On Friday, the FDA announced that the treatment, to be sold under the brand named Zurzuvae, has been approved as a once-daily pill taken over the course of 14 days.
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"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," Dr. Tiffany R. Farchione, director of the Division of Psychiatry in the FDA's Center for Drug Evaluation and Research said. "Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings."
The FDA added a boxed warning to the drug's labeling, noting it can impact a person's ability to drive and perform other potentially hazardous activities. Patients also may not be able to assess their degree of impairment. To reduce the risk of harm, the agency says patients should not drive or operate heavy machinery for at least 12 hours after taking the drug.
The FDA said the most common side effects include drowsiness, dizziness, diarrhea, fatigue, nasopharyngitis (the common cold), and urinary tract infection. The agency also said use of the drug may cause suicidal thoughts and behavior. It may also cause fetal harm. The agency said women should use effective contraception while taking, and for one week after taking the medication.
Women with severe postpartum depression may experience suicidal ideation, and maternal deaths from suicide account for about 20% of all deaths that occur postpartum.
It's estimated that each year in the United States, more than 400,000 babies are born to mothers who are depressed. Without any treatment, postpartum depression can last for months or even years, according to the National Institute of Mental Health.
Becoming the nation's second postpartum depression drug
In February, drugmakers Biogen and Sage Therapeutics, Inc. - the two companies behind zuranolone - announced that the FDA had accepted their application for the approval of zuranolone and their application was granted priority review.
"We see potential for zuranolone, if approved, to be a meaningful new option that can help address the serious unmet need faced by the diverse populations struggling with" major depressive disorder and postpartum depression, Dr. Priya Singhal, executive vice president and head of development at Biogen, said in a news release at the time.
Treatment options for postpartum depression have included counseling or therapy with a mental health professional and antidepressant medications, but until Zulresso and zuranolone, no antidepressant medication had been specifically FDA-approved to treat postpartum depression. Also, antidepressant medications generally don't provide immediate relief of symptoms and may take several weeks to help.
In 2019, Zulresso became the first postpartum depression drug to receive FDA approval.
That treatment is administered as a single 60-hour IV drip of the drug brexanolone and was found to have mild side effects, such as headache, dizziness or excessive sleepiness, but also sudden loss of consciousness. Some women may face barriers accessing this type of treatment, as it requires 60 hours of time and must be used within a health care setting. Whereas, with zuranolone, it is a pill you can take at home.
Both brexanolone and zuranolone are versions of a naturally occurring substance in the body called allopregnanolone, a neuroactive steroid that is a metabolite of the hormone progesterone. Levels of allopregnanolone can rise dramatically during pregnancy and then abruptly drop after childbirth, potentially contributing to postpartum depression.
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So restoring allopregnanolone with medications structurally similar to it, like brexanolone or zuranolone, can help provide some relief to people with postpartum depression. Both drugs work in a similar way; they are just administered differently.
"After years of dedicated research and collaboration with other scientists around the country, women living with postpartum and perinatal depression have a new, at-home, easy-to-use treatment option that has the potential to alleviate their symptoms," Dr. Kristina Deligiannidis, a professor at the Institute of Behavioral Science at the Feinstein Institutes for Medical Research in New York, who has been the principal investigator on national multi-site clinical trials that led to zuranolone's approval, said in a news release.
Postpartum depression "is often underdiagnosed and undertreated. With the FDA's decision today, we may be able to reverse this and help many more women in need," Deligiannidis said.
A previous Phase 3 clinical study of zuranolone, published in 2021 in the journal JAMA Psychiatry, found that among 151 women with severe postpartum depression, the patients taking daily zuranolone at 30 milligrams for two weeks experienced greater reductions in their depressive symptoms compared with those taking a placebo. Those reductions in symptoms were seen within three days and lasted through 45 days, according to the study, which was conducted in 2017 and 2018 at 27 sites.
