Taking Atypical Antipsychotics While Pregnant

With limited research data on the impact of newer atypical antipsychotics during pregancy, pregnant women with bipolar disorder or schizophrenia may be better off with the older antipsychotics.

The reproductive safety of the older typical antipsychotics, such as haloperidol, is supported by extensive data that have accumulated over the past 40 years, at least with respect to teratogenic risk. Much of the data come from their use in treating nausea, particularly with prochlorperazine (Compazine). While long-term neurobehavioral data have been somewhat sparse, no particular indications of risk have been raised in over four decades of use.

We have far less reproductive safety data on the newer "atypical" class of antipsychotics that have become widely used over the past decade because they lack some of the longterm side effects associated with the typical antipsychotics. These drugs - olanzapine (Zyprexa), risperidone (Risperdal), quetiapine Seroquel), aripiprazole (Abilify), riprasidone (Geodon), and clozapine (Clozaril) - are approved for schizophrenia; several are approved for acute mania indications as well.

But they are also being used widely across psychiatric disease states, including anxiety, agitation in the elderly, generalized anxiety disorder, and obsessive compulsive disorder), and as adjunctive treatment of depression.

Because reproductive safety data on the atypicals have been sparse, clinicians are again faced with the difficult situation where a relatively new class of medicine is being used frequently in a population of reproductive age women. What data are available have been largely limited to manufacturers' accumulated case series or spontaneous reports, which have their inherent biases with respect to over-reporting of adverse outcomes.

To date, such information has not suggested any "signals" with respect to specific concerns regarding their use during pregnancy but we can make only limited conclusions on such information. Thus, clinicians have been in a bind with respect to use of the atypicals during pregnancy. A study published in April - the first prospective study of the reproductive safety of the atypicals in the literature - provides some reassuring data regarding the risk of malformations, albeit in a relatively small sample of 151 patients. Investigators from the Motherrisk Program in Toronto prospectively followed these women who took olanzapine, risperidone, quetiapine, or clozapine during pregnancy. All of the women had taken one of these agents during the first trimester, and 48 were exposed throughout pregnancy. A total of 151 pregnant women who had taken a non-teratogenic drug also were followed.

In the atypical-exposed group, one child was born with a major malformation (0.9%) a rate lower than the 1%-3% background rate in the general population; compared with two (1.5%) babies in the control group - an insignificant difference.

Differences between groups in the rate of spontaneous abortions, stillbirths, or gestational age at birth were not statistically significant. Women taking atypical antipsychotics did have significantly higher rates of low birth weight babies (10% vs. 2%) and therapeutic abortions (10% vs. 1%) (J. Clin. Psychiatry 2005; 66:444-449).

As the authors point out, the sample was relatively small, the study was statistically underpowered, and long-term neurobehavioral outcomes were not evaluated. Still, this is the first prospective study that complements spontaneous reports from the manufacturers.

The authors included the number of spontaneous reports of pregnancy exposures to atypicals, provided by the respective manufacturers, with the exception of the newer atypicals. Among the 242 reports of olanzapine-exposed pregnancies, there was no increase of major malformations or other abnormal outcomes above baseline. Of the 523 clozapine exposed pregnancies reported, there were 22 "unspecified malformations." Of the 446 quetiapine-exposed pregnancies, 151 outcomes were reported, of which 8 were different congenital anomalies. Eight malformations were reported among the approximately 250 reports of pregnancies and lactation exposed to risperidone, but no pattern of abnormalities was noted.

Obviously, if a patient can do without the medication, then it would be appropriate to discontinue it, but this is frequently not the case and these decisions have to be made on a case-by-case basis weighing the relative risks versus benefits.

For a patient planning a pregnancy who has a severe psychiatric illness and who is maintained on an atypical antipsychotic to sustain functioning, switching to a typical antipsychotic may be prudent. However, we often see women who present when they are already pregnant and on an atypical agent. At this point a switch may not be the wisest decision, if she is at a risk of relapse. For those women, the Motherrisk data are not a guarantee of safety but provide information that is at least moderately reassuring to clinicians. Although this small study is encouraging, given the prevalence of reproductive age women on these agents, it would be ideal if industry performed post-marketing surveillance studies that would rapidly provide the amount of cases we need to reliably estimate reproductive risks. Such studies may soon be mandated by the Food and Drug Administration in this post-Vioxx era with increased emphasis on the safety of marketed drugs.

Dr. Lee Cohen is a psychiatrist and director of the perinatal psychiatry program at Massachusetts General Hospital, Boston. He is a consultant for and has received research support from manufacturers of several SSRIs. He is also a consultant to Astra Zeneca, Lilly and Jannsen - manufacturers of atypical antipsychotics. He originally wrote this article for ObGyn News.