How an innovative NARSAD grant helped launch research that benefits millions of women

From The Quarterly, Summer 2010



“Postpartum depression is the most common complication of childbearing.” That simple statement of fact is the opening line of an article in the prestigious New England Journal of Medicine, published in 2002. As little as two decades earlier, when the statement’s lead author, Katherine L. Wisner, M.D., was just setting out on her pioneering career, postpartum depression didn’t even merit a listing in the DSM, or Diagnostic and Statistical Manual, the “bible” of clinical psychiatrists across America.



“And that’s why I have such a great fondness and a deep respect for NARSAD,” Dr. Wisner says today. “My research on the relationship of reproductive hormones to mood symptoms in women was funded by a NARSAD grant, years ago — when other funding agencies scoffed at it. Back then they basically said, ‘Since the DSM doesn’t contain postpartum disorders, we’re not so sure it’s really important to study.’”



That Dr. Wisner received an early-career NARSAD Young Investigator grant was especially important in the evolution of her work. For her, as for so many other researchers in brain and behavioral disorders, a NARSAD grant opened doors, serving as a gateway to other funding, notably to much larger governmental grants. Although she is too modest to say so, Dr. Wisner, who now directs an influential program called Women’s Behavioral HealthCARE at the Western Psychiatric Institute and Clinic of the University of Pittsburgh Medical Center, is widely acknowledged to be one of the preeminent experts in the treatment of depression in pregnant women and during the postpartum period.

 

Depression has long been recognized as a major disabler of Americans, affecting tens of millions at any given moment and exceeded in its impact only by heart disease. Large studies have also indicated that women are about twice as likely as men to become clinically depressed at some point in their lives. But the story does not end there. The focus for Dr. Wisner and colleagues is the fact that women in the perinatal period — those about to give birth or who have just done so — are even more susceptible to depression than women at other times in their lives. They’re the most vulnerable of the vulnerable, in other words.



In protecting women, drug regulators exposed them to more risk

It turns out that one woman in seven gets postpartum depression, which in serious cases prevents a new mother from properly caring for her infant. Sometimes, it can lead to suicidal thoughts. One thing in particular caught the attention of Dr. Wisner when her career was in its early stages. At that time, a new class of medicines to treat serious depression was coming to the market — the so-called SSRI (selective serotonin reuptake inhibitor) antidepressant drugs, which have since become a mainstay of treatment, prescribed to tens of millions. Yet those like Dr. Wisner who were devoted to the problems of perinatal women found they had no information about how, or whether, the SSRI drugs might affect women in the vulnerable perinatal period. The astonishing fact, Dr. Wisner says today, is that “we still do not have any mandatory surveillance system

in this country when a new drug is released on the market. Even drugs commonly used in childbearing women are approved with no data about their use in human pregnancy!” A professor of psychiatry, obstetrics, gynecology and reproductive medicine at the University of Pittsburgh, Dr. Wisner is one of a group of ethicists, physicians and policy makers who have advocated for the responsible inclusion of women in medical research.

 

The lack of data on perinatal women is the unintended consequence of a well-meaning decision by regulators to protect vulnerable populations. Who would dare expose a pregnant woman or a new mother to unknown risks? Although no one intended it, depressed women therefore have been guinea pigs in an experiment no one would ever think of performing. Many pregnant women have indeed taken Prozac, Paxil, Lexapro, Zoloft, Celexa and other SSRIs, during all or part of pregnancy; many others have taken them while they were breastfeeding.



About a decade ago, Dr. Wisner and like-minded colleagues began to run trials to find out how these women were faring. “It’s been one of my passions to figure this out — to tease out the risks,” she says. “What are the risks of taking these medicines during pregnancy and while breastfeeding? But also, very importantly, what are the risks of not being treated with them at all? How will that impact the mother and the baby? This is the question that we were not asking until a few years ago. And it turns out to be the key.”



How to weigh the risks vs. benefits of drug treatment

Dr. Wisner is extremely careful, yet passionate about what these studies of the risks have shown.   “There is a huge and appropriate concern about whether medications used in pregnancy cause birth defects,” she says. But after many studies, she adds, it is now clear that risks in SSRI antidepressants in absolute terms are so small — really quite low — and, as research has shown, are often inseparable from risks caused by the underlying depression.”



This is possibly the most important discovery that Dr. Wisner and colleagues have made. And it applies, she says, to the risks of taking SSRI antidepressants during pregnancy and in the postpartum period, while breastfeeding. “There are measurable risks in both,” she says, “as there are risks in taking any drug. For each depressed mom or mom-to-be going off medication, the risks of recurrent depression must be considered. I mean not only the symptoms of the illness (mood, sleep and appetite disturbances) but the social consequences as well (low motivation and energy, not participating in obstetrical care or planning for infant care, isolation).” In summary: “Healthy mom, healthy baby, and that includes mental health!”



In other words, being depressed during pregnancy carries a risk of its own to mother and fetus (as do other conditions, such as obesity). Untreated depression can cause the same adverse results as SSRI treatment, such as pre-term births and low birth weight, and does so at a similar (very low) rate. What to do, then? In the postnatal period, an untreated mom with serious depression can be far worse off than if she had taken the small risk of remaining on drug treatment during breastfeeding in order to keep her depression in remission. Dr. Wisner has also helped to identify and develop non-drug options for women who eschew drug therapy. Among these are nutritional therapy and bright-light therapy, adapted from treatment of seasonal affective disorder. She also is studying a hormone, estradiol, delivered by skin patch, for postpartum depression.  



With all of these options, what kind of advice does Dr. Wisner give her patients? “You can’t get an optimally healthy baby from a mom who’s depressed. That’s a psychologically and physiologically abnormal state, and so there is always a risk-and-benefit situation. And in my practice, it’s always the mother’s individual clinical history and her own values that decide the matter. But I will be honest: it’s never a simple decision.  



“All of these risks are relative, and you try to measure them on what amounts to a balance-beam. The point of balance, between risk and benefit, shifts according to a woman’s unique history — for instance, of prior major depression, suicidal thoughts or actions, eating disorders, etc. I offer guidance, but in the end it’s the woman who should be at the center of the decision-making process.”



Dr. Wisner is keenly aware that questions such as these can be answered today with reasoning backed by actual scientific evidence — and that it all began, for her, with an idea that only NARSAD was willing to take seriously. “My perception is that NARSAD really sees what the needs are in mental health research, and that they have respect for the problems of real people and populations. It’s the opposite of a top-down approach that says, ‘this is the next big-ticket research item.’ It’s an approach to research that is really making a difference in people’s lives.”

Katherine L. Wisner M.D.

Professor of Psychiatry, Obstetrics and Gynecology and Reproductive Sciences and Epidemiology,

University of Pittsburgh School of Medicine;

Director, Women’s Behavioral HealthCARE Program,

Western Psychiatric Institute and Clinic