Postpartum depression is bordering on crisis, affecting three out of every 20 new mothers and contributing to mounting maternal deaths. Now, a new drug treatment could provide critical — even life-saving — relief within days.
Danielle Achrol always wanted to become a mother. She and her husband wanted to have several children, but after four miscarriages and, at the age of 40, a failed round of in vitro fertilization, she gave up on her dream of motherhood. “I thought, it’s just not happening for me,” she says. Then, seemingly out of nowhere, Danielle and her husband conceived. She feared losing the pregnancy due to what she describes as PTSD around infertility, but everything was normal. “Once we reached a point in the pregnancy when the fear went away, we thought, ‘Finally it’s our time to create a family.’”
Her daughter, Elakshi, had a healthy birth, and the moment that Danielle had waited for with so much anticipation finally arrived as her baby was laid against her chest. She expected to have “that rainbow baby feeling, to melt, to feel so in love, to have so many emotions. But,” Danielle says, “I quickly realized that I felt none of that.”
That realization created a new type of anxiety: “Why am I not enjoying this? Why is there not an overwhelming happiness?”
Over the next several weeks, Danielle was crippled by feelings of regret. “I felt like I had made a horrible mistake; it was wrong that I had her. It was all too overwhelming.” She sometimes avoided even being around her baby; she blamed hormones and sleep deprivation. “This is all going to go away,” she thought. But instead, it continued to get worse. Danielle was barely eating or sleeping. And while she wasn’t capable of caring for her daughter, she also couldn’t stand to be away from her. “It made me feel terrible, ungrateful and completely like a failure as a mother.”
Worse, Danielle started to feel hopeless. “That was very scary — to go that long feeling not like myself, and there was no light at the end of the tunnel. I thought, ‘I’m trapped and I’m never going to get better.’”
Danielle’s husband, Achal, who is a physician, saw her suffering — crying often, confessing to feeling like a failure, not eating or sleeping nearly enough — and recognized the signs of postpartum depression (PPD). While researching more about the condition he learned about Misty C. Richards, MD (RES ’15, FEL ’17), MS, a psychiatrist at UCLA Health with a particular interest in perinatal mental health, and reached out to her for help. Following medical treatment and therapy, Danielle did get better. Today, she and her baby are healthy and happy. “I’m 100% myself again,” she says.
Dr. Richards runs the Maternal Outpatient Mental Health Services (MOMS) clinic, which she describes as a psychiatric urgent care for perinatal women. The PPD Danielle was experiencing features the classic symptoms of depression — sadness, lack of energy, helplessness — but “with anxiety and agitation layered on. There’s a sense of urgency, a fear response when you have a baby,” Dr. Richards says.
Postpartum depression is not rare. It affects up to 15% of women who give birth, and, according to the U.S. Centers for Disease Control and Prevention (CDC), the diagnosis of PPD has skyrocketed, increasing seven-fold between 2000 and 2015. Further contributing to the rise in California is a 2019 state law requiring obstetricians to screen pregnant patients for mental health. Indeed, the rising PPD rates may, in part, be a result of ascertainment bias — more individuals now are identified because providers are more aware of the diagnosis.
Although Danielle knew about postpartum depression, it never occurred to her that’s what she was experiencing. “In my mind, postpartum depression means you want to hurt your baby — which I never, never, ever did!” she says. Nor did she want to harm herself. “I didn’t really know what it entails. I thought I was broken, that something was wrong with me.”
Danielle’s understanding — or misunderstanding — of PPD is not unusual; many people when they hear the term postpartum depression envision a mother bringing harm, or even death, to her child or herself. While such extreme incidents garner headlines, that outcome is rare.
Nevertheless, “there are real dangers, including loss of life,” says Catherine Monk, PhD, the Diana Vagelos Professor of Women’s Mental Health in the Department of Obstetrics and Gynecology and founder of the Perinatal Pathways Laboratory at Columbia University in New York. Even as maternal mortality across the globe dropped by nearly 40% between 2000 and 2017, that same measure increased by more than 25% in the United States, to the highest rate among developed countries.
Maternal deaths from physical causes such as hemorrhage and sepsis have been well studied, and they are in decline. Research on mental illness around pregnancy, though, is lacking. A 2019 review paper led by Dr. Monk “showed mental health as a leading cause of our very high rate of maternal mortality,” she says. Many of those deaths result from “what we call self-harm deaths, where there’s clear evidence of suicide or death by overdose, which can be an intentional or unintentional suicide.” A study released by the CDC in May 2024 found that mental health conditions were the No. 1 cause of pregnancy-related deaths in the U.S.
