11 Aug 2023 News in English

FDA approves postpartum depression pill from two Cambridge drug firms

The Food and Drug Administration on Friday approved the first pill designed to treat postpartum depression, a fast-acting antidepressant taken once a day for two weeks for a common disorder that affectsas many as one in eight women.

The drug, made by Cambridge-based biotechs Sage Therapeutics and Biogen, will be sold under the name Zurzuvae. It works differently from older antidepressants that are sometimes prescribed off label for postpartum depression. Those can take up to 12 weeks to provide full benefits, whileZurzuvae is taken once a day for 14 days and acts quickly. Some recipients of the pill in trials felt better after only two of the 14 doses, according to researchers.

Until now, the only drug specifically approved for postpartum depression was Zulresso, another Sage medicine that was cleared by regulators in 2019. It had a similar novel mechanism. But it had to be given as a 60-hour intravenous infusion at authorized health care facilities and cost $34,000 per patient. It was a commercial flop.

“Postpartum depression is a serious and potentially life-threatening condition in which women experience sadness, guilt, worthlessness — even, in severe cases, thoughts of harming themselves or their child. And, because postpartum depression can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development,” said Dr. Tiffany R. Farchione, director of the Division of Psychiatry in the FDA’s Center for Drug Evaluation and Research.

“Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings,” she said.

Regulators recommended the 50-milligram pill be taken in the evening with a fatty meal.

Neither Sage nor Biogen had an immediate comment on the FDA decision or would say how much the drug will cost.

But regulators evidently did not approve the companies’ request to clear the new pill to treat major depressive disorder, a far more prevalent condition for which there are already multiple slower-acting approved drugs. That appeared to be a setback for Sage and Biogen. They had hoped approval for both disorders would make the treatment a blockbuster boasting annual sales of $1 billion or more.

Postpartum depression affects about 500,000 women a year in the United States, according to the Centers for Disease Control and Prevention, although it is frequently underdiagnosed and untreated. For comparison’s sake, an estimated 21 million people age 18 or older, or about 8 percent of all adults in the country, had at least one major depressive episode in the prior year, according to a 2021 survey cited by the National Institute of Mental Health.

As with other forms of depression, postpartum is characterized by sadness and a decreased ability to feel pleasure. Other symptoms can include cognitive impairment, feelings of sadness or inadequacy, loss of energy, or suicidal ideation.

A study published last month in the American Journal of Psychiatry found that the 50-milligram pill taken once a day provided “significant improvements in depressive symptoms and was generally well tolerated.” The trial analyzed nearly 200 patients with severe postpartum depression who received the drug or a placebo for 14 days.

“Treatment with zuranolone compared with placebo resulted in statistically significant improvements in symptoms at day 15,” said the paper, whose lead author was Dr. Kristina Deligiannidis, a professor at the Feinstein Institutes for Medical Research at Northwell Health in Manhasset, N.Y.

A Houston mother of three who participated in the study of the only other approved drug for postpartum depression, Zulresso, was excited that a similar medicine might be available as a pill.

Stephanie Hathaway was tormented by intrusive suicidal thoughts after each of her two daughters were born but felt better within hours of starting the Zulresso infusion in the trial after the second birth, in 2017.

She and her husband, Adam Hathaway, adopted a son in 2021 because they didn’t want Stephanie to risk having postpartum depression again. But they recently discussed her becoming pregnant again if the pill was approved.

“I’m just really hopeful that a version of this drug that is more accessible will change more lives and give hope to more people,” Hathaway, 37, said. “The big thing for me in that suicidal state . . . was hopelessness.”

For years, postpartum depression has received scant attention from the pharmaceutical industry, which considered it a niche market, according drug developers.

A tragedy in Duxbury earlier this year thrust postpartum depression into the spotlight. Lindsay Clancy, a 32-year-old nurse at Massachusetts General Hospital, was charged with strangling her three young children, including her infant son. Clancy, who jumped out of an upstairs window at her home after the alleged Jan. 24 attacks, had said on social media beforehand that she was suffering from postpartum depression.

Clancy’s attorney, Kevin J. Reddington, has said that at the time of the killings Clancy was suffering from mental health issues linked to postpartum depression and was overmedicated on a number of psychiatric drugs, some of which can cause suicidal or homicidal ideation. He said in May that his client is permanently paralyzed from the waist down.

Intrusive and suicidal thoughts are common features of postpartum depression, but mothers seldom act on them, particularly by harming a baby, according to Dr. Nancy Byatt, a psychiatry professor at UMass Chan Medical School. She spoke in general and would not comment on Clancy’s case or her medications.

Although Byatt welcomed a fast-acting pill for postpartum depression, she said that fewer than a quarter of women with depression during pregnancy or in the year after childbirth can get an initial appointment with a mental health provider.

“Is it a game changer?” Byatt said of a pill that can be taken at home. “It’s only a game changer to the extent that people can access it.”

Deligiannidis, who led the clinical trials of zuranolone and Zulresso, said the most commonly prescribed antidepressants ― selective serotonin reuptake inhibitors, or SSRIs ― work more slowly and are usually prescribed for extended periods, sometimes for years. They also can cause distressing side effects, including sexual dysfunction and weight gain.

Like Zulresso, the new pill, Zurzuvae, can cause side effects, too, including dizziness, drowsiness, and sedation.

Both of those drugs are based on the natural molecule allopregnanolone, a byproduct of the hormone progesterone that increases during the third trimester of pregnancy then falls precipitously after the baby is born, Sage’s chief medical officer, Dr. Laura Gault, said earlier this year.

Zulresso is made from synthetic allopregnanolone, while Zurzuvae contains a version of the molecule that was chemically tweaked to help it work as a once-a-day pill. Yet Sage says that its drugs are not merely replacing something that is missing.

During depression, communications between brain regions become disrupted. Much like allopregnanolone, both of Sage’s medicines target brain receptors that use the neurochemical called GABA to reduce and slow communication between brain cells. “That really changes the way that brain regions are communicating with each other,” Gault said.

Dr. Greg Mattingly, a psychiatrist and associate clinical professor at Washington University who tested zuranolone in two clinical trials, compared GABA with the brakes in a car, and its counterpart brain chemical ― glutamate ― to the gas pedal. The two molecules become imbalanced in people with depression, he said early this year. “If either gets stuck, you’re not going to get where you need to be,” he told the Globe. The medicine makes the brain receptor more sensitive to GABA.

And patients should know quickly if it’s working. “It’s rapid onset,” he said Friday. “Within two days, you can start to see improvement. By the end of two weeks, you’re done with the treatment. I think the postpartum depression data is really solid.”