The FDA did not grant approval for the treatment for major depressive disorder.
The US Food & Drug Administration (FDA) has approved Zurzuvae (zuranolone) as the first oral treatment for postpartum depression (PPD) in adults, but did not approve the drug for the treatment of major depressive disorder (MDD).
“PPD 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 PPD can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development,” said Tiffany R. Farchione, MD, director of the FDA Center for Drug Evaluation and Research Division of Psychiatry, in a press release. “Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings.”1
The FDA’s decision to approve zuranolone for the treatment of PPD was based on the results of 2 randomized, double-blind, placebo-controlled, multicenter studies examining the efficacy of zuranolone. Both studies focused on patients with PPD who met DSM criteria for a major depressive episode, with symptoms that began either in their third trimester or within 4 weeks of delivery.1
In both studies, patients received either 50 mg (Study 1) or 40 mg (Study 2) of zuranolone or placebo once daily for 14 days and were monitored for at least 4 weeks following treatment. Upon evaluation at day 15, patients in the zuranolone groups showed significant improvement in symptoms based on their 17-item Hamilton depression rating scale (HAMD-17) scores compared to placebo, with the effect lasting until their final evaluation at the end of 4 weeks.1
Psychiatric Times® asked some psychiatric experts for their thoughts on what the approval of zuranolone means for psychiatry and for the care of patients with PPD. Here is what they told us.
“Approval of zuranolone for treatment of PPD offers a unique option in a 14-day course of treatment with 1 pill daily, with or without concomitant standard-of-care antidepressant medication, that is well tolerated, has demonstrated rapid improvement in depressive symptoms, separating from placebo after 2 doses, with the effect maintained for up to 1 year without additional treatment in about 50% of responders, and quickly leads to functional improvement in mental and physical health issues.
"Zuranolone is a neuroactive steroid—an allopregnanolone analogue that acts at both synaptic and extra-synaptic GABA-A receptors to change the balance of inhibition and excitation in the brain. It does not act directly on the function of monoamines like serotonin, dopamine, or norepinephrine like current antidepressants. This may have particular applicability in those with severe depression who have had an inadequate response or intolerance to a currently available antidepressant medication, and who would benefit from rapid improvement in depressive symptoms and functioning.”
Anita H. Clayton, MD
Chair of psychiatry and neurobehavioral sciences and professor of clinical obstetrics and gynecology at the University of Virginia
“This is a groundbreaking drug with a unique mechanism of action that has the potential to change how we treat major depression. It acts rapidly and is associated with a response and remission rate that is unheard of with standard antidepressant treatments. We will still need those standard antidepressants, and there is a lot of research that still needs to be done, but this drug will make a significant impact on the practice of psychiatry.”
Jennifer L. Payne, MD
Vice chair of research, professor of psychiatry and neurobehavioral sciences, and director of the Reproductive Psychiatry Research Program at the University of Virginia in Charlottesville
“Today the FDA approved zuranolone for the indication of PPD but did not approve it for the second indication of unipolar major depression in women and men. Zuranolone is a rapidly acting antidepressant that is a neurosteroid, which works as a positive allosteric modulator of the GABA-A receptor. It is administered as an oral tablet for 14 days. Two separate studies in PPD demonstrated good efficacy, with improvement in some patients as soon as day 3, with the improvements continuing out to the endpoint at day 45.
"For women with PPD, it provides an oral at-home welcome alternative to its predecessor brexanolone (approved in 2019, and the only other drug FDA approved for PPD), which has the same mechanism of action, but requires 60 continuous hours of IV infusion in a hospital. Sage and Biogen, collaborators in the zuranolone development project, will need to review the reasons why the FDA denied approval for unipolar major depression in women and men, and determine how to proceed.”
John J. Miller, MD
Medical director at Brain Health
Editor in chief of Psychiatric Times
Staff psychiatrist at Seacoast Mental Health Center
Consulting psychiatrist at Exeter Hospital and Insight Meditation Society
1. FDA approves first oral treatment for postpartum depression. US Food & Drug Administration. News release. August 4, 2023. Accessed August 4, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-postpartum-depression