Dr. Lee S. Cohen, Director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, recently shared his insights on zuranolone for postpartum depression with Ob.Gyn News on August fifteenth.
Postpartum depression (PPD) stays probably the most common complication in modern obstetrics, and a leading reason for postpartum mortality in the primary yr of life. The last 15 years have brought considerable progress with respect to adoption of systematic screening for PPD across America. Screening for PPD, most frequently using the Edinburgh Postnatal Depression Scale (EPDS), has turn out to be a part of routine obstetrical care, and can be widely utilized in pediatric settings.
That’s the excellent news. However the flip side of the identification of those women whose scores on the EPDS suggest significant depressive symptoms is that the variety of these patients who, following identification, receive referrals for adequate treatment that gets them well is unfortunately low. This “perinatal treatment cascade” refers to nearly all of women who, on the opposite side of identification of PPD, fail to receive adequate treatment and proceed to have persistent depression (Cox E. et al. J Clin Psychiatry. 2016 Sep;77[9]:1189-1200). This is maybe the best challenge to the sphere and to clinicians – how will we, on the opposite side of screening, see that these women get access to care and recuperate with the available treatments at hand?
Recently, a widely read and circulated article was published in The Wall Street Journal concerning the challenges related to navigating care resources for ladies affected by PPD. In that article, it was made clear, based on clinical vignette after clinical vignette from postpartum women across America, that neither obstetricians, mental health professionals, nor pediatricians are the “clinical home” for ladies affected by postpartum mood and anxiety disorders. The article painfully highlights the system-wide failure to coordinate mental health look after women affected by postpartum psychiatric illness.
Inside a day of the publication of The Wall Street Journal article, the Food and Drug Administration approved zuranolone (Zurzuvae; Sage Therapeutics; Cambridge, Mass.) for the treatment of PPD following the review of two studies demonstrating the prevalence of the brand new medicine over placebo. Women who were enrolled met criteria for major depressive disorder based on Diagnostic and Statistical Manual of Mental Disorders criteria starting in no sooner than the third trimester of pregnancy or later than 4 weeks of delivery. The 2 studies included a combined sample size of roughly 350 patients affected by severe PPD. Within the studies, women received either 50 mg or 40 mg of zuranolone, or placebo for 14 days. Treatment was associated with a big change within the Hamilton Depression Rating Scale at day 15, and treatment response was maintained at day 42, which was 4 weeks after the last dose of study medication.
Zuranolone is a neuroactive steroid, which is taken orally, unlike brexanolone (Zulresso; Sage Therapeutics; Cambridge, Mass.), which requires intravenous administration. Zuranolone will probably be commercially available based on estimates across the fourth quarter of 2023. Probably the most common unwanted side effects are drowsiness, dizziness, and sedation, and the FDA label may have a boxed warning about zuranolone’s potential to affect an individual’s driving ability, and performance of probably hazardous activities.
It’s noteworthy that while this recent medication received FDA approval for the PPD indication, it didn’t receive FDA approval for the treatment of major depressive disorder (MDD), and the agency issued a Complete Response Letter to the manufacturers noting their application didn’t provide substantial evidence of effectiveness in MDD. The FDA said within the Complete Response Letter that an extra study or studies will probably be needed; the manufacturers are currently evaluating next steps.
Where Zuranolone Suits Into the Treatment Algorithm for Severe PPD
Many clinicians who support women with PPD will wonder, upon hearing this news, where zuranolone matches into the treatment algorithm for severe postpartum major depression. Some relevant issues which will determine the reply are the next:
Cost. The associated fee of brexanolone was substantial, at $34,000 per yr, and was viewed by some as a limiting factor when it comes to its very limited uptake. As of this column’s publication, zuranolone’s manufacturer has not stated how much the medication will cost.
Breastfeeding. Unlike selective serotonin reuptake inhibitors, which have been demonstrated to be effective for the treatment of PPD and secure while pregnant and lactation, we’ve sparse data on the protection of zuranolone for ladies who want to breastfeed. It’s also unclear whether women eligible for zuranolone would, based on the limited data on safety in lactation, select deferral of breastfeeding for 14 days in exchange for treatment.
Duration of treatment. While zuranolone was studied within the context of 14 days of acute treatment, then out to day 42, we’ve no published data on what happens on the opposite side of this transient interval. As a straightforward example, in a patient with a history of recurrent major depression previously treated with antidepressants, but where antidepressants were perhaps deferred while pregnant, is PPD to be treated with zuranolone for 14 days? Or, hypothetically, should or not it’s followed by empiric antidepressant treatment at day 14? Alternatively, are patient and clinician presupposed to wait until reoccurrence occurs before pursuing adjunctive antidepressant therapy whether it’s pharmacologic, nonpharmacologic, or each?
Treatment in patients with bipolar disorder. It’s also unclear whether treatment with zuranolone applies to other populations of postpartum women. Definitely, for ladies with bipolar depression, which is common in postpartum women given the vulnerability of bipolar women to recent onset of depression or postpartum depressive relapse of underlying disorder, we simply haven’t any data regarding where zuranolone might slot in with respect to this group of patients.
The answers to those questions may help to find out whether zuranolone, a brand new antidepressant with efficacy, quick time to onset, and a novel mechanism of motion is a “game changer.” The article in The Wall Street Journal provided me with some optimism, because it gave PPD and the problems surrounding PPD the eye it deserves in a serious periodical. As a brand new treatment, it could help alleviate suffering at a critical time for patients and their families. We’re inching closer to mitigation of stigma related to this common illness.
Pondering back across the last 3 many years of my treating women affected by PPD, I even have reflected on what has gotten these patients well. I concluded that , together with family and community-based support groups, in addition to a culture that reduces stigma and by so doing lessens the toll of this necessary and too ceaselessly incompletely-treated illness.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. The Center for Women’s Mental Health at MGH was a non-enrolling site for the pivotal phase 3 SKYLARK trial evaluating zuranolone. Full disclosure information for Dr. Cohen is offered at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.