Pregnancy changes a woman’s body and brain in ways scientists are still working to understand.
Consider postpartum depression: some 10% to 20% of mothers feel a prolonged sadness, anxiety, irritability, and inability to bond with their newborns after giving birth, for anywhere between a few weeks and six months. The condition is likely due to a set of changes that occur after a woman gives birth as her body adjusts itself once more. Medical experts still don’t know all the pieces of this complicated adjustment process, nor do they know exactly what it might due to a woman’s mental health—or whether some element of those changes mimic what happens in the body of someone with clinical depression. Because many of their symptoms are similar to that clinical depression, these women are often treated with standard antidepressants, like selective serotonin reuptake inhibitors (SSRIs), even though postpartum depression might be a completely different condition.
But for the first time, a drug specifically tailored to treat postpartum depression is close to receiving approval from the US Food and Drug Administration (FDA). In April of this year, Sage Pharmaceuticals, a Massachusetts-based biotech startup, submitted a new drug application for brexaolone after successful phase III clinical trials. Positive results from small phase II clinical trials spurred the FDA to give brexaolone a breakthrough therapy status, which speeds up the approval process; it’s expected to be completed by mid-December.
While SSRIs prolong the life of the neurotransmitter serotonin in the brain, brexaolone targets a different chemical, called GABA. GABA works by telling cells in the brain to calm down. As Scientific American explains, during pregnancy, a woman’s body is flooded by all sorts of chemicals, including a steroid that activates GABA receptors. But these receptors are automatically shut down during pregnancy, because pregnant women need less of the dampening neurotransmitter. In other words, the extra steroid can’t override the GABA-receptor shutdown, and as a result, excess GABA remains in the brain.
When the woman gives birth, her body readjusts. She stops producing the steroid, and her GABA receptors wake up. Sometimes, though, the receptors don’t restart perfectly, and her brain can’t take up enough GABA—a hallmark of regular depression and anxiety.
Brexaolone works by activating more GABA receptors, enabling a new mother’s brain to utilize more of the neurotransmitter. In a phase III trial of 246 postpartum women, the majority of women who received brexaolone reported fewer symptoms of depression compared to those on a placebo. The drug is administered through an IV over the course of 60 hours; Sage is also developing a more convenient pill.
GABA may not be the only chemical change underlying postpartum depression, notes Joseph Lonstein, a psychologist at Michigan State University who was not involved in the research. Nevertheless, Lonstein told Scientific American, the discovery that targeting GABA can be an effective treatment for postpartum depression is certainly a welcome development in the field.
Should the FDA approve the drug, it would become the first treatment option specifically for women with postpartum depression, and could be used later on to treat other forms of depression or mood disorders.