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The Cautious Hope for a Drug to Treat Postpartum Depression

The week of her son’s first birthday, Allison Charette couldn’t get off the couch. For months, she’d been dealing with overwhelming levels of stress and increasingly common anxiety attacks, but it wasn’t until she spent seven straight days in a near-vegetative state that she realized something was very wrong.

“I searched for therapists who specialize in postpartum depression and found one who would take me,” Charette says. “I wanted to try cognitive behavioral therapy before considering medication. It helped me tremendously, but it took two or three months to get to functional, and another three to four months on top of that to get back to normal-feeling emotions and abilities.”

Postpartum depression, or PPD, is remarkably common. State-by-state estimates put the number of affected women as high as one in five. Despite the condition’s prevalence, only about half of the women who experience its symptoms — which can range from feeling sad, anxious, and numb to episodes of anger and thoughts about harming yourself or your baby — ever even bring it up with a doctor.

Experts theorize that women are reluctant to seek treatment because the condition is taboo. No mother wants to admit to feeling cold — or worse — toward her child, and if she does, she runs the risk of being deemed unfit. There’s also no existing clear-cut course of treatment. Though medications are available to treat depression and anxiety, they take weeks to actually work, and knowing her doctor can’t make her better right away might further discourage a new mom from asking for help.

Now, there is reason for cautious hope. Biotech firm Sage Therapeutics says it has developed a PPD-targeted drug that works — and fast. In the third round of the drug’s clinical trials, which wrapped up late last year, patients who’d previously been unable to eat, interact with their families, or even get out of bed were up and moving, eating, and laughing within days.

We talked to doctors and researchers to answer questions about PPD, and the first-of-its-kind drug that could help millions of new moms over the next few years.

What causes PPD, and what does it actually look like?

In the third trimester of pregnancy, women build up high levels of a neurosteroid called brexanolone, a by-product of progesterone that’s produced in the brain. When the baby is delivered, there’s a sudden drop in that hormone, which researchers believe is tied to the development of PPD.

“For the longest time, doctors blamed PPD symptoms on sleeplessness,” says Dr. Wendy Martinez, M.D., CEO of Advocare the Women’s Group for OB/GYN in New Jersey. “That might be the cause of the ‘baby blues,’ which is a period immediately after delivery when a woman might feel sad or overly emotional. That’s normal — she’s exhausted — and it will usually just go away on its own after a week or two. PPD is something else entirely.”

Martinez says PPD can develop anytime in the first year after childbirth, and women who’ve had depressive episodes or panic attacks in the past may be predisposed to the condition.

How is it treated now?

“All we can really do is put them on an SSRI,” Martinez says. “We like Zoloft because it doesn’t show up in the breast milk. But it takes four to six weeks for the SSRI to build up in your system and actually do something.”

Martinez remembers one new mother who said she couldn’t shake a horrible thought about dropping her baby down the stairs.

“She said, ‘I would never do it. I would never harm my baby, but I close my eyes and I just see it happening,’” Martinez says. “Thank god she was comfortable enough to say that to me, and I was able to talk to her husband and to her family and make sure she had the help she needed while she waited for the meds to kick in, but there are plenty of women in this same situation who don’t have that support at home, and for them, four weeks is much, much too long to wait.”

What is this new drug, and how does it work?

Sage Therapeutics created a process for turning brexanolone, the neurosteroid naturally produced during pregnancy, into a medication.

“There was a theory that suggested depression was the result of hyperactivity in the brain,” Jeff Jonas, M.D., CEO of Sage Therapeutics says. “A lot of things are sped up: You’re not sleeping, you don’t eat, you experience racing, negative thoughts. [Brexanolone] tones down brain activity, basically functioning as a natural relaxant.”

Patients in the clinical trials were given an IV infusion of brexanolone over the course of two days. “By the second trial, women had about a 70 percent remission rate,” Jonas says. “The changes were drastic. These were women who were profoundly depressed and then within 48 hours got significantly better. We followed these patients out to about a month, and the large majority remained well.”

Jonas says the drug acts like a “reset button” for the brain, and research suggests that once the hyperactivity is stopped, the brain is able to restore itself to normal and stay that way.

So when can we expect it to be available to the public?

Jonas says Sage Therapeutics is currently preparing to file a new drug application with the FDA. “If all goes well — and we’re very excited about the data — this could well be on the market in the first half of 2019,” he says.

Will the number of women diagnosed with PPD go down?

Actually, if and when brexanolone hits the market, diagnostic numbers are likely to go up; and that’s a good thing. Jonas says that having an effective treatment available for any disorder is a major step toward destigmatizing it, and he hopes that women will be more willing to talk to their doctors.

“This is not a social disease,” he says. “Often people with [PPD] are treated like there’s something wrong with them. This is an imbalance. It’s not a character flaw; it’s a medical complication of pregnancy.”

He also hopes that having a targeted drug on the market means medical professionals will be more likely to recognize PPD’s warning signs and act quickly.

“It would force a significant change in the way people think about treatment for mental health,” Jonas says. “Most treatments for depression take six weeks to show any effect, so there’s not always a lot of urgency to begin treatment. It’s not seen as an acute condition. But if you walk into the emergency room in diabetic shock or with a 105-degree fever, you see the specialist right away, and are treated immediately for a life-threatening condition. Now, you have a drug that potentially will make people better within two days, so maybe we’ll start to treat postpartum depression as the acute, life-threatening condition it is. The most common cause of maternal death after birth is suicide. It’s not a trivial issue. This is not something that should be treated in a leisurely fashion.”

The Cautious Hope for a Drug to Treat Postpartum Depression