Breakthrough Drug for New Moms

The FDA approves the first drug specifically designed to treat postpartum depression 
By Cheryl England

ABOUT 15% of all new mothers experience postpartum depression (PPD) within the first few months after childbirth, according to the National Institute of Mental Health— that’s about 1 in 7 new mothers. More incapacitating than the “baby blues,” postpartum depression is marked by severe sadness or emptiness, withdrawal from family and friends, a strong sense of failure, anger or rage, and even thoughts of suicide. These emotions can last up to a year or longer if untreated.

The Good News
In March, the Federal Drug Administration (FDA) approved a new drug designed to treat postpartum depression: The approval marks the first time a drug has been specifically approved to treat PPD. The new drug, brexanolone, will be marketed as Zulresso and has been found to significantly reduce postpartum depression. Two clinical trials of about 250 women with PPD showed that within 60 hours, 50% of the women who received brexanolone were no longer clinically depressed, compared with 25% of women who received a placebo.

The trials also showed that the relief lasts at least as long as 30 days, the maximum time the mothers were followed in the trials. As further scientific review is conducted, it will become more clear just how long the effects can last beyond 30 days. Yet, a month-long period gives physicians a chance to start other treatments for postpartum depression such as psychotherapy and gives the new mother time to garner additional support.

The Bad News
But Zulresso has its downsides. At $34,000 the drug is costly. In addition, it is delivered by a continuous IV infusion over 60 hours (2.5 days), during which a new mother must remain in a certified medical center, under supervision should she get dizzy or faint, as several patients did in clinical trials.

Zulresso, which is manufactured by Sage Therapeutics, will be available only through a restricted program called the Zulresso REMS Program that requires patients to be enrolled in the program prior to administration of the drug. Because of the risk of serious harm due to the sudden loss of consciousness, patients must be monitored for excessive sedation and have continuous pulse oximetry monitoring. While receiving the infusion, patients must be accompanied during interactions with their newborn and with any other children. Patients will be counseled on the risks of Zulresso treatment and instructed that they must be monitored for these effects at a health care facility for the entire 60 hours of infusion.

How It Works
Brexanolone is a synthetic version of a steroid called allopregnanolone, which people make naturally in their bodies. Allopregnanolone is a breakdown of progesterone. Blood levels of allopregnanolone increase during pregnancy and drop rapidly after childbirth. Fluctuations in levels of the steroid may trigger changes in the brain that contribute to depression and anxiety in some women, according to manufacturer Sage.

Sage says that it is unclear exactly how brexanolone works to treat postpartum depression. But it’s thought that the drug modifies the body’s stress response, which is abnormal in women with PPD. The drug binds to GABA receptors, which play a role in many brain functions. The binding may work to reverse or “reset” the brain activity tied to postpartum depression symptoms. Other drugs for depression typically don’t bind to GABA receptors.

While brexanolone has antidepressant effects, it seems to work differently from traditional antidepressants, which increase levels of neurotransmitters, such as serotonin or norepinephrine. It is hypothesized that brexanolone may exert its effects on anxiety and depression by modulating the hypothalamic-pituitary-adrenal or HPA axis that mediates the body’s response to stress and is modulated by GABAergic signaling, according to the MGH Center for Women’s Health.

Screening for PPD
While Zulresso may be a breakthrough drug, it cannot do its job if new mothers do not realize they are suffering from PPD—and many do not. They may mistake their symptoms for the baby blues or they may feel shame or they may not want to mention symptoms for fear of being seen as an unfit mother. Physicians can help, however, by screening patients for postpartum depression. The American College of Obstetrics and Gynecologists (www.acog.org) offers a variety of screening tools and resources for health care providers.

Taking the extra time to screen new mothers can lead to better outcomes for both the mother and child. A new mom with a mood disorder in the first year of her child’s life can disrupt the mother-infant relationship, thereby contributing to both short- and long-term adverse outcomes for the child. These include behavior problems, low selfesteem, poor self-regulation, and an increased risk of impaired mental and motor development.