The Food and Drug Administration on Friday approved the first pill for postpartum depression, a milestone considered likely to increase recognition and treatment of a debilitating condition that afflicts about a half-million women in the United States every year.
Clinical trial data show the pill works quickly, beginning to ease depression in as little as three days, significantly faster than general antidepressants, which can take two weeks or longer to have an effect. That — along with the fact that it is taken for just two weeks, not for months — may encourage more patients to accept treatment, maternal mental health experts said.
The most significant aspect of the approval may not be the features of the drug, but that it is explicitly designated for postpartum depression. Several doctors and other experts said that while there were other antidepressants that are effective in treating the condition, the availability of one specifically shown to address it could help reduce the stigma of postpartum depression by underscoring that it has biological underpinnings and is not something women should blame themselves for.
The hope is that it will encourage more women to seek help and prompt more obstetricians and family doctors to screen for symptoms and suggest counseling or treatment.
“This is a patient population that just so often falls through the cracks,” said Dr. Ruta Nonacs, a psychiatrist with the Center for Women’s Mental Health at Massachusetts General Hospital. “When women are told, ‘You have postpartum depression,’ it’s embarrassing, it is demeaning, it makes them feel like a bad mom.”
She added, “There’s also a lot of stigma about taking antidepressant medication, so that might make this treatment more appealing because it’s really a treatment specific for postpartum depression.”
An estimated 10 to 15 percent of women who give birth in the United States experience depression during pregnancy or in the year afterward. The condition can be accompanied by intense anxiety, shame, guilt, impaired sleep, panic attacks and suicidal thoughts or attempts. And it can make it difficult for mothers to provide their babies with the care, bonding and nurturing that is crucial for healthy development.
“Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings,” Dr. Tiffany R. Farchione, the director of the F.D.A. division responsible for the approval, said in a statement.
The pill, zuranolone, which will be marketed under the brand name Zurzuvae, was developed by Sage Therapeutics, a Massachusetts company that produces it in partnership with Biogen. It is expected to be available after the Drug Enforcement Administration completes a 90-day review required for drugs affecting the central nervous system, Sage said. The companies have not announced a price for the pill.
The companies had also applied for approval to use the drug for major depressive disorder (also called M.D.D.), a much larger potential market. Sage and Biogen said in a statement late Friday night that the F.D.A. had told the companies that “the application did not provide substantial evidence of effectiveness to support the approval of zuranolone for the treatment of M.D.D. and that an additional study or studies will be needed,” and it added that Sage and Biogen “are reviewing the feedback and evaluating next steps.” Several psychiatric experts have said the data for the drug’s use in treating that disorder is less convincing.
The only other drug approved for postpartum depression is brexanolone, also developed by Sage and marketed as Zulresso. But brexanolone, approved in 2019, requires a 60-hour intravenous infusion in a hospital, carries risks of loss of consciousness and costs $34,000. Sage says only about 1,000 patients have received it so far.
Taking a pill for two weeks is much easier, not requiring a mother to leave her baby for several days. However, the F.D.A. did require the label to include warnings about possible suicidal thoughts and behavior, sleepiness and confusion. The label will also include a so-called “black box warning” that patients should not drive or operate heavy machinery for at least 12 hours after taking the pill. The pill should be taken in the evening “with a fatty meal,” the agency’s announcement said.
Doctors said Zurzuvae would not be appropriate for everyone experiencing postpartum depression. For those with mild to moderate depression, talk therapy can work well. Dr. Kimberly Yonkers, chairwoman of the psychiatry department at University of Massachusetts Chan Medical School, said she would probably not recommend Zurzuvae for patients with longstanding recurrent depression or for “somebody who has a severe episode with a suicidal attempt or hospitalization because you don’t give them a treatment for two weeks and then stop it.”
Appropriate patients, she said, might include “people who have not had a complete response to another antidepressant.”
Dr. Alison Reminick, director of the women’s reproductive mental health program at the University of California, San Diego, said about 10 percent of her patients would be likely candidates. Those would include women experiencing depression for the first time. Such patients are at higher risk of developing bipolar disorder, she said. Although drugs such as Lexapro, Zoloft and other selective serotonin reuptake inhibitors (S.S.R.I.s) work, they can cause mania in those patients, she said.
She would also offer Zurzuvae to women whose depression was accompanied by anxiety or insomnia because studies suggest it may ease those symptoms.
“I’m a huge fan of S.S.R.I.s,” Dr. Reminick said, but noted that many patients resisted trying medication. “I think this will be much easier to get them to just try this for two weeks.”
