On Friday, August 4, 2023, the U.S. Food and Drug Administration (FDA) approved Zurzuvae™ (zuranolone), developed by pharmaceutical firms Biogen and Sage Therapeutics, to treat postpartum depression. The treatment is a pill taken once daily for 14 days, and is the first oral treatment approved for this condition.
“We’re happy there’s attention for a disease that has not gotten much attention thus far,” says Veerle Bergink, MD, PhD, Director of the Women’s Mental Health Program, and Professor of Psychiatry, and Obstetrics, Gynecology and Reproductive Science at the Icahn School of Medicine at Mount Sinai. Zurzavae had received Fast Track and Priority Review designations from the FDA, deemed as having potential to address a serious unmet need.
Veerle Bergink, MD, PhD (left) and Kimberly Mangla, MD (right)
Postpartum depression occurs often enough in mothers, yet the public’s understanding of it remains limited, says Kimberly Mangla, MD, Clinical Director of the Women’s Mental Health Program at Icahn Mount Sinai. “I’m glad we have an additional, possibly effective treatment for patients, and hopefully it will raise conversations and awareness of postpartum depression resources and treatment options,” she adds.
Drs. Bergink and Mangla explain what postpartum depression is, and how Zurzuvae could potentially treat it.
What is postpartum depression?
Postpartum depression can appear similar to other forms of clinical depression, with symptoms that include general low mood, lack of enjoyment, low energy, and low motivation, says Dr. Mangla. But there are unique aspects, such as difficulty bonding with the baby.
Postpartum depression is also different from what is commonly called “baby blues,” which is a common phenomenon of feeling overwhelmed, tearful, or being “hormonal,” notes Dr. Mangla. Baby blues tend to go away after two weeks. “What would be alarming might be feelings of hopelessness, suicidality, or a complete disconnect from the baby that aren’t necessarily a component of baby blues—those are reasons to seek support for what might be postpartum depression,” Dr. Mangla says.
While regulatory or insurance entities might define postpartum depression as occurring within four weeks after delivery, experts in the field—clinicians and researchers—agree that onset can be highly variable, even up to 12 months after delivery, says Dr. Bergink.
“From a psychological or physiological point of view, we know that it could take half a year for a woman’s hormones and immune system to go back to normal,” says Dr. Bergink. “And we have heard women say it could take up to a year before they feel like the person they were before delivery, and psychologically used to the new state of being a mother.”
What is Zurzavae, and how does it work?
Many current antidepressants work by targeting the serotonin system, but this drug works by targeting the gamma-aminobutyric acid receptor GABAA. While there are other drugs in this class of antidepressants, this is the first one approved for postpartum depression, says Dr. Bergink.
How common is postpartum depression?
One in Eight
or about 13 percent of women, have symptoms of depression after birth of baby.
>15 percent
of women in NYC experience depression symptoms after childbirth.
One in Five
women were not asked about depression during a prenatal visit.
>50 percent
of pregnant women with depression were not treated.
Source: Centers for Disease Control and Prevention
However, it is important to note that while this differs from serotonergic antidepressants, there have been no comparative studies done to demonstrate that Zurzavae is any better or worse than other antidepressant treatments out there, she points out. It is also unknown to what extent there is an antidepressant effect beyond the sedative effect, she adds.
What treatment options had been available for postpartum depression?
If the depression is not so severe, options include support therapy, such as cognitive behavioral therapy or psychotherapy, says Dr. Bergink. If it is more severe, then the doctor might consider using antidepressants, such as selective serotonin reuptake inhibitors (SSRIs).
How might Zurzavae differ from other antidepressants?
The way the drug has been marketed is that it works more rapidly than SSRIs, says Dr. Mangla. “Whether or not that’s true, and whether or not that benefit is sustained, we still have no idea,” she says, “but it would be wonderful to have a medication that starts working in three days instead of a few weeks.”
There are still some open questions clinicians might have with Zurzuvae at this point, notes Dr. Bergink. These include its effect on women who are breastfeeding, and whether the drug will keep depression away long beyond the study period, which was 45 days, she says.
What sources of support can mothers experiencing depression seek?
Generally, a mom experiencing depression symptoms should talk to anyone who is in her support system, says Dr. Mangla. This could include friends and family, but also a primary care doctor who might be able to make a referral to a general psychiatrist.
“Because the treatment of depression in postpartum is so similar to treatment of depression outside of postpartum, the disease is often well treated by general practitioners or general psychiatrists,” says Dr. Mangla.
Seeking help from social workers can be useful too. There are many ways mothers can access social workers, including through a local health institution, or even via online resources, such as Postpartum Support International, notes Dr. Mangla.
“Postpartum depression is a very treatable condition,” says Dr. Bergink. “We should do all we can to help mothers feel comfortable about reaching out for support.”
What has Zurzuvae shown in clinical trials?
Zurzuvae was approved based on data from two randomized, placebo-controlled trials in postpartum depression.
Here are the efficacy and safety highlights:
- Both studies achieved their primary endpoint: a significant mean reduction from baseline in the Hamilton Rating Scale for Depression (HAMD-17) total score, a 17-item questionnaire on depression symptoms compared to placebo.
- In one study, Zurzuvae achieved a significant reduction in depressive symptoms as early as day three.
- Most common side effects of patients on Zurzuvae included drowsiness, dizziness, diarrhea, fatigue, and urinary tract infection.
- The FDA has included a warning on Zurzuvae’s label that instructs health care providers to advise patients that the drug causes driving impairment due to sedative effects, and patients should not engage in activities that require mental alertness until at least 12 hours after the 14-day treatment.