Postpartum Depression’s New Fast-Acting Treatment May Be a Game Changer for Moms

Postpartum Depression’s New Fast-Acting Treatment


An exciting new development has been announced that is heralded as a game changer for postpartum depression (PPD). On Tuesday March 19th, the FDA approved brexanolone, a quick acting neuroactive steroid, as the first drug specifically approved for the treatment of PPD.1


Brexanolone created by Sage Therapeutics, is set to hit the markets late June under the name Zulresso. Currently it is only available at specifically certified clinics where the patient can be monitored.


Previously the common treatment for PPD was the same as the treatments for other forms of depression: prescribing antidepressant drugs like selective serotonin reuptake inhibitors (SSRIs). SSRIs block synapses in the brain from using up all the serotonin (and other neurotransmitters), effectively increases the concentration of serotonin available to bind. The actual result of this mechanism is that there is a noticeable increase of neurotransmitters at the molecular level right away, but the mood of the patient (or the clinical changes) are not generally noticed or reported until after a week or more.2


This is where brexanolone comes into play. During pregnancy, reproductive hormones fluctuate greatly in amount. In particular, a byproduct of progesterone called allopregnanolone increases a lot and then rapidly drops after the delivery. It is believed that PPD may be caused when receptors (GABA-A) that bind with allopregnanolone are not able to adapt back to the decreased amount of the hormone post-birth. Brexanolone is effectively recognized by the body as allopregnanolone, and so by extension it helps modulate the GABA-A receptors to adjust to the decreased levels of allopregnanolone. But the exciting part is that due to its nature of mechanism, brexanolone, unlike antidepressants, has the ability to affect change in the mother’s mood within 3 days.


As of now, brexanolone’s results have been promising, specifically for those with severe PPD. Studies often use a standardized test called the HAM-D (or the Hamilton Rating Scale for Depression) to detect changes in depression. With the HAM-D, the severity of depression is determined if one receives a score of a 26 or higher. In one study, the participants (a diverse group of moms all with severe PPD or HAM-D scores of 23 or higher) were either given brexanolone or a placebo. The groups that received brexanolone saw large changes in their HAM-D scores, around a 12.2 point difference from the placebo, or in other words the moms that were given brexanolone no longer had severe depression symptoms.3 Another study which was set up similarly, saw even larger changes at 21 point differences in the brexanolone group versus 8.8 points with the placebo.4


Unfortunately, brexanolone does have a few major hurdles for the postpartum community. Its primary one is that it is exorbitantly priced. At up to $35,000 a treatment for those without insurance, it may not be a possibility for many mothers in need.5


Its second hurdle is that the treatment requires infusion over 60 hours, and requires the mom to have her children present so her responses and reactions towards the children can be monitored. The time requirement could be a barrier for mothers that may not have ability to take off for 60 hours whenever it is time for treatment, or having their children with them the whole time.


There is also, as with all new medications, the worry about what long term effects brexanolone usage may have. Presently, we know that the intense time duration required for monitoring is in part due to loss of consciousness being a potential side effect. Other side effects observed in various studies include: headaches, fatigue, dizziness, pain at the infusion site, nausea, and somnolence.6


One last consideration is in regards to mothers who are breastfeeding. Brexanolone does increase the allopregnanolone concentration in breast milk during the 60-hour infusion, so mothers may not be able to use their milk to breastfeed during that time. There isn’t currently any information of the effect of elevated allopregnanolone levels on breastfed babies, but studies that have measured breastmilk during the infusions and after, have shown that by 3 days post-infusion the concentration was negligible.7






  1. U.S. Food & Drug Administration. FDA approves first treatment for postpartum depression. 2019 Mar 19.


  1. Harmer CJ, Duman RS, Cowen PJ. How do antidepressants work? New perspectives for refining future treatment approaches. Lancet Psychiatry. 2017 May; 4(5): 409-418.


  1. Kose S, Metin M. Brexanolone: an allosteric modulator of GABA-A receptors in the rapid treatment of postpartum depression. Psychiatry and Clinical Psychopharmacology. 2017 Sep 28; 27(4): 326-328.


  1. Kanes S, Colquhoun H, Funduz-Bruce H, Raines S, Arnold R, Schacherte A, Doherty J, Eiperson CN, Deligiannidis K, Riesenberg R, Hoffman E, Rubinow D, Jonas J, Paul S, Meltzer-Brody S. Brexanolone (SAGE-547 injection) in post-partum depression: a randomized controlled trial. The Lancet. 2017 Aug; 390(10093): 480-489.


  1. Nonacs R. FDA is Expected to Approve Brexanolone for the Treatment of Postpartum Depression. MGH Center for Women’s Mental Health: Reproductive Psychiatry Resource & Information Center. 2019 Mar 18.


  1. Nonacs R. Brexanolone: A New Drug for Postpartum Depression. MGH Center for Women’s Mental Health: Reproductive Psychiatry Resource & Information Center. 2018 Jun 11.


  1. Hoffman E, Wald J, Colquhoun H. Evaluation of breast milk concentrations following brexanolone iv administration to healthy lactating women: 850. American Journal of Obstetrics and Gynecology. 2019 Jan; 220(1): S554.


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