Data submitted to the F.D.A. came from two company-funded clinical trials involving about 350 patients. A majority of those receiving Zurzuvae (72 percent in one trial, 57 percent in another) clinically responded to the treatment after the two-week course, meaning that their scores on a standard depression scale improved by 50 percent or more.
Depression also improved in women receiving the placebo, a common phenomenon in studies of depression treatments, possibly because interacting with medical teams in a trial is itself helpful. But in the group receiving Zurzuvae, the improvement was consistently greater, by several points, beginning three days after starting the medication. Fifteen days after taking the first pill, Zurzuvae patients were significantly more likely to have a low enough depression score to be considered in remission.
The effect continued after the patients stopped taking the medicine, throughout the 45 days that they were monitored in the trials. But several maternal mental health experts said longer-term data was needed to determine if patients relapse.
The main side effects of Zurzuvae were sleepiness and dizziness. The trial participants did not show evidence of increased suicidal thoughts or withdrawal symptoms after stopping the drug.
Amy Bingham, 33, of Gibsonville, N.C., received Zurzuvae in a clinical trial in 2018, about six months after giving birth to her son Benjamin.
Ms. Bingham, who works from home for a call center, had experienced depression as a teenager, but her postpartum depression symptoms were different, including panic attacks, tears and shortness of breath.
“I was very anxious that I would do something wrong, that Ben would get hurt because of a mistake I would make,” she said, “that I wasn’t able to respond to his needs effectively and that because I wasn’t able to, he would be an unhappy baby.”
Sometimes, she said, “I would think I was a terrible mother because I couldn’t soothe my own child.”
Her depression scores recorded in the trial improved by the third day on the medicine and reached remission levels by Day 15, according to data shared with The New York Times.
Under standard procedure in such trials, Ms. Bingham did not know if the pill she took for two weeks was Zurzuvae or placebo. She said: “I didn’t feel a lot of improvement at first. It did take about a month for me to start feeling some of the benefits.”
But gradually, she said, “I did start to feel calmer.”
“I wasn’t having as many days where I was feeling as tearful,” she continued. Eventually, “I felt that I could enjoy my time with my son.”
Zurzuvae contains a synthetic version of a neurosteroid or brain hormone called allopregnanolone, which is produced by progesterone and helps regulate a mood-related neurotransmitter, said Dr. Samantha Meltzer-Brody, director of the Center for Women’s Mood Disorders at the University of North Carolina at Chapel Hill and a lead investigator for the trials of Zurzuvae for postpartum depression.
During pregnancy, “levels of estrogen and progesterone rise many-fold and then they fall precipitously at the time of childbirth,” she said. She added that, for genetic or other reasons, women who develop postpartum depression seem especially sensitive to that surge and drop-off, which also lowers allopregnanolone levels.
Typically, “increases in allopregnanolone help deal with acute stress,” said Amy VandenBerg, a psychiatric pharmacist at the University of Michigan. Zurzuvae might address postpartum depression by essentially replenishing depleted allopregnanolone and targeting the same neurotransmitters to stabilize mood, she said.
Although many cases of maternal depression begin in pregnancy, the pill is not being recommended until after childbirth because it operates on a hormonal pathway and wasn’t tested in pregnant women, Dr. Meltzer-Brody said. The label will warn that the drug could cause harm to a fetus and will advise women to use contraception while taking the pill and for a week afterward.
The pill was not tested in women who were breastfeeding their babies. Several doctors said they would inform patients who were considering taking it that there was little data about the drug’s effect on lactating. Some women might be able to pump milk for the two weeks they plan to take Zurzuvae and resume nursing afterward. Some S.S.R.I.s and other antidepressants have been found to be safe for breastfeeding.
About 15 to 20 percent of women in the trials continued taking other antidepressants they had been on for a while. Experts said it was possible that for some patients Zurzuvae would be an adjunct medication or would be used as a bridge to longer-term antidepressants.
“It’s not the only treatment that’s helpful for postpartum depression, but the innovation and the excitement about this is that it’s specific, designed to target postpartum depression based on potential biological causes,” said Wendy Davis, executive director of Postpartum Support International, a nonprofit that raises awareness and provides resources for those experiencing maternal mental health issues. “It gives the understanding that there is a biological reason for what you’re feeling right now,” she said, adding “It is not your fault.”
The fact that there’s a medication prescribed for a mother’s depression might prompt family members to “give recognition to it and increase how much help they give mom,” Dr. Reminick said.
“If it gets more people into treatment, that’s wonderful,” Dr. Nonacs said. “If it doesn’t work, they’re connected with providers and we can try other things. So it opens a door for treatment that has been hard to open in the past.”