In an article published last week in the Times, Roni Caryn Rabin highlighted the downside of antidepressant treatment during pregnancy, linking the use of S.S.R.I.s to an inventory of woes, including autism, A.D.H.D. (attention-deficit hyperactivity disorder), lower language competence at age three, preterm birth, cardiac defects, clubfoot, persistent pulmonary hypertension, lower Apgar scores, and low birth weight. “Other experts think it’s time to reconsider widespread use of these drugs in pregnant women altogether,” wrote Rabin. She quoted one such expert as saying, “This is a message people don’t necessarily want to hear. Everyone’s happier with this idea that the medications are O.K.”
The group Postpartum Support International, a leader in mental-health issues for pregnant women and new mothers, responded with considerable outrage. They said that Rabin’s piece was “likely to foster unnecessary fear,” and that “the implication that women idly choose to start or to remain on antidepressants … or any other medication during pregnancy is insulting and demeaning.” They continued: “The author has chosen to cherry pick studies to support her misguided, inaccurate hypothesis, and ignored studies that failed to find increased risks associated with SSRI use in pregnancy…. Rather than condemning the choices made, it is about time for society to support these women and show compassion for the painful ordeal they are experiencing.” The Center for Women’s Mental Health at Massachusetts General Hospital posted an equally dismayed reply to the Times story. “Ms. Rabin seems to trivialize depression, making it seem more like acne or athlete’s foot,” it read. “Cursory presentation of the complexity of decisions made around antidepressant use during pregnancy has the real potential to place patients in harm’s way. At best, such presentation is just incomplete; at its worst, it is irresponsible.”
Some fifteen per cent of women suffer from depression during pregnancy, and the use of antidepressants in expectant women is on the rise. One study found that rates more than doubled between 1999 and 2003 for women on Medicaid; at present, about six to seven per cent of pregnant women take these medications. For women with a history of depression, the rates are far higher. Pregnancy can easily trigger a relapse, and those who discontinue medications during pregnancy are nearly three times as likely to relapse as those who continue to take their medication.
Sampling of cord blood at birth indicates that the level of these medications in the fetal bloodstream is more than half of the level in the mother’s; the drugs are also present in amniotic fluid. Some studies suggest an association between S.S.R.I.s and certain types of infant cardiac defects (while another study has correlated S.S.R.I.s with a lower incidence of certain cardiac defects). There is also mixed data on antidepressants’ causal link to miscarriage, preterm birth, and low birth weight, and there is some support for a small increased risk of a lung condition called persistent pulmonary hypertension in the newborn. In about a third of cases, babies born to mothers on S.S.R.I.s develop neonatal adaptation syndrome, which involves jitteriness, reflux, and sneezing, but these symptoms are generally mild and often resolve within forty-eight hours — though neonatal seizures have occasionally been reported. Mice exposed to high levels of S.S.R.I.s during early development show reduction in sexual activity among adult males, inhibition of exploratory behavior, and altered REM sleep. All of this is of course terrifying to prospective mothers, who often choose against taking S.S.R.I.s because of these vague, hard to quantify, but undeniable risks.
Some authorities have suggested that antidepressants during pregnancy may increase the rate of autism among offspring. Five studies on this subject have been published since 2011. Three found some association. Since a considerable literature supports parental or family history of depression and other psychiatric illness as a risk factor for autism, however, it’s hard to know whether the treated mothers were producing autistic children because they took medication or because they carried genes of psychic fragility. The largest study, a 2013 population survey conducted in Denmark, attempted to control for maternal depression and did not find any association between the drugs and autism.
