By LAURIE TARKAN
New York Times
Published: January 13, 2004
When Jennifer Klein, a 32-year-old social worker in Los Angeles, discovered that she was pregnant, she immediately stopped taking her antidepressant to avoid exposing her baby to it. She had made the same choice with her first child and experienced only the normal ups and downs of pregnancy.
This time was drastically different. Several weeks after going off the drug Zoloft she slid into a major depression, which left her crying all day, feeling overwhelmed by simple tasks like going to the supermarket, feeling too tired to move, and extremely anxious, worrying about the pregnancy, her 2-year-old son and her job.
"I'd spend all day crying and I couldn't stop," Ms. Klein said. "I hated that my son saw me like that." When she was feeling the most overwhelmed, she said, she thought of giving away the new baby to her sister.
In her 15th week of pregnancy, she broke down in tears in front of her obstetrician, who recommended that she go back on Zoloft. The doctor told her that the risk of not taking it was greater than the risk of taking it.
"I was still worried about the effects of the medication on my baby, but I knew I needed to do something," Ms. Klein said. "I couldn't function anymore the way I was going."
She took a lower dosage of Zoloft to minimize exposure to the baby. It was just enough to keep her functioning, but not quite enough to alleviate the depression completely. After her son was born, she resumed her full dose and now says she feels much happier.
For some women, especially those with a history of significant depression, the risks of abandoning antidepressants during pregnancy may be far greater to the mother and the fetus than taking the drugs themselves.
Those who abruptly stop taking their medications, often on the advice of their obstetricians, put themselves in danger of a relapse. Others who switch to lower dosages may still suffer depressive symptoms.
Although there are known risks to taking antidepressants in pregnancy, and there may be unknown risks, mental health experts do not advise all pregnant women or those planning to conceive to stop their drug regimens.
"Most physicians would say we don't know what the risks of these medications are, so the safest thing to do is to go off them," said Dr. Lori Altshuler, a professor of psychiatry at the University of California, Los Angeles and the director of the Mood Disorders Research Program there. "The fact is, there are tremendous risks to the mother when she goes off antidepressants, and I don't think there's an appreciation on the part of the physician or the patient just how serious these are."
About 75 to 80 percent of women who go off antidepressants will relapse during the pregnancy, said Dr. Lee Cohen, director of the Perinatal and Reproductive Psychiatry Clinical Research Program at Massachusetts General Hospital. Some pregnant women with major depression have reported having suicidal thoughts or were unable to function at work or take care of their older children.
Depression in pregnancy is associated with poor eating, missing prenatal appointments and use of substances like tobacco and alcohol, Dr. Cohen said.
Missing prenatal visits alone is a strong predictor of problems, among them premature babies and low birth weights.
Depressed women also have a higher rate of obstetrical complications and preterm deliveries, and a review of 11 studies has shown that they have 45 percent more miscarriages, said Dr. Gideon Koren, a pediatrician and the director of the Motherisk program at the University of Toronto, a risk-counseling service for pregnant women.
In addition, being depressed during pregnancy is a strong predictor of postpartum depression, which can lead to poor mother-infant bonding and has been linked to emotional, behavioral and learning problems in the child.
In one study, Dr. Koren's group followed women who called the Motherisk hot line, which receives about 5,000 calls a year regarding the use of psychiatric drugs. Of 34 women who called and said they had stopped taking an antidepressant, a benzodiazepine (used to treat anxiety) or both, all reported withdrawal symptoms and psychological problems. Eleven reported suicidal thoughts, and four of them were admitted to hospitals.
Estimates from various studies indicate that about about 12 percent to 20 percent of pregnant women are depressed, yet the diagnosis may go undetected. About 12 percent of women in the general population suffer a depressive disorder each year.
According to one recent study published in The Journal of Women's Health, 20 percent of women screened in the waiting rooms of obstetrical clinics scored in the depression range, with fewer than 15 percent of those in that category indicating that they had received any formal treatment for depression, like psychotherapy, medication or counseling.
