Women who stop taking antidepressant medications during pregnancy are at a five times greater risk for recurrence of depression than are women who continue taking their medication throughout their pregnancies, according to a multi-institutional study published in the February 1 Journal of the American Medical Association. The findings, from the first systematic clinical study of depression relapse during pregnancy, run counter to a common belief that pregnancy's hormonal changes can prevent psychiatric problems.
"Clinical lore has held for decades that pregnancy protected women from mood disorders," says Lee Cohen, MD, director of the Perinatal and Reproductive Clinical Research Program at Massachusetts General Hospital (MGH), who led the investigation. "What drove this study was a divergence between that belief and what many of us were seeing clinically, that many women who stopped using antidepressants during pregnancy appeared to be relapsing."
Many published studies have supported the safety of antidepressant drugs taken during pregnancy, although there have been some reports that prenatal exposure to the popular selective serotonin reuptake inhibitors (SSRIs) might cause transient agitation or distress in newborns. Most recently, some preliminary unpublished data suggested a potentially increased risk of cardiovascular defects in infants exposed to the SSRI paroxetine. The current study was designed to examine risk for recurrent depression in pregnant women who chose to continue or to stop antidepressants during pregnancy.
The study enrolled 201 women treated at women's mental health centers at MGH, University of California Los Angeles (UCLA) School of Medicine, and Emory University School of Medicine. All participants were less than 16 weeks pregnant when entering the study, had a history of depression and had been successfully treated with antidepressant medications for at least three months before they became pregnant.
The women were provided with audiotapes outlining what was known about the risk of birth defects associated with antidepressants and about the possible risk that their depression could recur if medication was discontinued. They then made their own decisions whether to maintain or discontinue antidepressant medication during pregnancy. A total of 82 chose to maintain their medication dosage; 65 discontinued antidepressants; 34 decreased dosage and 20 increased dosage during their pregnancies. Out of all participants, 43 percent experienced relapse of depression symptoms during pregnancy, half during the first trimester. But while 68 percent of those who discontinued medication relapsed, only 26 percent of those who maintained their prepregnancy dosage had recurrence of symptoms.
"We know that women who become depressed during pregnancy may not take appropriate care of themselves or even make it to prenatal appointments, and there is evidence that maternal depression itself has an adverse effect on fetal and neonatal well being," says Cohen. "While this report does not offer explicit guidelines for individual patients, the study unequivocally suggests that women taking antidepressants who anticipate pregnancy need to address with their doctors not only potential risks to their babies if they continue taking the drugs but also the risk that their disease may recur if they stop antidepressants. Only by considering both sides of this risk/benefit equation can patients make informed decisions."
Members of the research team are currently analyzing additional data from these study participants to look for characteristics that may indicate who could safely discontinue treatment and who would be at risk for recurrence. They also are planning to examine the factors women used as a basis for deciding whether to continue medication as well as other information that could be helpful to patients and physicians.
The group at Emory was led by Zachary Stowe, MD, and the UCLA team was led by Lori Altshuler, MD. Other coauthors of the JAMA study are Ruta Nonacs, MD, PhD, Adele Viguera, MD, and Alison Reminick of MGH; Rita Suri, MD, Vivien Burt, MD, PhD, and Victoria Hendrick, MD, of UCLA; Jeffrey Newport, MD, and Ada Loughead of Emory; and Bernard Harlow, PhD, and Allison Vitonis of Brigham and Women's Hospital. The study was supported by grants from the National Institute of Mental Health.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $500 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.