Q&A: Rapid-acting medications needed to treat ‘devastating’ postpartum depression
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Key takeaways :
- Postpartum depression affects one in eight people who give birth and has long-term consequences for children and families.
- A novel rapid-acting antidepressant is under FDA review for the condition.
BALTIMORE — Postpartum depression, a leading cause of maternal death through suicide, should be treated as a public health priority, a speaker at the ACOG Annual Clinical & Scientific Meeting told Healio.
“Postpartum depression can be devastating if untreated. We need to take a population health approach so that all mothers are screened and all mothers have access to effective treatment. It makes a huge difference in both the outcome for the mother, but also for the next generation,” Samantha Meltzer-Brody, MD, MPH, chair of the department of psychiatry at the University of North Carolina School of Medicine at the University of North Carolina at Chapel Hill, told Healio.
Newly available antidepressants and at least one currently under review by the FDA could make a substantial difference in the treatment of postpartum depression.
Healio spoke with Meltzer-Brody about mental health during the critical life event of birthing, the effects of postpartum depression on families, and screening and treating condition.
Healio: How do you define postpartum depression?
Meltzer-Brody: Postpartum depression is defined as a major depressive episode that occurs in the postpartum period. It is characterized generally by being very proximal to childbirth. Women can be diagnosed with the current definition in the [Diagnostic and Statistical Manual of Mental Disorders, fifth edition] as having onset during pregnancy and within the first few months postpartum.
The symptoms are characterized by depressive symptoms, low mood, anhedonia, loss of interest or pleasure. Co-occurring anxiety can be very prominent, obsessional thoughts, ruminating thoughts. Many mothers report feeling overwhelmed, feeling not like themselves. With more severe symptoms, mothers can describe being unable to function. At its worst, we see suicidal thoughts, and in fact, suicide from postpartum depression is one of the greatest causes of maternal mortality.
Healio: So, is postpartum depression something that, if it occurred at any other time, would be a major depressive episode, but this just happens to be close to a birth?
Meltzer-Brody: That has been an area of great interest and research. I would say there are unique characteristics to the perinatal period. We’ve done work looking at genetic and other risks. It is true that prior history of depression prior to childbirth can increase your risk. It is also true that some women will be symptomatic and have depression only during the perinatal period. My guess would be that the underlying cause is multifactorial, and it is likely different things for different women, but we do know that one of the greatest times of risk for depression in a woman’s life is postpartum. There are unique characteristics, not the least being that this is a particularly vulnerable time because you have a new baby. The issues around taking care of the baby, attachment and bonding in this critical window are magnified, so there’s a great need for treatments that are fast-acting and that can be effective quickly.
Healio: How does postpartum depression affect the person with the condition, the family and the infant?
Meltzer-Brody: More severe postpartum depression can be devastating for families. When untreated, it has adverse consequences for the mother, the baby and the family unit. There is clear literature on postpartum depression causing neurodevelopmental delays in children, in worse psychiatric mental health and neurodevelopmental milestones. There are studies that have followed kids out to late adolescence, and we’re seeing worse outcomes for kids whose mother had postpartum depression. We certainly know it can have a horrible impact on relationships, on a marriage, and certainly for the mother who is suffering.
For all these reasons, it is critical that it is screened for and treated effectively.
Healio: How is postpartum depression diagnosed? Is it generally diagnosed appropriately?
Meltzer-Brody: Historically, it has been missed or underdiagnosed. There has been a great deal of progress — certainly in the last 20 years, and in particular, the last 10 years — on more regular screening and including screening as part of routine perinatal and postpartum care.
Postpartum depression affects one in eight women as a major depressive episode, so it’s exceedingly common. If we include less severe forms of illness or co-occurring anxiety, it’s even more common. The same way they should be screened for blood pressure and diabetes and any other obstetrical health concern, all women should be screened for depression given the prevalence.
Healio: How is postpartum depression currently treated, and what therapies are in development?
Meltzer-Brody: The gold standard treatments for mild to moderately severe postpartum depression have been first-line psychotherapeutic interventions, multiple forms of evidence-based psychotherapy that can be delivered many different ways. We now can deliver psychotherapy virtually, which is something positive that has come out of the pandemic. This has really improved our ability to increase access to people who live far from a mental health provider, which often would be in most rural areas of the country.
In terms of pharmacologic treatment, for many years the SSRIs — selective serotonin reuptake inhibitors — have been considered the first-line antidepressant treatment. There are many years of data, and while not specifically approved for postpartum depression, these have been used and are widely available.
Other antidepressants have been used more recently. Brexanolone (Zulresso, Sage Therapeutics) became the first FDA-approved medication for severe postpartum depression in March 2019. It is a fast-acting antidepressant, highly effective and well tolerated. However, it requires an IV 60-hour infusion in a medical setting, so that is certainly not convenient. It is a positive allosteric modulator of gamma-aminobutyric acid (GABA) — the first in class for that type of medication.
Zuranolone (Sage Therapeutics/Biogen) is being reviewed now by the FDA. Brexanolone is a proprietary formulation of allopregnanolone, which is a neuroactive metabolite of progesterone. In contrast, zuranolone is an oral drug, it is a neurosteroid, it is a positive allosteric modulator of GABA, but is not an oral form of allopregnanolone. That’s just an important distinction, zuranolone and brexanolone are similar but not identical in terms of structure.
Approval of zuranolone would be very exciting because it is a fast-acting antidepressant, which makes it unique. The SSRIs can take 4 to 6 weeks to be effective. In the zuranolone clinical trials, you see onset of action at day 3 of a 14-day treatment trial, and that effect persists out to 45 days of the study period in all the clinical trials. Something that really is having a positive impact by day 3 is a marked step forward.
I would add that in the brexanolone studies, we see an impact at the first day, at the 24-hour mark of treatment; it is an IV drug, but there is such a great need for rapid-acting antidepressants. Intranasal ketamine was also FDA-approved in March 2019. Ketamine certainly is fast acting, but there is a great need for therapies that can act rapidly to markedly decrease suffering.
In postpartum depression, in particular, because this is a vulnerable time and a mother needs to be well to take care of the baby, the treatment with a rapidly acting drug is a huge step forward and something that I think will be an important new tool among all the treatments available. If approved for postpartum depression — and it’s also being reviewed for major depressive disorder, in general, outside of the perinatal period — zuranolone would be a first-in-class oral drug that would be a new an important new tool in treating depression.