FDA approves first-ever drug for postpartum depression

Jamie Belsito had reached the limit. If she was honest with herself, she had already blown way past it.

New motherhood was supposed to be nothing but loving gazes and adorable photos. Instead, Belsito was constantly exhausted — she had no idea what to do with this new being, and no idea why she was so distressed.

As Belsito recalls today, this was “code red.” By the time she sought help, she was having scary thoughts of hurting herself.  

Belsito’s daughters are now six and nine years old. While she did not realize it when her oldest daughter was born, Belsito was experiencing severe postpartum depression, or PPD, which can occur during pregnancy or up to four weeks after delivery.

Up to 12% of new mothers in the U.S. experience PPD, according to the Centers for Disease Control and Prevention. The condition can strain the maternal-child bond and leave a mother feeling guilty, and in rare cases is linked to suicide. Until last month, there were no approved pharmaceutical treatments for PPD. In a culture that appears to readily supply a drug for seemingly every condition, maternal health advocates have long noted that postpartum depression is an exception to the rule.

That finally changed on March 19, when the Food and Drug Administration approved the use of brexanolone, a new treatment developed by Sage Therapeutics for postpartum depression.

Cognitive behavioral therapy and similar forms of interpersonal therapy have long been the main means of addressing PPD. These therapies are often helpful — so much so that a federal task force recently recommended that they be made available for free to pregnant women at high risk for depression. But unlike a drug, therapy cannot treat one of the root causes of postpartum depression: mood-altering biochemical changes that arise following pregnancy.

After giving birth, all new mothers experience a drop in the hormone allopregnanolone. Some women barely notice this change. But for others, this reduction spurs a host of biochemical changes that lead to postpartum depression. Brexanolone goes to the source of these changes by boosting production of allopregnanolone.

Brexanolone, which Sage will market as Zulresso, is no routine treatment. The 5 milligram injection takes 60 hours to administer. That’s right — patients must sit in a hospital bed, hooked up to an IV, for nearly three days straight. Sage initially requested that patients be allowed to receive the treatment while resting comfortably at home, but briefing documents prepared by the FDA showed that 6 out of 140 women lost consciousness while taking brexanolone. Although the side effect was not severe enough to derail approval of the drug, it caused the FDA to require that women patients check into a hospital or clinic to receive brexanolone.

Why 60 hours? That’s how long it took for brexanolone to boost women’s levels of allopregnanolone, and in turn reduce their levels of depression. A diagnostic tool known as the Hamilton Depression Rating Scale revealed that women who received brexanolone were significantly less depressed than women who did not. This effect held for 30 days, long enough to convince the FDA of brexanolone’s viability in reducing the effects of PPD.

Dr. Nicole Cirino, director of women’s health and wellness at Oregon Health and Sciences University, attributes the effectiveness of brexanolone to the drug’s ability to mimic allopregnanolone. The two chemicals are “technically identical,” Cirino says.

Cirino is optimistic about the clinical potential of Zulresso, but acknowledges the hurdles that stand in the way of widespread use. For starters, many hospitals and clinics have a shortage of beds, especially to treat psychiatric conditions like PPD. And although administering the infusion is straightforward, trained personnel do need to monitor the new mother to make sure nothing goes awry. While this should increase safety, it likely will reduce the number of facilities that offer the treatment, since not every potential medical facility will meet these safety criteria.

Cost is another major deterrent. Quoted list prices for a single Zulresso treatment range from $20,000 to $35,000, although with insurance it could drop to $14,000. Even the low estimate is quite steep — and not expected to drop anytime soon.

As of now, women cannot breastfeed when taking brexanolone because its effects on breastfeeding babies are unclear.

As for why it took so long to develop a drug treatment for PPD, Dr. Lauren Osborne has some ideas. Osborne, the assistant director of the Women’s Mood Disorders Center at Johns Hopkins University, argues that women’s mental health surrounding reproduction has only recently received serious attention. “The perinatal period is considered a time when women should be happy,” Osborne says. (The perinatal period encompasses pregnancy and up to four weeks after birth.) Any difficulties tend to be perceived as mere moodiness that new mothers will eventually surmount.

In addition to cultural barriers to addressing mental health during pregnancy, there also remains scientific challenges. All new mothers experience a sharp drop in allopregnanolone, but only some of them experience PPD. Osborne hopes that future research will address why some women are more biochemically prone to PPD and resolve whether breastfeeding can continue while taking brexanolone.

While Osborne recognizes these future obstacles in treating postpartum depression, she also sees clear signs of progress — like the development of brexanolone. “It is an incredibly important development that we have this drug,” she says.

Jamie Belsito agrees. She fought hard to receive appropriate mental health care after her oldest daughter was born and wants every struggling mother’s path from this point forward to be much easier. To that end, she says she is now running for the U.S. House of Representatives.

After Belsito’s pregnancies, brexanolone wasn’t an option, but she celebrates for the new mothers who now have this choice — even with that 60-hour injection. Belsito doesn’t see this time as an unnecessary burden — to the contrary, she sees it as a rare chunk of time during which an anxious new mother gets to relax, and be taken care of by other people. “Sign me up!” she says.