Evidence-Based Reviews

Atypical antipsychotics during pregnancy

Current Psychiatry. 2013 July;12(7):12-18

References

1. Chang J, Streitman D. Physiologic adaptations to pregnancy. Neurol Clin. 2012;30(3):781-789.

2. McKenna K, Koren G, Tetelbaum M, et al. Pregnancy outcome of women using atypical antipsychotic drugs: a prospective comparative study. J Clin Psychiatry. 2005;66(4): 444-449; quiz 546.

3. Newham JJ, Thomas SH, MacRitchie K, et al. Birth weight of infants after maternal exposure to typical and atypical antipsychotics: prospective comparison study. Br J Psychiatry. 2008;192(5):333-337.

4. Reis M, Kallen B. Maternal use of antipsychotics in early pregnancy and delivery outcome. J Clin Psychopharmacol. 2008;28(3):279-288.

5. Matevosyan NR. Pregnancy and postpartum specifics in women with schizophrenia: a meta-study. Arch Gynecol Obstet. 2011;283(2):141-147.

6. Mendhekar DN, Sunder KR, Andrade C. Aripiprazole use in a pregnant schizoaffective woman. Bipolar Disord. 2006;8(3):299-300.

7. Watanabe N, Kasahara M, Sugibayashi R, et al. Perinatal use of aripiprazole: a case report. J Clin Psychopharmacol. 2011;31(3):377-379.

8. Bodén R, Lundgren M, Brandt L, et al. Antipsychotics during pregnancy: relation to fetal and maternal metabolic effects. Arch Gen Psychiatry. 2012;69(7):715-721.

9. Maáková E, Hubicˇková L. Antidepressant drug exposure during pregnancy. CZTIS small prospective study. Neuro Endocrinol Lett. 2011;32(suppl 1):53-56.

10. Bristol-Myers Squibb (Ed.). Aripiprazole: Drugdex drug evaluations, 1974-2003. Princeton, NJ: Thomson Micromedex; 2003.

11. U.S. Food and Drug Administration. FDA datasheet: Aripiprazole. http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21436slr006_abilify_lbl.pdf. Accessed April 8, 2013.

12. Nguyen T, Teoh S, Hackett LP, et al. Placental transfer of aripiprazole. Aust N Z J Psychiatry. 2011;45(6):500-501.

13. Newport DJ, Calamaras MR, DeVane CL, et al. Atypical antipsychotic administration during late pregnancy: placental passage and obstetrical outcomes. Am J Psychiatry. 2007;164(8):1214-1220.

14. Barnas C, Bergant A, Hummer M, et al. Clozapine concentrations in maternal and fetal plasma, amniotic fluid, and breast milk. Am J Psychiatry. 1994;151(6):945.

15. Clozaril [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2013.

16. Lin H, Chen I, Chen Y, et al. Maternal schizophrenia and pregnancy outcome: does the use of antipsychotics make a difference? Schizophr Res. 2010;116(1):55-60.

17. Young CR, Bowers MB Jr, Mazure CM. Management of the adverse effects of clozapine. Schizophr Bull. 1998;24(3):
381-390.

18. Zyprexa [package insert]. Indianapolis, IN: Eli Lilly and Company; 1997.

19. Gilad O, Merlob P, Stahl B, et al. Outcome of infants exposed to olanzapine during breastfeeding. Breastfeed Med. 2011;6(2):55-58.

20. Klier CM, Mossaheb N, Saria A, et al. Pharmacokinetics and elimination of quetiapine, venlafaxine, and trazodone during pregnancy and postpartum. J Clin Psychopharmacol. 2007;27(6):720-722.

21. U.S. Food and Drug Administration. FDA datasheet: quetiapine. http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/20639se1-017,016_seroquel_lbl.pdf. Accessed April 11, 2013.

22. Coppola D, Russo LJ, Kwarta RF Jr, et al. Evaluating the postmarketing experience of risperidone use during pregnancy: pregnancy and neonatal outcomes. Drug Saf. 2007;30(3):247-264.

23. Mackay FJ, Wilton LV, Pearce GL, et al. The safety of risperidone: a post-marketing study on 7,684 patients. Hum Psychopharmacol. 1998;13(6):413-418.

24. Risperdal [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2012.

25. U.S. Food and Drug Administration. FDA datasheet: risperidone. http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020272s056,020588s044,021346s033,021444s03lbl.pdf. Accessed April 11, 2013.

