How Does Zurzuvae Compare With Other Antidepressants for Postpartum Depression?
Published on September 3, 2026
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Postpartum depression (PPD) affects about 1 in 8 women who’ve recently given birth. It’s often undiagnosed, however. “There are many reasons, including inconsistent clinical screening during pregnancy and the postpartum period, fear of the stigma attached to mental illness and patient reluctance to discuss symptoms with their doctor, and patient fear of consequences of medication effects,” says Kristina Deligiannidis, MD, director of women’s behavioral health for Northwell Health in New Hyde Park, New York.
A relatively new treatment, Zurzuvae (zuranolone), was approved by the U.S. Food and Drug Administration (FDA) in 2023 as the first oral, at-home treatment option specifically designed to specifically treat PPD. Prior to its approval, the only PPD-specific medication, Zulresso (brexanolone), requires a 60-hour hospital intravenous infusion.
Zurzuvae, developed by Sage Therapeutics in partnership with Biogen, is taken daily for 14 days.
How Zurzuvae Works and Why That's Different
Zurzuvae is a manmade version of the neurosteroid allopregnanolone, which the body makes naturally from the hormone progesterone. Women with PPD tend to have low levels of allopregnanolone. Zurzuvae also keeps GABA-A receptors working properly, which has been shown to be disrupted among women with PPD. “[Zurzuvae] helps stabilize GABA-A, which is responsible for calming the brain and helping you regulate your mood,” says Tamar Gur, MD, PhD, a maternal-fetal psychiatrist and professor at The Ohio State University Wexner Medical Center in Columbus. It helps reset the hormone and brain changes that can happen after childbirth, she adds.
SSRIs, another class of medications used to treat PPD, work differently by blocking the reuptake of serotonin, a neurotransmitter involved in mood regulation. This makes more serotonin available between nerve cells.
The speed at which Zurzuvae works is what sets it apart. Clinical trials found significant improvements in depressive symptoms compared with placebo as early as day 3 on the drug. That’s much quicker than SSRIs, like sertraline (Zoloft) and fluoxetine (Prozac), which can take several weeks to produce noticeable benefits.
“It’s important that we treat depression as quickly as possible given the many ill effects of untreated depression for the mother, the child or children, and family,” says Dr. Deligiannidis, who was a lead author on the Zurzuvae trials.
What Research on Zurzuvae Says
The Sage Therapeutics and Biogen team completed two phase 3 trials on Zurzuvae before FDA approval.
The SKYLARK trial included 196 women with severe PPD and evaluated changes to PPD symptoms as measured by the Hamilton Depression Rating Scale, a 17-item assessment designed to measure symptoms like mood, suicide risk, sleep, and anxiety. Women either took Zurzuvae or a placebo for 14 days, and while depression scores fell in both groups, the reduction was significantly greater among women taking Zurzuvae than those taking placebo by day 15.
The other trial, called the ROBIN trial, included 151 women with PPD who similarly were either given Zurzuvae or a placebo and saw a significant reduction in depressive symptoms after two weeks on the drug.
It’s worth noting that Zurzuvae and SSRIs have not yet been directly compared in a clinical trial, so researchers can't say definitively that Zurzuvae works faster than SSRIs.
Though these results are promising, don’t think of Zurzuvae as a miracle drug to cure PPD. “None of the antidepressants used to treat depression or PPD can completely resolve depression in all patients, but they will provide much or full benefit for many,” Deligiannidis says.
Zurzuvae vs. SSRIs
Zurzuvae and SSRIs can both be used to help treat PPD. Here are some of their key differences.
Side Effects
Women on Zurzuvae have seen symptoms improve as early as about three days into the 14-day course. The main side effects reported by trial participants were dizziness and sleepiness. Women who participated in the trial were told not to drive for at least 12 hours after taking the drug. Side effects of SSRIs, on the other hand, include upset stomach, headaches, trouble sleeping, sexual problems, and appetite changes.
Safety, Including During Breastfeeding
SSRIs have a much longer history of use than Zurzuvae, including more extensive safety data on their use during breastfeeding.
SSRIs are not controlled substances, but Zurzuvae is a schedule 4 controlled substance, meaning it carries a potential for misuse or dependence. It also may cause fetal harm, so it’s advised to use contraception during treatment and during the week afterward.