Some mental health experts believe that doctors set a much higher threshold to medicate pregnant women suffering depression than they do for pregnant women suffering other diseases like high blood pressure, peptic ulcer disease, bronchitis and other infections.
"I think the categorical belief is that depression is something you get over rather than something you take medication for," said Dr. Zachary N. Stowe, director of the Women's Mental Health Program at Emory University in Atlanta.
"We have more research on the safety of antidepressants in pregnant women than any other class of drugs in the world," Dr. Stowe said.
A number of studies have confirmed that neither the older tricyclic antidepressants nor the newer and more popular selective serotonin reuptake inhibitors, or S.S.R.I.'s, are associated with an increased risk of malformations in newborns.
"We have over 2,000 cases of women who have been exposed to Prozac during the first trimester, 400 cases of women exposed to Celexa, and several hundred cases for other S.S.R.I.'s like Zoloft and Paxil," Dr. Altshuler said. No study has shown an increased risk of congenital malformations, experts agree.
One study from Stanford, published in The Journal of Pediatrics, however, did find an increase in minor anomalies like delays in fine motor skills and increased tremors in babies 6 to 40 months old, though these findings did not show up in several longer-term studies.
Dr. Victoria Hendrick, associate professor in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said the findings "show that it is important not to assume these medications are safe simply because they do not seem to produce birth defects."
There is also concern about the long-term effects of antidepressants on a child's brain development.
Again, only a few studies have followed babies into childhood, the longest being up to age 6. These have found no association between exposure and a child's learning and behavioral development.
"Even though the data are very limited," Dr. Altshuler said, "it's encouraging that there aren't any studies that find that exposure in utero leads to any behavioral changes, lower I.Q. or failure to reach normal development or milestones."
Recent studies, however, are finding that babies exposed to antidepressants in the third trimester of pregnancy have a higher rate of newborn complications, like respiratory distress, shivering, hypoglycemia and jaundice.
One study by Dr. Koren's group looked at 55 newborns exposed to paroxetine, known as Paxil, during the third trimester. Twelve exposed newborns had complications requiring intensive treatment and prolonged hospitalization, compared with three in a control group. These symptoms, though worrisome, are transient, disappearing in one or two weeks.
Paroxetine appears to take a larger toll on newborns than other S.S.R.I.'s.
"It's such a hard decision," Dr. Altshuler said. "The evidence we have to date doesn't show any compelling risk to the developing fetus, but we have very limited data."
"I think it's really a question of accepting that there is no risk-free decision here," she said. "You have to weigh the risk of the mother relapsing by going off medication, and the potential risk that the fetus may have some long-term effects from this medication."
Most experts agree there is some risk to taking antidepressants. Dr. Stowe noted, "I don't use the word safe, but if the woman is depressed or anxious to the point that she needs to be treated, then an antidepressant is better than leaving her untreated."
Dr. Hendrick added, "My threshold for treating depression in pregnancy is certainly much higher than in a woman who is not pregnant."
People who choose to go off antidepressants can instead be treated with psychotherapy during pregnancy, but experts say that this may not be effective in women with major depression.
If women go off antidepressants, it is important to taper off the drugs gradually over a period of a couple of weeks, to avoid withdrawal symptoms.
Some women choose to stay off antidepressants during the first trimester, the period of fetal organ formation, although many will relapse before the end of the trimester. Others go off antidepressants toward the end of the third trimester to avoid newborn complications.
There is not enough data to recommend one drug over the other, but most experts believe women are safer with drugs that have been studied the most, like the tricyclics or Prozac. Some doctors do not recommend that women switch during pregnancy because the drug they switch to may not be effective for them.
A lesser but not insignificant problem is that many depressed women who are breast-feeding will not take antidepressants, or they will go back on the drugs but choose not to breast-feed their infants.
Most experts believe that the risk to the nursing infant is minimal. "Most of these drugs get into the breast milk in very small amounts, and it's not considered a risk," said Adrienne Einarson, assistant director of the Motherisk program.
"If a woman needs to be treated for depression, it's certainly not a reason to stop breast-feeding," she said.
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