26. Katz E, Adashi EY. Hyperprolactinemic disorders. Clin Obstet Gynecol. 1990;33(3):622-639.

27. Davis JR. Prolactin and reproductive medicine. Curr Opin Obstet Gynecol. 2004;16(4):331-337.

28. Johnson KC, Laprairie JL, Brennan PA, et al. Prenatal antipsychotic exposure and neuromotor performance during infancy. Arch Gen Psychiatry. 2012;69(8):787-794. doi: 10.1001/archgenpsychiatry.2012.160.

29. U.S. Food and Drug Administration. FDA datasheet: ziprasidone. http://www.fda.gov/downloads/Advisory
Committees/CommitteesMeetingMaterials/Pediatric AdvisoryCommittee/UCM191883.pdf. Accessed March 15, 2013.

30. U.S. Food and Drug Administration. FDA datasheet: lurasidone. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/200603Orig1s000PharmR.pdf. Accessed March 15, 2013.

31. U.S. Food and Drug Administration. FDA datasheet: asenapine. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022117s000_OtherR.pdf. Accessed March 15, 2013.

32. U.S. Food and Drug Administration. FDA datasheet: iloperidone. http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022192lbl.pdf. Accessed March 15, 2013.

33. U.S. Food and Drug Administration. FDA datasheet: paliperidone. http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021999s018lbl.pdf. Accessed March 15, 2013.

34. Weggelaar NM, Keijer WJ, Janssen PK. A case report of risperidone distribution and excretion into human milk: how to give good advice if you have not enough data available. J Clin Psychopharmacol. 2011;31(1):129-131.

Paliperidone. In animal studies, there were no increases in fetal abnormalities when pregnant rats and rabbits were treated with up to 8 times the maximum recommended human dose of paliperidone during the period of organogenesis.³³

A single case report³⁴ measured levels of risperidone and its 9-hydroxy metabolite, paliperidone, in the breast milk of a mother who had taken risperidone during pregnancy and in the serum of her child. 9-OH-risperidone dose in breast milk was calculated as 4.7% of the weight-adjusted maternal dose, and serum levels in the infant were undetectable. No ill effects on the child were observed.

It is not possible to draw solid conclusions about atypical antipsychotics’ potential effects on human development from animal studies. Because of the lack of human data for the newer atypical antipsychotics—asenapine, iloperidone, lurasidone, paliperidone—in general these agents would not be advisable as first-line medications for treating pregnant women.

A few caveats

All atypical antipsychotics share the propensity to trigger or worsen glucose intolerance, which can have significant negative consequences in a pregnant patient. When deciding to use an atypical antipsychotic during pregnancy, blood glucose should be monitored carefully and regularly.

Because all atypical antipsychotics (except clozapine) are FDA pregnancy class C—indicating that animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks—the decision to use these medications must be based on an individualized assessment of risks and benefits. Patients and their providers together should make a fully informed decision.

There is an urgent need for larger and better-designed investigations that will be sufficiently powered to detect differences in outcomes—particularly major malformations, preterm delivery, adverse events in labor and delivery, metabolic and anthropometric effects on the newborn, and neurodevelopmental and psychiatric outcomes for individuals exposed in utero—between women without mental illness, untreated women with mental illness, and women receiving atypical antipsychotics during pregnancy. Further research into the pharmacokinetics and clinical efficacy of antipsychotics in pregnant women also would be useful. Clinicians can assist with these efforts by submitting their patient data to a pregnancy registry maintained by the Massachusetts General Hospital (see Related Resources).

Bottom Line
Treatment with atypical antipsychotics during pregnancy may increase the risk of adverse birth outcomes, but inadequately controlled mental illness also carries some degree of risk. The decision to use any atypical antipsychotic during pregnancy must be based on an individualized assessment of risks and benefits and made by the pregnant patient and her provider.

Related Resources

Gentile S. Antipsychotic therapy during early and late pregnancy. A systematic review. Schizophr Bull. 2010;36(3):518-544. www.ncbi.nlm.nih.gov/pmc/articles/PMC2879689.

Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics. www.womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry.

Drug Brand Names

Aripiprazole • Abilify Olanzapine • Zyprexa

Asenapine • Saphris Paliperidone • Invega

Clozapine • Clozaril Quetiapine • Seroquel

Haloperidol • Haldol Risperidone • Risperdal

Iloperidone • Fanapt Ziprasidone • Geodon

Lurasidone • Latuda

Disclosures

The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.