Postpartum depression (PPD) is a devastating condition that affects many new mothers, often robbing them of joy and connection during a critical period of bonding with their infants. Kristina Leos, a 40-year-old nurse from Midlothian, Texas, experienced this firsthand after the birth of her daughter Victoria. Although surrounded by her loving family, Leos felt emotionally distant and disconnected, describing her state as “a heavy fog” that made her feel like a ghost passing through her own household. Despite trying various antidepressants, her condition worsened, leading her to contemplate death without fear or hesitation—a harrowing symptom of severe depression.
Leos’s story is emblematic of the struggles faced by many women with postpartum depression. After exhausting traditional treatments, she was presented with only drastic options such as ketamine infusions, electroconvulsive therapy, or psychiatric hospitalization. However, a new hope emerged when she learned about zuranolone, a novel medication specifically designed for postpartum depression. Approved by the U.S. Food and Drug Administration (FDA) in 2023, zuranolone works differently from older antidepressants like Prozac by targeting brain chemicals uniquely affected by pregnancy. After starting this medication on New Year’s Day 2024, Leos experienced a dramatic turnaround within three days—the emotional cloud lifted, and she began to recover rapidly.
This breakthrough is significant because postpartum depression is a leading cause of maternal mortality in the United States, surpassing physical causes such as bleeding or infection. Mental health complications account for about 23 percent of maternal deaths in the first year after childbirth. Despite this alarming statistic, less than half of affected women are diagnosed, and even fewer receive adequate treatment. The urgency for better interventions has never been greater.
Recent scientific research has revealed that postpartum depression is distinct from other mood disorders. It arises primarily from drastic hormonal changes during and after pregnancy. Progesterone and its related neurosteroid allopregnanolone surge during pregnancy but plummet sharply after birth. For some women, this sudden hormonal drop disrupts brain circuits governing mood and stress, rendering them vulnerable to depression. Zuranolone works by compensating for this hormonal deficiency, restoring balance in the brain’s mood-regulating systems.
The recognition of postpartum depression as a biologically rooted illness marks a critical shift in how the condition is understood and treated. Historically, postpartum depression was poorly defined and often misunderstood. Ancient texts described women with postpartum mood disturbances, but explanations ranged from demonic possession to imbalances of bodily humors. Even in modern psychiatry, postpartum depression was only formally recognized as a subtype of major depression in 1994 and remains categorized under “major depression with peripartum onset” in the current Diagnostic and Statistical Manual of Mental Disorders (DSM-5). This classification has led to treatments that largely mirror those for general depression, such as selective serotonin reuptake inhibitors (SSRIs), which target serotonin and norepinephrine neurotransmitters.
However, the unique neurobiology of postpartum depression involves more than just chemical imbalances of serotonin and norepinephrine. Scientists have uncovered the critical role of neurosteroids—hormones that act on the brain, such as allopregnanolone—in modulating mood. Jamie Maguire, a neuroscientist at Tufts University, made a groundbreaking discovery about the connection between neurosteroid signaling and postpartum mood disorders through her research with genetically modified mice. These mice, engineered to have impaired response to GABA (gamma-aminobutyric acid), a neurotransmitter that inhibits neural activity, exhibited severe maternal neglect and depressive-like behaviors after giving birth. Treatment that restored neurosteroid signaling reversed these symptoms, highlighting the importance of this pathway.
Maguire’s work led to a better understanding of how the brain adapts to the neurosteroid surge during pregnancy by downregulating GABA receptors to maintain alertness, and how failure to readjust these receptors postpartum creates vulnerability to depression. This disrupted regulation affects the hypothalamic-pituitary-adrenal (HPA) axis, the body’s central stress response system. Normally, neurosteroids suppress HPA axis activity during and immediately after pregnancy to promote calm maternal behavior, but prolonged suppression or improper receptor regulation can trigger depressive symptoms.
Capitalizing on these insights, pharmaceutical companies developed new treatments targeting neurosteroid pathways. Sage Therapeutics pioneered this effort with brexanolone, a synthetic intravenous form of allopregnanolone. Clinical trials showed remarkable improvement