How does Zurzuvae differ from traditional antidepressants?

Zurzuvae differs from traditional antidepressants as it is the first oral treatment approved for postpartum depression (PPD), but it’s not yet approved for major depressive disorder (MDD). It’s only taken for 14 days and it’s a faster-acting antidepressant, with symptom improvement starting as early as the third day.

Side effects

Zurzuvae should be taken in the evening, as it can cause sleepiness in about 36% of patients and dizziness in about 13%. Many traditional antidepressants may also be associated with drowsiness, sleepiness or dizziness as a side effect, but this will differ based on the treatment you are taking.

The most common side effects with Zurzuvae are somnolence (drowsiness, sleepiness), dizziness, diarrhea, fatigue, nasopharyngitis (common cold), and urinary tract infections.

Side effects with traditional antidepressants like the SSRIS will vary, but commonly include insomnia (trouble sleeping) or drowsiness, dizziness, anxiety, sexual dysfunction, nausea, diarrhea, and appetite changes.

Cost

Cost is not full known at this time. It is expected that Zurzuvae will be much more costly than traditional oral antidepressants, many of which are available generically. However, patient assistance programs from the manufacturer of Zurzuvae may be an option for some patients.

It should be available for prescribing by the fourth quarter of 2023.

Abuse potential

Zurzuvae is a controlled substance with the potential for misuse, abuse, addiction and withdrawal, but it’s only given as a one-time, 14 day treatment. Traditional antidepressants like the SSRIs, are not controlled by the DEA, and are typically taken for several months or longer when used for PPD.

The DEA is expected assign a Controlled Substance Schedule to Zurzuvae by early November 2023. Studies have shown it has abuse potential similar to alprazolam (Xanax), a CIV benzodiazepine.

How fast does Zurzuvae work?

In studies, Zurzuvae significantly improved symptoms of postpartum depression (PPD) as early as the 3rd day after starting treatment and effects were sustained through day 45, based on the SKYLARK Phase 3, placebo-controlled study.

• A quick-acting agent like Zurzuvae may have an advantage for patients with severe PPD, where faster onset may be preferable.
• Traditional oral antidepressants like the selective serotonin reuptake inhibitors (SSRIs) - for example fluoxetine (Prozac) or sertraline (Zoloft) - can take up 4 to 8 weeks for the full antidepressant effect to occur.

In addition, Zurzuvae has a different mechanism of action than many other antidepressants like SSRIs or SNRIs. It is a neuroactive steroid (NAS) gamma-aminobutyric acid (GABA)-A receptor positive modulator. GABA is the major inhibitor signaling pathway in the central nervous system and helps regulate brain function.

This differs from agents like the SSRIs. Zurzuvae’s mechanism for treatment of PPD is thought to be due to its action on GABA-A receptors, while SSRIs are thought to work at serotonin (5HT) receptors.

GABA and serotonin are both neurotransmitters that act as chemical messengers in the central nervous system and brain. In general, antidepressants may work at many other different receptors in the CNS, too, depending upon their pharmacology.

What is postpartum depression (PPD)?

Postpartum depression (PPD) is a major depressive episode that usually starts after childbirth but can also start during the later stages of pregnancy. PPD can make it difficult for a mother to bond with her child and can delay emotional and physical development.

Roughly 1 in 8 women (12.5%) experience symptoms of PPD, such as:

• intense anxiety
• trouble sleeping
• sadness, crying
• shame
• guilt
• stress
• panic attacks
• suicidal thoughts or actions

Which antidepressants are used for postpartum depression?

Two fast-acting antidepressants are specifically approved by the FDA to treat postpartum depression (PPD), Zulresso (brexanolone), given as an intravenous (IV) infusion and Zurzuvae (zuranolone), an oral treatment.

• In March 2019, the FDA approved Sage Therapeutics’ Zulresso (brexanolone) injection for PPD in adults.
• It’s given as a continuous intravenous (IV) infusion over 60 hours (2.5 days) in a certified healthcare facility. It’s also prescribed via a restricted REMS safety program due to possible loss of consciousness in the patient.
• In clinical studies, Zulresso demonstrated superiority to placebo in improvement of moderate and severe PPD symptoms at the end of the first infusion and at the end of a 30-day follow-up period.

In August 2023, the FDA approved Zurzuvae (zuranolone) from Sage Therapeutics / Biogen.

• It is the first approved oral agent to treat postpartum depression (PPD) in adults.
• It is taken by mouth once daily in the evening with a fat-containing food for 14 days. Talk to your healthcare provider about which types of high-fat foods you should eat.
• It causes drowsiness and somnolence and should only be taken in the evening. Do not drive or engage in other potentially hazardous activities until at least 12 hours after administration.

In severe cases of postpartum depression, a faster-acting option like Zurzuvae or Zulresso may be preferred. These medicines have a similar mechanism of action.

Electroconvulsive therapy is another option that may be used for PPD. Group or individual psychotherapy (“talk” therapy) should also be added to treatment options, when possible.

In addition to SSRIs, other traditional antidepressants that your doctor may prescribe for PPD include serotonin-norepinephrine reuptake inhibitors (SNRIs), mirtazapine, or nortriptyline.

Related: Medications used in the treatment of postpartum depression (PPD)

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How often do you take Zurzuvae?

Zurzuvae is taken by mouth once daily in the evening for 14 days, the full length of the treatment course. Take each dose with a fat-containing food. Talk to your healthcare provider about which types of high-fat foods you should eat.

Zurzuvae can make you sleepy, so you should take it in the evening for the entire 14-day treatment course.

• Take your dose in the evening so that it does not interfere with daily activities, like work, school or parenting. Also avoid driving, operating machinery or other dangerous activities for 12 hours after a dose.
• In studies, over one-third of people taking a Zurzuvae 50 mg dose experienced sleepiness.

Do not exceed the 14 day single treatment course, because it is not known if this is safe.

Zurzuvae, available as 20 mg, 25 mg and 30 mg oral capsules, can be used alone or in addition to other oral antidepressant therapy. Take Zurzuvae exactly as your healthcare provider tells you to take it.

Is Zurzuvae a controlled substance?

Zurzuvae is a controlled substance, but has not yet been scheduled by the DEA. In studies, zuranolone (the active ingredient) was shown to have abuse potential similar to alprazolam (Xanax), a schedule IV benzodiazepine controlled substance.

Zuranolone has the potential for the development of misuse, abuse, and substance use disorder including addiction. It can also cause physical dependence and has been reported to lead to mild-to-moderately severe withdrawal symptoms such as:

• trouble sleeping
• fast heart beat
• decreased appetite
• nightmares
• nausea
• excessive sweating
• paranoia

Most other traditional antidepressants such as the SSRIs or SNRIs are not classified as controlled substances, but can cause discontinuation symptoms (like insomnia, nausea, anxiety or fatigue) in some cases.

How much does Zurzuvae cost?

The exact price of Zurzuvae is not known yet, but pricing is expected by the 4th quarter of 2023. The treatment regimen could cost $10,000 or more. Sage Therapeutics, the manufacturer, has stated that they plan to support patients with patient access programs and copay assistance for eligible patients.

Many other antidepressants, including most of the SSRIs, are now available in the US as a generic option, which can bring their costs to less than $20 per month, depending upon the generic option prescribed and any pharmacy discounts.

Talk to your healthcare provider if you have concerns about the costs of your PPD treatment, as more affordable options may be available for you.

This is not all the information you need to know about Zurzuvae (zuranolone) for safe and effective use and does not take the place of your doctor’s directions. Review the full product information and discuss this information and any questions you have with your doctor or other health care provider.