- A new medication to treat postpartum depression (PPD) could be available to patients in late 2023.
- The FDA is currently reviewing the New Drug Application for zuranolone, a new approach to treating PPD and major depressive disorder.
- The medication is in pill form and meant to be taken once a day for 14 days for fast-acting treatment.
A novel medication to treat postpartum depression (PPD) could be available to patients later this year.
The drug, zuranolone, designed by the pharmaceutical companies Biogen Inc. and Sage Therapeutics, Inc., is a completely new approach to treating both PPD and major depressive disorder (MDD), offering hope during a critical period of time for mother and baby.
“Mental health issues are one of the most common complications in pregnancy and postpartum,” Christopher Zahn, MD chief of Clinical Practice and Health Equity and Quality at the American College of Obstetrics and Gynecology (ACOG), told Health.
PPD affects half a million people in the United States every year, according to data published in 2020. Although the Food and Drug Administration (FDA) is currently reviewing the New Drug Application for zuranolone and has not yet approved the medication, “it is encouraging that postpartum individuals may now have more options to manage what can be a debilitating condition,” Dr. Zahn said.
A Novel Approach to Depression Treatment
While current antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) target the brain’s serotonin receptors, zuranolone is designed to bind to GABA receptors, the main neurotransmitter in the nervous system.
“It's a major driver in the brain,” said Laura Gault, MD, PhD, chief medical officer of Sage Therapeutics, Inc. “We think of depression as the disruption of brain function—disconnections in the brain that are driven by GABA disruption.”
Zuranolone works by restoring the connections between GABA receptors that depression disrupts, which, Dr. Gault said, restores normal brain function.
The concept isn’t novel, but the way the drug is administered and how long it lasts is a huge step forward. The FDA approved Zulresso (brexanolone) injection in 2019, which also acts on the GABA receptors but presents a host of access issues. The injection is administered over 60 hours, or about 2.5 days, and must be done in a monitored setting, such as a hospital.
“It limited the access to that medication for a lot of people who otherwise would have qualified for it. An oral form that has the same efficacy would be huge,” Elizabeth M. Fitelson, MD, director of the Women's Program at the Columbia University Department of Psychiatry, told Health.
A Fast- and Long-Acting Treatment
In total, studies on zuranolone have included 3,500 patients. A Phase 3 clinical trial for zuranolone included 200 people who had recently given birth. Half were given a placebo and half took a pill that contained 50mg of zuranolone every day for 14 days. The researchers found that not only did those who took the novel antidepressant report fewer depressive symptoms, the medication appeared to be both fact-acting and long-lasting, something that also set it apart from existing antidepressants.
During the trial, the first check-in was three days after participants took the first dose, and already, they saw improvements, Dr. Gault said. The effects appeared to magnify over the 14 days in which the medication was administered and the effects lasted an average of 249 days. Zuranalone can be administered in pill form because it has a much longer half life than Zulresso. It’s also the reason the drug’s effects can last so long. Most people in the trial—80%—needed just one or two courses to get them through their PPD.
“They either needed 14 or 28 days of treatment in a whole year. It’s a paradigm shift in how we think about treating depression,” Dr. Gault said.
Although they can be used during the postpartum period, it’s common for SSRIs and SNRIs to take weeks or months to become effective, which cuts into a critical time for bonding.
“It’s such a meaningful time in a family’s life,” Dr. Fitelson said. “The baby needs to form attachment bonds and if a parent is anxious or depressed, that can be delayed. Rapid improvement is actually very significant because timing does matter.”
A Huge Step in Postpartum Medicine
According to Dr. Fitelson, both zuranolone and the IV-administered Zulresso are significant products of improvements in research on the female reproductive life cycle and an effort to understand why women are twice as likely as men to have a depressive episode in their lifetime.
“For so long, even in animal studies, females were left out of psychological research. Our biases about gender have blocked novel pathways and there have been a dearth of truly novel treatments because of that,” Dr. Fitelson said.
Researchers have traditionally shied away from using females, even in rodent studies, because of natural hormonal shifts that were thought to interfere with data. But understanding these hormonal shifts is key to creating novel treatments, especially for the period during and after pregnancy.
ACOG defines PPD as depression that onsets within the first year of giving birth. While the symptoms for PPD and MDD are generally the same, the triggers are thought to be different. A key risk factor is sensitivity to the radical hormonal shifts that happen during delivery.
According to Dr. Fitelson, the placenta pumps out huge amounts of hormones, including estrogen, throughout pregnancy.
“When the placenta is delivered, those plummet to essentially none. It’s a 20-fold higher change than hormone shifts that occur during the menstrual cycle. For some, that’s a trigger for PDD,” she said.
There are also factors including complications that can happen during pregnancy and delivery and the flood of stress hormones that are released during labor.
“Then you have this baby to take care of, you’re sleep deprived and isolated from your normal life. It’s not just one factor that is the answer for why people seem to be at higher risk for depression and anxiety during this time,” Dr. Fitelson said.
Treatment Could Be Available to Patients in Late 2023
While the FDA is set to announce whether or not it will approve zuranolone by early August, Gault said additional paperwork is required before a new drug hits the market. If it is approved, Dr. Gault guesses zuranolone will be available to the public sometime in November.
Like all drugs, zuranolone can produce side effects, though the majority were mild or moderate in severity. Trials showed that zuranolone caused somnolence (excessive sleepiness) in about 15% of people and headache in about 11%. Nearly 14% of people who took the novel antidepressant experienced dizziness.
Dr. Fitelson noted patients should not see zuranolone as the only depression treatment for PPD if it isn’t accessible or agreeable with them. “I don’t want people to think it’s the only medication and that if they don’t get it, they won’t get better,” she said. “There are many ways to get better, including therapy.”
Still, the drug remains an exciting opportunity for postpartum mental health care. “To be able to take a once-a-day medication at home,” Dr. Fitelson said, “and not interrupt time with the child, to have your usual supports at home, and to increase access, is really exciting.”
Biogen. Biogen and Sage Therapeutics announce FDA accepts filing of new drug application and grants priority review of zuranolone in the treatment of major depressive disorder and postpartum depression.
Bauman BL, Ko JY, Cox S, et al. Vital signs: postpartum depressive symptoms and provider discussions about perinatal depression - United States, 2018. MMWR Morb Mortal Wkly Rep. 2020;69(19):575-581. doi:10.15585/mmwr.mm6919a2
Food and Drug Administration. FDA approves first treatment for postpartum depression.
Biogen. Sage Therapeutics and Biogen announce consistent clinically meaningful data for zuranolone across the LANDSCAPE and NEST clinical development programs presented at the European College of Neuropsychopharmacology (ECNP) Congress.
Beery AK. Inclusion of females does not increase variability in rodent research studies. Curr Opin Behav Sci. 2018;23:143-149. doi:10.1016/j.cobeha.2018.06.016
American College of Obstetricians and Gynecologists. Postpartum depression.