FDA Approves Oral Treatment for Postpartum Depression

The FDA has approved Zurzuvae (zuranolone) to treat adults with postpartum depression (PPD). Postpartum depression is a major depressive episode that typically occurs after childbirth but can also begin during the later stages of pregnancy. Until now, treatment was only available as an IV injection given by a healthcare provider.

Developed by Sage Therapeutics and Biogen, Zurzuvae is a rapid-acting neuroactive steroid that targets the GABA-A receptor with an effect seen in as little as three days. The GABA system is the major inhibitory signaling pathway of the brain and central nervous system and contributes to regulating brain function. It is thought to work by rapidly rebalancing dysregulated neuronal networks to help reset brain function. Zurzuvae targets brain networks responsible for functions such as mood, arousal, behavior, and cognition.

Zurzuvae is a once-daily tablet that is expected to be commercially available in the fourth quarter of 2023. The therapy will be scheduled as a controlled substance by the Drug Enforcement Administration, which is anticipated to occur within 90 days. A company spokesperson said the list price will be released closer to launch.

Tiffany R. Farchione, M.D.

“Postpartum depression is a serious and potentially life-threatening condition in which women experience sadness, guilt, worthlessness — even, in severe cases, thoughts of harming themselves or their child. And, because postpartum depression can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development,” Tiffany R. Farchione, M.D., director of the Division of Psychiatry in the FDA’s Center for Drug Evaluation and Research, said in a press release.

The efficacy of Zurzuvae in postpartum depression was demonstrated in two randomized, double-blind, placebo-controlled, multicenter studies. The primary endpoint of both studies was the change in depressive symptoms using the total score from the 17-item Hamilton depression rating scale. Patients in the Zurzuvae groups showed significantly more improvement in their symptoms compared with those in the placebo groups. The treatment effect was seen as early as day three and was maintained four weeks after the last dose of Zurzuvae.

The labeling contains a boxed warning noting that Zurzuvae can impact a person’s ability to drive. The most common side effects include drowsiness, dizziness, diarrhea, fatigue, nasopharyngitis (the common cold), and urinary tract infection.

Additionally, the FDA issued a complete response letter (CRL) for zuranolone to treat adults with major depressive disorder (MDD). The CRL stated that the application did not provide substantial evidence of effectiveness to support the approval of zuranolone MDD and that an additional study or studies will be needed. Biogen and Sage are reviewing the feedback and evaluating next steps, the companies said in a press release.