Postpartum depression (PPD) is a common type of major depressive disorder (MDD) that affects up to 15% of mothers, with significant implications for maternal health, mother-child bonding, and child development.1 These complications illuminate the need for early and effective treatment of PPD.
Psychotherapy and antidepressants have led to symptom improvement in many cases of PPD.2 However, established pharmacologic approaches for MDD do not target the proposed mechanisms of PPD, and studies have shown that a substantial number of patients with PPD do not achieve remission with antidepressants. Additionally, for those who do respond to standard antidepressants, improvement in symptoms may not take effect for weeks or months.3
In 2019, following a demonstration of safety and efficacy in 3 double-blind, randomized, placebo-controlled trials, the antidepressant brexanolone became the first pharmacologic therapy approved by the US Food and Drug Administration for PPD treatment.4,5,1 As an analog of the progesterone metabolite allopregnanolone, brexanolone, it “enhances the inhibitory effects of GABAA, restores dysfunctional GABAA transmembrane channels, and mimics” allopregnanolone.6
Trial results showed greater remission rates (defined as Hamilton Depression Rating Scale [HAM-D] total score ≤7) with brexanolone compared with placebo. In a phase II trial, for example, remission rates with brexanolone were 70% at both 60 hours and 30 days vs 9% and 18%, respectively, with placebo.7 Since its approval, brexanolone has proven to be a valuable addition to the range of treatment options for PPD, although disparities in patient access represent a key challenge.
For an in-depth discussion about the current role of brexanolone and other updates in PPD management, we interviewed the following experts:
Jennifer L. Payne, MD, professor and vice-chair of research in the department of psychiatry and neurobehavioral sciences at the University of Virginia in Charlottesville
Riah Patterson, MD, assistant professor in the departments of psychiatry and emergency medicine and medical director of the Perinatal Psychiatry In-Patient Unit at the University of North Carolina School of Medicine in Chapel Hill
Andrew M. Novick, MD, assistant professor in the department of psychiatry and clinician in the Center for Women’s Behavioral Health and Wellness at the University of Colorado School of Medicine Anschutz Medical Campus (CU Anschutz) in Aurora
Dr Payne and Dr Novick each co-authored recent papers discussing PPD and brexanolone, and Dr Patterson and colleagues published a study in 2022 detailing the outcomes of 16 patients treated with brexanolone at UNC Hospitals.8,9,1
What are currently the main treatment approaches for PPD, and what are some of the top challenges in PPD management?
Dr Payne: The main treatment approach for PPD is to use standard antidepressants, typically SSRIs. Challenges include the length of time SSRIs take to work, side effects, the need for ongoing treatment while breastfeeding, and a median response rate of about 50%.
Dr Patterson: PPD remains the most common complication of childbirth, and sadly it still goes largely untreated or undertreated. Many new mothers will look for nonpharmacological options such as therapy and increased social support. Yet many will need treatment with a combination of therapy and medication management, typically in the SSRI/SNRI antidepressant category. These medications can be successful but can also take 6 to 8 weeks to be fully effective, which is really difficult during such a critical time in a family’s development.
Dr Novick: In general, current treatment approaches for PPD mirror those for MDD outside the postpartum period. The reason for this is likely 2-fold: There’s still a relative lack of research on treatment specific to PPD, especially novel treatments; and standard treatments for MDD are likely able to target, albeit imperfectly, the biopsychosocial aspects of PPD that are both unique from and similar to MDD outside the postpartum period.
So that means monoamine-based antidepressants, such as SSRIs/SNRIs, as well as psychotherapy, remain our cornerstone treatment tools. While the evidence for antidepressant and psychotherapy strategies in PPD pales in comparison to what’s available for MDD outside the postpartum period, we have enough evidence and experience to recommend them. We also have promising evidence suggesting that other interventions used in MDD are effective in PPD, such as ECT [Electroconvulsive Therapy], TMS [Transcranial Magnetic Stimulation], and bright light therapy.10,11 Of course, a huge win for psychiatry and PPD was the arrival of brexanolone as the first FDA-approved treatment specifically for PPD.
Managing PPD does have some unique challenges. When it comes to medications, we need to consider and respect the patient’s preference for breastfeeding. Most antidepressant medications have very favorable safety profiles in breastfeeding, but obviously nothing comes with zero risk, and the amount of safety data we have on medications varies.
Also, besides issues of access to quality mental health care that exist for all populations, there are additional barriers with postpartum patients. We live in a society that places tremendous expectations and pressures on new parents, and yet does little in terms of providing resources. Even with the spread of telehealth, it’s a lot to ask a new parent to attend postpartum follow-ups with their OB/GYN, appointments with a psychiatric practitioner to manage medication, and regular psychotherapy sessions.
How has brexanolone changed the landscape of PPD treatment, and what have been your personal observations in treating patients with this drug?
Dr Payne: Brexanolone has given us another alternative to starting antidepressants and waiting weeks for them to work. Brexanolone has a very high response and remission rate compared with standard antidepressants, begins to work within the first day, and has a sustained response. Standard antidepressants take weeks to work and have a lower response rate overall. With brexanolone, women with PPD are relieved of their symptoms quickly and can go home to enjoy their expanded family.
Dr Patterson: Brexanolone became commercially available in mid-2019, and it is a really good option for women with moderate to severe PPD who are insured and less than 6 months postpartum. This treatment is a 60-hour infusion that takes place in a medical facility. Brexanolone has a boxed warning for excessive sedation and potential loss of consciousness, and so it requires sedation scale monitoring every 2 hours and continuous pulse oximetry. Despite these challenges, it is generally well-tolerated and rapidly acting, so women can start to get relief during the infusion and many reach remission by the end of the infusion, making this the preferred treatment.
The vast majority of my patients are pleased to have received this treatment and report improved depression, anxiety, and better sleep quality and quantity. It is amazing to see mothers dramatically improve over a few days. I have witnessed moms come into the hospital depressed and quiet, and then they leave excited to be with their infants, wanting to share pictures, and talking about hopes and dreams for their family.
Dr Novick: Brexanolone is unique from almost all other drugs we use in PPD, and in psychiatry in general, in that it was developed based on prior biological knowledge of PPD. In psychiatry, we’ve had a tradition of working backwards, ie, “Here’s a drug that seems to work for depression, so what does that tell us about the biology of depression?” With brexanolone, there was data that allopregnanolone seemed to be really important for mood and also data that allopregnanolone levels took a nosedive following delivery. So, it only made sense to start researching the antidepressant potential of giving allopregnanolone in the postpartum period.
The result was a rapid-acting drug that specifically addresses biological factors in PPD — and one of the keywords is “rapid.” We all hate the fact that our depression treatments take so long to work, especially since there’s always the possibility that they may not be effective for any given individual. And even though everyone deserves rapid relief from depression, there’s a particular urgency in the postpartum period.
The sooner we effectively treat PPD, the sooner we have a parent who is back to functioning optimally, and the less time we expose the infant to a depressed caregiver. We know that the longer depression persists, the harder it can be to treat. With brexanolone, not only can you get a really rapid response, but even if it doesn’t work, you haven’t lost the 4-plus weeks that you might have when evaluating the efficacy of traditional treatments.