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--:-- Sean Rameswaram: Hi, this is Karen Kurdoff calling from Salt Lake City, Utah.
--:-- Karen Kurdoff: Having a baby is hard enough, but for a lot of people, things can get even tougher after birth. I had my first child back in January and experienced postpartum depression. My doctor was willing to prescribe me medication, but I didn't feel comfortable going on medication without having counseling or supervision. That was granted short-term disability, but it was really hard to get that extended. And on top of that, I was just isolated by myself.
--:-- Sean Rameswaram: But now, for the first time ever, there's a pill to treat postpartum depression. I think a new medication to directly deal with postpartum effects would be awesome. We're going to figure out if this pill is going to be a game changer on Today Explained.
--:-- Karen Kurdoff: I think it's awesome you're doing a show about postpartum depression, And I just hope that it encourages anybody out there that's suffering.
--:-- Sean Rameswaram: Support for Today Explained comes from Adio. Adio is an AI-native customer relationship management platform that Adio says is built for the next era of companies.
--:-- Karen Kurdoff: Adio is an AI-native customer relationship management platform that Adio says is built for the next era of companies. A powerful data structure adapts to your business model, sinks in all your contacts in minutes, and enriches your business with actionable data. Adio says it also allows you to create those email sequences, those real-time reports, those powerful automations, which they claim can help you build what matters most, your company.
--:-- Sean Rameswaram: You can go to adio.com slash todayexplained to get 15% off your first year. That's A-T-T-I-O dot com slash todayexplained.
--:-- Karen Kurdoff: Support for this show comes from Macy's. Layering is an art form. All it takes is a bit of intention, style, and, of course, the perfect cold-weather staples. So find the perfect look for you with the help of Macy's Fall Fashion Guide, your one-stop shop for fall's latest trends and must-haves, curated by their experts.
--:-- Sean Rameswaram: When you want to talk about postpartum depression, you want to talk to Dr. Nancy Byatt.
--:-- Dr. Nancy Byatt: I'm a professor with tenure of psychiatry at UMass Chan Medical School. And I'm a psychiatrist that focuses on working with pregnant and postpartum individuals. And I direct a center here at UMass Chan Medical School called Lifeline for Families.
--:-- Sean Rameswaram: And there's an exciting new medication that was just approved by the FDA called xeranolone. Zoranilone. Zoranilone is exciting because it works quickly. Most of the medications that we have available, in fact, all of the medications we have available that someone can take by mouth, take quite a lot of time to work.
--:-- Dr. Nancy Byatt: So typically, the available antidepressants that we have that we use for pregnant and postpartum individuals that people can take by mouth, take several weeks to work, often four to six weeks. And Zoranilone. Zoranilone. It's exciting because people get better within three days. Those improvement in depression symptoms are sustained at 15 days and then also at 45 days.
--:-- Sean Rameswaram: And it's also the first medication that people can take by mouth that's specifically approved for postpartum depression. But presumably postpartum depression's been around for a minute. What took so long?
--:-- Dr. Nancy Byatt: I think there's a few things as to why we're seeing this now. So one, there has been an evolution in the recognition of women's health care in general, where many of the research over the years and studies and evidence-based protocols were more based on men than on women historically.
--:-- Sean Rameswaram: What is misogyny?
--:-- Dr. Nancy Byatt: And so research that specifically includes women is more recent. And research focused on the perinatal time period, and when I use that term, I'm referring to pregnancy and the year postpartum, is also more recent.
--:-- Sean Rameswaram: So we've had an evolution and want to focus on general women's health, and specifically we've had more focus on women's mental health, And also within that, we've had an increased focus on perinatal mental health, so that pregnancy and the postpartum period.
--:-- Dr. Nancy Byatt: And then along with that, we've had novel treatments like this that, you know, are recognizing that women's physiology is different during pregnancy and the postpartum period, both for obstetric care, but also for mental health care.
--:-- Sean Rameswaram: Mental health and substance use disorders that occur during pregnancy and the year postpartum are actually the leading cause of maternal mortality in the united states so the leading cause of pregnancy related deaths and that includes things beyond depression but depression is including among those illnesses that are of the leading causes of maternal mortality 23 percent of deaths in the united states are due to mental health and substance use disorders during the perinatal time period.
--:-- Dr. Nancy Byatt: And we also know that these illnesses are very common. One in seven individuals will experience depression. And when we think about mood and anxiety disorders together, that's as many as one in five.
--:-- Sean Rameswaram: So these illnesses are common. We know that women are dying. And we also know they have a negative impact on the individuals themselves that are experiencing this and also their families. They've been linked with negative outcomes for the baby, negative outcomes for kids later on, and also negative obstetric outcomes.
