PHILADELPHIA—The Andrea Yates murder case thrust postpartum mental illness into the headlines, and the fact that Ms. Yates’ antipsychotic treatment had been discontinued figured into that story. In a presentation at the American Psychiatric Association’s 2002 Annual Meeting, Zachary N. Stowe, MD, said that physicians are too hesitant to prescribe psychoactive drugs for patients during pregnancy and the postpartum period. Dr. Stowe observed that although there is almost no evidence that maternal use of most psychiatric drugs harms either the fetus or the breast-fed infant, psychiatric drugs are held to a higher standard than treatments for physical illness. Clinicians must weigh the risk of treatment against the risk that untreated or inadequately treated maternal illness poses for both mother and child. Faced with such a decision, Dr. Stowe advises that physicians should generally continue the treatment regimen that has worked in the past. Dr. Stowe is Assistant Professor of Psychiatry at Emory University School of Medicine in Atlanta.

LITTLE PROOF OF TREATMENT HAZARDS

“Both psychiatric illness and treatment provide exposure to risk. Your job as a clinician is to see which path is best—pick the medicine appropriate to the diagnosis, and if it has a history of effective treatment, continue it. Do not experiment with the pregnant or breast-feeding woman,” Dr. Stowe advised. “Pregnant and breast-feeding women should not be punished for being pregnant or nursing. They are routinely treated for medical conditions that have far less morbidity and mortality than psychiatric illness, and treatments are used that have far less [safety] data than psychiatric medicines,” Dr. Stowe said. Physician contact and antidepressant medication “can prevent postnatal illness in the majority of your patients with mild depression or who have had one or two episodes of depression,” Dr. Stowe added.

RISKS DURING PREGNANCY

Concern about the risks associated with drug treatment should be balanced by recognition of the risks associated with untreated mental illness, Dr. Stowe said. Stress in late pregnancy changes blood flow in the umbilical cord “and is associated with preterm delivery,” Dr. Stowe explained. “This is not even a psychiatric diagnosis, just stress. And there is no evidence that any psychiatric condition improves during pregnancy. Depression incidence is the same in pregnant as in nonpregnant women.” Dr. Stowe estimated that at least 30% of patients with bipolar disorder have an episode during the 40 weeks of gestation if they are not adequately treated. Data on panic disorders are conflicting. “The consensus on obsessive-compulsive disorder is that it certainly gets no better and probably gets worse during pregnancy, and psychotic disorders probably get worse,” he said.

Untreated maternal depression increases the risk of preterm delivery and small-for-gestational-age infants. “In the ideal pregnant population of college-educated, married women with good prenatal care, we found that depression was associated with a 10% drop in birth weight. Low birth weight is an important predictor of long-term psychosocial function, it is the best predictor of early-onset hypertension, and it is associated with abnormal hypothalamic-pituitary-adrenal axis function at 6 months of age. These are not benign events,” Dr. Stowe cautioned. “It is my clinical belief that severe maternal anxiety has a worse impact on pregnancy outcome than depression,” he added.

UNSUBSTANTIATED ASSUMPTIONS

Most antidepressants have labeling restrictions that include pregnancy, but Dr. Stowe countered, “We have no evidence from clinical studies that any antidepressant causes birth defects with the exception of monoamine oxidase inhibitors. Long-term follow-up studies are limited, although pharmaceutical companies have some information and when requested can give it.”

This has led to some widely held but unsupported assumptions about the risks of antidepressants and anxiolytics. For example, Dr. Stowe said that benzodiazepines are thought to increase the risk of cleft lip, but this perceived increased risk did not result in any confirmed birth defects in his survey of worldwide pregnancy databases.

“We found that alprazolam was associated with the highest rate of elective abortion of any medicine. Basically, women were being told that alprazolam was bad in pregnancy, so they aborted the pregnancies. Those who continued their pregnancies actually had a lower birth defect rate than the general population,” Dr. Stowe stated.

Dr. Stowe described electroconvulsive therapy as “probably the most underutilized treatment for mental illness in pregnancy,” despite data extending from 1940 showing no adverse effects in pregnancy.

Likewise, little is known about how antidepressants, antipsychotics, and other psychiatric drugs cross the placenta. Dr. Stowe’s group has been measuring drug and metabolite levels in amniotic fluid. “There are a few antidepressants we have never found in amniotic fluid, including sertraline and paroxetine,” he said. A normal placental enzyme appears to prevent highly protein-bound drugs and metabolites from crossing the placenta; fluoxetine does cross the placenta.

Neonatal toxicity or withdrawal symptoms such as hypertonia, sedation, irritability, and jaundice do occur with maternal use of some psychiatric drugs. “Let me put this into perspective,” Dr. Stowe said. “Psychotropic medicines have not been implicated in any developmental problems in follow-up studies of the kids.”

POSTPARTUM RISKS

Postpartum risks of treatment—or lack of treatment—affect both the mother and the child, whether or not the infant is breast-fed. “The postpartum period is associated with the highest rate of psychiatric hospitalization in a woman’s life,” said Dr. Stowe. “Postpartum illness in women is so common we call it normal.” One of the most understudied issues in medicine, he said, is determining how much of this is new illness and how much is subclinical psychiatric illness that becomes acute during pregnancy or in the postpartum period. Medical and family history are the main prenatal factors that predict postpartum psychiatric illness. “The big ones you look for are death of a loved one, moving away from family, or marital discord,” Dr. Stowe said. “The only postpartum risk factor is the baby’s illness.”

Maternal depression has detrimental effects on infant relationships, as does maternal anxiety. “I cannot imagine that bipolar disorder and psychosis would not have the same effect,” Dr. Stowe conjectured.

Untreated postpartum depression is also associated with increased cortisol levels in the breast milk, which normalize when the mother’s depression is treated, according to Dr. Stowe. “This is not a big cortisol increase, but it raises the question of whether other constituents of breast milk are changed when Mom’s depressed,” he said.

For treatment during the postpartum period, Dr. Stowe strongly urged clinicians to continue any treatment that has worked in the past. He pointed out that the dose the infant is exposed to through breast milk is tiny compared to the level of exposure that would occur in utero. “A woman would have to breast-feed a child for three and a half years to equal one month of exposure during pregnancy,” he said. “Switching medicines at delivery is the dumbest thing I ever heard and involves a change at the time of the woman’s highest risk for illness.”

In a study of blood levels of 250 breast-fed infants of mothers taking various psychiatric drugs, Dr. Stowe found no clinically important changes. “I was sticking these kids for research purposes, but it never changed my clinical care, and I don’t recommend drawing blood without a clinical correlate,” he said. “Infant monitoring should be consistent with adult monitoring. If you have a woman on medication who is breast-feeding, the baby should be monitored as if it were taking that pill.”

—Janis Kelly

Suggested Reading
Newport DJ, Hostetter A, Arnold A, Stowe ZN. The treatment of postpartum depression: minimizing infant exposures. J Clin Psychiatry. 2002;63(suppl 7):33-44.

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