Perinatal Mood and Anxiety Disorders: Redefining Postpartum Depression

Depression is often daunting for patients to go through and for their physicians to treat. About 13% of pregnant women and new mothers have depression, according to the Office on Women’s Health of the US Department of Health & Human Services (HHS).¹

The CDC clarifies that the number of women suffering from postpartum depression varies from state to state and that as many as 1 in 5 women reports the condition.² Even so, the illness is poorly defined.

Lauren M. Osborne, MD, assistant director of the Johns Hopkins Women’s Mood Disorders Center and assistant professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine, is an expert in the diagnosis and treatment of mood and anxiety disorders during pregnancy and postpartum. Her research focuses on the biological pathways that contribute to mental illness during times of reproductive life cycle transition, with an emphasis on the immune system’s role.

“The diagnostic is not well defined; the [Diagnostic and Statistical Manual of Mental Disorders] does not even really acknowledge postpartum depression in this current iteration,” Osborne told MD Magazine^Ò. “They have a specifier that says ‘Major Depressive Disorder With Peripartum Onset,’ but that refers to anything beginning in pregnancy or afterward. We think that people who are depressed in pregnancy and people who are depressed postpartum are in biologically distinct states because there’s a very different biological environment going on during those 2 periods.”

Catherine Birndorf, MD, medical director of The Motherhood Center in New York, New York, and board member of Postpartum Support International (PSI), clinical associate professor of psychiatry and obstetrics/gynecology, and founding director of NewYork-Presbyterian Hospital’s Payne Whitney Women’s Program, believes part of the problem of defining postpartum depression is that “depression” is not what many women feel they experience.

“Many patients say, ‘I do not have postpartum depression because I’m not depressed!’” Birndorf told MD Magazine^Ò. “People get very confused because it’s the only term we have, but they do not feel sad; they feel anxious. So the new term—and we’re really trying to get it out there—is PMADS, perinatal mood and anxiety disorders. It’s a much more inclusive and descriptive acronym.”

“We see more anxiety here than mood disorders,” Sarah Homitsky, MD, a psychiatrist with clinical expertise in perinatal psychiatric services, including postpartum depression, and medical director of the Women’s Perinatal Psychiatry Program at West Penn Hospital, told MD Magazine^Ò.

Homitsky also pointed out that depression is not the only piece of the postpartum puzzle. Her team screens for bipolar illness along with postpartum depression.

Risk Factors for Postpartum Depression

“I think that is important because 60% of the time, a woman who has bipolar disorder could present a positive depression screen and therefore be misdiagnosed; if you are diagnosed with depression but actually have bipolar illness, a medication for depression can sometimes make the symptoms worse,” Homitsky said. “So we screen all women during their initial prenatal visit in their third trimester and then again postpartum for both because that way, we can identify the roughly 20% of women who have bipolar disorder and screened positive in [bipolar screening].”Historically, hormones have been blamed for postpartum depression. During pregnancy, levels of estrogen and progesterone are highly elevated; within 24 hours of childbirth, however, those levels crash down about 1000-fold.

“The problem is, that crash happens to every woman, but not every woman gets postpartum depression. There has been some really interesting work that has clarified that instead, there is a certain group of women who are vulnerable to that change in hormones,” Osborne noted.

Postpartum depression has biological roots, but it is also characterized by psychosocial risk factors.

“It’s an enormous transition from being a free person to being a person with a child,” Osborne said. “The biggest risk factor for developing postpartum depression is depression during pregnancy, but other risk factors are poor social support, high rates of trauma or adverse life events, and lack of sleep.”

People joke about missing sleep all the time, but it is a huge risk factor, Osborne stressed.

New Therapy Options

“One of the things I do clinically is make every pregnant patient come in and bring her partner or some supporter at 36 weeks to create a sleep plan because it has an enormous impact,” she said.Because research has now indicated that some women are more vulnerable than others to the hormonal transition that marks the postpartum period, investigators in this area are attempting to tease out the other biological factors contributing to the illness. Osborne’s work focuses on the immune system and how the hormonal and stress response systems interact with it; other recent work from her colleagues describes the hormonal environment.

“One of the studies that my group did recently was on allopregnanolone, a metabolite of progesterone that is also sometimes called the antianxiety hormone,” Osborne said. “It’s a very calming hormone and has the same effect on the brain as alcohol or benzodiazepines like [lorazepam] and [diazepam]; it attacks the same receptors.”

Osborne noted that results from a 2017 study showed that pregnant women who went on to develop postpartum depression had lower levels of allopregnanolone in early pregnancy. “Every additional nanogram per liter of allopregnanolone reduced the odds of developing postpartum depression by 63%, which is huge,” she said.

Jennifer L. Payne, MD, and Zac A. Kaminsky, PhD, colleagues of Osborne’s, are searching for something in the epigenetic signature of women with postpartum depression that is making them vulnerable.

“They have discovered epigenetic biomarkers that predict the development of postpartum depression with an accuracy of about 82%, and we do not know what these genes really do,” said Osborne. “There’s a different pattern of DNA methylation in these genes in the women who go on to develop postpartum depression, and we’ve now replicated that several times, so that’s a promising avenue.”