--:-- Dr. Nancy Byatt: What do we know about postpartum depression in terms of how it differs from your regular run-of-the-mill depression?
--:-- Sean Rameswaram: When we think about the perineal time, this is a few things that are happening that are different during this time period than other time periods in people's lives.
--:-- Dr. Nancy Byatt: So one, there's a physiological changes. So during pregnancy, we see a surge in hormones. They continue to increase throughout pregnancy, and there's a quick drop in the postpartum period. So that's physiologically very different. And this is why we think that there is increased risk of mood anxiety disorders during this time period because many women are sensitive to those hormonal fluctuations that can increase the risk of mood or anxiety disorders or symptoms.
--:-- Sean Rameswaram: I also want to make a note that I'm saying women, sometimes I say peringal individuals, not all people that are pregnant or postpartum identify as women so I sort of use those terms interchangeably just to note that and so that's one piece is that physiologically things are different.
--:-- Dr. Nancy Byatt: The other piece is that it's an extraordinarily challenging time period because of what's going on from a psychosocial perspective. So during the parental time period, transitioning to being a parent is a huge transition and it rocks a relationship it rocks a family and it can really cause a lot of challenges psychosocially
--:-- Sean Rameswaram: And when we think about this from a trauma perspective many of us have experienced trauma and experienced adversity And a lot of times that related to the relationships that we had
--:-- Dr. Nancy Byatt: When we've experienced adversity and trauma, those things tend to come up more so when we are all of a sudden a parent because now we have a baby we have to take care of. And any of our own unmet needs when we're younger tend to come more to the surface during the parental time period.
--:-- Sean Rameswaram: So when we think about it from that perspective, that's one of the big differences. And I'd say the other big difference is that the process of becoming pregnant, delivering, and having a baby is challenging from a perspective of if someone has a history of trauma, you know, the delivery itself can often be traumatic for people.
--:-- Dr. Nancy Byatt: Interactions with the healthcare system can be traumatic. So those other pieces, and physiologically, depending on what kind of birth somebody has, there can be physical injuries from that. And so those pieces that are happening too that sort of culminate in this being a really challenging time period for people that is often more challenging than other times in people's lives.
--:-- Sean Rameswaram: Prior to this, what sounds like game-changing pill, Zoranolone, how was a professional like yourself typically treating someone with postpartum depression?
--:-- Dr. Nancy Byatt: The mainstay of treatment for mild to moderate depression, first-line treatment is psychotherapy. So we have evidence-based psychotherapies that work. We'll continue to use those. We also have an evidence base for psychosocial treatments. So those are often a mainstay of treatment.
--:-- Sean Rameswaram: If someone has more severe depression or depression that medications indicated, we were typically using antidepressants. The challenge with those, as I noted earlier, is that they often take weeks to work.
--:-- Dr. Nancy Byatt: They typically take four to six weeks to work. And when someone's pregnant or postpartum, time is of the essence. And four to six weeks is a really long time to wait when someone's postpartum, when they have a baby, and they're already in this extraordinarily challenging time period.
--:-- Sean Rameswaram: There is a medication called brexanolone that was recently became available and FDA approved that is similar to ziranolone. The difference is brexanolone is an IV medication that requires an IV infusion and also requires monitoring.
--:-- Dr. Nancy Byatt: And so while it works really quickly, similar to the way xeranolone does, implementing that was challenging because one needs to be monitored for a few days, often in a hospital setting, which is challenging. And then they're separated from their baby and so forth.
--:-- Sean Rameswaram: So the great thing about xeranolone is it's a by-mouth medication that is going to be, I think, much easier to access from a logistical perspective than brixenolone was.
--:-- Dr. Nancy Byatt: What's different about this treatment, this pill, other than the fact that it's a pill? What exactly is it doing to the brain of someone with postpartum that's a game changer?
--:-- Sean Rameswaram: The way it works is that when people are pregnant or postpartum, you know, we have an increase in hormone start pregnancy and then a decrease postpartum. One of those hormones is allopregnenolone. Allopregnenolone increases in pregnancy, decreases in postpartum. xeranolone is a neuroactive steroid that really aims to balance out those levels in the system.
--:-- Dr. Nancy Byatt: So we know that allopregnenolone interacts with pathways in our brain that regulate our emotions. They can regulate our mood. They can regulate whether we experience anxiety symptoms. And what xeranolone does is it interacts with those pathways in the brain to balance that out. Really balancing out that decrease in hormones that we see in the postpartum period.
