Zuranolone proved safe and effective in reducing symptoms of postpartum depression in a phase III clinical trial.
Patients who took zuranolone, an investigational treatment for depressive disorders, had significant improvements in their depression scores at day 15 versus those in the placebo group (-17.8 vs -13.6 points, respectively), reported Kristina Deligiannidis, MD, of Northwell Health in Manhasset, New York, and colleagues.
Compared to the placebo group, greater reductions of Hamilton Rating Scale for Depression (HAMD-17) scores were observed in the zuranolone group as early as day 3 (difference -2.7, 95% CI -5.1 to -0.3), and up until day 45 (-4.1, 95% CI -6.7 to -1.4), they wrote in JAMA Psychiatry.
Among women who took zuranolone, around three-quarters had a 50% reduction or more in depression scores after 2 weeks of treatment. Additionally, 48% went into remission in that time period.
“Women with postpartum depression who participated in this study had a rapid reduction in both depressive and anxiety symptoms,” Deligiannidis told MedPage Today.
Deligiannidis added that this research represents the “first-ever oral neuroactive steroid to be tested in women with postpartum depression,” with the drug having the potential to become a rapid-acting option for patients. Currently, brexanolone (Zulresso) is available for patients to take in clinical settings, and patients may receive selective serotonin or norepinephrine reuptake inhibitors (SSRIs or SNRIs) to treat perinatal or postpartum mood disorders. Clinicians may see results from these standard-of-care treatments between 8 and 12 weeks, Deligiannidis said.
She added that a 14-day course of zuranolone would change the paradigm of how we treat this group of patients. “This study holds promise, because it’s the first step towards a very different way of treating women with postpartum depression,” she said.
“Zuranolone looks very promising, and may be the first effective oral treatment that has an indication for postpartum depression,” said Sheryl Kingsberg, PhD, division chief of ob/gyn behavioral medicine at University Hospitals in Cleveland.
Kingsberg, who was not involved in this research, told MedPage Today via email that while brexanolone is available via infusion, zuranolone is a much-needed oral alternative. “Clinicians need safe and effective treatments for postpartum depression with rapid reduction in symptoms that patients can tolerate, and use as safely and easily as the current standard of care of SSRIs and SNRIs, which do not have postpartum depression indications,” she said.
Around 13.2% of new mothers experience symptoms of postpartum depression, Deligiannidis and colleagues noted. While postpartum depression is one of the most common complications during and after pregnancy, it is underdiagnosed and undertreated.
In 2019, brexanolone became the first and only drug to be approved by the FDA specifically for postpartum depression. Brexanolone is currently under risk evaluation and mitigation strategies (REMS) protocols, and is IV administered in a clinical setting over a 60-hour period. Zuranolone has a similar mechanism to this drug, but was designed to be taken orally, once a day.
Deligiannidis’s group reported results from a double-blind, randomized trial to evaluate the safety and efficacy of zuranolone. The trial was conducted in 27 U.S. sites, and took place between January 2017 and December 2018. All participants were ages 18 to 45, were within 6 months postpartum, had signs of postpartum depression during the third trimester up to a month after delivery, and had a HAMD-17 score of 26 or higher at baseline.
Patients who received the intervention took 30 mg of zuranolone once daily, but reduced their dose to 20 mg if the initial dose was not tolerable. Trial investigators conducted post-treatment assessments at outpatient clinics, and followed participants for up to 45 days.
A total of 148 patients completed treatment, 76 in the zuranolone group and 72 in the placebo group. Of all patients who completed treatment with zuranolone, three reduced their dose to 20 mg.
Mean age of patients was 29 in the zuranolone group, and 27 in the placebo group. In both groups, more than half of participants were white, and approximately 40% were Black. At baseline, around 18% of patients in the zuranolone group and 21% in the placebo group reported that they were taking stable doses of antidepressants.
At day 15, patients on zuranolone were more than twice as likely to experience remission (OR 2.53, 95% CI 1.24-5.17) or HAMD-17 response (≥50% score reduction; OR 2.63, 95% CI 1.34-5.16) compared to those in the placebo group. Researchers also observed improved global and maternal functioning among patients who took zuranolone.
The most common side effects reported with zuranolone were drowsiness, headache, dizziness, upper respiratory tract infection, diarrhea, and sedation. One patient in each group experienced a serious adverse event. One patient in the zuranolone cohort experienced confusion and sedation, and one in the placebo group developed pancreatitis.
Deligiannidis and colleagues acknowledged that results in a U.S. population may not be generalizable on a global level. Additionally, as the follow-up period ended at day 45, sustained effects of the treatment beyond this period is unknown.
Further trials will evaluate zuranolone at different doses, and for an extended time period. But as many women still endure symptoms of postpartum depression without treatment, Deligiannidis said it is critical for clinicians to identify at-risk patients.
“There are so many more women out there that aren’t being detected or not accessing treatment,” she said. “We encourage clinicians to screen women for perinatal mood and anxiety disorders.”
This study was funded by Sage Therapeutics.
Deligiannidis and co-authors disclosed outside funding from Sage, Vorso, Janssen, and the NIH.