Olanzapine. In postmarketing surveillance studies and case reports, there have been have anecdotal cases of fetal malformations related to olanzapine use during pregnancy. Several larger studies2-4,8,16 did not find higher rates of congenital malformations or any pattern of malformation types, although none were designed or powered to examine rare events. Animal data show no evidence of teratogenicity.18 A study comparing rates of placental passage of antipsychotics13 found higher rates for olanzapine than for quetiapine and risperidone, as well as higher prevalence of low birth weight and perinatal complications. A neonatal withdrawal syndrome has also been reported.19 Boden et al8 found an increased risk for gestational diabetes and macrocephaly with olanzapine.
Data suggest that olanzapine may be associated with somewhat higher rates of the adverse effects attributable to atypical antipsychotics (gestational diabetes and possibly macrocephaly), which could be related to olanzapine’s relatively higher rate of placental passage. Olanzapine could be a reasonable choice in a woman who had a history of good response to this medication, but would be lower priority than quetiapine when a new drug is indicated during pregnancy.
Quetiapine. In clinical trials, quetiapine had lower rates of placental passage compared with risperidone and olanzapine.13 One case report found only small changes in quetiapine serum levels during pregnancy.20 Prospective studies (90 exposures,8 36 exposures,2 7 exposures,16 4 exposures,3 and 4 exposures4) show no increase in fetal malformations or adverse neonatal health outcomes related to quetiapine, and manufacturer safety data reveal no teratogenic effect, although delays in fetal skeletal ossification were seen in rats and rabbits at doses comparable to the recommended human range.21
Quetiapine is a reasonable first choice when a new atypical antipsychotic is indicated for a pregnant patient.
Risperidone. Rates of placental passage of risperidone are higher compared with quetiapine.13 Postmarketing surveillance data (265 exposures22 and 10 exposures23) and prospective studies (including 72 exposures,8 49 exposures,2 51 exposures,4 16 exposures,16 and 5 exposures3) suggest risperidone has no major teratogenic effect. When malformations were present, they were similar to expected rates and types of malformations, and no specific malformation type was overrepresented. However, in some cases, researchers noted a withdrawal-emergent syndrome that included various combinations of tremors, irritability, poor feeding, and somnolence.22 Animal data are similarly reassuring, although increases in early fetal mortality and (potentially related) changes in maternal behavior have been observed in rats.24,25 A major caveat with risperidone is its propensity to cause hyperprolactinemia, which is detrimental to efforts to conceive and maintain a pregnancy.26,27
Risperidone is not associated with higher rates of adverse events in pregnancy than other atypical antipsychotics. It would not be a first choice for a woman trying to conceive or in the early stages of pregnancy, but would be a reasonable choice for a woman already well into pregnancy.
Ziprasidone. Available reports are few and generally do not report findings on ziprasidone separately.8,28 Manufacturer data includes 5 spontaneous abortions, one malformation, and one stillbirth among 57 exposures,4 and available animal data suggest significant developmental toxicity and impaired fertility.29 In pregnant rats, ziprasidone dosed as low as 0.5 times the maximum human recommended dose resulted in delayed fetal skeletal ossification, increased stillbirths, and decreased fetal weight and postnatal survival, and ziprasidone dosed as low as 0.2 times the maximum recommended human dose resulted in developmental delays and neurobehavioral impairments in offspring. In pregnant rabbits, ziprasidone dosed at 3 times the maximum recommended human dose resulted in cardiac and renal malformations.29
Although available data are too sparse to draw reliable conclusions, the small amount of human data plus animal data suggest that ziprasidone should be less preferred than other atypical antipsychotics during pregnancy.
Lurasidone. No data addressing lurasidone use in humans during pregnancy are available. Material submitted to the FDA includes no evidence of teratogenicity or embryo-fetal toxicity in rat and rabbit studies using 3 and 12 times the maximum recommended human dose (80 mg) based on a body surface area comparison.30
Asenapine. No data specifically addressing asenapine use in humans during pregnancy are available. Studies in rats and rabbits found no increase in teratogenicity, but did find increases in postimplantation loss and decreases in pup survival and weight gain with maternal doses equivalent to less than the maximum recommended human dose.31
Iloperidone. No data specifically addressing iloperidone use in humans during pregnancy are available. Animal studies of iloperidone found multiple developmental toxicities when iloperidone was administered during gestation.32 In one study, pregnant rats were given up to 26 times the maximum recommended human dose of 24 mg/d during the period of organogenesis. The highest dose caused increased early intrauterine deaths, decreased fetal weight and length, decreased fetal skeletal ossification, and increased minor fetal skeletal anomalies and variations. In a similar study using pregnant rabbits, the highest dose caused increased early intrauterine deaths and decreased fetal viability at term.