--:-- Sean Rameswaram: How available will xeranolone be?
--:-- Dr. Nancy Byatt: So that is a major question and an excellent question. I hope it's going to be available. One of the big challenges and what tempers my enthusiasm for xeranolone is that it will be effective and helpful to the extent that people can access it.
--:-- Sean Rameswaram: It's great. We're going to have a medication that decreases symptoms within a few days. However, to give our state as an example, in Massachusetts, if someone has public health insurance, it can take three to six months to see a psychiatrist.
--:-- Dr. Nancy Byatt: So it's great if we have medication that works quickly. Along with that, we need to have access to available treatment. And also some of our work, we found that without a system in place, even if somebody screens positive for depression in the perinatal time period, less than a quarter of those individuals will get even to an initial mental health appointment.
--:-- Sean Rameswaram: Great, we have a new medication, but if only a quarter of people are able to get to an initial appointment, then its impact becomes much more limited.
--:-- Dr. Nancy Byatt: I would also add that when we think about, you know, the perennial time period, there's multiple barriers to care that people experience. So I mentioned that, you know, less than a quarter of people get to an appointment, even if they screen positive. And we see that there are major inequities by race, by socioeconomic situation, by what insurance people have.
--:-- Sean Rameswaram: And, you know, when we think about the increase in mortality rates we have in America, much of the reasons that many of us believe that those are there is because of these challenges with access.
--:-- Dr. Nancy Byatt: And, you know, we know that there's disparities in the rates of maternal mortality. So great, we have a game-changing pill. We have to be paralleling these novel, really exciting, rapid-acting treatments with work that focuses on increasing access to these treatments, and that also focuses on doing that in a way that's equitable and doing that in a way that, people can actually access these treatments that we have available because right now that's not the case.
--:-- Sean Rameswaram: And so whenever I'm thinking about xaranolone, it's not a panacea because we need to accompany it by all these other things. And also medication treatment is one piece. When we think about paranormal health care, we have a lot of evidence-based treatment options if medications are one of them.
--:-- Dr. Nancy Byatt: So there's very clear evidence that the treatment for depression is best when it's, you know, medication treatment combined with psychotherapy and other psychosocial treatments. So along with having rapid acting treatments like xeranolone, we also need to be focusing on increasing access to other treatments that we know are really important and are often the first line when we're thinking about, you know, mild to moderate depression.
--:-- Sean Rameswaram: Dr. Nancy Byatt is a professor of psychiatry with tenure at UMass Chan Medical School.
--:-- Sean Rameswaram: I Sean Ramos and when we back on Today Explained we going to hear an argument that you and I are currently living in a golden age of medicine support for today show comes from adio what is adio adio is an ai native customer relationship management system built specifically for the next era of companies.
--:-- Sean Rameswaram: They say it's extremely powerful, adapts to your unique data structures and scales with any business model. According to Adio, Adio takes less than a minute to set up, and within seconds you will have your email and calendars synced.
--:-- Sean Rameswaram: You'll see all your relationships in a fully-fledged platform, they say, all enriched with that actionable data. And they say you can build AI-powered automations and use its research agent to tackle some of your most complex processes to seize so that you can focus on what matters, building your company.
--:-- Sean Rameswaram: You can join industry leaders such as Flatfile, Replicate, Modal, and so much more. You can go to adio.com slash todayexplained to get 15% off your first year. That's A-T-T-I-O dot com slash todayexplained.
--:-- Sean Rameswaram: Let's be honest. Are you happy with your job? Like, really happy?
--:-- Sean Rameswaram: The unfortunate fact is that a huge number of people can't say yes to that. Far too many of us are stuck in a job we've outgrown, or one we never wanted in the first place.
--:-- Sean Rameswaram: But still, we stick it out. And we give reasons like, what if the next move is even worse? I've already put years into this place. And maybe the most common one, isn't everyone kind of miserable at work?
--:-- Sean Rameswaram: But there's a difference between reasons for staying and excuses for not leaving. It's time to get unstuck. It's time for Strawberry.me. They match you with a certified career coach who helps you go from where you are to where you actually want to be.
--:-- Sean Rameswaram: Your coach helps you get clear on your goals, create a plan, build your confidence, and keeps you accountable along the way. So don't leave your career to chance. Take action and own your future with a professional coach in your corner.
--:-- Sean Rameswaram: Go to strawberry.me slash unstuck to claim a special offer. That's strawberry.me slash unstuck.
--:-- Sean Rameswaram: Today Explained. I'm David Wallace-Wells.
--:-- David Wallace-Wells: I'm a writer for the New York Times Opinion section and a columnist for the New York Times Magazine.
