Postpartum depression afflicts 10 to 20 percent of the nearly four million women who give birth in the U.S. every year. The condition can interfere with normal bonding between mothers and infants and jeopardize children’s development through adolescence. There is no specific treatment, but a promising new drug may change that.
“There is a real need to identify [depressed] women and treat them—and treat them quickly,” says Samantha Meltzer-Brody, director of the Perinatal Psychiatry Program at the University of North Carolina Center for Women’s Mood Disorders. She conducted recent trials of the drug, which targets hormonal changes in new mothers.
Many women who suffer from postpartum depression receive standard antidepressants, including selective serotonin reuptake inhibitors such as Prozac. It is unclear how well these drugs work, however, because the neurotransmitter serotonin may play only a secondary role in the condition or may not be involved at all. Instead researchers suspect a different biological process may be the culprit.
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Pregnancy causes a dramatic rise in the reproductive hormones estrogen and progesterone. It also produces a spike in brain levels of a steroid called allopregnanolone, which normally activates receptors for GABA—a neurochemical that signals brain cells to stop firing. GABA receptors go dormant during pregnancy to avoid overactivation by allopregnanolone; otherwise a pregnant woman would become virtually anesthetized. Immediately following birth, estrogen, progesterone and allopregnanolone drop back to normal levels, after which GABA receptor levels rebound quickly. But in some new mothers, this rebound takes longer, which may result in postpartum depression.
The new drug, developed by Sage Therapeutics, works by elevating allopregnanolone. Doing so activates GABA receptors and keeps the neurochemical at a healthy level. In one of Meltzer-Brody’s studies, a phase II clinical trial of 21 severely depressed postpartum women, 70 percent of those who received the drug went into remission. Most important, the effect occurred immediately after it was administered, and benefits persisted for 30 days. Sage Therapeutics has since conducted two phase III trials with a combined 226 postpartum women, and preliminary reports are promising. The drug, called brexanolone, is now under review by the U.S. Food and Drug Administration.
Not everyone is convinced that a single hormonal pathway is responsible, however. Joseph Lonstein, a professor of psychology at Michigan State University, who was not involved in the research, says, “I very much doubt this is the only system that’s atypical in women [who] might suffer from postpartum depression or anxiety, but I think it’s a completely reasonable one.”