While the drugs are risky, depression during pregnancy is at least as problematical. Animal studies show that stressed mammalian mothers are likely to have offspring with poor neurodevelopment. Pregnant women experiencing depression or anxiety are under greater stress and may have altered neurobiology themselves, which could affect fetal development via changes in the uterine environment. Indeed, untreated depression during pregnancy is associated with increased miscarriage rates, preterm birth, and low birth weight — some of the very risks associated with maternal use of S.S.R.I.s. Depressed mothers are at increased risk for preeclampsia. Recent research has shown that the fetus of a depressed, expectant mother has alterations in the microstructure of the right amygdala. There is even some evidence that mothers who are extremely stressed during their first trimesters may be more likely to have children who later develop schizophrenia. One review notes that pregnant women’s experience of stress has been linked to an increased risk of mixed-handedness, affective disorders, and reduced cognitive ability. Anxiety and depression during pregnancy are associated with increased risk for future mental illness in the offspring. A longitudinal study of inner-city women found that the children of those mothers who had been depressed during pregnancy were almost five times as likely to be depressed as those not exposed to depression in utero. Other research indicates that newborns of depressed mothers have “lower motor tone and endurance, are less active, less robust, more irritable, and less easily soothed.” Yet another recent study showed that, while children of mothers treated with antidepressants showed standard language and cognitive skills, children of depressed mothers who were not treated had reduced language and cognition. One review acknowledges, “The notion that the mother’s mood disturbance or stress levels during pregnancy may influence the developing child has a robust history across cultures and is widely embedded in folk psychology.”
At the same time, it is important not to blame mothers for their children’s neurological challenges. The shadow of the “refrigerator mother,” who was said to cause autism, falls long across this research. It may be counterproductive to tell women under stresses they cannot avoid that they are damaging their children by being unhappy — or by being treated for their distress. Blaming some women for injuring their children by taking antidepressants and others for injuring their children because they are depressed creates a no-win situation that is itself depressing. There is no universal right answer here, and, under those circumstances, quoting the studies may seem counterproductive. But women need the leeway to make their own choices — to look, as one does in many areas of health care, at two unsatisfactory options and select between them, and to do so with as much information as possible. For some, the depression may be so acute that medication is clearly the best option; for others, the complications that could result from taking medication may be too terrifying to contemplate. Most will fall somewhere in the treacherous middle, and they will need to consult with physicians and psychiatrists to decide what to do. Some who choose not to take medication may need to change their minds during a pregnancy. The whole enterprise requires enormous flexibility in the face of uncertainty. Any false simplicity cheats women of their right to self-determination.
Elizabeth Fitelson, a Columbia psychiatrist who works primarily with pregnant women, wrote to me, “SSRI exposure does have neurodevelopmental effects on some (but certainly not all) babies exposed in utero, but the jury is basically still out about what, if any, long-term neurodevelopmental effects there are.” She continued: “We don’t know whether the relatively subtle neurodevelopmental effects observed in exposed babies continue to be significant later on in childhood, which babies are more likely to be affected in utero by either medication or maternal mood, and how to tease apart the effects of each. There is continued social ambivalence about whether women ‘need’ to be on antidepressant medication during pregnancy and even afterwards. When I’m speaking with women about this, I frame it as an issue of balancing known and unknown risks.”
There may well be women whose pregnancies are adversely affected by antidepressants; the number who experience significant and persistent problems is probably small. For those able to control their depression during pregnancy through cognitive-behavioral therapy or other non-pharmacological treatments, that is often the best option. Most women will try to make that work. But talk therapy alone is not sufficient for many depressed people, pregnant or otherwise, and the broader literature suggests that the risks associated with severe depression can often be more serious than the risks associated with medications. The debate rages, and the choice is a difficult one: to be depressed during pregnancy, with troubling consequences, or to be on medication during pregnancy, with unclear ramifications. It is not helpful when the complexity of the decision is belittled. “Everyone’s happier with this idea that the medications are O.K.,” Rabin wrote, quoting an expert. Everyone is second most happy learning, as Rabin suggests, that the medications are poison but depression is fine — because clarity and simplicity make life easy. If the meds help more than they harm, you take them; if they harm more than they help, you don’t take them. The problem is that this is a highly nuanced question to which there is no consistent answer, and about which we know too little. That makes everyone excruciatingly uncomfortable.