Just as for major depression, the first-line treatment for PPD includes psychotherapy and anti-depressant medication, typically a selective serotonin reuptake inhibitor, or SSRI, which is effective for about half of patients and, along with therapy, can take several weeks to work. But getting a diagnosis and a prescription was so validating, “it was like night and day,” says Danielle. “It was, ‘Now I know why I’m feeling this way, and there’s something to make it better.’”
“We’re in a crisis, with rising maternal mortality, morbidity, suicide. A contributing factor is the lack of access to care. It’s a huge problem in the field, resting on the shoulders of a broken health care system. But what can we do about it? ... Collaborative care models are the future.”
Dr. Misty C. Richards
It did take three weeks for the medication to work and for Danielle to start to feel like herself again, and several months later she is treasuring her time with her daughter. “I feel more and more happy that I have her, and more looking forward to all the things I’m going to do with her,” she says.
Danielle wishes she could reclaim those lost weeks with her newborn daughter as her healthy self. Today, women diagnosed with postpartum depression have access to new medications that can deliver that relief more quickly.
In August 2023, the U.S. Food and Drug Administration approved a drug called zuranolone that, taken as a single daily pill for two weeks, works in just days. A study published in the American Journal of Psychiatry found that symptoms can improve after just three days, with positive effects most often seen after nine days of adherence.
That fast action could be a game-changer for treating postpartum depression, Dr. Richards says. Early studies estimate that the new medicine is effective in about 50% of patients, giving it a slight edge over SSRIs, but “you have to wait a long time for SSRIs to work, really four-to-six weeks. If someone is in crisis and sees a provider at two weeks postpartum, you can give them an SSRI, but you have to tell them to hang on real tight for the next month. The beauty of this new medication is that it works pretty quickly. It’s as effective, if not more effective, as an SSRI, but it’s faster,” Dr. Richards says.
“Once [postpartum depression is] identified, we want to address and tackle the problem quickly. It makes a difference not just for mom, but also for baby. We know babies do better when they have ongoing good maternal care ... and to establish that, you have to have a mother who is available.”
Dr. Vivien K. Burt
While zuranolone on its face “looks very interesting and exciting,” what’s “great” about it, says Vivien K. Burt, MD, PhD, professor emeritus of psychiatry and biobehavioral sciences at UCLA, is that it may, according to the data, have lasting effects. In the study, six weeks after starting treatment (and a month after stopping treatment), participants’ symptoms were still improved.
On the flip side, little is known about the medication’s longer-term effects. The drug appears safe (its main side effects were sleepiness and dizziness), but further studies will be needed to establish how the drug is transmitted to babies via breastmilk, and whether or not it could be addictive. Biologically, Dr. Richards says, “this is similar, though not identical, to how benzos work,” referring to benzodiazepines, an addictive class of anti-anxiety medications. “So, could it [also] have addictive potential?”
Zuranolone is the first pill, but not the first medication, approved specifically for PPD. In a small clinical trial, brexanalone, which works in a similar fashion to zuranolone, dramatically decreased severe PPD symptoms in four women. But that drug has to be delivered intravenously over 60 hours, requires a hospital stay and costs $34,000. “It was impractical,” Dr. Richards says. “There was no possible way that we could justify this in our patient population, so it fell flat, frankly.”
Zuranolone may turn out to be effective for other types of depression, too. “There are a lot of eyes on this medication,” Dr. Richards says. Because it’s not an SSRI, “it’s working on depression through a completely new mechanism. This is going to be a big deal.”
The new drug represents a change in thinking about how depression arises in the brain, says Kimberly A. Yonkers, PhD, a neuroscientist at the University of Massachusetts Chan Medical School. “There’s the old serotonin sensitivity-deficit theory, where it was thought that the signaling or amount of serotonin was abnormal.” Serotonin is a neurotransmitter in the brain long associated with mood. But decades of research and drug development based on that theory have yielded little progress in new treatments or understanding of depression. “Inflammation is really having a renaissance these days,” Dr. Yonkers says, referring to the theory that immune cells and molecules play a role in depression. “And now we have the neurosteroid hypothesis, which is far more complex.”
