FDA Approves First Oral Treatment for Postpartum Depression

WASHINGTON — The U.S. Food and Drug Administration has given its approval of the first oral medication to treat postpartum depression, a condition that is believed to impact one in seven women during the latter stages of pregnancy and after the birth of their child.

The agency’s approval of Sage Therapeutics’ Zurzuvae is a significant breakthrough as, up to now, treatment for postpartum depression has only been available as an IV injection that had to be given by a health care provider and was not universally available at health care facilities.

“We are thrilled at this news, and know it will help so many new mothers and families,” said Elaine DeaKyne, executive director of Postpartum Support Charleston, in Charleston, South Carolina.

“Postpartum depression is an all-encompassing struggle that often goes unaddressed, leaving so many women feeling isolated and overwhelmed,” DeaKyne continued. “The approval of this new drug marks a pivotal moment for maternal mental health. 

“This treatment not only addresses the urgent need for effective solutions to help address postpartum depression but also helps to bring much-needed awareness and attention to the critical issue of maternal mental illness,” she said.

Wendy N. Davis, Ph.D., PMH-C, executive director at Postpartum Support International in Portland, Oregon, was equally enthusiastic in a written statement provided to The Well News, calling the approval “welcome news for the estimated 500,000 women in the United States who report experiencing symptoms of this devastating and often misunderstood illness each year.”

“Women with PPD desperately need prompt care and additional treatment options that can provide quick relief so they can be healthy and present during this momentous time in their lives,” Davis said.

Dr. Tiffany R. Farchione, director of the Division of Psychiatry in the FDA’s Center for Drug Evaluation and Research, described postpartum depression as 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.”

DeaKyne said just this year in Charleston, at least two first-time mothers are known to have lost their lives to the condition.

“Suicide is the leading cause of death in the first year postpartum,” she said. “Mothers need our support, and this news signifies a significant step forward in acknowledging and validating the challenges faced by new mothers, dispelling any stigma surrounding maternal mental illness, and encouraging open conversations around the importance of maternal mental health.”

As with other forms of depression, postpartum depression is characterized by sadness and/or loss of interest in activities that one used to enjoy and a decreased ability to feel pleasure. 

It can present with symptoms such as cognitive impairment, feelings of sadness or inadequacy, loss of energy or suicidal ideation. 

The efficacy of Zurzuvae for the treatment of postpartum depression in adults was demonstrated in two randomized, double-blind, placebo-controlled, multicenter studies. 

The trial participants were women with postpartum depression who met the Diagnostic and Statistical Manual of Mental Disorders criteria for a major depressive episode and whose symptoms began in the third trimester or within four weeks of delivery.

In the first study, patients received 50mg of Zurzuvae or placebo once daily in the evening for 14 days. 

In the second, patients received another zuranolone product that was approximately equal to 40 mg of Zurzuvae or placebo, also for 14 days. 

Patients in both studies were monitored for at least four weeks after the 14-day treatment. The primary endpoint of both studies was the change in depressive symptoms using the total score from the 17-item Hamilton depression rating scale, measured at day 15. 

The Hamilton depression rating scale is the most widely used clinician-administered depression assessment scale. 

The standard version of the scale contains 17 items pertaining to symptoms of depression experienced over the past week. 

The scale was designed for completion after an unstructured clinical interview with hospital inpatients, with an emphasis on melancholic and physical symptoms of depression.

Patients in the Zurzuvae groups showed significantly more improvement in their symptoms compared to those in the placebo groups. The treatment effect was maintained at day 42 — four weeks after the last dose of the drug.

The FDA has set the daily recommended dose for Zurzuvae at 50 mg, and said it should be taken once every day for 14 days, in the evening with a fatty meal. 

However, the treatment does come with a warning. The labeling approved by the FDA states that Zurzuvae 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, patients should not drive or operate heavy machinery for at least 12 hours after taking Zurzuvae, the agency said.

The most common side effects include drowsiness, dizziness, diarrhea, fatigue, nasopharyngitis (the common cold) and urinary tract infection. In some extreme cases, the FDA said, use of Zurzuvae may cause suicidal thoughts and behavior, and fetal harm. 

Experts in dealing with postpartum depression note that any woman who is pregnant, recently had a baby, miscarried, recently weaned a child from breast feeding or adopted a child can suffer from postpartum depression, regardless of how many previously non-complicated pregnancies and postpartum adjustments she has had. 

A woman may experience this regardless of her age, socioeconomic status and number of children she has borne.

Mandolin Restivo, director of Support and Development at Postpartum Support Virginia, said adding a new and effective tool to treat postpartum depression is an excellent step forward in addressing a wide range of maternal mental health issues.

“The full spectrum of maternal mental health issues includes perinatal anxiety, depression, obsessive compulsive disorder, psychosis and the diagnosis of bipolar disorder during the perinatal time,” she said. 

Restivo went on to suggest that because it can be taken at home, zuranolone could help expand the pool of women seeking treatment.

And that, in and of itself, is a big deal because, “research shows that up to one in seven childbearing people will experience depression during pregnancy or after childbirth, but only half will receive treatment. 

“For women of color, rates of screening and treatment are even lower,” she added.

Restivo also cautioned that despite all the excitement surrounding zuranalone’s FDA approval, “it is not a magic pill.”

“Those most at risk for postpartum depression and other maternal mental health issues include childbearing people of color, those with low socioeconomic status and women with a history of trauma. These women are least likely to be screened and referred for treatment,” she said.

“We need to think about solving maternal mental health issues holistically, and it starts with excellent medical care, access to quality mental health care, proper screening and referral, and the reduction of systemic trauma,” Restivo added.

Zuranolone is expected to be commercially available in the fourth quarter of 2023.  

In the meantime, “Mothers seeking treatment should get help now from their OB, mental health provider or another trusted individual. Do not wait for this drug to be available to seek help,” Restivo said. 

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