Reproductive Safety of Lurasidone and Quetiapine: Update from the National Pregnancy Registry for Psychiatric Medications
Abstract
Background:
Second-generation antipsychotics (SGAs), also called atypical antipsychotics, are common therapies for women with a spectrum of psychiatric disorders. No systematically ascertained human reproductive safety data are available for lurasidone, and prospective data for quetiapine are limited, making decisions regarding use of these medications during pregnancy complicated.
Materials and Methods:
The National Pregnancy Registry for Psychiatric Medications is a prospective cohort study designed to collect reproductive safety data relative to SGAs. Pregnant women aged 18–45 years, with psychiatric illness and prenatal psychotropic medication exposure completed three phone interviews during pregnancy and the postpartum period. Cases of presumed malformations are abstracted from medical records for adjudication by a teratologist blinded to medication exposure.
Results:
Of 2,293 women enrolled at the time of analysis, 134 in the lurasidone group, 264 in the quetiapine group, and 886 controls completed the postpartum interview and were therefore eligible for inclusion. Dropped or lost-to-follow-up participants (13%) and those currently pregnant were excluded. Participants were predominantly White, college-educated, and married (lurasidone = 88.1%, 76.9%, 77.6%; quetiapine = 89.8%, 71.2%, 75.0%; controls = 92.7%, 86.7%, 89.1%). Absolute risks of major malformations were 2.19% (lurasidone), 1.85% (quetiapine), and 1.77% (controls). Odds ratios comparing lurasidone and quetiapine with controls were 1.24 (95% confidence interval [CI] = 0.36–4.32) and 1.04 (95% CI = 0.38–2.85), respectively.
Conclusions:
No specific patterns of malformations were observed in infants exposed to the medications of interest. Lurasidone and quetiapine did not appear to be major teratogens, but further information is needed to refine risk estimates. Food and Drug Administration guidance underscores the importance of pregnancy registries.
Clinical trial number: NCT01246765.
Get full access to this article
View all access and purchase options for this article.
Disclaimer
Sponsors have no role in research design, data collection, analysis, release of findings, or article preparation.
References
1. Halfdanarson O, Zoega H, Aagaard L, et al. International trends in antipsychotic use: A study in 16 countries, 2005–2014. Eur Neuropsychopharmacol, 2017; 27(10):1064–1076.
2. Epstein RA, Moore KM, Bobo WV. Treatment of bipolar disorders during pregnancy: Maternal and fetal safety and challenges. Drug Healthc Patient Saf, 2015; 7:7–29.
3. Maglione M, Maher AR, Hu J, et al. Off-Label Use of Atypical Antipsychotics: An Update. Comparative Effectiveness Reviews. AHRQ: Rockville, MD, USA; 2011.
4. Administration USFD. Review Guidance: Evaluating the Risks of Drug Exposure in Human Pregnancies. 2005.
5. Lupattelli A, Spigset O, Nordeng H. Learning the effects of psychotropic drugs during pregnancy using real-world safety data: A paradigm shift toward modern pharmacovigilance. Int J Clin Pharm, 2018; 40(4):783–786.
6. van der Graaf R, van der Zande ISE, den Ruijter HM, et al. Fair inclusion of pregnant women in clinical trials: An integrated scientific and ethical approach. Trials, 2018; 19(1):78.
7. Administration USFD. Pregnancy and Lactation Labeling (Drugs) Final Rule 2014. Available from: https://www.fda.gov/drugs/labeling-information-drug-products/pregnancy-and-lactation-labeling-drugs-final-rule [Last accessed: October 24, 2022].
8. Pernia S, DeMaagd G. The new pregnancy and lactation labeling rule. P T, 2016; 41(11):713–715.
9. Ramoz LL, Patel-Shori NM. Recent changes in pregnancy and lactation labeling: Retirement of risk categories. Pharmacotherapy, 2014; 34(4):389–395.
10. Habermann F, Fritzsche J, Fuhlbruck F, et al. Atypical antipsychotic drugs and pregnancy outcome: A prospective, cohort study. J Clin Psychopharmacol, 2013; 33(4):453–462.
11. 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.
