Research For First Postpartum Depression Medication

More than the blues: Impacts of PPD on women’s mental health

Depression is a common but serious mood disorder. According to the Centers for Disease Control and Prevention (CDC), rates of depression are high—and rising—among postpartum women. Using data from the 2018 Pregnancy Risk Assessment Monitoring System , the CDC found that about 1 in 8 postpartum women had symptoms of depression, while another CDC study  showed rates of PPD that were seven times higher in 2015 compared to 2000.

Depression can happen to anyone, and it’s especially tough for new moms dealing with the physical challenges of childbirth and the stresses of caring for a young child. When women experience PPD, they often have strong feelings of sadness, anxiety, worthlessness, and guilt. Their sleep, eating, thoughts, and actions can all change noticeably. These mood and behavior changes can be highly distressing and even life-threatening, making it difficult for a woman to do everyday things and take care of herself or her child. In extreme cases, women with PPD may be at risk of hurting themselves or their child or attempting suicide.

Fast-acting, effective treatment for PPD can be life-changing and potentially lifesaving. However, for too long, such care was hard to reach, leaving many women to struggle with depression at a pivotal point in life. Despite some similarities, PPD is not the same as major depression at other times in life. Because of this, usual depression treatments are much less effective in managing the symptoms of PPD.

“PPD is very difficult to treat,” said Mi Hillefors, M.D., Ph.D., Deputy Director of the NIMH Division of Translational Research. “It is usually treated with medications originally approved for major depression—despite limited evidence that they are effective in treating PPD. Standard depression treatments, including antidepressants, psychotherapy, and brain stimulation therapy, can also take weeks or longer to work.”

PPD’s unique risk factors reflect the physical changes of pregnancy and the postpartum period, which include dramatic changes in levels of many hormones and other molecules.

These biological changes had long been seen as a possible source of postpartum mood disorders like depression. But could they also be a solution?

Taking allopregnanolone from bench to bedside

Extensive research, supported by NIMH and other NIH institutes, found that neurosteroids play a key role in how people deal with stress. They also contribute to the development of mood disorders like anxiety and depression. For allopregnanolone, evidence that it sharply decreases after pregnancy and regulates GABA activity gave rise to the notion that it contributes to PPD—and inspired hope it could be used to treat the disorder.

The biopharmaceutical company Sage Therapeutics utilized this basic research to develop brexanolone. Administered intravenously by a health care professional in a doctor’s office or clinic, brexanolone mimics the effects of allopregnanolone, increasing the inhibitory actions of GABA receptors.

Stephen Kanes, M.D., Ph.D., at Sage Therapeutics and Samantha Meltzer-Brody, M.D., MPH, at the University of North Carolina led several randomized clinical trials to measure the effectiveness of the medication in treating PPD and evaluate its safety and tolerability. The studies, which recruited adult women with PPD from hospitals, research centers, and psychiatric clinics across the United States, measured the effects of brexanolone compared to a placebo over 4 weeks.

The trials were a success. Brexanolone significantly and meaningfully reduced PPD symptoms , and it had only mild side effects. Compared to usual depression treatments, brexanolone brought about a faster response and greater improvement . Whereas most antidepressants take weeks to work, brexanolone improved symptoms and functioning in women with PPD within a few hours to days. And the effects lasted up to a month after the treatment stopped. Not only was brexanolone more effective, but it also worked faster than other depression medications.

Based on this promising evidence, the U.S. Food and Drug Administration (FDA) gave brexanolone priority review and breakthrough therapy designation in September 2016. Then, in March 2019, the FDA approved brexanolone , making it the first drug to treat PPD.

Brightening the future for women with PPD

For women with PPD, brexanolone was a long-awaited reason to celebrate. For NIMH, it was a testament to discoveries made through the decades of research it supported. Although some barriers to treatment persisted, women now had greater hope for treating depression symptoms after pregnancy.

“The approval of brexanolone was an important milestone. Finally, an effective, fast-acting medication specifically to treat PPD,” said Dr. Hillefors. “It was also a victory for psychiatric neuroscience because basic and translational research—by design, not chance—led to a truly novel and effective treatment for a psychiatric disorder.”

Without NIMH-supported studies providing the foundational knowledge of neurosteroids, researchers may have never made the connection between allopregnanolone and treating PPD.

The success of brexanolone has continued to open the door to exciting advancements in mental health care. For instance, researchers and clinicians are investigating ways to make brexanolone work better for all postpartum people. Researchers are also testing how neurosteroids can be used to treat other forms of depression and other mental health conditions.

Just the beginning of treatment advances for PPD

Brexanolone is only the start of what will hopefully be a new future for PPD treatment. In August 2023, the FDA approved zuranolone  as the first oral medication for PPD. Zuranolone acts via similar biological mechanisms as brexanolone. Its approval reflects the next step in NIMH-supported basic research being translated into clinical practice with real-world benefits.

The success of the drug, which is taken in pill form, was shown in two randomized multicenter clinical trials . Women with severe PPD who received zuranolone showed statistically significant and clinically meaningful improvements in depression symptoms compared to women who received a placebo. These effects were rapid, sustained through 45 days, and seen across a range of clinical measures. The benefits were mirrored in patients’ self-assessment of their depression symptoms.

According to Dr. Schmidt, “The approval of zuranolone to treat PPD provides women with a rapid and effective treatment that avoids some of the limitations of the original intravenous medication.”

And the journey is far from over. Researchers, clinicians, and industry are continuing to innovate new treatments for PPD to increase access and availability to ensure all people can receive help for their postpartum symptoms.