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Review: women with schizophrenia have poorer pregnancy outcomes than other women, but it is unclear whether antipsychotic medications affect their infants
  1. Andrea Levinson, MD
  1. Resident in Psychiatry
    The Motherisk Program
    The Hospital for Sick Children
    Toronto, Ontario, Canada

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QUESTION: Does exposing infants to antipsychotic medication during pregnancy and lactation increase the risk of teratogenic, neonatal, and long-term neurobehavioural effects? Are schizophrenia symptoms altered by pregnancy and lactation, and vice versa?

Design

Systematic review.

Data sources

The authors searched Medline to December 2001 and the reference lists of identified articles.

Study selection

Studies of any design were eligible if they examined the extent to which antipsychotic medication exposure during pregnancy or lactation contributes to poor obstetrical outcomes in women with schizophrenia or poor developmental outcomes in their babies.

Data extraction

The authors did not provide detailed inclusion or exclusion criteria, nor did they describe how data were extracted for the review.

Main results

Few prospective studies were identified. There is inconsistent reporting about medication dosage and duration for infants exposed to antipsychotic medication during pregnancy and medication levels in breast milk and in infant blood and urine. Most studies include little detail about possible confounding factors, such as the mother’s use of drugs or alcohol during pregnancy and lactation.

Women with schizophrenia have a greater risk of poor obstetrical outcomes, including preterm delivery, low birth weight, and babies small for their gestational age. Exposure to typical antipsychotics (phenothiazines) during weeks 4-10 gestation may increase the risk of congenital malformations. There is a lack of data about the effects of exposing developing infants to atypical antipsychotics. There is also little evidence about whether changes associated with pregnancy and lactation alter schizophrenia symptoms.

Conclusions

Women with schizophrenia have a greater risk of adverse pregnancy outcomes compared with other women. The relative risk of using antipsychotic medications during pregnancy and lactation remains uncertain. There is no clear evidence that antipsychotic drugs are associated with major malformations. The authors suggest that further research is needed so that clinicians can limit treatment to situations in which the risk of untreated maternal illness outweighs the risk of exposing a developing infant to medications. The authors recommend against breastfeeding while a woman is receiving antipsychotics.

COMMENTARY

For the most part, this timely review addresses the authors’ objectives. The findings suggest that women with schizophrenia have increased risks during pregnancy that other women do not have, including preterm deliveries, other obstetrical complications and increased possibility of a psychotic breakdown during pregnancy or the post-partum period. With increased use of atypical antipsychotics, which are less likely to cause hyperprolactinemia induced infertility, more women with schizophrenia are likely to become pregnant, especially with unplanned pregnancies. The available evidence suggests that these drugs are relatively safe to use during pregnancy and lactation.

The main problem with this review is that the authors’ conclusions somewhat contradict their findings, specifically regarding the safety of typical antipsychotic drugs during pregnancy and lactation. The authors do not present compelling evidence that these drugs are harmful in pregnancy or lactation, and even caution about abruptly discontinuing them. These drugs have been on the market for more than forty years. There is no convincing evidence that any of them increase the baseline rate for major malformations or other long term neuro-developmental problems.1,2 The amount of drugs excreted in breastmilk is also minimal. There have been only occasional reports of sedation in exposed babies.3

Patton et el used limited search terms. For example, the key word “phenothiazines” was absent, resulting in the omission of two important papers. If included, these may have altered the conclusions of the review and implications for clinical practice. One of the omitted papers was the largest study from the Collaborative Perinatal Project, involving 1309 children exposed to phenothiazines during pregnancy. This study found no adverse effects on physical or mental development.4 The other omitted study was a review of phenothiazines used for nausea and vomiting in pregnancy. Here again, there was no increased risk of birth defects.5

The authors suggest that antipsychotic medications should be avoided in the first trimester if possible. This may be difficult, as more than 50% of pregnancies are unplanned in the general population, and probably an even higher proportion in people with schizophrenia. It is therefore likely that many women with schizophrenia will be on medication when they become pregnant, exposing the fetus during the first trimester.

We feel that a pregnant or lactating woman with schizophrenia should be treated with these drugs if indicated, after being given evidence-based information to assist in her decision making. Withholding the medication could impair the mother’s mental health and limit her potential to care for and interact appropriately with her baby.

References

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  • Publisher Correction
    Please note that there is an error in the author listing. The first and second authors of the Commentary for this article were ommitted
    The correct author list is shown here:

    Adrienne Einarson, Kate McKenna and Andrea Levinson (Commentators)

     

    The journal apologises for this error

    Footnotes

    • Source of funding: not specified.

    • For correspondence: S Patton, British Columbia Women’s Hospital, Reproductive Mental Health Program, Vancouver, Canada.

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      BMJ Publishing Group Ltd, Royal College of Psychiatrists and British Psychological Society