ZURZUVAE is thought to help address one of the underlying causes of PPD1

Explore the mechanism of disease of postpartum depression (PPD) and the mechanism of action of ZURZUVAE® (zuranolone)

Mechanism of disease Mechanism of action
How ZURZUVAE is thought to work

Drs. Greg Mattingly, Danielle Johnson, and Bassem Maximos explore the pathophysiology of PPD and the role ZURZUVAE may play.

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Mechanism of disease

How does postpartum depression (PPD) develop?

Throughout the perinatal period, the GABA system typically adapts to changing levels of allopregnanolone and progesterone1
One theory of PPD is that the GABA system fails to fully adapt to hormonal changes after delivery, resulting in reduced GABA signaling1

This reduction in GABA signaling alters the brain's ability to regulate stress and may contribute to the symptoms seen in PPD. There may also be other neurotransmitters involved in PPD.1

These biological changes and stressors can affect any woman, which means any woman can be at risk for PPD2

How hormones & GABA help manage stress responses

In the central nervous system, hormones such as allopregnanolone work with neurotransmitters
like GABA to manage emotion and stress responses during the perinatal period3,4

Mechanism of action

How is ZURZUVAE thought to work?

ZURZUVAE modulates GABAA receptors to increase GABA signaling​5

It does not directly affect monoaminergic systems like serotonin and dopamine5
Explore dosing

It's only 14 days of dosing and done 
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Why conversations matter

See why it's important to keep postpartum depression top of mind

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References: 1. Meltzer-Brody S, Kanes SJ. Allopregnanolone in postpartum depression: Role in pathophysiology and treatment. Neurobiol Stress. 2020;12:100212. 2. Perinatal depression. National Institutes of Mental Health. https://www.nimh.nih.gov/health/publications/perinatal-depression. Accessed January 20, 2026. 3. Almeida FB, Pinna G, Barros HMT. The Role of HPA Axis and Allopregnanolone on the Neurobiology of Major Depressive Disorders and PTSD. Int J Mol Sci. 2021;22(11):5495 4. Maguire J. Neuroactive Steroids and GABAergic Involvement in the Neuroendocrine Dysfunction Associated With Major Depressive Disorder and Postpartum Depression. Front Cell Neurosci. 2019;13:83. 5. ZURZUVAE Prescribing Information. Cambridge, MA: Biogen and Sage Therapeutics.

INDICATION

ZURZUVAE® (zuranolone) is indicated for the treatment of postpartum depression (PPD) in adults.

 

IMPORTANT SAFETY INFORMATION

WARNING: IMPAIRED ABILITY TO DRIVE OR ENGAGE IN OTHER POTENTIALLY HAZARDOUS ACTIVITIES

ZURZUVAE causes driving impairment due to central nervous system (CNS) depressant effects.

Advise patients not to drive or engage in other potentially hazardous activities until at least 12 hours after ZURZUVAE administration for the duration of the 14-day treatment course. Inform patients that they may not be able to assess their own driving competence, or the degree of driving impairment caused by ZURZUVAE.

 

WARNINGS AND PRECAUTIONS

Impaired Ability to Drive or Engage in Other Potentially Hazardous Activities

  • ZURZUVAE causes driving impairment due to central nervous system (CNS) depressant effects
  • Advise patients not to drive a motor vehicle or engage in other potentially hazardous activities requiring complete mental alertness, such as operating machinery, until at least 12 hours after ZURZUVAE administration for the duration of the 14-day treatment course. Inform patients that they may not be able to assess their own driving competence or the degree of driving impairment caused by ZURZUVAE

Central Nervous System Depressant Effects

  • ZURZUVAE can cause CNS depressant effects such as somnolence and confusion
  • Somnolence developed in 36% of patients who received ZURZUVAE (50 mg) and in 6% of patients who received placebo daily. Some ZURZUVAE-treated patients developed confusional state. One of these cases was severe, and was also associated with somnolence, dizziness, and gait disturbance
  • A higher percentage of ZURZUVAE-treated patients, compared to placebo-treated patients, experienced somnolence, dizziness, or confusion that required dosage reduction, interruption, or discontinuation
  • Because ZURZUVAE can cause CNS depressant effects, patients may be at higher risk of falls
  • Other CNS depressants such as alcohol, benzodiazepines, opioids, tricyclic antidepressants, or drugs that increase zuranolone concentration, may increase impairment of psychomotor performance or CNS depressant effects such as somnolence, cognitive impairment, and the risk of respiratory depression in ZURZUVAE-treated patients
  • To reduce the risk of CNS depressant effects and/or mitigate CNS depressant effects that occurs with ZURZUVAE treatment:
    • If patients develop CNS depressant effects, consider dosage reduction or discontinuation of ZURZUVAE
    • If use with another CNS depressant is unavoidable, consider dosage reduction
    • Reduce the ZURZUVAE dosage in patients taking strong CYP3A4 inhibitors

Suicidal Thoughts and Behavior

  • In pooled analyses of placebo-controlled trials of chronically administered antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with major depressive disorder (MDD)
  • ZURZUVAE does not directly affect monoaminergic systems. Consider changing the therapeutic regimen, including discontinuing ZURZUVAE, in patients whose depression becomes worse or who experience emergent suicidal thoughts and behaviors

Embryo-fetal Toxicity

  • Based on findings from animal studies, ZURZUVAE may cause fetal harm when administered to a pregnant woman
  • Advise a pregnant woman of the potential risk to an infant exposed to ZURZUVAE in utero. Advise females of reproductive potential to use effective contraception during treatment with ZURZUVAE and for one week after the final dose
 

ADVERSE REACTIONS

  • The most common adverse reactions (≥5% and greater than placebo) in ZURZUVAE-treated patients were somnolence, dizziness, diarrhea, fatigue, nasopharyngitis, and urinary tract infection
 

DRUG INTERACTIONS

CNS Depressant Drugs and Alcohol

  • Caution should be used when ZURZUVAE is administered in combination with other CNS drugs or alcohol. If use with another CNS depressant is unavoidable, consider dosage reduction

Strong CYP3A4 Inhibitors

  • Reduce the ZURZUVAE dosage when used with a strong CYP3A4 inhibitor

CYP3A4 Inducers

  • Avoid concomitant use of ZURZUVAE with CYP3A4 inducers
 

USE IN SPECIFIC POPULATIONS

Pregnancy

  • There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants, including ZURZUVAE, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/
  • Based on findings from animal studies, ZURZUVAE may cause fetal harm. Advise pregnant women of the potential risk to a fetus. Available data on ZURZUVAE use in pregnant women from the clinical development program are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Lactation

  • Available data from a clinical lactation study in 14 women indicate that zuranolone is present in low levels in human milk. There are no data on the effects of zuranolone on a breastfed infant and limited data on the effects on milk production
  • The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZURZUVAE and any potential adverse effects on the breastfed child from ZURZUVAE or from the underlying maternal condition

Hepatic Impairment

  • The recommended ZURZUVAE dosage in patients with severe hepatic impairment (Child-Pugh C) is lower than patients with normal hepatic function

Renal Impairment

  • The recommended ZURZUVAE dosage in patients with moderate and severe renal impairment is lower than those with normal renal function
 

DRUG ABUSE AND DEPENDENCE

  • ZURZUVAE contains zuranolone, a Schedule IV controlled substance
  • Zuranolone has abuse potential with associated risks of misuse, abuse, and substance use disorder including addiction
  • ZURZUVAE may produce physical dependence
 

Please see full Prescribing Information, including Boxed Warning.

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