Neurosteroid hormones are fatty molecules that can transmit signals between cells in the body. Zuranolone acts by mimicking a hormone called allopregnanolone, which has a key role in pregnancy. Allopregnanolone protects the fetal brain from dangerous levels of stress hormones circulating in the maternal body. It also prevents secretion of oxytocin, a hormone that stimulates lactation and uterine contractions, which can lead to premature birth. But at birth, that protection is no longer needed. So, after building throughout pregnancy, allopregnanolone levels plummet. “Hormones spike in the third trimester, and then within 72 hours of birth, they fall to pre-pregnancy levels,” Dr. Richards says. That drop, which occurs in everyone, combines with stress and exhaustion to cause the baby blues. “Moms are anxious, not sleeping. This is why 80% of moms experience postpartum blues. It’s not mythology.”
According to the neurosteroid hypothesis, fluctuations in allopregnanolone may cause depression and anxiety through the hormone’s effects not on the body but in the brain. GABA, or gamma-amino butyric acid, is the brain’s major inhibitory neurotransmitter. Wherever GABA is released, it puts the brakes on neural activity. Most anxiolytic, or anti-anxiety, medications work by altering GABA activity. Allopregnanolone adjusts the sensitivity of GABA’s receptors, tiny proteins found on nerve cells that, when activated, dial down the neuron’s activity. Zuranolone works by mimicking allogpregnanolone’s effects on GABA receptors.
Columbia’s Dr. Monk says “this new, fast-acting drug is exciting because it’s a new biological target leveraging our knowledge of hormones. And it’s very exciting to see a new medication for what is predominantly a women’s problem. But the root of the nationwide crisis is not a lack of tools and treatment, she says. “The problem is a lack of care. We have the tools; it’s that we can’t get people into treatment.”
Even with the weeks she lost to her depression, Danielle’s is a success story. It is far more common that women have difficulty getting access to treatment for postpartum depression. “We’re in a crisis, with rising maternal mortality, morbidity, suicide,” Dr. Richards says. “A contributing factor is the lack of access to care.” Too many women are faced with scant options, such as weeks-long wait times for private mental health providers that don’t take insurance and charge exorbitant rates — and even those are few and far between, she says. “It’s a huge problem in the field, resting on the shoulders of a broken health care system. But what can we do about it?”
From a policy level, achieving “genuine parity between physical and mental health treatment so that reimbursement rates to mental health providers are reasonable” would be a good place to start, Dr. Monk says. Implementing programs like loan forgiveness for providers who see patients for mental health treatment and thereby broadening acceptance of commercial and Medicaid insurance “would go a long way toward attracting and maintaining more mental health providers in the workforce who take insurance.”
At UCLA, Dr. Richards’ response was to create the MOMS clinic. Demand has been high since the clinic opened in 2019. “Usually a new clinic will open with a slow ramp-up, but we were never slow,” Dr. Richards says. “There’s always been a wave of patients in need.”
MOMS offers care to women in crisis when other providers are not available. “We’re a psychiatric urgent care, a bridge clinic,” she explains. “The idea is to see women as quickly as possible,” particularly if they’re suicidal, and then refer them to a community provider after they’re stabilized. The MOMS clinic frequently refers patients to both the UCLA Women’s Life Center for ongoing outpatient psychiatric perinatal care, and the partial hospitalization program, an intensive outpatient treatment program for people with severe depression or psychosis that allows moms to stay out of the hospital.
Despite the recent increase in diagnosis of PPD, the problem is not new, says Dr. Burt, who established the Women’s Life Center at UCLA 30 years ago for women who need ongoing care. “We really needed something for women going through the psychiatric challenges during reproductive life transitions. It’s really a very vulnerable time for all women, even those with no history of anxiety or mood disorders, and certainly for women with a history of mood disorder.”
Dr. Burt says prompt medical treatment is key, particularly for women in crisis. “But at the same time, we generally emphasize the importance of psychotherapy.” New moms, Dr. Burt says, “are challenged in so many ways, so psychotherapeutic support is incredibly important.”
The stakes are high if postpartum depression is left untreated, Dr. Burt says. “Once identified, we want to address and tackle the problem quickly. It makes a difference not just for mom, but also for baby. We know babies do better when they have ongoing good maternal care: bonding, skin to skin connections. And to establish that, you have to have a mother who is available.” And while mothers with depression “want to be available, they’re not capable.”
