Popular drugs for depression may lead to more risks than benefits for pregnant women, a review of research finds. The review focused on women who had problems getting pregnant. But the studies reviewed also included other pregnant women. The most popular drugs for depression are called selective serotonin reuptake inhibitors. Prior research has linked the use of some of these drugs during pregnancy with higher risks of miscarriage, birth defects and preterm (early) birth. The strongest evidence of risk has been seen for paroxetine (Paxil). Some studies also suggest effects on the babies' behavior and health. The new review of research found no evidence that treating depression with drugs can lead to a healthier pregnancy or birth. The study did conclude that talk therapy can reduce depression symptoms. This type of treatment does not require drugs. Experts interviewed by USA Today disagreed with the conclusion that drug treatment does not benefit the mother and baby. They said each woman should decide about treatment with her doctor. The journal Human Reproduction published the study online. USA Today wrote about it October 31.

By Mary Pickett, M.D.
Harvard Medical School

What Is the Doctor's Reaction?

Untreated depression during pregnancy might lead to a less healthy baby. Antidepressant medicines during pregnancy may also harm the baby. Which is the bigger risk for the newborn?

A newly published review highlights what we know about the risks of antidepressants in pregnancy. The authors' conclusion: We are sure there are risks from these drugs in pregnancy, and we are not sure there is very much benefit.

About 13% of pregnant women take a drug for depression during all or part of their pregnancy. What are the risks?

• Birth defects -- In 2005, paroxetine (Paxil) was shown to raise the risk of two heart birth defects if it is used during early pregnancy.. One defect is known as an atrial septal defect. The other is a ventricular septal defect. The usual risk of these defects is about 1 in every 100 babies. Two studies showed a risk of 1 out of 50 to 70 for the babies of women treated with Paxil during their first 3 months (trimester) of pregnancy. A third heart problem that has been linked to antidepressants is pulmonary hypertension.



• Withdrawal symptoms -- Use of an antidepressant can also be a problem late in pregnancy. In this case, the newborn may go through withdrawal symptoms after birth. The newborn may be jittery, irritable or have abnormal breathing patterns.

The newly published review says antidepressants also increase the risk of:

• Miscarriage
• A premature baby

There is a weak connection between antidepressants in pregnancy and autism. No one has shown whether the drugs can cause autism, however.

Several years ago the Food and Drug Administration changed the pregnancy safety rating of Paxil. The new rating is D for the entire pregnancy. This means there is evidence showing the drug is unsafe. Other drugs in the same class as Paxil include:

• Fluoxetine (Prozac)
• Sertraline (Zoloft)
• Citalopram (Celexa)
• Escitalopram (Lexapro)
• Fluvoxamine (Luvox)

These other drugs have pregnancy safety rating C for the first and second trimesters. This means we don't have enough evidence to know much. They are generally unsafe in the third trimester. Most other antidepressants have a safety rating of C for the whole pregnancy.

What Changes Can I Make Now?

If you have new or continuing depression when you are pregnant, think carefully about your need for drug treatment. Get guidance from a doctor or therapist. Together, weigh the risks of taking the medicine versus delaying or stopping it.

Here are some things to think about as you make your decision:

• Avoid paroxetine (Paxil) during pregnancy. Of all antidepressants, Paxil has the most proven risk for heart defects.



• If you don't take an antidepressant, treat your depression in other ways. Remember that you are looking out for the health of two people -- the baby and yourself. Psychotherapy is a helpful treatment for depression in pregnant women. If you still need to take medicine, psychotherapy can help to reduce the length of time you need it. Two types of psychotherapy can be helpful. With interpersonal psychotherapy, a therapist helps you to sort out which people in your life are your supporters, and which people are unreliable for you. It can help you to resolve stressful disputes and learn to take care of your own needs. Cognitive behavioral therapy can help you to learn ways to think positively, solve problems and rediscover simple pleasures.



• Make sure that you have been diagnosed correctly. During the last 20 years, the rate of antidepressant use in the United States has increased 400%. Many people who take these drugs do not have severe enough symptoms to require medicine. Some may have started treatment before a complete evaluation was done. Make sure your doctor has checked for problems with thyroid function, sleep disorders and iron deficiency or anemia. These common medical problems can cause symptoms of fatigue and low mood. Antidepressants are not the best way to manage depression caused by substance abuse.



• Use antidepressants no longer than you need them. Discuss your depression history with a trusted doctor or therapist. If you have serious depression symptoms or if you have a history of suicide planning, then drug treatment may be appropriate during a pregnancy. If you have been doing well for at least six months, consider gradually stopping your medicine before (or at the start of) pregnancy.

Most women should avoid antidepressant drugs during pregnancy. In severe cases, it is important to treat depression with all resources that we have -- drugs, social support and psychotherapy.

What Can I Expect Looking to the Future?

We still have only a short experience with antidepressant drugs and pregnancy, so long-term effects on babies are unknown. One small study did not find anything abnormal in the brain function or development of exposed babies once they were 8 months old. This is reassuring, though more research is needed.