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Reproductive safety of aripiprazole: data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics

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Abstract

Aripiprazole has become one of the most commonly prescribed psychotropics, making a more comprehensive understanding of its reproductive safety profile a priority. The goal of the current analysis was to determine the risk of major malformations in infants exposed during the first trimester of pregnancy to aripiprazole compared to infants whose mothers had psychiatric diagnoses but did not use an atypical antipsychotic during pregnancy. The National Pregnancy Registry for Atypical Antipsychotics is a prospective pharmacovigilance program in which pregnant women are enrolled and interviewed during pregnancy and the postpartum period. Medical records are assessed to confirm presence or absence of major malformations. Pregnant women ages 18–45 with psychiatric diagnoses are enrolled. As of April 2020, N = 848 women who had delivered infants were eligible for analyses. A total of 158 women with first trimester exposure to aripiprazole were compared to 690 controls. For 163 infants born to women in the exposed group, seven major malformations were confirmed (4.29%), compared to fourteen of the 690 unexposed infants (1.99%). The unadjusted odds ratio for major malformations between aripiprazole-exposed and unexposed infants was 2.21 (95% confidence interval [CI] = (0.88, 5.57) The adjusted odds ratio for major malformations was 1.35 (95% confidence interval [CI] = (0.43, 4.20). After adjustment for confounding variables, the risk of major malformations after first trimester exposure to aripiprazole was not significant compared to controls. While these results are reassuring, they are limited by relatively small numbers of participants. Future analyses with larger numbers are expected to provide more of a complete and precise reproductive safety profile regarding aripiprazole use during pregnancy. Trial registration: clinicaltrials.gov NCT01246765

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Data is not available. The data that has been used is confidential.

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Acknowledgements

We thank and recognize Peter Gaccione, MA, for his contributions to data management and for his statistical programing for the National Pregnancy Registry.

Code availability

Code is not available. The code and data that have been used are confidential.

Funding

Current Sponsors of the NPRAA: Alkermes, Inc. (2016–present); Johnson and Johnson/Jannsen Pharmaceuticals, Inc. (2019–present) Janssen Pharmaceutica (2019–present); Otsuka America Pharmaceutical, Inc. (2008–present); Sunovion Pharmaceuticals, Inc. (2011–present); SAGE Therapeutics (2019–present); Teva Pharmaceuticals (2018–present); Aurobindo Pharma (2020–present); Past Sponsors of the NPRAA: Forest/Actavis Pharmaceuticals (2016–2018) AstraZeneca Pharmaceuticals (2009–2014, declined to sponsor: 2014–present); Ortho-McNeil-Janssen Pharmaceuticals, Inc. (2009–2014, declined to sponsor: 2015–present); Pfizer, Inc. (2009–2011, declined to sponsor: 2012–present).

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Authors and Affiliations

  1. Ammon-Pinizzotto Center for Women’s Mental Health, Massachusetts General Hospital, Boston, MA, USA

    Marlene P. Freeman, Adele C. Viguera, Lina Góez-Mogollón, Amanda V. Young, Phoebe S. Caplin, Sara A. McElheny, Taylor R. Church & Lee S. Cohen

  2. Harvard Medical School, Boston, MA, USA

    Marlene P. Freeman, Adele C. Viguera & Lee S. Cohen

  3. Cleveland Clinic, Cleveland Clinic Neurological Institute, Cleveland, OH, USA

    Adele C. Viguera

  4. Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital, Toronto, Ontario, Canada

    David Chitayat

  5. Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Sonia Hernández-Díaz

Authors
  1. Marlene P. Freeman
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  2. Adele C. Viguera
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  3. Lina Góez-Mogollón
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  4. Amanda V. Young
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  5. Phoebe S. Caplin
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  6. Sara A. McElheny
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  7. Taylor R. Church
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  8. David Chitayat
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  9. Sonia Hernández-Díaz
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  10. Lee S. Cohen
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Contributions

All authors contributed to this manuscript. Doctors Lee Cohen, Adele Viguera, and Marlene Freeman designed the study. Dr. Sonia Hernández-Díaz guided statistical analysis. Dr. Lina Góez-Mogollón designed the statistical code used for data analysis. Dr. David Chitayat is the blinded dysmorphologist for determining major malformations. The following authors were responsible for recruiting participants, guiding implementation, and collecting data from participants and hospitals: Phoebe Caplin, Taylor Church, Sara McElheny, and Amanda Young.

