KOLOA, HAWAII — Although labeling typically doesn't support the use of psychotropic drugs in pregnant women, the drugs might be needed during pregnancy, according to an observational study done at Emory University, Atlanta.
“What I want you to recognize is that you're going to expose the child to something, be it illness or treatment, and in the context of that, some decisions are far worse than others,” Dr. Zachary N. Stowe said at the annual meeting of the American College of Psychiatrists. “Abruptly stopping or changing treatment at knowledge of conception is an effort on your part to reduce your anxiety. It doesn't change outcome. In fact, it probably worsens outcome,” Dr. Stowe asserted.
The need for treatment cannot be ignored. A large number of women who become pregnant have a mental health problem.
“We're talking about [400,000] or 500,000 women every year with a neuropsychiatric illness that” begins before family planning, or that might have been treated or needed to be treated during family planning, said Dr. Stowe, who is director of the women's mental health program at Emory University.
And with 4 million U.S. deliveries per year, he pointed out, “over 50% of pregnancies are unplanned.”
Studies of antenatal depression and its consequences led the American College of Obstetricians and Gynecologists to issue the following guideline statement in November 2007:
“Maternal psychiatric illness, if inadequately treated or untreated, may result in poor compliance with prenatal care, inadequate nutrition, exposure to additional medications or herbal remedies, increased alcohol and tobacco use, deficits in mother-infant bonding, and disruptions within the family environment.”
Other antenatal depression study findings include increases in suicide, postpartum depression, premature birth, low birth weight, neonatal complications, and fetal demise, said Dr. Stowe.
In the observational study that he and his colleagues conducted, pregnant women who had depression decided for themselves whether to discontinue their antidepressant medication.
Of the women who discontinued, 68% became “sick” before delivery, said Dr. Stowe. The other 32% were able to stop taking their antidepressant safely, but 25% who stayed on their antidepressant still became sick.
For women with bipolar disorder who discontinued their mood-stabilizing medication, 85% became sick before delivery.
A big problem, of course, is the typical drug labeling statement that “use in pregnancy is not recommended unless the potential benefits justify the potential risks to the fetus,” which Dr. Stowe called “handwashing.”
There's no question that psychotropic drugs will reach the fetus. Psychotropic medicines are designed to get past the blood-brain barrier and reach the brain, which means they will likely pass through the placental barrier without any difficulty. His own unpublished research has supported this, but he wondered if it is always harmful.
“You can actually statistically argue that antidepressants reduce your risk of birth defects,” he said. “To date, we have no confirmed evidence of increased birth defects on our antidepressants.”
In some psychotropic categories, however, some drugs are better than others—or much worse.
“Valproate has consistently the highest placental passage of any medicine we've studied, and it has the worst outcome,” said Dr. Stowe. “It is worse than Accutane.”
“In my opinion, there is no justification for first-line use of valproic acid in women of reproductive years,” he continued. In babies whose mothers used valproic acid during pregnancy, “the mean IQ drop is 15 points. One in 10 children is mentally retarded,” he said.
On the other hand, “lamotrigine is the cleanest anticonvulsant we've seen. It is emerging as the number-one treatment for epilepsy during pregnancy. The overall malformation rate is lower than the national average,” he pointed out.
A recent, not-yet-published study of the use of lamotrigine in 26 women with bipolar disorder found that they did well if they continued the drug throughout pregnancy but not if they discontinued.
A higher dosage is needed for treatment of bipolar disorder, just as it is needed for epilepsy, Dr. Stowe said.
Another unpublished study found that pregnant women using olanzapine “failed their blood sugar test, independent of dose,” he said. “We should not trade gestational diabetes to treat mental illness during pregnancy, because what you're actually trading is the risk for adult-onset diabetes after pregnancy. Gestational diabetes is a well-known risk factor for that.”
Not much is known about the use of atypical antipsychotic drugs during pregnancy, he said.
As for pregnant women using lithium, be aware that dehydration at birth can cause lithium toxicity in the infant, he said (Am. J. Psychiatry 2005;162:2162–70).
Switching drugs during the course of pregnancy with the thought that drug B has more safety data than drug A is entering “the world of the unknown,” Dr. Stowe said, “because all the data for medicine B were not derived from babies that first got medicine A. Everything we know about teratology says two medicines are worse than one. And please remember, the later trimesters can be just as important as the first trimester.”