--:-- Sean Rameswaram: And David, we just got news about the first ever pill to treat postpartum depression. And you recently wrote for The New York Times that we might be living in a golden age of medicine. Why did you write that?
--:-- David Wallace-Wells: Well, just over the last couple of years, especially in the aftermath of the pandemic and the incredible, I think, miraculous development of the COVID vaccines, we've seen a huge wave of new treatments and therapies either come online or begin clinical trials.
--:-- Sean Rameswaram: 12 countries in Africa are to receive 18 million doses of the malaria vaccine over the next two years.
--:-- David Wallace-Wells: The CRISPR technology allows scientists to make changes to the DNA in cells that could allow us to cure genetic disease.
--:-- Sean Rameswaram: All together, they don't represent the end of disease or anything like that. But it seemed to me like a watershed, sort of phase shift moment in a lot of different areas of medicine.
--:-- David Wallace-Wells: And each drug, each therapy on its own seemed impressive and exciting, but altogether it felt like a whole new horizon of treatment possibility was opening up that most Americans, I think, just haven't yet begun to appreciate.
--:-- Sean Rameswaram: I do think it's worth pausing for a second on just how incredible the COVID vaccines are.
--:-- David Wallace-Wells: I think in part because we experienced them in such a time of panic and desperation, in part because the uptake was so politicized, the rollout was politicized. I think most Americans don't appreciate just how completely unprecedented a biomedical innovation this really was.
--:-- Sean Rameswaram: Today, our nation has achieved a medical miracle. We have delivered a safe and effective vaccine in just nine months.
--:-- David Wallace-Wells: So within two days of the time that the virus's genome was posted publicly, within two days, Moderna had designed an mRNA vaccine to fight it. And that is the mRNA vaccine that we, most of us, got in America. Within two days.
--:-- Sean Rameswaram: Designed it in two days, had it manufactured in the space of a couple of months. You know, most vaccines, as we were told at the beginning of the pandemic, take at least a decade to produce.
--:-- David Wallace-Wells: Even the most impressive drug development stories of the last few decades are on that sort of five to 10 year timescale. And this was we're talking about literally just a few months before it was going into people's arms.
--:-- Sean Rameswaram: So we're talking about an astonishing medical miracle that most of us treated as like the workaday development of public health and medicine.
--:-- David Wallace-Wells: We're just like, OK, the vaccines are here and now we'll take it. But one of the incredible side effects of mRNA COVID vaccines is that because they worked so effectively, they then brought into the sphere of possibility all of these other potential mRNA applications.
--:-- Sean Rameswaram: So now we're testing it to treat a whole raft of other diseases, which are whole new potential applications for this platform.
--:-- David Wallace-Wells: Thinking about using Ozempic not just to treat weight loss, but to treat cardiac events, which it seems that they're reducing that by 20 percent. Or we're talking about immunotherapy and cancer.
--:-- Sean Rameswaram: This is not something we're just using in one area, but really across the board. And that's what's so exciting is that we're not just dealing with individual drugs. We're dealing with a whole new toolbox, each of which may ultimately be used in not just one application, but in many, many applications.
--:-- David Wallace-Wells: With stuff like a potential cancer vaccine, though, who will realistically have access to those treatments and technologies first?
--:-- Sean Rameswaram: Well, you know, when I think about the sort of equity and justice aspects of these new drug developments, I think primarily in terms of the global picture, which is to say, I worry a lot more about the billions of people in the global South who almost none of whom will have access to these drugs than I do about Americans.
--:-- David Wallace-Wells: Because while we live in a quite imperfect public health system you know not every American is insured. American insurance companies can be quite rapacious and skimpy when it comes to approving especially new expensive drugs.
--:-- Sean Rameswaram: There certainly will be shortfalls. There will certainly be Americans who will not have access to these drugs who could benefit from them. But I think in the grand scheme of things, the greater tragedy is that they're going to be relatively commonplace and available to most Americans with insurance in relatively short order.
--:-- David Wallace-Wells: And we might be talking about maybe even more years to come before they're available in, say, parts of sub-Saharan Africa or South Asia.
--:-- Sean Rameswaram: That's not to say that none of these drugs have applications elsewhere. I mean, when you talk about some of the new, say, malaria vaccines, dengue vaccines, there are large-scale trials underway in other parts of the world.
--:-- David Wallace-Wells: And in theory, those could be quite effective and useful there.
--:-- Sean Rameswaram: What do you think our blind spots are in this possible golden age?
--:-- David Wallace-Wells: Well, you know, when you look at the list of leading causes of death in the US, we have made large improvements in number of heart disease deaths, but that's still a huge killer.
