The Food and Drug Administration approved the first oral medication for the treatment of postpartum depression.  Zuranolone will be marketed under the brand name Zurzuvae by Sage Therapeutics in partnership with Biogen and is expected to be available after the Drug Enforcement Administration completes a 90-day review.  No information was provided regarding the price of the medication.

 We have been talking about zuranolone for a while and are eagerly awaiting its arrival.  Zuranolone is similar to brexanolone, which was approved in 2019 by the FDA for the treatment of PPD.  Like brexanolone, zuranolone is a neuroactive steroid with antidepressant activity and a novel mechanism of action as positive allosteric modulators of GABA-A receptors.  The big difference between the two is that zuranolone is available as a pill, while brexanolone is administered as an intravenous infusion.  This is a huge advantage when it comes to ease of use and accessibility.  

Thus far there have been several randomized controlled trials supporting the efficacy of zuranolone for the treatment of postpartum depression (PPD).  In the most recent study, a double-blind phase 3 trial published in the American Journal of Psychiatry, women with severe PPD were randomized to receive zuranolone (50 mg/day) or placebo for 14 days.  Zuranolone was superior to placebo starting at day 3, and this trend was observed at every subsequent study visit.  

Although traditional antidepressants, including the selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRIs and SNRIs), are not specifically approved by the FDA for the treatment of PPD, they are effective in this setting.  The real advantage of zuranolone is that it starts to work so much earlier than typical antidepressants, which can take 2-4 weeks to elicit significant improvements in depressive symptoms.  

Zuranolone is generally well-tolerated.  The most common adverse events are somnolence, dizziness, and sedation. No loss of consciousness, withdrawal symptoms, or increased suicidal ideation or behavior were observed.

Who is a Good Candidate for Zuranolone?

Zuranolone would represent a new option for the treatment of PPD, a rapidly acting antidepressant with a good safety profile.  However, zuranolone may not be the first choice for every women.   

At this point, we do not have any information on the use of zuranolone in breastfeeding women.   Participants in the zuranolone clinical trials were asked to forgo breastfeeding while taking zuranolone.  We do not yet have information regarding the secretion of zuranolone into the breast milk or the effects of zuranolone found in the breast milk on the nursing infant.  Nor do we know if zuranolone affects breast milk production.   For many women, having to interrupt or avoid breastfeeding while receiving treatment for PPD may be a significant deterrent.

In addition, women who have histories of recurrent depression and have responded well to a particular medication in the past may choose to return to that medication rather than try zuranolone for the first time.  

Although further study is required and zuranolone may not represent a first-line treatment for all women with PPD, there are many women who will benefit from having another treatment option, including women with severe symptoms or suicidal ideation and those unable to access long-term psychiatric care. 

Ruta Nonacs, MD PhD

For the First Time, There’s a Pill for Postpartum Depression (New York Times)



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