12. Sadowski A, Todorow M, Yazdani Brojeni P, et al. Pregnancy outcomes following maternal exposure to second-generation antipsychotics given with other psychotropic drugs: A cohort study. BMJ Open, 2013; 3(7):e003062.
13. Paulus W, Schloemp S, Sterzik K, et al. Atypical antipsychotics in early pregnancy. Reprod Toxicol, 2005; 20:453–491.
14. Paulus W. Is the use of aripiprazole safe during first trimester of pregnancy?. Reprod Toxicol, 2013; 37:87.
15. Bellet F, Beyens MN, Bernard N, et al. Pregnancy outcome in women exposed to aripiprazole during the embryonic period: A prospective multicentric cohort. Fundam Clin Pharmacol, 2013; 27:43.
16. Reis M, Kallen B. Maternal use of antipsychotics in early pregnancy and delivery outcome. J Clin Psychopharmacol, 2008; 28(3):279–288.
17. Peng M, Gao K, Ding Y, et al. Effects of prenatal exposure to atypical antipsychotics on postnatal development and growth of infants: A case-controlled, prospective study. Psychopharmacology (Berl), 2013; 228(4):577–584.
18. Wichman CL. Atypical antipsychotic use in pregnancy: A retrospective review. Arch Womens Ment Health, 2009; 12(1):53–57.
19. Twaites BR, Wilton LV, Shakir SA. The safety of quetiapine: Results of a post-marketing surveillance study on 1728 patients in England. J Psychopharmacol, 2007; 21(4):392–399.
20. Terrana N, Koren G, Pivovarov J, et al. Pregnancy outcomes following in utero exposure to second-generation antipsychotics: A systematic review and meta-analysis. J Clin Psychopharmacol, 2015; 35(5):559–565.
21. Park Y, Huybrechts KF, Cohen JM, et al. Antipsychotic medication use among publicly insured pregnant women in the United States. Psychiatr Serv, 2017; 68(11):1112–1119.
22. Administration USFD. Pharmacology Review(s): Application Number: 200603. 2009.
23. Kulkarni J, Worsley R, Gilbert H, et al. A prospective cohort study of antipsychotic medications in pregnancy: The first 147 pregnancies and 100 one year old babies. PLoS One, 2014; 9(5):e94788.
24. Cohen LS, Viguera AC, McInerney KA, et al. Establishment of the National Pregnancy Registry for Atypical Antipsychotics. J Clin Psychiatry, 2015; 76(7):986–989.
25. Cohen LS, Viguera AC, McInerney KA, et al. Reproductive safety of second-generation antipsychotics: Current data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics. Am J Psychiatry, 2016; 173(3):263–270.
26. Viguera AC, Freeman MP, Goez-Mogollon L, et al. Reproductive safety of second-generation antipsychotics: Updated data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics. J Clin Psychiatry, 2021; 82(4):20m13745.
27. Huybrechts KF, Hernandez-Diaz S, Patorno E, et al. Antipsychotic use in pregnancy and the risk for congenital malformations. JAMA Psychiatry, 2016; 73(9):938–946.
28. Cohen LS, Goez-Mogollon L, Sosinsky AZ, et al. Risk of major malformations in infants following first-trimester exposure to quetiapine. Am J Psychiatry, 2018; 175(12):1225–1231.
29. Sheehan DV, Lecrubier Y, Sheehan KH, et al. The Mini-International Neuropsychiatric Interview (MINI): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry, 1998; 59(20):22–33.
30. Centers for Disease Control and Prevention. Update on overall prevalence of major birth defects—Atlanta, Georgia, 1978–2005. MMWR Morb Mortal Wkly Rep, 2008; 57(1):1–5.
31. Holmes LB, Nasri H, Westgate MN, et al. The Active Malformations Surveillance Program, Boston in 1972–2012: Methodology and demographic characteristics. Birth Defects Res, 2018; 110(2):148–156.
32. Health MGHCfWsM. National Pregnancy Registry for Psychiatric Medications 2021. Available from: https://womensmentalhealth.org/research/pregnancyregistry/ [Last accessed: October 24, 2022].
33. Freeman MP, Viguera AC, Goez-Mogollon L, et al. Reproductive safety of aripiprazole: Data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics. Arch Womens Ment Health, 2021; 24(4):659–667.
