Zuranolone for Symptoms of Depression in Women with Postpartum Depression

May 2022

Postpartum depression (PPD) is a major depressive episode that occurs in the perinatal period. It can potentially last for years if not treated. According to researchers involved in a randomized clinical trial of zuranolone that was published in JAMA Psychiatry, “The need for rapid and effective resolution of PPD symptoms cannot be overstated, given the prevalence of PPD and the negative effect untreated PPD can have on mothers, children, and partners.”

Neurosteroids that are positive allosteric modulators of gamma-aminobutyric acid signaling are thought to play a key role in the development of PPD. The US Food and Drug Administration recently approved the neurosteroid brexanolone for symptoms of PPD. The drawback of brexanolone, however, is that it must be injected. Zuranolone, an investigational neurosteroid with a similar mechanism of action, can be taken orally.

This phase 3, double-blind trial of zuranolone tested whether it reduced symptoms of PPD; the study included 153 women who had received a diagnosis of PPD and were within 6 months of delivery. PPD was defined as a major depressive episode in the third trimester through the fourth week after delivery and a score of ≥26 on the 17-item Hamilton Rating Scale for Depression (HAMD-17). Participants were randomized to receive 30 mg of oral zuranolone or placebo daily for 2 weeks.

The primary end point was a change in the HAMD-17 score from baseline on day 15. Secondary end points included changes in HAMD-17 scores at other time points and changes in scores on other scales for depression, anxiety, and maternal functioning.

Regarding the primary end point, the zuranolone group showed significantly improved HAMD-17 scores from baseline compared with the placebo group at day 15. Secondary end points showed greater reductions in HAMD-17 scores on day 3 through the end of the study on day 45. Zuranolone was also associated with a higher proportion of patients in HAMD-17 remission compared with the placebo group. By day 45, 53% of participants in the zuranolone group were in remission compared with 30% of participants in the placebo group, even though dosing ended on day 14. Reductions in scores on other scales for depression, anxiety, and maternal functioning were also significantly greater in the zuranolone group compared with the placebo group.

Zuranolone was well-tolerated, but the safety of the drug during breastfeeding is unknown because participants in the trial were not allowed to breastfeed. The durability of the response beyond 45 days is also unknown.

Because zuranolone improved both depressive symptoms and functioning and is a once-daily oral medication, the authors conclude that these results support “the potential for short-term, outpatient utility of zuranolone in PPD.”

Source

Deligiannidis KM, Meltzer-Brody S, Gunduz-Bruce H, et al. Effect of zuranolone vs placebo in postpartum depression: a randomized clinical trial. JAMA Psychiatry. 2021;78(9):951-959.

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