A more recent Phase 3 study, published last week in the American Journal of Psychiatry, found that a 50-milligram dose of zuranolone was well tolerated and effective. The study found that among 196 women with postpartum depression, the patients taking daily zuranolone at 50 milligrams for 14 days demonstrated "significant improvements in depressive symptoms" compared with those taking a placebo.
The day after the women completed the 14-day treatment course, the researchers found that 57% reported a 50% or higher improvement in their depressive symptoms, compared with 38% of those on a placebo. As the researchers continued to follow the women through 45 days, 61.9% of participants who received zuranolone, compared with 54.1% of those taking a placebo, saw such high improvements in their symptoms.
The FDA approval of zuranolone marks "a very important step forward" for the field of maternal mental health, Dr. Samantha Meltzer-Brody, director of the Center for Women's Mood Disorders at the University of North Carolina at Chapel Hill, said in an email. She was one of the investigators on the zuranolone clinical trials.
"It will be an important tool in treating postpartum depression. Rapidly acting antidepressant therapies are needed and this would be the first oral drug formulation of a rapidly acting antidepressant. That is a very big deal for moving the bar forward to improve treatment options for women with postpartum depression," Meltzer-Brody said in the email.
"I believe that many women will be very eager for a rapidly acting antidepressant," she said, adding that if a mother can have relief from postpartum depression within three days, which was found for some participants in the zuranolone clinical trials, "that is extremely important as the postpartum period is such a vulnerable time."
Some mental health experts raise concerns
Approval of this medication is an important milestone in postpartum depression treatment, specifically as it has a new biological target and is fast-acting, said Catherine Monk, professor and chief of the division of women's mental health in Obstetrics & Gynecology at Columbia University Vagelos College of Physicians and Surgeons.
Yet she added that there are certain concerns among some maternal mental health experts when it comes to zuranolone - the medication was originally tested primarily on women with severe postpartum depression, not mild or moderate depression, and patients should still consider psychotherapy as an intervention for depression.
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"There's a concern that this medication will just get used for everybody. Whereas for people with mild to moderate depression, the gold standard of care is to start with psychotherapy and other behavioral and lifestyle changes," Monk said, adding that the pill should not be a first response for patients with mild to moderate postpartum depression.
"It needs to be clear that it originally was established as having efficacy mainly with people who had severe depression," she said. "Also, there are significant health disparities in the rates of postpartum depression, much higher rates for those living in poverty and minoritized populations."
While such disparities are a social-political problem, Monk said, "we must address the social determinants of health in the causal pathway to postpartum depression and not let the excitement of a new medication overshadow these issues."
Judite Blanc, assistant professor of psychiatry and behavioral sciences at the University of Miami Miller School of Medicine, had similar sentiments.
Zuranolone "could be particularly beneficial for women who face barriers to accessing long-term treatments, such as low-income women or those with limited healthcare access. However, from a scientific, social, and ethical standpoint, this clinical trial is not the panacea to tackle the maternal health crisis in the U.S. and globally," Blanc wrote in an email last month.
"Medications shouldn't be the first or only line of treatment for mental health conditions, particularly among women, children, and historically oppressed populations," she said.
And as the effect of zuranolone reported in the trial was followed only for 45 days among postpartum women who don't breastfeed, Blanc added that "we need further studies to assess the long-term impact of Zuranolone, including among breastfeeding mothers, as well as the patient-child interaction."
Postpartum depression symptoms may include crying spells, difficulty bonding with your baby, inability to sleep, or feelings of hopelessness. With severe postpartum depression, women are unable to function with daily routines and often have recurring thoughts of suicide, self-harm or harming the baby, which are very serious symptoms that require immediate evaluation and attention.
"Someone with a really severe depression, often there is suicidal ideation, and very concerning, a plan," Monk said. But she added that, for any new mother, "if you feel like you could use some support and help, it doesn't matter if you have what we call a subclinical depression, please reach out and you should get help - and it may be that you don't need as much help as someone else with a very serious depression, but let's get you the support and help you need - especially to prevent the situation from worsening."
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