By Liisa Hantsoo, Ph.D.
This month marked a major milestone in women’s health research. In an announcement that created a lot of buzz, Sage Therapeutics announced that its medication for postpartum depression (PPD), Brexanolone, had been approved by the FDA. This is a breakthrough in women’s mental health treatment, as this is the first medication that specifically treats PPD.
As many as one in ten women experience postpartum depression (PPD) [1–3]. PPD is a form of depression that starts in the 4-6 weeks following childbirth, and includes symptoms such as low mood and loss of interest, irritability, or anxiety [4]. The weeks following childbirth are challenging, whether PPD occurs or not. It is a time marked by psychosocial changes (adjusting to a new baby and new family roles), physical demands (healing following delivery, managing breastfeeding, interrupted sleep), and major hormonal shifts (progesterone levels drop by 20x and estrogen by 200x in the hours following delivery) [5]. Clearly, PPD has qualities that make it unique from typical major depression. Despite these differences, PPD is often treated with the same tools used to treat major depression. These include psychotherapy, medications such as selective serotonin reuptake inhibitors (SSRIs), or a combination of therapy and meds [6–8]. In fact, SSRIs are a common tool in the psychiatrist’s toolkit, used to treat a range of concerns including major depression and anxiety disorders. SSRIs work for many women with PPD [9], and seem to be most effective for women with mild to moderate PPD. However, there is a small percentage of women with PPD for whom SSRIs don’t work [10]. These treatment-resistant cases of PPD are often severe, and can be life-threatening if suicidality occurs [11]. This puts not only mom’s health at risk, but also the health of her infant. Therefore, having a treatment specifically targeted for PPD is an important development for women who experience severe PPD.
The medication, Brexanolone, is unique – instead of targeting classic neurotransmitters (such as SSRIs, which target the serotonin system), it targets hormone metabolites called neurosteroids. In particular, Brexanolone is a synthetic version of a progesterone metabolite called allopregnanolone. Allopregnanolone, like progesterone, drops rapidly following delivery, and recent studies have suggested that allopregnanolone may play a role in PPD [12,13].
Because Brexanolone’s mechanism of action is based on neurosteroids, not neurotransmitters, it produces a response that is quite different from SSRIs. Namely, it acts quickly, inducing symptom relief in about 48 hours in most cases [14,15], compared with the weeks that it may take for SSRIs to reduce symptoms. Further, this response from a single IV infusion lasts at least thirty days [15]. These placebo-controlled randomized clinical trials administered Brexanolone to nearly 150 women, and were performed at multiple sites, including the UNC Center for Women’s Mood Disorders, and the center where I am based, the Penn Center for Women’s Behavioral Wellness at the University of Pennsylvania.
However, there are drawbacks to Brexanolone. First, its pricetag. A course of Brexanolone treatment is estimated to cost roughly $34,000. This is clearly out of reach for many women. If insurance companies opt to cover Brexanolone treatment, the pricetag may drop, but it’s not clear yet how quickly this may happen. Second, it’s currently only available as an IV infusion. The infusion is administered over the course of 60 hours in a certified medical facility , via a restricted program called the Zulresso REMS Program. This is to ensure continuous monitoring of the woman, to protect her safety. However, this means that to be treated, a woman must check into a medical facility for 2.5 days, which may be especially challenging in the postpartum period when she is caring for an infant or potentially breastfeeding. Fortunately, a pill form may be developed down the road, making treatment more accessible.
Despite these shortcomings, the FDA approval of Brexanolone is an important step in women’s mental health care. With more tailored treatments, it’s possible that women with PPD will be able to find a treatment that works for them, whether that’s psychotherapy or a medication. Importantly, Brexanolone represents an important development for women with severe, treatment-resistant PPD who to date have received inadequate help from traditional SSRIs.
References
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