Atypical Antipsychotic Medications: What Do We Know About Their Reproductive Safety?

Atypical Antipsychotic Medications: What Do We Know About Their Reproductive Safety?

Atypical antipsychotic medications are commonly used for the treatment of schizophrenia and bipolar disorder.  Despite the increasing use of these medications in women of child-bearing age, there is still relatively little data regarding the reproductive safety and long-term neurodevelopmental effects of these medications. A recent study assessed the development of 76 infants with fetal exposure to atypical antipsychotics.

Women who were seeking prenatal care and who had a diagnosis of schizophrenia and a singleton pregnancy were recruited into the study. Outcomes of 76 children exposed to atypical antipsychotics (clozapine n=33, risperidone n=16, sulpiride=13, olanzapine n=8, and quetiapine n=6) were compared to outcomes in a control group of 76 non-exposed infants. Control cases were recruited among women seeking prenatal care, but they did not have any psychiatric disorder and did not receive treatment with any antipsychotic medication.

Assessments included Apgar scores and the cognitive, language, motor, social-emotional, and adaptive behavior composite scores of the Bayley Scales of Infant and Toddler Development (BSID-III).

There were some important differences between the mothers taking antipsychotic medications and the mothers in the control group. Significantly more mothers in the exposed group than those in the control group did not take prenatal vitamins, either folic acid or a multivitamin, at any point during their pregnancy (23.7 % vs. 5.3 %). 40.8% of the mothers in the exposed group had a BMI >23.9 kg/m2(normal range, 18.5–23.9 kg/m2) compared to 17.1% of the controls. Fewer mothers in the exposed group breast-fed their infants for longer than 1 month (14.5 % vs. 82.9 %).

The investigators did not observe any malformations in the 76 newborns exposed to atypical antipsychotics during pregnancy.  The mean gestational age at birth did not differ between the two groups. Low birth weight was more common in antipsychotic-exposed infants than in controls (13.2 vs. 2.6 %, P =0.031), although there were no significant difference in mean birth weight and height between the two groups.

At 2 months of age, the mean composite scores of cognitive, motor, social-emotional, and adaptive behaviors as assessed using the BSID-III were significantly lower in infants exposed to atypical antipsychotics as compared to the infants in the control group. More antipsychotic-exposed infants met criteria for delayed development in these domains as defined by a composite score of <85 on these subscales of the BSID-III.

At 12 months of age, there were no significant differences between the two groups on all mean composite scores of the BSID-III.

The findings of this study are similar to those from a previous study which demonstrated some delays in motor development in children exposed to both atypical and typical antipsychotic agents. While the authors conclude that fetal exposure to atypical antipsychotics may cause short-term delays in cognitive, motor, social–emotional, and adaptive behavior development, there are some important limitations of this study.

First of all, the control group in this study is a group of women with no medication exposure and no psychiatric illness.  We recently reviewed a study in which pregnancy outcomes were assessed in women with bipolar disorder; bipolar disorder in women, whether treated or not, was associated with worse pregnancy outcomes than observed in women without psychiatric illness.  There is evidence that the same may be true in women with schizophrenia.

The other important point is that the women taking antipsychotic medications differed significantly from the controls on a number of important variables which may have a negative impact on pregnancy outcomes, including higher BMI, lower use of folic acid and prenatal vitamins, lower rates of breastfeeding.  Nor did the authors comment on the use of tobacco or alcohol in this group; in many other studies, smoking and substance use/abuse appears to be more common among women with psychiatric illness, even during pregnancy, and may be associated with worse outcomes.

So how does this study influence how clinicians should advise their patients regarding the use of atypical antipsychotic medications during pregnancy?  What we can tell our patients is that several studies have raised concerns regarding delays in cognitive and motor development in children exposed to atypical antipsychotic medications.  It is reassuring that in this study, the differences between the two groups disappeared by 12 months of age.  While these findings may raise concerns, we clearly need more data to better understand how maternal illness may be contributing to this clinical picture and to fully appreciate the long-term implications of these clinical findings.

This is a particularly difficult clinical situation.  Many women who take antipsychotic medications have severe or refractory illness and cannot reasonably consider discontinuing the antipsychotic or have no other clinically effective alternatives.  Women who are pregnant or planning to conceive are forced to make decisions in the absence of adequate data regarding the reproductive safety of the antipsychotic medications.  While there is a tendency to consider discontinuing or avoiding medications in the mothers as the safest option, there is considerable evidence to indicate that untreated illness in the mother also carries significant risks.

To gather more accurate information on the atypical antipsychotics, we have founded the National Pregnancy Registry for Atypical Antipsychotics, based at Massachusetts GeneralHospital in Boston.  We are now enrolling pregnant women aged 18-45 years who are treated with one or more atypical antipsychotics, and prospectively following them for a spectrum of outcomes, including organ malformations and maternal or newborn complications.

Those drugs include aripiprazole (Abilify), clozapine (Clozaril), ziprasidone (Geodon), paliperidone (Invega), risperidone (Risperdal), quetiapine (Seroquel), olanzapine (Zyprexa), asenapine (Saphris), lurasidone (Latuda), and Iloperidone (Fanapt).  Eligible patients for the MGH National Pregnancy Registry for Atypical Antipsychotics can enroll by calling 1-866-961-2388 or emailing registry@womensmentalhealth.org. Any clinicians who are interested in receiving print materials (including patient literature) about the Registry can sign up here.

Ruta Nonacs, MD PhD

Peng M, Gao K, Ding Y, Ou J, et al.  Effects of prenatal exposure to atypical antipsychotics on postnatal development and growth of infants: a case-controlled, prospective study.  Psychopharmacology (Berl) 2013 Apr 5.

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