Confusing Times for Depressed Pregnant Women--and Their Doctors

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Three new studies make the treatment of pregnant women suffering from depression somewhat more complicated.

Depression is common among women of childbearing age, with perhaps 10-15% of women suffering from it at some point in their childbearing years. Contrary to common belief, pregnancy has been shown not to protect women against its ravages. Thankfully, effective anti-depressive therapy has been available for many years, and it keeps getting better: while older tricyclic drugs still remain useful in certain circumstances, the newer SSRIs (such as Prozac, Paxil, Celexa, and Zoloft) are at least as beneficial and free of some of the worst side effects of the older drugs.

Now, in the Feb. 1 issue of the Journal of the American Medical Association, a group of researchers from Massachusetts General Hospital and Harvard Medical School report that, in a group of women with major depression who discontinued their anti-depression medications during pregnancy, over two-thirds (68%) experienced a relapse of their affective disorder. Among those who did not stop their therapy, only one-quarter flared during pregnancy. Thus, those who stopped their medication were two and a half times more likely to relapse. One-half of those who did relapse -- either on or off their medications -- experienced their renewed symptoms during the first three months (first trimester) of pregnancy. It is important to note that depression during pregnancy, besides the obvious risk to the mother of poor nutrition and self-destructive behavior, has direct adverse effects on the fetus and newborn as well, including low birth weight and slowed development. Their conclusion: pregnancy does not protect against an exacerbation of untreated depression. Cessation of medication during pregnancy is associated with a high risk of relapse. The treatment approach seems straightforward: don't stop anti-depressive therapy in pregnant women unless clearly necessary. But not so fast...

Another study, released this week in the Archives of Pediatric and Adolescent Medicine, finds that almost one-third of infants born to mothers on SSRI antidepressants at or near term experienced withdrawal symptoms -- neonatal abstinence syndrome, or NAS. This syndrome is characterized by high-pitched crying, tremors, and sleep disturbances, according to the study authors from the Schneider Children's Medical Center of Israel in Petah Tiqwa, and other Israeli scientists. NAS tends to go away on its own and be of short duration. While none of the infants with NAS who were studied suffered from severe or life-threatening withdrawal, this possibility must be considered when discussing therapeutic plans with pregnant women whose depression is "euthymic" (under control) due to treatment.

As if these considerations weren't complex enough, yet a third study relevant to depression in pregnancy and its treatment appears in today's New England Journal of Medicine. A group of researchers from Boston and San Diego analyzed, retrospectively, the effect on the newborn of having a mother who took an SSRI in the last twenty weeks of pregnancy. They found that there was a significantly increased risk of a condition called persistent pulmonary hypertension of the newborn (PPHN) in neonates of mothers on SSRIs after the twentieth week. While the relative risk of PPHN was about six-fold higher than in mothers who took other antidepressants or none, the actual risk of PPHN rises from two in a thousand (among those not on any medications) to about ten in a thousand, or 1%. PPHN often has severe consequences, ranging from chronic diseases of the brain and nervous system, to death in about 7% of those affected. Other studies, however, have found a much lower risk of PPHN in those on an SSRI, with the largest study finding a rate of only three per thousand. Further, the new study was small, comprising only 377 women with infants who developed PPHN, and was not a controlled, randomized study. While such controlled studies need to be done, and should include not only SSRIs but also the newer SNRIs (serotonin and norepinephrine release inhibitors), the benefits and the risks -- to mother, fetus, and newborn -- of choosing to remain on or go off antidepressants should be discussed among individual women, their obstetricians, their psychiatrists, and a significant other when appropriate. (Also: see ACSH's report on drug benefits and risks.)

Most studies have shown that maternal treatment with SSRIs and related drugs has no major effect on the newborn -- but both short-term minor effects (such as mild NAS) and the possibility of long-term effects, whether PPHN or those as yet undiscovered, should be thoroughly evaluated before a final treatment decision is made. Indeed, such "final" plans may need to be modified as circumstances demand it. Some things, however, are certain: depression during pregnancy is a major problem; it is not eased by the pregnant state; and relapse is likely if medications are stopped, with attendant adverse effects on both mother and baby possible. Although there is some risk to the newborn from commonly used antidepressants, mothers and obstetricians who might have reflexively stopped medications when pregnancy occurs should at least now think twice.

Gilbert Ross, M.D., is Executive and Medical Director of the American Council on Science and Health (ACSH.org, HealthFactsAndFears.com).