Zuranolone (Zurzuvae) vs. Brexanolone (Zulresso) for Postpartum Depression: 5 Things to Know

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Welcoming a new baby is life-changing, and it's completely normal to feel tired, nervous, and even sad after giving birth. These feelings, often called the "baby blues," typically go away after a couple of weeks. But sometimes the symptoms linger, which can be a sign of postpartum depression (PPD).

PPD is a common condition that affects an estimated 1 in 10 women. And the actual number may be even higher. Zuranolone (Zurzuvae) and brexanolone (Zulresso) are two FDA-approved medications for treating PPD. But what's the difference between them? Here, we'll look at five things to know about zuranolone versus brexanolone.

1. Brexanolone may start working faster than zuranolone

Zuranolone and brexanolone start working faster than traditional antidepressants. Other antidepressants can take weeks to start working. This isn't ideal if you're trying to care for a new infant while managing your PPD symptoms.

Zuranolone starts working within 3 days. And brexanolone starts working even faster - often symptoms improve within a few hours of starting it.

It's not clear exactly how zuranolone and brexanolone work to treat depression. But they belong to a class of medications called neuroactive steroids. This means they affect the nervous system (brain and spinal cord) in a way that's similar to natural steroids made by the body.

Specifically, zuranolone and brexanolone mimic the actions of a natural steroid called allopregnanolone. Allopregnanolone is a natural form of progesterone that helps lessen depression symptoms and reduce anxiety. Low levels of allopregnanolone may contribute to PPD symptoms.

2. You can take zuranolone at home; brexanolone is given in a hospital setting

Zuranolone is an oral capsule. You'll take it once a day in the evening for 14 days. It's best to take it with a fatty food such as avocado or nut butter. This helps your body absorb the medication. Since it's an oral capsule, you can take it on your own at home. But it's still a good idea to have someone with you for support - more on that later.

Brexanolone, on the other hand, is only available as an infusion into your vein. The infusion is administered over a 60-hour time period (about 2.5 days). You'll need to stay at the hospital while you're receiving the medication, and possibly longer if you experience side effects.

The difference between how these two medications are given can matter when choosing one treatment over the other. A hospital stay has added costs to consider. But you'll also receive extra medical support and monitoring that may be helpful for some people.

3. Zuranolone's side effects seem to be less severe than brexanolone's

Sedation is the most common side effect of both zuranolone and brexanolone. This is because these medications increase GABA signals in the brain, which can make you feel tired.

However, the sleepiness caused by brexanolone can come on suddenly and without any warning. And in rare cases, you may even lose consciousness. Brexanolone has a boxed warning, the FDA's most serious medication warning, about this side effect. It's the main reason it must be administered in a hospital setting with constant monitoring. This allows your healthcare team to stop the infusion if you pass out and ensure your safety.

Other brexanolone side effects include dry mouth and hot flashes. In contrast, zuranolone's side effects include dizziness and diarrhea as well as urinary tract infections and common cold symptoms.

4. You'll likely need child care assistance while you're taking either medication

Since zuranolone and brexanolone affect your mental alertness and cause sedation, it may be unsafe to care for your infant on your own while you're receiving treatment.

Since brexanolone requires a hospital stay, your infant may also be under hospital care while you're receiving treatment. But if not, you'll want to arrange for extra help for the 3 days or so you'll be receiving the medication. If your infant or other children come to visit you in the hospital, make sure someone stays in the room with you. This is because sedation and loss of consciousness can occur suddenly and without warning.

Since you can take zuranolone at home, child care might not seem to be an issue. But zuranolone can affect your mental alertness for at least 12 hours after each dose. Since you'll take it at night, the majority of the sedation occurs while you're sleeping. But it can linger throughout the day for some people. And you may not always be able to tell that you're not as alert as usual after taking it. So, you'll want to have child care help for the 2 weeks you're taking zuranolone.

Good to know: Both zuranolone and brexanolone may enter your breastmilk in small amounts while you're taking them. And their sedating effects may make it unsafe for you to breastfeed your infant without a helping hand. Talk to your prescriber if you have questions or concerns about breastfeeding while taking either of these medications.

5. Neither zuranolone nor brexanolone is approved for the long-term treatment of depression

Both zuranolone and brexanolone are only approved for short-term use. Their effects typically last for up to 4 weeks (1 month) after your last dose of medication.

If your depression symptoms persist, traditional antidepressants are the preferred treatment option. These include selective serotonin reuptake inhibitors (SSRIs) such as sertraline (Zoloft) and fluoxetine (Prozac). Other options include bupropion (Wellbutrin XL) and venlafaxine (Effexor). Let your prescriber know if you're breastfeeding, since that may affect which treatment option is best. Talk therapy is also a helpful option.

In some cases, your prescriber may have you start taking an antidepressant along with zuranolone or brexanolone. That way, by the time your PPD treatment wears off, the antidepressant will have time to start working.

There are ways to save on the cost of zuranolone and brexanolone

Zuranolone and brexanolone are only available as brand-name medications. But GoodRx can help you navigate ways to save on your prescription.

If you have commercial insurance and meet eligibility requirements, zuranolone's price is as low as $0 if you use the manufacturer's savings card. Zuranolone is a specialty medication, so you may need to use a specific pharmacy that will ship the medication to you. Their staff will help you access the medication at the lowest possible cost.

Since brexanolone is administered in a hospital setting, you won't pick up the medication at a pharmacy the way you usually would. And there are costs related to your hospital stay as well as the medication itself. If you have commercial insurance, brexanolone's financial assistance program can help you save up to $15,000 on the cost of the medication and up to $2,000 on the infusion cost.

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