--:-- Sean Rameswaram: And we're very far from eliminating it as a problem.
--:-- David Wallace-Wells: Diabetes is another one where we're still essentially using generation-old treatments.
--:-- Sean Rameswaram: There are also a whole lot of things which we consider sort of currently treatable. I mean, I think about the whole range of mental health.
--:-- David Wallace-Wells: We have people with depression taking drugs that are not very effective. And while there may be piecemeal improvements here and there, I don't think we're expecting a major step change in those areas. And that's unfortunate.
--:-- Sean Rameswaram: Where do you think this golden age ends?
--:-- David Wallace-Wells: I think there's some real potential for quite dramatic transformative growth. So just to take CRISPR for a second, I think people have probably read some headlines about CRISPR when it was first announced.
--:-- Sean Rameswaram: But this is an absolutely astonishing technology. It allows the editing of DNA in your body while you are alive.
--:-- David Wallace-Wells: It's not like you have to be editing the DNA of a baby as it's an embryo and only then can help cure the rare congenital disease that that baby will get. You can make those changes in later life too.
--:-- Sean Rameswaram: In theory, CRISPR is an absolutely radically revolutionary medical technology, which would allow for a huge range of applications well beyond, I think, what the average person not working on it really appreciates.
--:-- David Wallace-Wells: Since so much of our lives and our health is based on genetics, there's almost nothing that couldn't be affected by or helped by CRISPR therapy once we sort of fine tune and calibrate the particular approaches to particular problems.
--:-- Sean Rameswaram: And with AI, we're able to unlock and solve the problem of protein folding using AI tools.
--:-- David Wallace-Wells: How do proteins fold up? How do proteins go from a string of amino acids to a compact shape that acts as a machine and drives life?
--:-- Sean Rameswaram: There are probably many more medical applications in terms of drug discovery just like that, where artificial intelligence working at a really high level, scanning huge bodies of data, will be able to highlight potentially new applications for existing drugs and potentially new exciting pathways of research for the development of new drugs.
--:-- David Wallace-Wells: And I think we are very far from appreciating just how profoundly and dramatically that could change the landscape going forward.
--:-- Sean Rameswaram: But even so, the U.S. is falling way behind our peer countries elsewhere in the world in terms of life expectancy and mortality outcomes.
--:-- David Wallace-Wells: I wrote a piece this week showing that compared to our peer countries, every single year before the pandemic, more than 500,000 more Americans were dying than would have died if our mortality rates matched the mortality rates of our peers.
--:-- Sean Rameswaram: So every single year, there were half a million additional American deaths than would be expected if Americans were dying at the rate of other rich countries in the world.
--:-- David Wallace-Wells: And that's despite some pretty impressive medical breakthroughs over the last couple of decades.
--:-- Sean Rameswaram: I think when we talk about this frontier, it's easy to get pulled into a sort of a sci-fi futurist vision where like disease is, if not entirely defeated, then really pushed back, not just for, you know, the well-to-do, but for almost everybody.
--:-- David Wallace-Wells: And I think there is going to be real progress across the board in America, particularly over the next decade or two.
--:-- Sean Rameswaram: But I think the mortality statistics tell us also that there's a lot more going on contributing to and shaping human well-being, biological health, mental health and human flourishing than whether you can expect to live 12 years when you get diagnosed with stage four lung cancer or two years when you get diagnosed with stage four lung cancer.
--:-- David Wallace-Wells: And there's a little bit of a losing the forest for the trees here.
--:-- Sean Rameswaram: And I want to emphasize, if I can, that we really need to take seriously the fact that many Americans are suffering, many more Americans are dying and living less healthy, less comfortable, less happy lives than we might hope, even as we are rushing headlong into a pretty exciting time for biomedicine.
--:-- Sean Rameswaram: David Wallace-Wells writes for the New York Times.
--:-- Sean Rameswaram: Back in June, he wrote that suddenly it looks like we're in a golden age for medicine.
--:-- Sean Rameswaram: I used to struggle with a brain that was constantly empty and hurting. But then I asked my doctor about Today Explained.
--:-- Sean Rameswaram: Ask your doctor about Today Explained.
--:-- Sean Rameswaram: The program was produced by John Ahrens.
--:-- Sean Rameswaram: Edited by Amina Alsadi.
--:-- Sean Rameswaram: Fact Check by Laura Bullard and Serena Solon and Mixed by Patrick Boyd
--:-- Sean Rameswaram: The host was Sean Ramiswaran
--:-- Sean Rameswaram: This is Today Explained
