New pill to treat postpartum depression could be a game changer

The drug acts much more quickly than what is currently available.
The new pill to treat postpartum depression could be a game changer.

The first pill specifically designed to treat postpartum depression, which was recently approved by the U.S. Food and Drug Administration, could revolutionize treatment for new parents because the drug is so fast-acting and effective.

Misty Richards, MD, MS, a UCLA Health reproductive psychiatrist, said zuranolone, which will be prescribed under the brand name Zurzuvae, could begin providing relief from debilitating symptoms in a matter of days.

By comparison, the antidepressants currently used for postpartum depression can take up to six weeks to work.

“We’ve never before had an oral, FDA-approved antidepressant work this quickly,” said Dr. Richards, co-medical director of the Maternal Outpatient Mental Health Services (MOMS) Clinic. “This covers a major gap, which is the waiting period for the other medications to work.”

On Aug. 4, the FDA approved Zurzuvae, which is to be taken once a day for 14 days. The drug is expected to become available at the end of the year. Pricing and coverage by insurers have not yet been announced.

Dr. Richards, an assistant clinical professor at the David Geffen School of Medicine at UCLA, said the oral medication improves upon a once heralded infusion treatment, called Zulresso, which was approved in 2019 as the first medication for postpartum depression. Despite its effectiveness, it never gained traction because of an array of barriers, including expense and the need to administer it over several days in a hospital.

“The promise of this medication, why it’s a game changer, is that it’s an oral version,” she said of Zurzuvae. “It doesn’t involve an infusion. It doesn’t involve an inpatient stay. The side effects are mild.”

Timely results

When it comes to postpartum depression, time is of the essence for both parents and babies.

According to research, adverse outcomes from postpartum depression may include reduced breastfeeding initiation rates, poor bonding and increased infant behavioral, emotional and cognitive impairment.

Dr. Richards said Zurzuvae could provide quick relief until other antidepressants designed for longer term use begin to work.

“It’s almost like an antibiotic – you use zuranolone for 14 days and then you’re done,” she said. “The benefits can begin as early as three days. The median response rate is about nine days. In a little over a week, you’re going to be noticing a peak effect.”

The new pill differs from traditional antidepressants, which are effective only with daily use. Zurzuvae’s benefits last for about 45 days. But since postpartum depression lasts on average for about a year, Dr. Richards said most people would need more treatment than just Zurzuvae.

She said she envisions prescribing the new drug to patients along with a selective serotonin reuptake inhibitor (SSRI), such as Zoloft. When taking both, by the time the Zurzuvae wears off, the SSRI would kick in.

“It can bridge a patient to when an antidepressant becomes effective,” she said. “This isn’t a magic pill. It’s a promising pill in combination with other treatment modalities that we know are tried and true.”

Dr. Richards said the medicine could be prescribed by a psychiatrist or ob/gyn.

She said physicians are still waiting for studies on how the new oral medication interacts with breastmilk. She expects data to be available soon.

The medication should be taken in the evening with a fatty meal, according to the FDA. The most common side effects include dizziness and sedation.

Dr. Richards said she’s optimistic that Zurzuvae will increase adherence to treatment because the results come so quickly.

“If you’re on a medication and see an effect as early as three days, you’re going to have some buy-in,” she said.

Sadness vs. depression

Perinatal or postpartum depression affects people during pregnancy or within the first year after giving birth. It differs from the extremely common baby blues, which are feelings of sadness or anxiety that resolve in a couple of weeks after giving birth.

“Four out of five women suffer from postpartum blues,” Dr. Richards said. “It’s not pathology, it’s almost like a rite of passage to motherhood.”

Postpartum depression is more severe and persistent. Up to 20% of parents who give birth may be affected, Dr. Richards said. Symptoms may include extreme sadness, guilt, anxiety, difficulty caring for the baby and thoughts of self-harm.

“If you are feeling overly anxious, agitated or melancholic, to where it’s impairing your ability to function, that’s when you see a medical professional,” she said.

Research has shown that suicide is a leading cause of pregnancy-related deaths, before and after giving birth.

“This could save lives,” Dr. Richards said of the new medication. “It serves as another barrier against severe postpartum depression and suicidality.”

Zurzuvae hasn’t been studied for use during pregnancy, so it should only be prescribed after delivery.

Dr. Richards said one risk factor for postpartum depression is a personal or family history of a mood disorder. Those who previously experienced postpartum depression have a 30% to 50% chance of experiencing it again.

Lack of social support also contributes. She said postpartum depression rates increased by 30% at the UCLA MOMS clinic during the pandemic when new parents couldn’t lean on others for help.

Dr. Richards said stigma is a huge barrier to care, with women sometimes comparing themselves to family and friends and feeling inadequate.

“If you’re feeling like you’re different and you’re not cutting it as a mother, the tendency is to isolate,” Dr. Richards said. “When you do that, not only do you suffer, but there’s impact on the mother-infant or parent-infant bond and development of the child.”

While the precise causes of postpartum depression are unknown, hormonal changes appear to play some role.

Dr. Richards said the first three days after delivery is when estrogen, progesterone and allopregnanolone, a derivative of progesterone, plunge back to pre-pregnancy levels.

“A lot of women who suffer from postpartum depression are exquisitely sensitive to hormonal shifts,” she said.

Drug profile

The new drug is a synthetic form of allopregnanolone, a naturally occurring neurosteroid that increases during pregnancy and helps regulate mood. Dr. Richards said allopregnanolone is present in the body all the time but levels increase during the third trimester of pregnancy.

Dr. Richards said Zurzuvae works by supplementing the major drop in progesterone and allopregnanolone after giving birth.

“It actually acts naturally to calm you and calm your anxiety,” she said.

According to a 2021 review of synthetic allopregnanolone published in the journal Drug Design, Development and Therapy, while the “unique mechanism of action is not fully understood,” such medications “could restore allopregnanolone concentrations and reset neural networks, resulting in improved PPD symptoms.”

The first synthetic version of allopregnanolone, Zulresso, was developed by the same drug company that makes Zurzuvae. That drug cost $34,000 and was delivered intravenously over the course of 60 hours in the hospital. Treatment required the separation of parent and baby.

Studies showed the treatment was rapid and effective, but it wasn’t practical or attainable for most people.

“I don’t know that any patient could endure any of that,” Dr. Richards said. 

But she said the more accessible Zurzuvae offers hope to families dealing with postpartum depression.

“This has the potential to offer the near immediate relief that many mothers are wanting,” she said. “I think it can really help preserve the bond between baby and mother, that frankly, is one of the most important things in that first year of life.”

Courtney Perkes is the author of this article.

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