Corresponding author

Correspondence to Marlene P. Freeman.

Ethics declarations

Ethics approval and consent to participate

Ethical approval was obtained from the institutional review board of Massachusetts General Brigham (IRB reference # 2008P001861).

For all participants, informed consent was obtained prior to data collection. Consent was obtained using Massachusetts Brigham IRB approved materials.

Consent for publication

All authors agree to publish the manuscript in the Archives of Women’s Mental Health.

Conflict of interest

LSC: National Pregnancy Registry for Atypical Antipsychotics: Alkermes Biopharmaceuticals; Aurobindo Pharma; Janssen Pharmaceutica; Otsuka Pharmaceuticals; Sunovion Pharmaceuticals, Inc.; Teva Pharmaceuticals; Sage Therapeutics, Inc. Other Research Support: Brain & Behavior Research Foundation; JayMac Pharmaceuticals; National Institute on Aging; National Institutes of Health; National Institute of Mental Health; SAGE Therapeutics; Takeda/Lundbeck Pharmaceuticals Advisory/Consulting: Alkermes Biopharmaceuticals (through MGH Clinical Trials Network Initiative); JDS Therapeutics LLC; Praxis Precision Medicines, Inc. (through MGH Clinical Trials Network Initiative) Honoraria: None Royalty/patent, other income: None.

ACV: Research Support: National Pregnancy Registry for Atypical Antipsychotics: Alkermes Biopharmaceuticals; Aurobindo Pharma; Janssen Pharmaceutica; Otsuka Pharmaceuticals;Sunovion Pharmaceuticals, Inc.; Teva Pharmaceuticals; Sage Therapeutics, Inc. Other Research Support: None; Advisory/Consulting: Up-to-Date; Speaking/Honoraria: None;Royalty/patent, other income: None.

MPF: National Pregnancy Registry for Atypical Antipsychotics: Alkermes Biopharmaceuticals; Aurobindo Pharma; Janssen Pharmaceutica; Otsuka Pharmaceuticals; Sunovion Pharmaceuticals, Inc.; Teva Pharmaceuticals; Sage Therapeutics, Inc. Other research support: JayMac Pharmaceuticals LLC, SAGE Therapeutics; As an employee of MGH, Dr. Freeman works with the MGH CTNI, which has had research funding from multiple pharmaceutical companies and NIMH. Advisory/Consulting: Advisory Boards: Eliem, Sage; Independent Data Safety and Monitoring Committee: Janssen (Johnson& Johnson), Novartis; Steering Committee for Educational Activities: Medscape; educational activities: WebMD. Speaking/Honoraria: None; Royalty/patent, other income: None.

SHD: Consulting fees (e.g. advisory boards): Roche and UCB, and her institution received funding from Takeda for unrelated project; epidemiologist for the North American Antiepileptic Drugs pregnancy registry and advisor for the Antipsychotics Pregnancy Registry, which are funded by multiple companies; The Pharmacoepidemiology Program at the Harvard T.H. Chan School of Public Health is partially supported by training grants from Pfizer, UCB, Bayer and Asisa.

LGM, AZS, SAM, TRC, AVY, PSC, DC: Nothing to disclose.

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Freeman, M.P., Viguera, A.C., Góez-Mogollón, L. et al. Reproductive safety of aripiprazole: data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics. Arch Womens Ment Health 24, 659–667 (2021). https://doi.org/10.1007/s00737-021-01115-6

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  • DOI: https://doi.org/10.1007/s00737-021-01115-6

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