Raising the Bar: New Progress and Potential in Treating Postpartum Depression

By Sheryl Kingsberg, PhD

Postpartum depression (PPD) is a potentially serious mood disorder that affects approximately one in seven women within the first year after giving birth. As with general depression, the combination of symptoms can be debilitating and even fatal: PPD has been shown to raise the risk of maternal suicide, along with comorbidities including diabetes, hypertension, hyperlipidemia and stroke. The emotional and physical devastation can ripple through a woman’s life, disrupting careers, relationships and family life.

From my perspective as a clinical psychologist and chief of a behavioral medicine division housed within an academic OBGYN department, I’ve been studying, teaching, treating and advocating for women’s health issues for over 30 years. I’ve seen important advances in recent years, despite women’s health concerns being historically underserved for centuries.

Confronting PPD

Postpartum mood disorders fall into three general categories: postpartum blues, postpartum depression and postpartum psychosis. The “baby blues” affects 50% to 80% of women after delivering a newborn, and usually resolves within a week. It is not a diagnosable psychiatric condition, but rather a form of mood lability that is, short-lived, and experienced as exaggerated emotional changes. Women with postpartum blues describe feeling moody or tearful for no discernable reason. A typical lament I’ve heard is “Why am I crying when I feel so happy?”

Postpartum depression (PPD) is a subtype of a major depression and far more serious. It can actually begin during pregnancy (called antepartum depression or perinatal depression), or with onset up to three months afterward. Although PPD can be diagnosed up to a year after giving birth, its onset is typically within those first three months. However, many times the depression goes undiagnosed and untreated. As noted above, 10% to 15% of women experience this mood disorder.

PPD can often present as postpartum anxiety, similar to the anxious thinking and catastrophic worries of obsessive-compulsive disorder. At other times, PPD shows up much more like a typical depressive disorder, with symptoms including anhedonia—the loss of interest in things that once gave pleasure—and avolition, when the motivation to do things drains away. Trouble connecting with the baby or difficulty feeling bonded with one’s baby can lead to sadness, guilt and shame. The disparity between a mother’s hope coming true and the terrible feelings that follow makes no sense to her.

Postpartum psychosis is the third of these disorders, and fortunately it is rare. Only one or two women out of 1,000 get this very distinct disorder. Postpartum psychosis typically develops within the first days or weeks (by four weeks) after giving birth. Women who have a bipolar mood disorder (or past or family history of bipolar disorder) are at higher risk, but others do not have a known history of psychiatric disorders and this is a new onset that may persist into a chronic psychiatric condition. Postpartum psychosis is considered a psychiatric emergency with potential suicide and infanticidal risk. Symptoms may include hallucinations, agitation, unusual behavior, disorganized thoughts and delusions.

While we don’t know exactly what causes postpartum mood disorders, it is likely multifactorial and includes hormonal, genetic, situational, and psychological factors. For some women, the hormonal changes during a pregnancy may predispose them to depression. Many of these women never had a mood disorder before getting pregnant, and they won’t experience another after their postpartum disorder resolves. Some women have already demonstrated a hormonal sensitivity, such as women who have had premenstrual dysphoric disorder (PMDD). Similarly, those women who have had a prior mood or anxiety disorder, may be at a higher risk of a pregnancy or postpartum mood disorder.

Historically, women’s health needs have been underserved, and PPD is a classic example. The result is that women often avoid seeking treatment because the condition is clouded in shame, and they feel like bad mothers or that they will be perceived as bad mothers because of it. Due to a generally low awareness of the causes and prevalence of PPD, some women may not even know their symptoms can be treated. Likewise, many obstetricians, family practice physicians and pediatricians have no specific training in perinatal and postpartum mood disorders. Raising awareness among women and caregivers must be a top priority.

Treating PPD

Cognitive behavior therapy (CBT) has been demonstrated to be effective in treating depressive disorders including PPD. If CBT alone is not sufficient, pharmacologic approaches can be added to CBT or used alone. SSRIs and SNRIs have been used as first-line approaches to treat PPD for decades and have considerable efficacy but do not have a specific indication for PPD. However, more recently, with more focus on the high prevalence and seriousness of PPD, new treatments specifically for PPD have been developed and are in development including brexanolone and zuranolone. Brexanolone and zuranolone are exogenous analogs of allopregnanolone, a metabolite of progresterone, and have been shown to aid with rapidly restoring hormonal balance through positive allosteric modulation of GABA_A. But these are new treatments and their uptake and efficacy is still to be determined.

It’s remarkable how quickly these drugs were identified, when postpartum depression has only recently been classified in diagnostic and statistical manuals. PPD is now officially identified as a unique disorder with a biologic basis, requiring precisely targeted treatments.

To identify PPD, the U.S. Preventive Task Force has recommended that the Edinburgh Postpartum Depression Scale be used as a standard screening test during obstetrician visits. Wearable technologies can also play a part, with some devices able to monitor a woman’s mood, vital signs, and sleep patterns and sound an alert if signs of PPD are detected. These sorts of improved screening tools can help clinicians quantify the problem and start conversations about it with women. But more mental health coverage is necessary to ensure every woman has access to appropriate care. Every clinician should be asking pregnant and postpartum women about PPD, and every woman should feel respected and secure when seeking treatment for it.

Another positive trend is that pharmaceutical companies are becoming more interested in developing PPD treatments, and research is beginning to ramp up. One of the clinical studies I’ve helped design is called RECONNECT. It’s leveraging our newest understanding of psychedelic medicine and exploring its potential in treating psychiatric conditions. We’ve also built in unprecedented safety protocols to protect the study participants. The investigational drug being studied in the RECONNECT program is called RE104, and early signs indicate it has potential to become a first-line treatment for PPD.

RE104 could be a breakthrough treatment because it’s designed to be delivered in one dose. No matter how effective current treatments may be, including CBT, they cannot resolve PPD in one session or dose. Since an RE104 treatment can be completed in an afternoon, there may be few restrictions on breastfeeding based on results from an ongoing lactation study, a common concern with the continued use of some other medications. Other drug options take days or weeks to achieve their full therapeutic effect. If RE104 fulfills its early promise, that agonizing delay is resolved.

Postpartum depression is highly prevalent and can have devastating impacts on women, their babies and their families. Increased attention in the media and in pharmacologic research is improving awareness and access to treatments. We are poised to make additional progress in identifying and treating women who are suffering. Now is the time to get the word out to women and healthcare providers alike.

Sheryl Kingsberg, PhD, is a clinical psychologist and Chief of the Division of Behavioral Medicine in the OBGYN Department at University Hospitals Cleveland Medical Center. She’s also a professor in the Department of Reproductive Biology, Psychiatry and Urology at Case Western Reserve University School of Medicine.