Thursday, July 1, 2021

Oral Medication Shows Promise for Postpartum Depression in Phase 3 Trial

Daily zuranolone—a GABA receptor–binding steroid—was more effective than placebo at reducing symptoms of postpartum depression in women, according to a report published Wednesday in JAMA Psychiatry. Zuranolone, developed by Sage Therapeutics, is similar to brexanolone in its mechanism of action but can be taken orally. Brexanolone is the intravenous medication that in 2019 became the first to receive FDA approval for the treatment of postpartum depression.

“In this first phase 3, randomized, placebo-controlled outpatient trial in women with [postpartum depression], zuranolone demonstrated rapid, clinically meaningful, and sustained antidepressant effects, as well as rapid and sustained improvements in anxiety and improved global and maternal functioning compared with placebo, despite the relatively high placebo response observed in this trial,” wrote Kristina Deligiannidis, M.D., of Zucker Hillside Hospital in Glen Oaks, N.Y., and colleagues.

The trial involved 153 women aged 18 to 45 who had given birth in the past six months; all of the participants had been diagnosed with a major depressive episode without psychosis that began between the third trimester of pregnancy and four weeks postdelivery. The participants randomly received 30 mg of zuranolone daily or matching placebo pills for two weeks, which was followed by 30 days of posttreatment monitoring. The primary outcome was change in depressive symptoms from baseline to day 15, as measured using the 17-item Hamilton Rating Scale for Depression (HAMD-17).

After two weeks, HAMD-17 scores in women receiving zuranolone fell by 17.8 points compared with 13.6 points in the placebo group—a difference that the authors noted was statistically significant. Noticeable differences in depression scores between zuranolone and placebo were evident at day 3 and remained superior for zuranolone during the entire 45-day follow-up period. At day 45—four weeks after the women had stopped taking either zuranolone or placebo—53% of women in the zuranolone group were in remission (defined as a HAMD-17 score of 7 or less) compared with 30% of women in the placebo group.

Zuranolone was also tolerated. The most common side effects included drowsiness, headache, and dizziness, and the effects were mostly mild or moderate in severity.

This study was funded by Sage Therapeutics, which also manufactures brexanolone.

To read more on this topic, see the Psychiatric News article “Novel Medication Speeds Recovery From Postpartum Depression.”

(Image: iStock/fotostorm)