patients,” she says. “It’s OK to need the ongoing support.”

Dr. Samantha Meltzer-Brody, who was also involved in the study, says zuranolone is “very exciting” in terms of how quickly it works. She is a Sage Therapeutics clinical trial investigator and received research funding from Sage Therapeutics.

The pill could reduce some of the stigma associated with postpartum depression, she hopes.

“If you have something (that works quickly and is) convenient to take … for a short period of time, then that will be a positive step forward,” Meltzer-Brody, director of the University of North Carolina Center for Women’s Mood Disorders, says. “Most people will say, ‘I’ll feel better in a few days,’ especially in a very vulnerable period after giving birth.

Yet there is a stigma surrounding postpartum depression, so some who experience it never receive treatment and push themselves through their feelings. Many believe their symptoms are normal or feel so guilty about experiencing them that they don’t ask for help.

“We detect only about half of women with perinatal depression at this time. Also of those, only 10% receive adequate treatment,” says Deligiannidis. “We need to do better with detection. We need to get better at connecting patients to care.”

Life with two toddlers

When McMahon visited her obstetrician six weeks after the birth of Lenora, she completed a depression assessment, and she believes she may have also been screened at previous pediatrician visits. She suspects she downplayed her symptoms.

“I don’t quite remember,” she says. “I don’t think there was as much focus on me as there was on, ‘is the baby healthy?'”

After participating in the study, McMahon had no other symptoms of postpartum depression. She has stayed at home with the girls until they can both go to school, but she hopes to return to work in sales or marketing. Since taking the medication, she has gone to the gym and lost 40 pounds. Now she and her daughters attend playdates and swimming lessons, and McMahon has made mom friends. She finds that she enjoys motherhood more and doesn’t feel overwhelmed and hopeless when things get tough, like when she struggles with Lenora during potty training.

“She wants her diaper on. She wants her diaper off,” says McMahon. “It’s stressful, but fun.”

Ophelia, 4, loves unicorns, dinosaurs and Venus flytrap plants – she has “eclectic interests.” Lenora, 2, is a “skull-headed direct child. She knows what she wants.” McMahon feels grateful that she was able to participate and have access to this medication.

“I can’t imagine where I would be if I hadn’t been a part of that studio,” she says.