Psychiatric Drugs, Pregnancy and Lactation: Antipsychotics in Pregnancy: More safety data on older antipsychotics make them first choice for use during pregnancy

July 1, 2000 from ObGynNews

by ELIZABETH MECHCATIE
Senior Writer

Women typically have been counseled to avoid using psychiatric medications during pregnancy because of known or unknown risks of prenatal exposure to these medications. But data suggest that pregnancy does not protect women from new onset or relapse of psychiatric disorders. This is particularly true for women who have disorders such as schizophrenia or bipolar illness, which is also now treated with antipsychotics, according to Dr. Lee Cohen, director of the perinatal psychiatry program at Massachusetts General Hospital, Boston. Therefore, women with schizophrenia who stop their antipsychotics are at a great risk for relapse, at which point they frequently pursue behaviors that can be harmful to them and their fetuses, he noted.

The newer atypical antipsychotics are becoming first-line treatment for many people with schizophrenia because they do not have some of the side effects of the older medications and they appear to result in better acute and long-term responses. They are also increasingly being used for a range of other psychiatric disorders, including obsessive-compulsive disorder, posttraumatic stress disorder, anxiety disorders, and depression. But most of the available reproductive safety data come from literature on the typical antipsychotics and are several decades old, he pointed out. These data suggest that there is no increased risk of congenital malformations associated with first-trimester exposure to high-potency antipsychotics like haloperidol (Haldol) or midpotency antipsychotics like perphenazine (Trilafon).

There also appear to be no safety issues when these drugs are used in labor and delivery or postpartum, and there is literature suggesting that these agents are not problematic when used during lactation, said Dr. Cohen, also associate professor of psychiatry, Harvard Medical School, Boston. "Therefore in our clinic, it is our standard approach to continue treatment in patients who are dependent on a typical high-potency antipsychotic, such as haloperidol, fluphenazine hydrochloride (Prolixin, Permitil), or trifluoperazine (Stelazine), or a midpotency antipsychotic," he said in an interview. "We avoid using low-potency antipsychotics, such as chlorpromazine, because of side effects, such as hypotension, and a suggestion that they might be associated with a slightly increased risk for malformations."

There are only sparse data on the reproductive safety of the currently available newer compounds, clozapine (Clozaril), risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), and ziprasidone (Geodon). "So we typically suggest that pregnant women who require treatment with antipsychotics and are on an atypical agent should switch to one of the older drugs," he said. He and his associates also recommend that they not breast-feed while on an atypical agent until better safety data become available.

Some patients do not respond to treatment with typical antipsychotics but respond only to an atypical agent. "We have followed a small number of such patients who have stayed on the atypical drug during pregnancy and so far have not observed any unexpected problems," Dr. Cohen said. The manufacturer of olanzapine has developed a registry of fewer than 100 women exposed to this drug during pregnancy. To date, there's been no evidence of an increased risk for congenital malformations or other treatment-emergent difficulties, he said. Typical agents are increasingly being used for psychiatric disorders in women who may be more likely to bear children, such as those with anxiety or mood disorders, compared with those with schizophrenia. As a result, "we may be seeing more women on these drugs becoming pregnant, because they have less of an impact on fertility than the older drugs, which increase prolactin secretion," he pointed out. With the exception of risperidone, which causes relatively high rates of hyperprolactinemia, ziprasidone, quetiapine, olanzapine, and clozapine are prolactin-sparing compounds.

An option for a woman with bipolar disease who is taking an atypical antipsychotic is to switch her to lithium during pregnancy. "We know that the absolute risk of having a child with Ebstein's anomaly after first-trimester exposure is about 1 in 1,000 to 1 in 2,000," Dr. Cohen observed. "And since we basically know nothing about the reproductive safety of atypical antipsychotics, I would rather see a woman who has been on a drug like olanzapine or quetiapine for bipolar disease switched to lithium during pregnancy since it has a known teratogenic potential," he said.

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Reviewed: 03/2006