Research has shown that mothers’ dampened responses to their babies may contribute to poor infant emotional development, says Michelle G. Craske, PhD, Distinguished Professor of Psychology and of Psychiatry and Biobehavioral Sciences, Kevin Love Fund Centennial Chair and director of the UCLA Anxiety and Depression Research Center. But that can be difficult to talk about with a depressed mom. “This is a sensitive area,” Dr. Craske says. “Women who are depressed and have a baby — the last thing they want to feel is guilt or shame” about any harm they may be causing their child.
Research also has revealed clear risk factors that can help predict who will develop postpartum depression. Women with a prior history of mental illness and depression are at double the risk for PPD compared with women with none. Not surprisingly, a lack of partner or family support and financial insecurity also increase the chances a woman will suffer with postpartum depression. And the risk for PPD also appears to increase with Cesarean section birth.
Could pre-treatment, with either therapy or medication, prevent PPD for those at high risk? “One thing we don’t know is, what about prophylaxis?” Dr. Burt says. “We believe it’s those vicissitudes, those changes in hormones for vulnerable women who are otherwise predisposed to anxiety or depression,” that trigger depression. “If you watch them, you can catch it quite quickly.”
That’s the goal, says Dr. Monk, who runs a program at Columbia called PREPP, for Practical Resources for Effective Postpartum Parenting, a brief intervention to promote skills and well-being to prevent PPD. Dr. Monk and colleagues are researching the best approaches, she says, “to bring in psychological awareness and support to the whole transition to parenthood experience.”
Part of the solution will come from a team-based approach to health care. “Collaborative care models are the future,” Dr. Richards says. Obstetricians, she notes, do not have adequate time to treat mental health. “They already have so much on their plate, and we cannot possibly train enough reproductive mental health providers” to meet demand, she says.
While many obstacles remain, access to care has improved in the wake of the COVID-19 pandemic, thanks in large part to the expansion of telehealth. “Having the virtual clinic has been a game changer in the best ways,” making it much easier for new moms to be seen at home, Dr. Richards says. As an added bonus, “we get to see them in their home element; it’s like a simulation of a home visit, which has been so clinically helpful.”
That is an approach that Dr. Craske is exploring further with a program of care called STAND, for Screening and Treatment for Anxiety and Depression. “We are testing a model of care that heavily relies on digital therapy, because that’s more accessible to women who are home with a baby,” she says. Women in the study with moderate-to-severe depression were randomly assigned to the STAND care model or to standard treatment. In the STAND arm, moderately depressed women met remotely with coaches who supported their understanding and application of cognitive and behavioral skills that were delivered digitally. Women with severe depression received individual psychological therapy from a clinician, whereas all women (moderately or severely depressed) were seen by psychiatrists in the standard treatment condition. “We’re testing to see if digital therapy is as effective as in-person care” for moderate depression, Dr. Craske says. The hope is that “digital therapy will work for those who are not in extreme distress, and it’s particularly suited for women with newborns, because they can’t come into the clinic.”
Dr. Craske’s STAND study is just one of several research projects on postpartum depression that are part of UCLA’s Depression Grand Challenge, a university-wide initiative bringing together the diverse expertise of UCLA with the stated goal “to cut the global burden of depression on health and well-being in half by 2050.”
The Depression Grand Challenge stands upon four pillars, explains Dr. Craske, who, with Nelson Freimer, MD, the Maggie G. Gilbert Endowed Chair and Distinguished Professor of Psychiatry and Human Genetics, and Jonathan Flint, MD, the Billy and Audrey Wilder Endowed Chair in Psychiatry and Neuroscience, is co-director of the initiative. “One pillar is looking at the causes and trajectories — the genetic and environmental factors that contribute to depression. Another is neuroscience discovery; one is how to develop new treatments and make them more available. And the fourth pillar is about reducing stigma and raising hope and awareness,” she explains.
Ultimately, say Dr. Burt and others, that fourth pillar is key to reducing suffering. A greater awareness of postpartum depression — and less stigma — can help people recognize it, talk about it and get help. Women with postpartum depression, like Danielle, “have internalized all these emotions,” Dr. Burt says. “They’re feeling completely inadequate. They often can’t breastfeed. They feel like they’re not good mothers. It is on us to change that.”
Stephani Sutherland is a neuroscientist and science journalist whose work has been published in New Scientist, Scientific American, the Los Angeles Times and BrainFacts.org.
For information about the UCLA MOMS clinic, go here.