Cost
“Zurzuvae does cost more than SSRIs since it is a newer medication,” Deligiannidis says. Insurance coverage and the manufacturer savings program can substantially affect what an individual pays, but a 14-day dose of Zurzuvae can cost nearly $16,000, according to GoodRX. “It's not something that's going to be readily available to a lot of people,” Gur says.
SSRIs, on the other hand, have wider insurance coverage and generic versions can cost about $15 a month, though the price can change based on drug, dose, pharmacy, and insurance.
Speed
SSRIs can take weeks to work. Unlike Zurzuvae's 14-day course, SSRIs are generally taken continuously for months, with treatment duration depending on the individual's symptoms and risk of recurrence.
Zurzuvae
SSRIs
Speed
Benefits seen as early as day 3 of treatment, with significant reduction in depressive symptoms by day 15
May take weeks to work
Length of Treatment
14-day course
May be taken continuously for months
Cost
List price of nearly $16,000, but insurance coverage and the manufacturer savings program can substantially affect what an individual pays
Wider insurance coverage and generic versions can cost about $15 a month
Side Effects
Dizziness and sleepiness reported by trial participants, who were told not to drive for at least 12 hours after taking the drug
Upset stomach, headaches, trouble sleeping, sexual problems, and appetite changes
Safety
May cause fetal harm, so using contraception during treatment and during the week afterward is advised; breastfeeding data limited
Extensive safety data has shown SSRIs safe to take while breastfeeding
Who Might Be a Good Candidate for Zurzuvae?
“Zurzuvae may be a good choice for women with clinical depression (that’s not due to bipolar disorder) that began in pregnancy or in the postpartum period who do not have a medical reason for not being able to tolerate the medication,” Deligiannidis says. Zurzuvae can interact with some medications, including drugs that cause sedation, so patients should review all medications and supplements with their provider.
Zurzuvae offers fast-acting relief, but because it can impair a person's ability to drive or perform other potentially hazardous activities, patients are advised not to engage in these activities until at least 12 hours after each dose. “It would be helpful to have another adult awake and alert [to help with overnight childcare duties],” Dr. Gur says, adding that this is especially important for the first few days that you’re taking the medication to see how your body reacts.
Speak with your doctor about Zurzuvae if you have liver or kidney problems or a history of drug or alcohol abuse. Small amounts of Zurzuvae may pass into breast milk. Patients who are breastfeeding should discuss the potential benefits and risks with their healthcare provider because data on effects in breastfed infants remains limited, Deligiannidis says.
EDITORIAL SOURCES
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Resources
- Symptoms of Depression Among Women. Centers for Disease Control and Prevention. May 15, 2024.
- Macmillan C. What to Know About Zurzuvae, the New Pill to Treat Postpartum Depression. Yale Medicine. September 15, 2023.
- Meltzer-Brody S et al. Allopregnanolone in Postpartum Depression: Role in Pathophysiology and Treatment. Neurobiology of Stress. Februry 3, 2020.
- Selective Serotonin Reuptake Inhibitors (SSRIs). Mayo Clinic. September 11, 2024.
- Postpartum Depression. Cleveland Clinic. March 26, 2026.
- Deligiannidis KM et al. Zuranolone for the Treatment of Postpartum Depression. American Journal of Psychiatry. September 1, 2023.
- Deligiannidis KM et al. Effect of Zuranolone vs Placebo in Postpartum Depression. JAMA Psychiatry. June 30, 2021.
- Zurzuvae- zuranolone capsule. DailyMed. June 15, 2026.
- Breastfeeding & Psychiatric Medications. MGH Center for Women’s Mental Health.
- Drug Scheduling. U.S. Drug Enforcement Administration.
- FDA Approves First Oral Treatment for Postpartum Depression. U.S. Food & Drug Administration. August 4, 2023.
- Lusk V. How Much Does Zurzuvae Cost With and Without Insurance? GoodRX. November 20, 2025.
- SSRIs. GoodRX.
- FDA Approves ZURZUVAE™ (zuranolone), the First and Only Oral Treatment Approved for Women with Postpartum Depression, and Issues a Complete Response Letter for Major Depressive Disorder. Biogen. August 4, 2023.
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