Groundbreaking First Pill to Treat: “Postpartum Depression” — Zuranolone

Joseph R, Anticaglia, MD
Medical Advisory Board

Welcoming a child into the family is usually a joyous occasion. But for one in eight women, per CDC, during pregnancy or soon after giving birth, that time is anything but joyous.

Peripartum and postpartum depression is a major subtype of depression. Today, better awareness, understanding and diagnosis of this condition has removed some of the guilt, confusion and stigma experienced by mothers trying to cope with the sadness and lack of interest in the newborn child.

On August 4, 2023, the Food and Drug Administration (FDA) approved the first oral treatment for Postpartum Depression (PPD). It is a common complication of pregnancy, causing adverse effects on mothers and infants. A study published in the American Journal of Psychiatry, confirmed the safety and efficacy of the new medication called Zuranolone.

Zuranolone

The groundbreaking drug, zuranolone, is the first fast acting oral drug approved for postpartum depression.

It is chemically similar to the injection drug, brexanolone, which was approved by the FDA in 2019 for PPD.

They both have antidepressant activity that target the mood, behavior, cognitive and emotional areas of the brain. However, the huge downside of the 2019 drug is that it has to be administered in the vein (intravenously) continuously while in the hospital, for a total of sixty hours (2.5 days) because of the risk of sedation and loss of consciousness.

Symptoms of Postpartum Depression versus ‘Baby Blues’

Baby Blues are common to new mothers and symptoms usually occur within the first few days of childbirth. Women might feel anxious, sad, tearful and overwhelmed. They might experience high and low mood swings.

Baby Blues are a mild temporary depression, and the symptoms tend to resolve on their own within a few weeks. Medical attention is not necessary. Not getting enough sleep and hormonal changes are contributing factors.

Postpartum Depression (PPD) usually happens within the first few weeks to months after childbirth. It’s a more severe form of depression that can last “for months or longer.”

Women experience intense symptoms of depression, that include persistent feelings of sadness, anxiety, changes in appetite and sleep, despair. loss of interest in activities, and difficulty bonding with the baby. It often affects a woman’s ability to function and requires medical attention.

Doctors welcomed the approval of the oral drug, zuranalone. They talked about managing one aspect of postpartum depression with an oral medication, just as they treat other conditions with oral drugs (e. g. hypertension, diabetes).

How Does Zuranolone Work?

During pregnancy there is a significant increase in the levels of estrogen and progesterone. After childbirth there is a precipitous drop in the levels of these hormones. Neurosteroids, brain hormones [like the naturally occurring allopregnanolone in the brain and its synthetic counterpart, brexanolone, manufactured in the laboratory], work to regulate the biochemical changes mothers experience before and after giving birth. They also work to repair neural networks in the brain.

Although the exact mechanisms of action are not fully understood, neurosteroids…

  • Help to balance hormone levels and lessen mood disturbances after childbirth
  • Support the growth and survival of neurons
  • Help regulate the body’s stress response
  • Reduce anxiety and minimize emotional swings that can have beneficial effects on PPD

Treatment

Zuranolone is an innovative treatment for postpartum depression. The recommended dose of zuranolone is 50 milligrams to be taken once daily, in the evening for 14 days with a fatty meal. It acts to improve PPD symptoms as quickly as day three after starting the medication.

Other medications (antidepressants) given for PPD may take weeks or months before they start to work.

Side Effects

Zuranolone may increase your risk of suicidal thoughts, drowsiness, dizziness and confusion. It’s recommended that you wait 12 hours after taking the pill before driving a car or operating heavy machinery.

Zuranolone is a major breakthrough drug in the treatment of PPD. It will be available in the fourth quarter of this year. The cost has yet to be determined.

The authors in the 2023 American Journal of Psychiatry article concluded: “Zuranalone demonstrated significant improvements in depressive symptoms and was generally well tolerated — supporting the potential of zuranolone as a novel, rapid-acting oral treatment for PPD.”

As often is the case, a more sober evaluation of the drug’s efficacy, contraindication and side effects will be reported in the months and years ahead.

It’s useful for new mothers with PPD symptoms to take advantage of psychological counseling, keep their follow-up examinations and consider zuranolone as another component in the management of PPD.

Glossary

Allopregnanolone is a naturally occurring neurosteroid synthesized in the central nervous system. Brexanolone is a synthetic neurosteroid (manufactured in the laboratory).

Zuranolone — trade name, Zurzuvae,
Brexanolone — trade name, Zulresso

References

  1. FDA Approves First Oral Treatment for Postpartum Depression; Food and Drug Administration, August 4, 2023
  2. Deligiannidis Kristina M., et al; Zuranolone for the Treatment of Postpartum Depression; Am J Psychiatry, 2023
  3. CDC; Depression During and After Pregnancy; May 1, 2023
  4. CDC: Four in 5 pregnancy-related deaths in the U. S. are preventable; September 19, 2022
  5. ACOG Committee Opinion No. 757: Screening for Perinatal Depression; Obstetrics and Gynecology, November 2018
  6. Bauman BL, Ko JY, Cox S, et al. Vital signs: postpartum depressive symptoms and provider discussions about perinatal depression — United States, 2018.; CDC, May 15,2020
  7. Sage Therapeutics; FDA Approves Zurzuvae (Zuranolone), the First and Only Oral Treatment Approved for Women with Postpartum Depression; August 4, 2023

This article is intended solely as a learning experience. Please consult your physician for diagnostic and treatment options.