Trimipramine

Women who use antidepressants during pregnancy are not significantly increasing the risk of congenital malformations in their infants, according to results of a large prospective study

Dr. A. Ericson of the Centre for Epidemiology in Stockholm and colleagues followed 969 women who reported antidepressant use at a prenatal visit around weeks 10-12. There were 980 births, including 11 sets of twins.

The incidence of birth defects was 4%, and the incidence of infant mortality was 0.7%--no different from the rates in the general population (Eur. J. Clin. Pharmacol. 55[7]:503-08, 1999).

But Dr. Zachary Stowe, director of the Pregnancy and Postpartum Mood Disorders Program at Emory University, Atlanta, offered this caveat: "My only reservation about taking studies such as this one as prima facie evidence [that antidepressants are safe during pregnancy] is that they're uncontrolled case studies. We need more large prospective studies in this area, he said in an interview.

Women using antidepressants smoked more, had higher parity, and were significantly older (independent of parity) than women in the general population. They had a tendency to deliver preterm (before 37 weeks' gestation) and to deliver infants with lower birth weights--except for the subclass of women taking non-SSRI antidepressants, who had infants who were slightly heavier than the average.

The low birth weight in the antidepressant group was not significant after controlling for age, parity, and smoking habits. In fact, the mean birth weight was slightly higher than in the controls when these factors were accounted for. The tendency toward short gestation was not completely explained by these confounders.

Data came from the Swedish Medical Birth Registry, which includes information from prenatal visits, delivery, and the first pediatric exam for nearly all the births in Sweden.

A total of 531 women used SSRIs alone during pregnancy, 15 used SSRIs in combination with another antidepressant, and 423 used a non-SSRI antidepressant alone.

The SSRIs used were citalopram, fluoxetine, paroxetine, and sertraline. The non-SSRIs used were amitriptyline, clomipramine, imipramine, lofepramine, nortriptyline, maprotiline, mianserin, moclobemide, trimipramine, and venlaflaxine.

Citalopram, for which no previous data on teratogenic effects exist, was the most popular antidepressant and was used by 39% of the women. Congenital anomalies did not appear more frequently in the infants of these women than in infants exposed to other SSRIs.

Over 40% of the women reported using other medications during pregnancy including psycholeptics, analgesics, anti-asthmatic drugs, antibiotics, anti-inflammatory drugs, sex hormones, thyroid hormones, antiepileptics, and insulin. There was no correlation between use of other medications and use of any class of antidepressant.

Dr. Stowe said it's nearly impossible to know how much the outcome is affected by the concurrent use of these medications, smoking and alcohol use, socioeconomic status, prenatal care, and underlying uncontrolled depression.

In the meantime, women are getting a lot of mixed messages. Ob.gyns. are regularly treating pregnant women for their depression, but most psychiatrists don't know the data well enough to advise women about pregnancy while pediatricians often tell women they have to stop taking antidepressants if they want to breast-feed.

Ob.gyns. need to provide more guidance and reassurance in this area to combat the overcautious stance of other doctors and the misinformation women may find on the Internet, Dr. Stowe said. He reminds his own patients that antidepressants have shown no effect on infant health at any dose.

He agreed with the suggestion of Dr. Ericson and colleagues that untreated depression can expose the mother and child to risks associated with substance abuse, poor nutrition, and suicidal tendencies.

"If they have a history of being able to come off [their antidepressant] and be OK, then do it. But if you take them off the medication and they get sick and need to go back on it, you're exposing the fetus both to antidepressant and. to untreated depression." In his view, this is the worst of both worlds.

In a recent multicenter prospective study by Dr. Stowe, 112 women were taking antidepressants when they became pregnant, and all discontinued medication as soon as they discovered their pregnancy Around 70% of them developed depressive symptoms in the course of pregnancy, and by the time their babies were born, 50% had started taking antidepressants again.

Even if a woman is able to stay off her antidepressant for the duration of pregnancy it may not help that much. Most women don't know they're pregnant until week 4 or 5, and even if they stop taking their medication immediately it takes another week to clear the system. By that time, organogenesis is well underway and the critical period when antidepressants could have affected fetal development is over.

Another reason to keep women on antidepressants is Dr. Stowe's own finding that both SSRIs and tricyclic antidepressants have incomplete placental passage. A fetus receives a very low dose of these drugs, compared with other drugs--antibiotics or anticonvulsants, for example--that have complete placental passage.

In Dr. Stowe's recent study of 90 women who took fluoxetine, paroxetine, or sertraline during pregnancy all three medications showed incomplete placental passage. All the babies born were healthy with normal weight and a complication rate well below the national standards.

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