On August 6th, the Food and Drug Administration (FDA) approved the first oral medication for the treatment of postpartum depression. The last time we had a medication approved for postpartum depression was in 2019 when the FDA approved brexanolone. While many were very excited about brexanolone’s release, patients had a hard time accessing the treatment as it required administration through an intravenous infusion over the course of 60 hours; requiring an individual to be admitted in a hospital during the infusion and in many cases, separated from their newborn and families. Shortly after the approval of brexanolone, a worldwide pandemic occured which led to most individuals fearful of any kind of hospital admission. Brexanolone was ground-breaking for its unique mechanism of action compared to traditional antidepressants used for perinatal mood and anxiety disorders but access to the medication has been very limited.
Zuranolone, like brexanolone, is a neuroactive steroid with antidepressant activity with a novel mechanism of action as positive allosteric modulators of GABA-A receptors. This difference in “how it works” is one of the advantages of this medication in that individuals can expect improvement in symptoms as early as 3 days after starting the medication. Individuals take a 50 mg capsule in the evening for 14 days and can expect sustained symptom improvement for up to 30 days after taking their last dose. It is recommended to take the medication with fat-containing food (400 to 1,000 calories) for improved absorption. Zuranolone will be available in three capsule dosage strengths (20 mg, 25 mg and 30 mg) to allow for flexibility to adjust dosing if CNS depressant effects (i.e. somnolence, confusion) occur or if the individual has hepatic or renal impairment. Participants in the studies most commonly reported somnolence, dizziness and sedation as adverse events while being treated with zuranolone 50 mg. As a result, there is a warning in the prescribing information advising patients not to drive or engage in other potentially hazardous activities until at least 12 hours after administration of the dose for the entire treatment course.
Zuranolone is anticipated to make its debut on the market before the end of 2023 and will be marketed under the name Zurzuvae. It is estimated to be released after a 90-day review by the Drug Enforcement Administration (DEA); sometime early November. At this time, we do not have any information about how much the medication will cost, which insurance companies will cover it or if individuals will have to show previous failure on antidepressants before being prescribed this novel medication. In other words, it may not be considered a first-line treatment medication for women who have taken alternative medication treatments with proven symptom improvement.
Many questions still exist about the efficacy and safety of zuranolone. Individuals in studies were asked to refrain from breastfeeding so we do not have any data on whether or not zuranolone is safe during breastfeeding. Further studies will need to be conducted to determine what percentage of medication transfers to breastmilk, whether or not the medication will have negative side effects for the baby and whether or not it will impact milk supply. At this time, zuranolone is not recommended to be used during pregnancy as it is considered a teratogen. The highlights of prescribing information for Zurzuvae (zuranolone) can be found here: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217369s000lbl.pdf
Other remaining questions we do not currently have answers to include the following:
- Will patients need to repeat treatment or some form of a maintenance course after completing the initial 14-day course?
- Should patients be started on an alternative psychiatric treatment (i.e., antidepressant) once completing the 2 weeks of oral zuranolone treatment?
While we wait for more details to be announced from the FDA and DEA, we should still celebrate this ground-breaking achievement in maternal mental health. Hopefully, the FDA approving this medication for postpartum depression will help to spread increasing awareness about a subject that so often is not given the attention it deserves.
I participate every Wednesday in the virtual grand rounds at the Mass General Hospital (MGH) Center for Women’s Mental Health. To read the latest insights posted on August 24, 2023, on zuranolone for postpartum depression by Dr. Lee S. Cohen, Director of the Ammon-Pinizzotto Center for Women’s Mental Health at MGH, please click the link here: https://womensmentalhealth.org/posts/zuranolone-for-postpartum-depression/
Deligiannidis, K. M., Meltzer-Brody, S., Maximos, B., Peeper, E. Q., Freeman, M., Lasser, R., Bullock, A., Kotecha, M., Li, S., Forrestal, F., Rana, N., Garcia, M., Leclair, B., & Doherty, J. (2023). Zuranolone for the Treatment of Postpartum Depression. The American journal of psychiatry, appiajp20220785. Advance online publication. https://doi.org/10.1176/appi.ajp.20220785