FDA Approves Zuranolone for Postpartum Depression

Zuranolone (Zurzuvae) won FDA approval as the first fast-acting pill for postpartum depression.

Medically Reviewed
FDA-Approves-Zuranolone-for-MDD-and-Postpartum-1440x810

The FDA approved Zuranolone (Zurzuvae) for postpartum depression on August 4, 2023.

Everyday Health

The U.S. Food and Drug Administration (FDA) has approved the first pill to treat postpartum depression (PPD), offering people a new way to get rapid symptom relief.

The new drug, zuranolone (Zurzuvae), is only the second FDA-approved treatment for PPD, according to the FDA. The only other FDA-approved medicine for PPD, brexanolone (Zulresso), has the same active ingredient as zuranolone but is administered intravenously over 2.5 days in a hospital because of the risk of excessive sedation or loss of consciousness that it poses, according to the FDA. Because of the risk of sudden loss of consciousness, people receiving Zulresso cannot be left alone with their children during treatment, the FDA states.

“There is a great need for treatments that work quickly to relieve the suffering from depressive disorders,” says Samantha Meltzer-Brody, MD, MPH, the Assad Meymandi Distinguished Professor and Chair of the department of psychiatry and the director of the Center for Women’s Mood Disorders at the University of North Carolina in Chapel Hill, who was involved with clinical trials for zuranolone. “In postpartum depression, the mother is caring for an infant and the time sensitivity for rapid onset of action is very important.”

Zuranolone should be taken once daily in the evening with a high-fat meal, for two weeks, per the FDA. The recommended daily dose is 50 milligrams (mg).

Clinical trials reviewed by the FDA prior to approval showed that zuranolone can help relieve depressive symptoms in a matter of days. Some patients may be able to get lasting symptom relief by taking zuranolone for just two weeks, doctors say.

Standard antidepressant treatments can take as long as six weeks to be fully effective, according to Mayo Clinic.

Zuranolone Works Differently From Standard Antidepressants

Zuranolone is a fast-acting antidepressant with a unique mechanism of action, says Dr. Meltzer-Brody.

It belongs to a new class of medicines known as neuroactive steroids. Drugs in this class are believed to work by rebalancing malfunctioning networks of neurons, or messenger cells in the brain, in people with depression, according to a news release from Biogen and Sage Therapeutics, the manufacturers of zuranolone. The networks zuranolone targets are involved with mood, cognition, behavior, and arousal, per the news release.

“This is a very different approach to treating clinical depression,” says Kristina Deligiannidis, MD, the director of women’s behavioral health at Zucker Hillside Hospital and a professor of psychiatry at the Hofstra/Northwell Zucker School of Medicine in Hempstead, New York, who studies depression treatments and was involved with clinical trials for zuranolone.

“For many patients, they may only need a short, acute treatment course followed by close monitoring for any return of depressive symptoms rather than taking an antidepressant chronically for many months or years,” says Dr. Deligiannidis.

Other antidepressants can take weeks or even months to work effectively, and doctors often need to gradually adjust the doses for their patients until they find the right amount of medicine to ease their symptoms, Deligiannidis adds. Plus, people often need to take them for years.

One common option is a family of medicines known as selective serotonin reuptake inhibitors (SSRIs), which are thought to work by acting on a brain chemical called serotonin that helps regulate mood, according to the Mayo Clinic. SSRIs include fluoxetine (Prozac), paroxetine (Paxil, Pexeva), sertraline (Zoloft), citalopram (Celexa), and escitalopram (Lexapro).

Another, similar option is a family of medicines known as serotonin and norepinephrine reuptake inhibitors (SNRIs), which includes the drugs duloxetine (Cymbalta, Drizalma Sprinkle), venlafaxine (Effexor XR), desvenlafaxine (Pristiq), and levomilnacipran (Fetzima). SNRIs are thought to act on serotonin as well as the brain chemical norepinephrine to help improve mood, according to the Mayo Clinic.

Zuranolone Relieved Postpartum Depression Symptoms Within 3 Days in Clinical Trials

In the SKYLARK study, a late-stage clinical trial of nearly 200 women with PPD that was sponsored by Sage Therapeutics, people were randomly assigned to take either a 50 mg zuranolone pill or a placebo pill daily for two weeks. Those who took zuranolone experienced significantly greater symptom relief than participants who took placebo, according to a news release from Biogen and Sage Therapeutics.

In fact, people who took zuranolone had significantly reduced symptoms after just three days, a steady improvement in symptoms throughout treatment, and results that persisted for 30 days after they finished treatment, per the press release.

The data were published July 26, 2023, in the American Journal of Psychiatry.

Specifically, symptom relief was measured with a scale for depression used by doctors, called the 17-item Hamilton Depression Rating Scale (HAM-D). On average, those who took zuranolone experienced a reduction of about four additional points on the HAM-D than those who took the placebo. On this scale, which goes up to 52 points, a score of more than 17 points indicates moderate depression, and more than 24 points indicates severe depression.

Most side effects of zuranolone were mild to moderate and included excessive sleepiness, dizziness, sedation, headache, nausea, and diarrhea, among others.

Sedation is the main side effect of concern with zuranolone, says Meltzer-Brody. “But this has not been severe in the majority of patients who have taken zuranolone in clinical trials,” she adds.

Zuranolone Not Approved for Major Depressive Disorder 

Biogen and Sage Therapeutics had also requested the FDA to approve zuranolone to treat major depressive disorder (MDD), also known as clinical depression. But the FDA did not approve zuranolone for MDD, instead issuing what’s known as a complete response letter indicating that one or more additional studies are needed to demonstrate the effectiveness of the drug for this use, the co-manufacturers said in a joint statement.

Black Box Warning About Driving While Taking Zuranolone

Zuranolone carries a black box warning — reserved by the FDA for the most serious side effects — which cautions people taking the drug not to drive or operate heavy machinery for at least 12 hours after taking each dose of this medicine, according to the FDA. Patients on zuranolone may not be able to recognize the degree of their impairment while on the drug, and it may impact their ability to drive safely, per the FDA.

Availability of Zuranolone

Zuranolone is expected to be available for purchase in late 2023, according to the joint statement from Sage Therapeutics and Biogen. Neither have disclosed pricing information for zuranolone.