Another new treatment that was given Breakthrough Therapy designation by the FDA is brexanolone, which is being developed by Sage Therapeutics. It is an intravenous (IV) infusion that is a synthetic version of allopregnanolone. Initial trials for brexanolone showed a dramatic effect: remission symptoms within 3 days for 70% of the women.

While results from the most recent studies showed that the difference between the placebo and experimental groups was not as statistically significant, investigators like Osborne are hopeful.

“We do not yet know whether it is going to be able to be turned into something reasonable,” Osborne said. “Right now, it requires the woman to stop breast-feeding and have an IV infusion, come into the hospital, and be in a clinical trial. But a lot of us in the field are excited about the possibilities of this drug, if the results hold.

“It’s really the first drug in ages that people have tried specifically for postpartum depression and the first new thing to come along,” she added.

In her work at PSI, Birndorf is focusing on rolling out resources for people providing care to patients with postpartum depression. The PSI education committee is currently creating a frontline training program for any health care professional who treats these patients but is not a specialist in the field.

“In most places in the country, there really are not any specialists in this area,” Birndorf said. “The program is called Expert Provider Training in Perinatal Mood and Anxiety Disorders, and it is 5 different hour-long webinars of training, or there is a 1-day live version. Each includes everything from what is PMADS and how to screen for it to psychotropic medications during the perinatal period.”

Birndorf also wants to expand the ways in which professionals in the field can assist one another day to day. She noted another project she is helping to develop, a national consultation service.

Medication and Moms

“This is going to be provider to provider across state lines—no patient care, no money exchanged, just giving advice,” she said. “It’s not about a specific patient; it’s education for people who are far away from experts in the field and need expert advice on prescribing and other issues.”One of the challenges of treating postpartum depression is that many pregnant women are reluctant to take any medication and feel they should grin and bear feelings of depression rather than put their babies at risk. However, experts say that this is a misconception of the actual risks.

“The reality is, we know that untreated depression and anxiety in pregnancy can actually affect the baby,” Osborne said. “Untreated depression and anxiety are associated with preterm birth, a higher rate of miscarriage, and deleterious effects on the baby, such as higher rates of depression, anxiety, and attention problems in that child eventually.”

“If you do not treat the depression, there’s a risk of untreated illness,” Birndorf noted. “And it hurts the fetal environment because the baby is bathing in cortisol because you’re so depressed or anxious. That’s also not good for a developing person.”

Treating depression with medication during pregnancy has a great track record for safety—but getting this across to patients is not always easy.

“There is a huge amount of literature available, and most of it is incredibly reassuring that antidepressants are extremely safe drugs to take in pregnancy,” Osborne said. “If you have a woman who you know is at high risk and who has severe depression, it makes sense to treat that depression in pregnancy. Remember, the biggest risk factor for postpartum depression is depression in pregnancy.”

Another common problem that Osborne and Birndorf see regularly is undertreatment in women for their depression because they are pregnant.

The Direction for the Future

“I think that’s largely because doctors believe they should give pregnant patients a lower dose, when in fact what we know about the pregnant body is that it metabolizes the drugs at a higher rate,” noted Osborne. “So actually the effective dose that the mom is getting even if she stays at the same dose is going to be lower by the end of pregnancy.”Despite the impressive progress being made in the treatment of postpartum depression, notable challenges remain for every doctor involved. Lack of access to care and insurance is one.

“Access to care is a challenge for every mental health clinic,” said Homitsky. “We are diligently thinking of ways to provide care to people who have a barrage of barriers, whether those are a lack of insurance, a lack of transportation, or multiple other children, and I think a big part of the whole treatment in the future will be figuring out how to bring the care to patients instead of having them have to conform to the traditional outpatient setting.”

Osborne noted that the most important facet of postpartum depression is that it is a treatable condition, despite its high prevalence.

“Even so, it’s misunderstood, mistreated, and misdiagnosed,” she said. “Health care professionals should be asking women in postpartum questions in a nonjudgmental way to see how they’re feeling because if you do not catch it—if you do not diagnose and treat it—it affects not only that mom but also that child, the next generation. Then it affects that generation’s risk for passing something on to their kids.

“If we’re not aware of it and do not look for it, we’re not going to find it,” she added.

Birndorf also feels strongly about simply taking the time to look for the problem and reaching out for help from other health care professionals if needed.

“I think most important, we can recognize it if we ask women, if we look them in the eye and hold their gaze and ask them how they’re doing,” Birndorf added. “I mean, it’s not that hard to diagnose. But the reason people do not always ask is they do not know what to do with it or where to send people for treatment because there’s a dearth of treatment options out there.”

REFERENCES:

1. How common is depression during and after pregnancy? Office on Women’s Health website. womenshealth.gov/a-z-topics/depression-during-and-after-pregnancy. Updated June 12, 2017. Accessed January 20, 2018.

2. Depression among women. CDC website. cdc.gov/reproductivehealth/depression/index.htm. Updated December 13, 2017. Accessed January 20, 2018.