34. Huybrechts KF, Hernandez-Diaz S, Avorn J. Antidepressant use in pregnancy and the risk of cardiac defects. N Engl J Med, 2014; 371(12):1168–1169.
35. Ennis ZN, Damkier P. Pregnancy exposure to olanzapine, quetiapine, risperidone, aripiprazole and risk of congenital malformations: A systematic review. Basic Clin Pharmacol Toxicol, 2015; 116(4):315–320.
36. Bar-Oz B, Einarson T, Einarson A, et al. Paroxetine and congenital malformations: Meta-analysis and consideration of potential confounding factors. Clin Ther, 2007; 29(5):918–926.
37. Damkier P, Videbech P. The safety of second-generation antipsychotics during pregnancy: A clinically focused review. CNS Drugs, 2018; 32(4):351–366.
38. Hatters Friedman S, Moller-Olsen C, Prakash C, et al. Atypical antipsychotic use and outcomes in an urban maternal mental health service. Int J Psychiatry Med, 2016; 51(6):521–533.
39. Arnold LM, Strakowski SM, Schwiers ML, et al. Sex, ethnicity, and antipsychotic medication use in patients with psychosis. Schizophr Res, 2004; 66(2–3):169–175.
40. Tosato S, Albert U, Tomassi S, et al. A systematized review of atypical antipsychotics in pregnant women: Balancing between risks of untreated illness and risks of drug-related adverse effects. J Clin Psychiatry, 2017; 78(5):e477–e489.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
Cite
Cite
Cite
OR
Download to reference manager
If you have citation software installed, you can download citation data to the citation manager of your choice
Information, rights and permissions
Information
Published In
Article first published online: April 4, 2023
Issue published: April 2023
Keywords
PubMed: 36716275
Authors
Authors' Contributions
L.S.C.: supervision, conceptualization, funding acquisition, methodology, writing—original draft; T.R.C.: investigation, data curation, visualization, writing—original draft; M.P.F.: supervision, conceptualization, funding acquisition, methodology, writing—review and editing; P.G.: formal analysis, data curation, visualization; P.S.C.: investigation, data curation, writing—review and editing; L.A.K.: investigation, data curation, visualization, writing—review and editing; M.A.: investigation; E.T.R.: investigation, data curation, visualization, writing—review and editing; D.C.: conceptualization, methodology, investigation, writing—review and editing; S.H.-D.: conceptualization, methodology, writing—review and editing; A.C.V.: supervision, conceptualization, funding acquisition, methodology, writing—review and editing
Metrics and citations
Metrics
Publication usage*
Total views and downloads: 227
*Publication usage tracking started in December 2016
Publications citing this one
Receive email alerts when this publication is cited
Web of Science: 0
Crossref: 15
- The postpartum period and bipolar disorder: early identification, prevention, and management
- Perinatal Safety of Quetiapine During Pregnancy
- Antipsychotic drug use during pregnancy and neonatal outcomes: a systematic review and meta-analysis
- Management of Bipolar Disorder in Pregnancy and Postpartum: A Clinicians’ Guide
- Bipolar Disorder
- The safety analysis of lurasidone based on the real-world data of FAERS database
- The Maudsley Prescribing Guidelines in Psychiatry
- Antipsychotic use during pregnancy and outcomes in pregnant individuals and newborns
- Prescribing Patterns for the Treatment of Bipolar Disorder in Pregnancy: A Retrospective Cohort Study
- Canadian Network for Mood and Anxiety Treatments 2024 Clinical Practice Guideline for the Management of Perinatal Mood, Anxiety, and Related Disorders: Guide de pratique 2024 du Canadian Network for Mood and Anxiety Treatments pour le traitement des troubles de l'humeur, des troubles anxieux et des troubles connexes périnatals
- View More
Figures and tables
Figures & Media
Tables
View Options
Access options
If you have access to journal content via a personal subscription, university, library, employer or society, select from the options below:
I am signed in as:
View my profileSign out
I can access personal subscriptions, purchases, paired institutional access and free tools such as favourite journals, email alerts and saved searches.
loading institutional access options
Alternatively, view purchase options below:
Purchase 24 hour online access to view and download content.
Access journal content via a DeepDyve subscription or find out more about this option.
