How Does the New Postpartum Depression Drug Work?

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On Tuesday (March 19), the U.S. Food and Drug Administration (FDA) announced the first-ever approval of a drug specifically meant to treat postpartum depression.

But how exactly does the drug work, and what makes it different from other medications for depression?

The drug, called brexanolone (brand name Zulresso), needs to be given in a health care facility under medical supervision and is delivered intravenously over the course of 60 hours (2.5 days), the FDA said.

Brexanolone is "unlike anything else we have currently approved for depression," said Dr. Kristina Deligiannidis, director of women's behavioral health at Zucker Hillside Hospital in New York, who was involved with the clinical trials of the drug leading up to its approval. [7 Ways Depression Differs in Men and Women]

The drug is a synthetic version of a steroid called allopregnanolone, which people make naturally in their bodies. Allopregnanolone is a breakdown product of the sex hormone progesterone, and is produced in the brain and ovaries, as well as in the placenta during pregnancy.

It's known that blood levels of allopregnanolone increase during pregnancy and drop rapidly after childbirth. And it's thought that fluctuations in levels of the steroid may trigger changes in the brain that contribute to depression and anxiety in some women, according to Sage Therapeutics Inc., the company that makes brexanolone.

It's unclear exactly how brexanolone works to treat postpartum depression. But it's thought that the drug modifies the body's stress response, which is abnormal in women with postpartum depression, Deligiannidis told Live Science. The drug binds to GABA receptors, which play a role in many brain functions.

The binding may work to reverse or "reset" the brain activity tied to postpartum depression symptoms, the company said.

A different type of treatment

Brexanolone works in a different way than other drugs for depression, which typically don't bind to GABA receptors, Deligiannidis said. A class of drugs called benzodiazepines, sometimes referred to as tranquilizers, also bind to GABA receptors, but they bind to a different type of GABA receptor than brexanolone and have a different function, she said.

Studies of brexanolone found that the drug had quick and effective results. Two clinical trials of about 250 women with postpartum depression showed that within 60 hours, 50 percent of the women who received brexanolone were no longer clinically depressed, compared with 25 percent of women who received a placebo, Deligiannidis said. (Clinical depression was assessed using a questionnaire that gave women a depression score.)

It's still unclear how brexanolone works so quickly compared with other drugs for depression, which can take weeks to have an effect, she said.

The effects from a single drug infusion of brexanolone appeared to last at least 30 days, the maximum time the women were followed during the studies. As doctors prescribe the drug, they'll get a better understanding of how long the effects last beyond 30 days, Deligiannidis said. But a monthlong period also gives doctors a chance to start other treatments for depression, such as talk therapy, she added.

Because some women who received brexanolone experienced excessive sedation and sudden loss of consciousness, the drug needs to be administered under supervision, the FDA said.

Sage Therapeutics is also working on a similar drug for postpartum depression that can be taken as a pill once a day. That drug is currently in clinical trials and is not yet FDA-approved.

Originally published on Live Science.

Rachael Rettner

Rachael is a Live Science contributor, and was a former channel editor and senior writer for Live Science between 2010 and 2022. She has a master's degree in journalism from New York University's Science, Health and Environmental Reporting Program. She also holds a B.S. in molecular biology and an M.S. in biology from the University of California, San Diego. Her work has appeared in Scienceline, The Washington Post and Scientific American.