New Treatment Option for Postpartum Depression

Once upon a time, there was a little girl who dreamed of being a mommy. She wanted, more than anything, to have a child and knew her dream would come true one day. She would sit for hours thinking up names to call her baby….And then one day, finally, she became pregnant. She was thrilled beyond belief. She had a wonderful pregnancy and a perfect baby girl. At long last, her dream of being a mommy had come true. But instead of being relieved and happy, all she could do was cry. —Brooke Shields, Down Came the Rain

Source: Liza Summer / Pixabay

In 2005, Shields bravely published her account of postpartum depression (PPD), helping to destigmatize a previously less public disease. However, this disorder is not a new phenomenon.

It has been recognized for centuries. Hippocrates made the first known reference to PPD in the fourth century B.C. He proposed that if fluid draining from the uterus after birth was suppressed, it would flow to the brain causing an agitated state of mania.

Following this idea, a 13th-century female physician believed postpartum mental disturbances were caused by increased moisture in the body following childbirth. In the Middle Ages, women suffering from sadness during or after childbirth were considered witches or victims of witchcraft.

Fortunately, modern medicine views mood disorders occurring after childbirth in a very different light. PPD is the most common psychiatric disorder observed in the postpartum period.

Beginning a few days to a few weeks following delivery, it generally appears in the first, two-to-three months following childbirth. Initially, PPD may be confused with the ubiquitous baby blues. Baby blues are experienced by up to 85 percent of new moms and generally involve tearfulness, increased anxiety, a sense of feeling overwhelmed, and increased irritability along with the ever-present loss of sleep.

However, as opposed to PPD, baby blues resolves in a matter of days to a week or two.

PPD is experienced by 10 percent to 15 percent of postpartum women. Aside from the postpartum time specifier, the diagnostic criteria are similar to major depression occurring at any other time in a person’s life.

Symptoms include insomnia, loss of appetite, poor concentration, sadness, tearfulness, hopelessness, and often guilt. Many women feel that this is a time of life that should bring joy instead of mental anguish.

Historically, postpartum psychiatric disorders have been underdiagnosed, resulting in a lack of appropriate treatment. This is mainly because patients experience delays and difficulties in help-seeking due to feelings of guilt and fear of stigmatization.

However, more recently screening for this disorder has become part of the routine, six-week post-delivery checkup performed by obstetrical caregivers. In 2016, the official recommendation from the American College of Obstetricians and Gynecologists was “routine screening for depression for all women at least once during the perinatal period.” The gold standard screening tool is the Edinburgh Postnatal Depression Scale (EPDS).

Treatment Options

In general, a multifactorial approach for treating PPD is most effective.

• Psychoeducation: This intervention is helpful by teaching new mothers and their partners and/or associated caregivers about the symptoms and treatment options for PPD. Many women have never heard of PPD, and it is often a relief to learn that they are not alone and that options for symptom relief are available. Learning behavioral strategies, such as encouraging sleep and self-care, can go a long way toward relieving the sense of feeling overwhelmed.
• Psychotherapy: Cognitive behavioral therapy (CBT) has demonstrated the most short- and long-term effectiveness. CBT approaches include strategies to address dysfunctional patterns of thoughts and behaviors. Mindfulness acceptance-based CBT approaches may also emphasize changing the way one relates or responds to thoughts or emotions, rather than trying to change the experience itself.
• Medication: Typically, first-line antidepressant treatments for PPD are selective serotonin reuptake inhibitors (SSRI), which carry low toxicity risks and have fewer side effects. The SSRIs with the most randomized controlled trials to treat PPD are sertraline (Zoloft) and fluoxetine (Prozac). A different class of antidepressants, SNRIs (serotonin and norepinephrine reuptake inhibitors) include venlafaxine (Effexor) and its metabolite desvenlafaxine (Pristiq), which are also supported for the treatment of PPD. As a class, antidepressants, particularly SSRIs, have the largest database in breastfeeding and appear largely free of adverse effects.
• Brexanalone: In 2019, the Food and Drug Administration (FDA) approved Zulresso (brexanolone) as a novel treatment for PPD. Initially, this medication was only available through a restricted distribution program at certified healthcare facilities. Unfortunately, this posed real limitations on access to care due to time and distance. Women suffering from PPD had to travel to select locations to receive this medication, which was delivered through a 60-hour infusion. It was, however, very effective and demonstrated superiority to placebo even after the first infusion. It also appeared to have continuous benefits for up to 30 days after treatment.
• Zurnolone: Last month, the FDA approved the release of Zurzuvae (zurnolone), the first oral medication indicated to treat postpartum depression. Zuranolone is a synthetic form of allopregnanolone, a naturally occurring steroid that your body makes from the hormone progesterone. Allopregnanolone helps the GABA-A receptors (which regulate mood and behavior) in the brain function more effectively, resulting in a calming, antidepressant effect.

The effectiveness of zurnolone was demonstrated in two randomized double-blind, placebo-controlled multicenter studies. Eligible study participants included women who met the criteria for major depression during the third trimester of pregnancy or within four weeks of delivery.

Treatment was delivered over two weeks. Women in the active drug group showed significant improvement versus placebo, even within the first few days. The most common side effects were drowsiness, dizziness fatigue, and gastrointestinal symptoms.

This is a real breakthrough. However, the FDA indication is limited to postpartum depression only, It has not received approval for treating major depression occurring outside of the postpartum period.

Zurzuvae can be taken along with a more standard SSRI or SNRI. The benefit of this combination is timing. Typically, SSRI or SNRI antidepressants can take up to six to eight weeks for full effectiveness. With Zurzuvae, patients can receive significant relief within days while waiting for the longer-acting medications to take effect.

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However, as of this writing, the cost and availability of the drug in the U.S. has not been published. Additionally, it will be interesting to see if health insurance carriers will cover the cost of this novel medication.